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Use and effects of chemical agents on Australian personnel in Vietnam - Royal Commission (Hon. Mr Justice P. Evatt) - Final report, dated 31 July 1985 - Report - Volume 3 - Birth anomalies

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The Parliament of the Commonwealth of Australia


Commissioner: The Hon. Mr Justice P. Evatt, DSC , LLB

Final Report—July 1985

Volume 3: Birth Anomalies

Presented 22 August 1985 Ordered to be printed 19 September 1985

Parliamentary Paper No. 290/1985


Commissioner: The Hon. Mr Justice Phillip Evatt DSC. LLB.

A Judge of the Federal Court of Australia


July 1985


Australian Government Publishing Service Canberra 1985

© Commonwealth of Australia 1985

ISBN 0 644 04339 3 Set of Volumes ISBN 0 644 04342 3 Report Volume Three

Printed by Canberra Publishing and Printing Co., Fyshwick, A.C.T.


Commissioner: The Hon. Mr Justice Phillip Evatt DSC

G.P.O. Box 4842 Sydney, N.S.W. 2001 Telephone: (02) 239 6222

Your Excellency,

Secretary: Mr B.D. Meade

31 July 1985

In accordance with Letters Patent issued to me on 13 May 1983, 27 June 1984, 3 August 1984 and 23 April 1985, I have the honour to present to you the Final Report of my inquiry.

I believe that the Report complies with those Letters Patent and that my task is therefore completed.

Yours sincerely


His Excellency the Right Honourable Sir Ninian Stephen, A.K., G.C.M.G., G.C.V.O., K.B.E. Governor-General and Commander-in-chief Government House CANBERRA A.C.T. 2600

File Ref.:







3.1 Study Design 17

3.2 International Opinion of Australian Study 24 3.3 Criticisms of AVHS Birth Defects Study 28

3.4 Consistency 37


4.1 Study Design 43

4.2 WAA's Final Submission on Ranch Hand II 51


5.2 Spina Bifida 62

5.3 Coloboma 63

5.4 Cleft Lip 64

5.5 Congenital Neoplasms 65

6. NEW ZEALAND APPLICATORS STUDIES 6.1 Smith et al (1981) 66

6.2 Smith et al (1982) 67


7.2 Descriptive Studies (a) Tung et al 1980 72

(b) Ministry of Health/US Military Assistance Command Vietnam and US Department of Defense 73

(c) Huong and Phuong (1983) 75

(d) Tuyen et al 77

(e) Trung et al 78

(f) Phuong & Huong (1983) 79

(g) Trung & Chien (1983) 80

(h) Can et al (1983) 81

(j) Lang. Van and Tung (1983) 83

7.3 Analytical Studies (a) Can et al (1983) 84

(b) Huong & Puong (1983) 86

7.4 Conclusion 87


(a) Field and Kerr 1979 88

(b) Thomas (1980).Thomas and Czeizel (1982) 88 (c) Nelson et al (1979) 90

(d) Hanify et al (1981) 90

(e) Townsend et al 91

(f) Balajaran and McDowell 93

(g) The Seveso Accident 94

(h) Alsea 2 95

(j) Conclusion 96







13.1 Summary of Dr Pearn's Background Report to the Senate (1982) re Birth Anomalies and Chemicals 106

13.2 Genetic Toxicology - Mutagenicity -Dr Brusick 117


2,4,5-T 125

TCDD 126

Diquat 128

Paraquat 128

Picloram 128

Dalapon 129

Diuron 129

Monuron 129

Bromacil 130

Cacodylic Acid 130

Creosote/Distillate 131

Borate/Chlorate 131

DDT 131

Malathion 132

Dieldrin 132

Ch.lordane 133

Lindane 133

Diazinon 133

Pyrethrins 134

Diethyl-m-Toluamide (DEBT) 134

Dimethyl-Phthalate (DMP) Insect Repellent 134 Di-n~Butyl Phthalete (DBP) (Tick and Mite Repellent 135

Dapsone, Chloroquine, Primaquine & Paludrin 135 Solvents 136

Conclusion 136








21. ADDENDUM WAA's Tasmanian Study 166






I Introduction II Standard of Proof III Ascertainment of Claims IV Exposure


V Toxicology and Safe Doses VI Health Effects General


VII Health Effects. Reproductive Outcomes and Birth Anomalies


VIII Health Effects, Cancer


IX Health Effects. Mental


X Mortality XI Class Action XII Status of W A A XIII Interim Report and S. 47


XIV Benefits and Treatment


XV Conclusions and Recommendations Epilogue





"Felix qui potuit rerum cognoscere causes"

Virgil, Georgies ii. 490

(trans) "Happy is one who knows the causes of things




No aspect of this Inquiry has been approached with more

concern than this. One only has to use the words 'Vietnam

conflict1, 1 multi-national chemical company1 and 1 birth

defect1 in a sentence to realise that here indeed is a

volatile emotional mix.


Prior to the commencement of this Inquiry the allegation

both in Australia and in the United States was that

exposure of service personnel to Agent Orange in Vietnam

had led to congenital anomalies or birth defects in their

children conceived after their return to their home


That this was the allegation is reflected in the Terms of


Paragraph j of the Letters Patent reads:


j. Evidence relating to the extent to which exposure to the chemical agents used has resulted in congenital anomalies among the children of Australian personnel;

The Commission has decided against a narrow approach to

this paragraph of the Terms of Reference. Stillbirths and

miscarriages could. if causally connected, be described as

"effects on Australian personnel of exposure to the

chemical agents" and also of course as "effects on the

.... health and well-being of their spouses". referred to

in paragraph (i) of the Letters Patent.

Accordingly, this section of the Report will deal with

untoward reproductive outcomes of all kinds including

infertility, miscarriage, stillbirths as well as

congenital anomalies.

The initial submission of W A A included the following:

The submission is that a large number of

veterans' children have suffered from congenital disabilities. The consistency of reports of similar disabilities and the number of veterans complaining of those disabilities is


In relation to wives of veterans, the submission included

the following:


The most common complaint is (sic) stillbirths, miscarriages, urinary tract infection and cervical cancer.3

At pp 65-66 is to be found the following.

It is submitted that there is an abnormal rate of congenital defects. Whilst some such as talipes, hair lip, cleft palate are not rare in the

general population, it would appear that the incident (sic) is much higher than the normal population expectation. More rare forms of disability such as absence of limbs or digits, absence of bones in limbs, bone abnormalities and

the like are appearing. Other disabilities which are common are kidney abnormalities, asthma, children are small or underweight, hyperactivity, deafness, eye problems, enlarged head, enlarged

liver, internal haemorrhaging, spina bifida, slow learning capacity, epilepsy, heart problems and skin rashes.

It would appear that further research is needed to establish how the veterans' exposure to chemicals is passed on to the wives and children.

Deformities in children, stillbirths and miscarriages may be explained by chromosonal (sic) alterations * in the veterans and passed on in the spermatozoa" (sic).

The other area which needs investigation is the possibility that the seminal fluid has been altered in some way to become caracinogenic (sic) or has some other characteristic which causes urinary tract infection and/or birth deformities.


In its final submission W A A has not attempted to

summarise its position nor to put into orderly form the

conclusions which in its submission ought to be drawn from

the evidence.


However, in the first: paragraphs

final submission does focus on

question. It reads:

on Birth Defects the

what is a critical

The first question which must be asked is whether it is biologically feasable (sic). to have paternally mediated birth defects. It is

submitted that clearly the answer to this

question is in the affirmative.

In support of this claim the submission appears to rely


(a) Joffe;

(b) An assertion of a positive male-mediated effect from

anaesthetic gas exposure;

(c) An allegation of an increase in spontaneous abortions

following the Seveso incident;

(d) The Vietnamese studies;

(e) The C.D.C. Study;**

** A number of the comments made in the submissions of W A A indicate misunderstanding of the nature of case-control studies and the meaning of statistical significance


The Commission will deal with what it takes to be the

underlying bases for the submission as well as its bald


(f) Criticisms of the Australian Birth Defects Study.8


Finding WAA's approach inadequate. the Commission dealt

with the problem from basic epidemiological principles.

The allegation which is made, namely, that there is an

increase in the incidence of certain outcomes amongst

those with a certain exposure, is of a type validly tested

only by epidemiological science. In truth, the exposure

alleged is Vietnam service, although chemical use in

Vietnam is postulated as the reason for the untoward


Epidemiology is that science which is concerned with the

patterns of disease or outcomes occurring in human

populations and with the factors that influence those



The science involves basically three forms of activity,

counting, comparing and interpreting.

Counting involves ascertaining the frequency of occurrence

of the condition in the particular population or group.

The frequency must be expressed as a rate where the cases

(or numerator) are related to the population (or

denominator) and both numerator and denominator must be

carefully defined.

Next, a comparison is made of the frequency of occurrence

of the condition of interest under two or more different

circumstances, (e.g. the birth defect rates amongst the

offspring of men with chemical exposure compared with

those of men with no chemical exposure).

The next step is interpretation. This involves first the

identification of circumstances under which the frequency

of the condition cited as an outcome is different.

Then one must determine whether the differences observed

are likely to have come about by chance. This is done by

statistical testing, a mathematical operation.


Next, in circumstances where differences are unlikely to

have occurred by chance, all the possible plausible,

biological explanations of the observed relationship

between the circumstances and the condition should be

considered and a judgment should then be made as to the

most likely explanation for the association which has been


It has been said that epidemiological data alone cannot

establish that a certain factor really causes an outcome.

This is because what is being measured is association not

causation. (Laboratory investigations of causation are

difficult when the subjects are men and putative

poisons.) Nonetheless, an inference of causation is

logically reliable if the following are present:

(a) A strong association between the risk factor and the

outcome (called a high relative risk);

(b) Consistency - that is. if the association is found in

many different data sets. sometimes called


(c) Specificity - that is to say, whether the association

between the risk factor and the outcome has some


significant teature which distinguishes it from

associations shown by other risk factors and other


(d) A dose-response relationship - that is to say, if

increasing exposure to the risk factor is associated

with increasing occurrence of the outcome;

(e) An association between the risk factor and the outcome

is biologically plausible;

(f) Changes in the prevalence of the risk factor results

in the predicted change in prevalence of the


On the other hand if:

(a) there is no association or a very weak one between the

risk factor and the disease;

(b) the association is not found in different data sets;

(c) exposure to the risk factor does not produce the

particular condition of interest with regularity;


(d) there is no dose-response relationship;

(e) the association is biologically implausible;

(f) changes in the prevalence of the risk factor do not

produce change in the prevalence of the condition;

it is probable that there is no causal connection between

the risk factor and the outcome.

The Commission will adhere to these principles so as to

ascertain whether or not a connection between chemical

exposure in Vietnam and untoward reproductive outcomes has

been established in the epidemiological sense. This may

permit inferences as to causation to be drawn.

At the outset it must be said that no evidence of adverse

reproductive outcomes associated with either Vietnam

service or chemical exposure of any kind was in fact

produced by W A A in the course of the Commission. ** This

is perhaps surprising despite the high cost of good

quality epidemiological studies.

** Apart from the Tasmanian study and the Kerr and Field Report thereon, see Addendum.


In view of the substantial amount of Government money-

provided to W A A for preparation and presentation of its

case, the comment must be made that no expert was called

by Counsel representing W A A to make any analysis in

support of the allegation that, "the consistency of

reports of similar disabilities and the number of veterans

complaining of these disabilities is significant".10

Nor was any lay person called to speak to any numbers.

It is important to remember that the standard texts stress

that only a small percentage of the total burden of human

developmental defects can be attributed to drugs or

chemicals.11 Indeed, environmental causes including

radiation, infection, maternal metabolic imbalance and

drugs and chemicals have been responsibly estimated as

causing only between 8 and 11% of birth defects. The


following table gives more detail.


Causes of Developmental Defects in Man- Estimates Based on Surveys and Case Reports in the Medical Literature

Known genetic transmission 20%)

Chromosomal aberration Environmental causes


Ionizing radiations 1%)

Therapeutic Nuclear )

Infections 2-3%)

Rubella virus Varicella virus(?) )

Herpes virus hominis Syphilis )

Maternal metabolic imbalance 1-2%)

Endemic cretinism Phenylketonuria )

Diabetes Virilizing tumors )

Drugs and environmental chemicals 4-5%)

Androgenic hormone Anticonvulsants )

Folic antagonists Oral hypoglycemics(?) )

Thalidomide Few neurotropic- )

anorectics(?) )

Oral anticoagulants Organic mercury )

Maternal alcoholism )

Combinations and interactions ?)

Unknown 65-70%

Again, in every 100 live births there will be between 2

and 7 children with a congenital defect requiring

treatment sooner or later. The size of the percentage

depends on the method of counting and to some degree on

the standard of living. But the underlying load of

defects has been found to be present in all countries and

at all times when reliable measurements have been taken.

- 11%



The Commission is fortunate in that it had available to it

an extensive study measuring the incidence of birth

defects amongst the offspring of Australia's Vietnam

veterans. This was conducted by the Australian Veteran's

Health Study Group, (AVHS), a special section of CIH, in

1982 - 1983.

Since this study constitutes the only direct evidence

concerning reproductive outcomes amongst Australian

Vietnam veterans, it is dealt with in some detail at this


This is both epidemiclogically and forensically

appropriate - epidemiclogically, because "counting" and

"assessing the relative risk" ought to be the first steps:

forensically. because of the "best evidence" rule.

14 As has been previously described. there was prior to 1980 much public concern, particularly amongst Vietnam

veterans, that the frequency of congenital anomalies in

their children was disproportionately high. The alleged

higher frequency was attributed by some to exposure to

Agent Orange although herbicides of other kinds and


insecticides as well as some other aspects of Vietnam

service have been blamed.

In 1980 the Commonwealth Institute of Health (CIH), an

academic institution within the University of Sydney (and

constituting that University's School of Public Health),

agreed with the Australian Government to conduct a series

of scientific investigations into the health of Vietnam

veterans and their families and for that purpose set up a

special and separate unit, AVHS.

Part of this series was a case-control study of congenital

anomalies and Vietnam service. Planning for the study

began in May 1981. A protocol or plan for the study was

prepared and referred by the then Minister for Veterans'

Affairs to a Scientific Advisory Committee (SAC) which had

been established to advise him on the scientific merit of

such studies. The study was originally designed by Dr

Robert Maclennan who was Associate Professor of

Epidemiology within CIH.

The SAC consisted of Australian public health and

epidemiological experts. They are all of such eminence

that in the ordinary course one would not bother to

reproduce curriculum vitae. However, as things were said


of some by advisers to W A A in the course of conferences

designed to reach agreement on the structure of the

15 proposed Morbidity Study to be conducted by the same scientific group, the Commission is of the view that its

opinion of the impartiality, integrity and high

qualification of two at least should be stressed. They


1. Dr Bruce Armstrong

Since 1979, Dr Armstrong has been the Director of the

National Health and Medical Research Council Unit in

Epidemiology and Preventive Medicine within the

University of Western Australia. He graduated in

medicine from that University in 1969 and then trained

as a specialist in internal medicine at the Royal

Perth Hospital, becoming a Member of the Royal

Australian College of Physicians in 1972. He became a

Fellow of the College in 1975. He trained in

epidemiology between 1972 and 1975 and obtained a

Doctorate in that discipline in 1975. Subsequently he

was Senior Lecturer in Medicine at the University of

Western Australia. thereafter. Director of Health,

Research and Planning in the Department of Health,

Western Australia, which position he held until 1979.


2 . Dr Tony McMichael

Dr McMichael is presently Principal Research Scientist

at the CSIRO Division of Human Nutrition, Adelaide.

He is a most highly regarded epidemiologist,

particularly known for his work on the "Healthy

Worker" effect.

The SAC, following a meeting oil 11 August 1981, reported

to the then Minister for Veterans' Affairs that the

proposed study, "could produce scientifically valid data

on the association between Vietnam service and the

fathering of malformed children".16

The study was under the ultimate direction of Emeritus

Professor, R.J. Walsh, the Director of Scientific Studies.

The investigation was commenced by Dr Robert Maclennan and

continued by Dr John Donovan, a Senior Adviser in

Epidemiology within the Commonwealth Department of

Health. Dr Donovan was assisted by Dr Michael A. Adena, a

statistician; Mr Glen Rose, a Senior Research Officer and

M/s Diana Battistutta also a statistician.

Again, in view of some inappropriate comments by the

advisers to WAA, the Curriculum Vitae of Dr Donovan and

Dr Adena are set out.


Dr John Donovan

MB BS 1965

PhD 1970

FFCM 1984 (MFCM 1973)


1965 Junior Resident; Medical Officer, Royal Prince Alfred Hospital. Camperdown. NSW.

1966-1969 Postgraduate Medical Research Scholar, Dept of Mathematical Statistics, University of Sydney.

1969-1971 C.J. Martin Travelling Fellow of National Health and Medical Research Council of Australia. in Dept of Medical Statistics and Epidemiology, London School of Hygiene and Tropical Medicine.

1971-1974 Jointly, Lecturer in Epidemiology, Dept of Medical Statistics and Epidemiology. London School of Hygiene and Tropical Medicine, and Medical Statistician, Office of Population Censuses and Surveys.

From 1974 Australian Dept of Health. Canberra. May 1974 to July 1975 - Specialist (Epidemiology); twice during this time acted as Assistant Director-General. July 1975 - Promoted to Medical Services Adviser Class 1; following that acted as Director of State Division, and several times as First Assistant Director-General. June 1978 - promoted to Medical Services Adviser, Class 2; since then acted several times as First Assistant Director-General, and as Deputy Chairman, Capital Territory Health Commission.


Michael Adena

1971-1974 BSc University of Melbourne.

1975-1978 PhD. Australian National University.

1971-1972 Research Associate with Dr D.A. Holton, Dept of Mathematics. University of Melbourne.

1973-1974 Programmer/analyst with UC Compunet Ltd.

1974 Research Associate with Miss B Laby, Dept of

Statistics. University of Melbourne.

1978-1980 Research Officer, Dept of Population Biology, Australian National University.

1980-1982 Post-doctoral Fellow. Dept of Population Biology, Australian National University.

1982- 1983 Statistician, Australian Veterans Health Studies.

1983-Managing Director. INTSTAT Australia Pty Ltd. Fellow of the Royal Statistical Society.

3.1 Study Design

The basic design of the study was that of a case-control

study with one individually matched control for each

case. In case-control studies groups of individuals are

selected who do (cases) and do not (controls) have the

"disease state" under study. In this study the "disease


state" was strictly being the father of a child with a

defined congenital anomaly or anomalies; however, the

terms "case" and "control" are used loosely to refer to

the children. The children of the cases will be referred

to as "malformed" and those of the controls as "healthy",

using that word in the sense of not malformed.

The two groups were then compared with respect to the

exposure characteristic alleged to have caused the disease

state, namely. Vietnam service of the father.

In case-control studies, controls are matched to cases.

In this study healthy infants born in the same hospitals,

to mothers of similar ages to the mothers of children with

anomalies, and born as closely as possible in time to the

births of children with anomalies were selected as

potential controls. Where the "payment category" of the

mother of the malformed child was readily available, the

mother of the healthy child had to be in the same payment

category, e.g. Private (expensive), Intermediate, or

Public (free).

The investigation involved examination of hospital and

cytogenetic laboratory records of Infants born with

anomalies in New South Wales, Victoria and the Australian


Capital Territory between the years 1966 and 1979

inclusive. In all, 34 hospitals and 4 cytogenetic

laboratories were involved and co-operated fully with the

investigating team. To emphasise, whenever the birth of

an infant with an anomaly was detected. it was matched to

a healthy control infant born in the same hospital to a

mother of similar age and as close as possible in time to

the birth of the child with the anomaly.

The fathers of both cases and controls were identified in

8517 instances and those identified were compared with the

list of every man who served in the Australian Army

between 1962 and 1972, which was the period of Australian

involvement in Vietnam. Fathers identified as having

served in the Army during this period were then classified

according to whether or not they had served in Vietnam.

The sample was. as a matter of statistics, large enough to

enable the study to meet its stated aims.

An important thing to notice is that the original pool was

a pool of birth defects selected by their occurrence and

without reference to any question of service or

non-service, whether in Vietnam or otherwise. In short,

without bias.


In other words, there were to be 8,500 pairs or sets of

infants. Of these, one was a malformed infant and the

other a healthy infant matched in an appropriate way by

maternal status to the malformed infant. Thereafter, the

question was asked, "Is a malformed infant (case) more

likely to have been exposed in the sense of having a

Vietnam veteran for a father than an infant in the healthy

group? (control)."

It is emphasised that this study exceeded the statistical

power usually sought in epidemiological studies and had a

90.5% chance of detecting as statistically significant a

true 1.5-fold risk of anomalies in the children of Vietnam

veterans had there been such an increase. (R/R = 1.5)

One hundred and twenty-seven of the fathers of children

with anomalies were Vietnam veterans whilst 123 veterans

were amongst the fathers of healthy children. This study

provides no basis for the suggestion that Army service in

Vietnam relates to the risk of fathering a child with an

anomaly. It is of such quality and size as to be strong

evidence that no such association exists.


The study of course did not stop there. It needed

confirmation by statistical analyses. These used methods

which have been described by all who have examined them as

the most appropriate and up to date. Amongst the

statistical analyses was one which confirmed that the

matching of malformed with healthy infants was generally

adequate but which suggested that an adjustment for the

age of the mother might be necessary in a more detailed

analysis. Observe that risk was least for mothers aged

25, which accords with known community norms.

Other factors on which information was available and which

might bear upon the risk were then examined. Factors

which were found to be of relevance were that the risk of

malformation is higher in male children than in female, in

multiple rather than in single births. The country of

birth of the father also affected the risk.

Factors examined which proved to be irrelevant (i. e.,

statistically insignificant) included the age of the

father, the socio-economic group of the father. the birth

place of the mother and perhaps most significantly urban

or rural residence of the parents. Significantly, because

it is generally agreed that rural residence increases the


likelihood of exposure to the constituents of Agent

Orange, namely 2,4-D and 2.4,5-T.

These examinations provided internal statistical

validation of the study and its methods.

The study also produced other most useful information.

First, the risk of fathering a malformed child is

independent of service' in the Army whether as a National

Serviceman or as a member of the Australian Regular Army.

It is also independent of service in Vietnam either as a

National Serviceman or as a member of the Australian

Regular Army.

Furthermore, the risk for both groups was found to be

independent of length of service in Vietnam. If exposure

to chemicals in Vietnam was associated with birth defects

one would have expected to find an increase in risk by

increase in length of service. In fact the study found

the contrary, there was a tendency towards lower risk

amongst veterans with longer Vietnam service.

Furthermore. the risk for both National Servicemen and

members of the Australian Regular Army is independent of

the time between homecoming and conception of a child, and


also of the time between year of departure for Vietnam and

conception. That is to say, the time between service in

Vietnam and the time of conception of the child was

irrelevant, as was the year or years of service.

The significance of these matters is apparent. One of the

mechanisms postulated by W A A for the production of birth

defects in the children of Vietnam veterans conceived

after the father had returned was a theory of contaminated

sperm or semen.

No healthy young soldier's mature sperm or semen would 17

remain in his system for more than 90 days. If

chemicals were to blame, then, on this postulate, birth

defects would cluster in babies born around 9-12 months

after the fathers' return from Vietnam. They did not.

Again, if Agent Orange were to blame one would expect

clusters in the offspring of those who served during

periods when the chemical agents were used and a falling

off after cessation of possible exposure. Neither

phenomenon appeared.

Dr Armstrong assisted in the supervision of the

investigation and critically reviewed the final report and

its relationship to the data. Dr Mathews, as consultant


Uo AVHS, was also Involved. Dr Armstrong and Dr Mathews

later became consultants to the Commission. During a

period in excess of 12 months the Commission has developed

the highest possible regard for their capacity, their

integrity and their total lack of bias.

Dr John Donovan who headed the team which prepared the

final report was examined and cross-examined before the

Commission. His conscientiousness in performance of the

study and his capacity, integrity and total lack of bias

in reporting have been clearly demonstrated.

3.2 International Opinion of Australian Study

The Commission's untutored views of the study are

confirmed by independent experts of the highest

international repute. Amongst those experts were a number

interviewed personally by the Commission but not called to

give evidence at formal hearings. These included Dr George

Lathrop and Dr William Wolfe, Epidemiologists of high

qualification and the principal investigators in the Ranch

Hand studies. The principal investigator in the Centre for

Disease Control's (CDC) Birth Defect Study, Dr Dave

Eriksson, also discussed the Australian Study with the



All three approved the study and indeed expressed

admiration for its design, size and execution.

Professor Bo Holmstedt was called as a witness before the

Commission. He is a physician but his special interest and

qualif ication is in toxicology. It is fair to say that

there is probably no more highly respected toxicologist in

the world. Prior to retirement he was Professor of

Toxicology at the Karolinska Institute, Stockholm,

Sweden. He remains the President of the International

Union of Toxicology.

His comments on the Australian Study are:- "I think it is

an extremely well conducted study and it takes care of the

confounding factors in the way you would expect of a

modern toxicological ‘ epidemiological study and I am very

impressed with the way they went about this".18

Dr David Brusick, an eminent scientist and internationally

renowned expert on genetic toxicology although anxious to

disavow any expertise as an epidemiologist said:

(The study) appears to have been careful in searching for any possible effects that might have arisen. It seems to be consistent with the conclusions that I have generated on the basis of


the discussion in that it would be unlikely in my opinion for an agent, which I consider to be non-mu tagenic, to have been expected to produce any elevated inheritable genetic effects which would have then resulted in an increase in

congenital malformations in the offspring of women.19

Doctor Fiona Stanley, a medical doctor and presently

Deputy Director and Senior Research Fellow in the National

Health and Medical Research Council's Research Unit in

Epidemiology and Preventive Medicine at the University of

Western Australia, is a most eminent expert on birth

defects both in Australia and abroad. She became a

consultant to the Royal Commission with particular

reference to the Vietnamese studies.

Of the Australian study she said:

. . . the value of this study is that it was large and was extremely well done. It could not really have been better done. ... It is set up with a

large enough number to answer the question that it wanted to ask ... (the cases) in fact were

matched well and (the researchers) found a relative risk which was not significantly different from zero which means that the study basically found a negative association. Now that

really means that you can say with confidence that a Vietnam veteran is not more likely than anyone else to father a child with a structural malformation noted at birth. (emphasis


The Professor of Public Health (Epidemiology) in the

Columbia University School of Public Health, New York

State. Dr Zena Athene Stein, gave evidence before the

VII -2 6

Commission. She has for many years specialised in the

epidemiology of reproduction and birth outcomes with

particular emphasis on developmental disorders.

She gave general evidence about the likelihood of birth

anomalies consequential upon chemical exposure but also

considered the AVHS study. Of this, she said:

In some senses many epidemiologists would like the Donovan study best.. They would like it

best, first of all it is very big and that is

important. It is bigger ... than the CDC study. But what they like particularly is the design which takes the birth defects from the hospital and links them with the fact of Vietnam service and the circumstances of service. and there is no

intermediary group of people who would have - would be able to contaminate the two sets of findings."21 ....

It is difficult to find a flaw in that study

insofar as it set out to look at birth defects that could be discovered at birth on the one hand as an end point .and then the fact of service in Vietnam on the other. One feels that on these

two issues the result is a very strong


It is a very big study and a major study and I do not think anyone has really found a serious flaw in it.22

There are many other comments to be found in the

transcript approving of the study. Those selected are

well qualified and representative.


3.3 Criticisms of the AVHS Birth Defects Study

The first and most valid criticism is that the study

focused upon birth defects generally, rather than upon

defects of notorious genetic origin. As structural

defects are the predominant anomalies apparent within the

first week of birth in any population, it came as no

surprise that this position was demonstrated in the data

collected by the investigators.

Amongst the hypothesis suggested by W A A for the

production of male-mediated birth defects is only one

hypothesis which has even the remotest plausibility,

namely, that the male gonads were in some way affected by

chemicals so as to continuously produce defective mature

sperm cells causing consequential birth anomalies. This

mutagenic hypothesis would lead one, with hindsight, to be

looking for chromosomal and other genetic abnormalities

and a study which focused on such abnormalities might have

been logically more appropriate.

This criticism was one of the two caveats that were

suggested by Drs Armstrong and Stanley in their review of 23

the study in the Medical Journal of Australia.

However, it should be noted that when the study was being


designed there was no emphasis on genetic/chromosomal

abnormalities. Those complaining were complaining "across

the board". Indeed, up until the final written submission 24

made on behalf of W A A in late January 1985, no such

emphasis appears.

Accordingly, it would have been politically pointless for

a study to be designed around a limited class of

abnormalities when what was being complained about was a

general increase in birth anomalies, including structural

ones, amongst the children of veterans.

The second criticism is that the study was only of defects

discoverable in the first week of life. The argument goes

that many defects are discovered after the first week of

life and that the study is therefore flawed by. in effect,

missing the many defects which manifest themselves after

the first week of life. But there must be some end

point. Some birth defects or congenital anomalies are

discovered in the teens of the child, in early adulthood

and indeed in middle age.

The criticism has very limited validity. But to suggest

that by reason of it the study is flawed reveals some

misunderstanding of the concepts. If the case was that


the children of Vietnam veterans were vulnerable only to

those defects discovered after the first week there might

be some validity in the criticism.

2 5

Dr Armstrong and Dr Stanley have pointed out that this

limitation on the scope of the study means that most

congenital heart defects, some chromosomal anomalies,

metabolic disorders, renal anomalies and some major gut

defects are not taken into account. However, they go on

to point out that:

Whether or not their exclusion limits the value of the study depends on the prior credibility of the proposition that paternal exposures suffered in Vietnam would have produced only defects of

this type, (emphasis added)26

No mechanism has been suggested by which such a narrow

range of effect might be postulated. Moreover, as will be

discussed later, the results of the Australian Study are 27

very similar to those found in the CDC Study, which

was not so limited, but which took into account defects

discovered during the first year of life.

But the study chose as its subject that which was readily

ascertainable, namely, defects discovered in the first

week of life. This was a valid decision on epidemiological

grounds. Not the least of those grounds was that the data


were recorded by people unconnected with the study before

any furore about Agent Orange and birth defects.

The particular case-control design which required no

interview and which used extant data records meant that no

bias is introduced by the selection of the subject matter

of the study. Accordingly, on a true understanding of

epidemiology, this study remains valid.

Thirdly, it is said that the numbers are too small to

detect small increases in relative risk. This is a valid

criticism in the sense that it is true that the study will

not detect increases in relative risk smaller than that

which it says it will detect.

However, the study exceeds the statistical power usually

sought in epidemiological studies. Of course any study is

improved by the increase in its statistical power which

flows from the increase in the numbers.

Dr Schneiderman1s suggestion that the numbers were too

small was adopted by W A A . 28 That the truth of this

criticism does not bear upon the validity of the study is

however emphasised by the evidence of Dr Schneiderman.

The transcript when he was being cross-examined by Mr


O'Keefe in respect of some mathematics he had worked out

concerning the study and which workings were

2 9

exhibited , reads:

.... If for example I was looking at a birth defect which constituted perhaps 5% of all birth defects I would have to divide that 17,997 and 14,538 by decimal 05 in other words multiply it by 20.

MR O'KEEFE: So you would multiply 17.997 X 20? --- Yes.

Can you tell me what that is? --- Approximately 360,000.

And if you wanted it at about 90% you would multiply it by about 290,000? --- Yes.

And you would be looking at 290,000 births. ---Births.

I gather from your comments that if you had done the study you would have done it differently would you? --- I would probably have done it very much as the people who did it did

it. What I would have done was perhaps - I think that I would have attempted to do a substantially larger study than they have done.

What, using 360,000 and 290,000 births as a test structure? --- Possibly if I could do such a thing."30

It flows from what Dr Schne.iderman said that his imaginary

study would have involved an examination of more children

with birth defects than would have been born in

Australia. The postulation of such a study is

mathematically and theoretically correct. In practical

terms it is impossible.


Perhaps it should be observed that Dr Schneiderman is not

an epidemiologist.

Dr Armstrong and Dr Stanley also point to the study's lack

of power to detect an increase in any single defect or

category of defects.31

This difficulty was acknowledged by the authors at p 35 of

the study. However, the study did separately consider

those diagnostic groups of malformations in which the

prevalence of the condition was sufficient to detect odds

ratios of more than 1.5 and found that in each such

diagnostic group there was no statistically significant

difference in the risk of fathering a malformed child by


veteran or non-veteran fathers.

3 3 It has also been suggested by Reznik et al that as the exposure studied was service in Vietnam and not exposure

to any particular herbicide, the concluding statements

made by the investigators in an article published in the


Medical Journal of Australia of 31 March 1984 was

unjustified. The conclusion referred to was in the

following terms:


The potential hazard which we studied was service in Vietnam. In the public mind this has become associated with exposure to chemicals,

particularly to herbicides and their

contaminants. The failure to identify any risk of fathering malformed offspring associated with Vietnam service means that these postulated causes do not need to be considered.35

In response to Reznik et al's criticism of that

conclusion, the investigators pointed out36 that the

study was commissioned in response to allegations of

increased anomaly rates in children of Vietnam veterans as

a whole and that accordingly the design was appropriate to

that situation, no groups of veterans with high exposure

to chemicals having then been identified and the

possibility of their existence being no more than


The evidence as to exposure given before the Commission

has done nothing to elevate that possibility: on the

contrary, exposure, except in a handful of veterans,

remains a speculation which is now shown on the balance of 37

probabilities to be without real foundation.

Accordingly, this criticism fails, and the investigators'

conclusion is valid.


As well, at the time of the study, the investigators

believed that the construction of a reliable herbicide or

other chemical exposure index was not feasible but more

up-to-date research by AVHS has led to the view that such

an index may be possible. In the result, however, it is,

in a sense, fortunate that no attempt at an exposure index

was made at the earlier stage.

In the time between the commencement of the Birth Defect

Study and the commencement of this Commission the veterans

had changed their ground from Agent Orange exposure to a

blanket allegation of chemical exposure. One of the

benefits of the Birth Defect Study is that it negates

service in Vietnam as an exposure which increased birth

defects apparent in the first week of life. It

accordingly answers the allegation about other chemical


It is normally a valid criticism of an epidemiological

study that it does not address dose-response

relationship. The present study did consider dose

relationship, in the sense of length of service in

Vietnam. In an ideal world it would also have addressed

the herbicide exposure question, as the CDC Study did.


This failure does not undermine the force of the study for

the Commission's purposes.

The study is also subjected to a criticism which, frankly,

is not understood. WAA's final written submission38

says. "The AVHS study is limited to the statement that the

study for all practical purposes does not support an

association between Vietnam service and birth defects."

It continues. "Alternatively it does not show that there

is no association between Vietnam service and birth


These statements are contrasted with what the study itself

says at p 29 of the summary, "There is no evidence that

army service in Vietnam has increased the risk of the

birth of a child with an anomaly."

If WAA's submission means that there could be an

association between Vietnam service and birth defects of a

size smaller than that which the study design is able to

detect with high confidence, that is simply a truism.

But the study was sufficiently powerful to detect that

fathers born in Australia. The United Kingdom, New Zealand

or Eire were more likely to father a malformed child than


fathers born in Greece. Italy. Yugoslavia or Lebanon. The

odds ratio for this effect was 1.13 with a 95% confidence

interval of 1.05 to 1.23.

If the evidence before the Commission in respect of birth

defects had been only the AVHS Birth Defects Study and had

the criticism of that study been only that which was led

before the Commission. then the Commission would have

determined, on the balance of probabilities, that Vietnam

service by the father did not increase the risk of the

veteran fathering a malformed child.

But the Commission is fortunate to be able to test such a

determination by the consideration of other evidence,

namely, the biological implausibility, consistency of the

evidence with thosa of other studies and other

epidemiological and logical factors. These matters are

now considered.

3.4 Consistency

The next step in the process is to consider whether the

non-association found in an examination of the actual

group which the Commission is charged to study is

consistent with other data.


There are a number of studies directed to the presence in

Vietnam of various male populations and the subsequent

reproductive history of those populations. A consideration

of the mechanisms postulated for increased birth defects

amongst the children of Australian Vietnam veterans will

show that epidemiological studies of human reproductive

outcomes based upon the exposure of the female or of both

partners are of limited value in the present context.

This Inquiry is concerned with an alleged association

between male-only exposure in Vietnam and untoward

reproductive outcomes. The Commission will deal with

female experimental data in a limited way but in this

section will consider those studies which are of direct


Those studies include:


(a) Ranch Hand II (1984);


(b) The CDC (Atlanta) Birth Defects Study (1984);

(c) Tung et al (1980) - The Problem of Mutagenic Effects 41

on the First Generation Exposed to Herbicides;


(d) Other Vietnamese Studies.

The three studies first mentioned are those most directly

relevant to this Inquiry.

There are also two other studies of the reproductive

effects of male exposure to phenoxy herbicides in a

context other than Vietnam:

(a) J.C. Townsend et al (1982) Survey of Reproductive

Events of Wives of Employees Exposed to Chlorinated


(b) A.H. Smith et al (1981) Congenital Defects and 43

Miscarriages Amongst New Zealand 2,4,5-T Sprayers.


In the search for consistency or otherwise. the first

target is the birth defect aspects of Ranch Hand II.

Senior Counsel Assisting and the Senior Consultant, Dr

John Mathews, were present at the release of the Ranch

Hand Base Line Morbidity Study in Washington, DC USA on

February 24, 1984. They advise that the pressures upon

the investigators were apparent. Those pressures were

both internal and external.


Internal pressures resulted from a need to give value to

self-reported data without over-emphasis and a need to

report in a way which precluded suggestions of cover-up.

There seemed also to be some tension created by differing

epidemiological/medical judgments and statistical ones.

External pressures included: the extraordinary interest

(even harassment) of the American media; pressure to meet

a reporting date imposed by Congress; lack of time for

follow-up in areas where technically statistically

significant results might be misleading.

Whilst in the US, the Commission interviewed not only the

principal investigators but also the staff employed in the

study and found their professionalism, objectivity and

dedication outstanding.

At the heart of the Ranch Hand study was the dose-response

principle. If the Ranch Hand population was more exposed

to herbicides and dioxin than others, then it should

manifest stronger and/or earlier indications of adverse

health if such consequences are connected with that



It has been widely accepted that the average Ranch Hander

was substantially exposed to the herbicides and dioxin.

Exposure calculations estimate that an average Ranch

Hander received, as a minimum, 1000 times more exposure to

Agent Orange than would an average sized naked man,

standing in an open field directly beneath a spraying 44 aircraft.

For some reason this degree of Ranch Hand personnel

exposure vis-a-vis ground personnel has been consistently

undervalued. Various adversary groups and the media have

sought to reverse it. It was seriously challenged in

WAA's submission to the Commission. The basis for the

undervaluing. the reversal and the challenge remain a

mystery. Certainly, no evidence before the Commission

contradicts rational inference or the dose calculations

mentioned above.

The Commission finds that the Ranch Hand population was

the most herbicide exposed military cohort to serve in

Vietnam. The exposure data in respect of Australian

personnel is at best equivocal.

The undeniable exposure of a totally ascertained

population, matched to an equally clear cut non-exposed


cohort, provided for the Ranch Hand II study as ideal an

epidemiological setting as is possible from this war time


In view of the controversy however, reference to the

evidence of the two Ranch Hand officers who were called

before the Commission is appropriate.

The Commission finds each of these men to be a witness of

truth and reliable in his recollection. They were

straightforward military men and in a sense just what one

would expect to find amongst a group who volunteered for

one of the most dangerous jobs to be done in South


Mr R.J. Dudenhoeffer in his statement said:

The flight engineer was often drenched in the herbicide. It was the duty of members of the air crew to check the herbicide level in the tank before commencing a mission. I was often

drenched by herbicide under pressure escaping when the filling cap was removed for this

purpose. Nobody worried about being drenched in this way. Getting wet with the herbicide was regarded as an inconvenience and not as a health hazard. We would continue with the mission and put up with the inconvenience of being wet.45


Colonel Hubbs in his statement said:

Agent Orange was in puddles on the ground in the vicinity of where the aircraft were being

filled. I walked through this area as did the others. Some Agent Orange was always on the floor of the aircraft. It was guite common for our boots to be wet with Agent Orange. Unless a

tank or hose had been shot out and you were

really saturated in herbicide, it was not normal to shower until the end of the day, even though you smelled of Agent Orange, had been walking in it and it was all over your boots. The spray

from the lead aircraft was at times sucked

through the open windows and funnelled back through the aircraft.46

Each of these men was cross-examined but no undermining of

their evidence about exposure was achieved.

The Commission's considered view is that no Australian

achieved an exposure to Agent Orange equivalent to direct

spraying in an open field whilst naked. It follows that

an average Ranch Hander received at least 1000 times more

exposure to this chemical agent than an average Australian.

4.1 Study Design

Ranch Hand II used a matched cohort design in a concurrent

prospective setting, incorporating mortality, morbidity

and follow-up studies. A detailed population

ascertainment process identified 1269 Ranch Hand personnel

who served in Vietnam, during the period 1962-1971. A


comparison group was formed by identifying all individuals

assiqned to selected Air Force organisational units with a

mission of flying cargo to, from and in the Republic of

Vietnam during the same period.

By a computerised "nearest neighbour" selection process,

up to 10 comparison individuals were matched to each Ranch

Hander by job category, race and age to the closest month

of birth. An average of 8.2 comparison individuals for

each Ranch Hander was determined by record review to be

fully suitable for study.

Each living Ranch Hander and the first living member of

this comparison set were selected to participate in the

Morbidity Study which consisted of an in-home interview

and a comprehensive physical examination.

Data concerning fertility and reproductive events were

collected during the questionnaire and the physical


It must be borne in mind that the analyses were based on

non-verified and therefore subjective questionnaire

reporting. In addition, the data on children is data on

parent-reported defects, not defects per se.


Fertility and reproductive information was limited to

reproductive events that occurred whilst the participant

was married or living with a partner, unless reported in

the questionnaire as "other pregnancies." Such

information was reconciled as far as possible with data

collected from all available spouses and partners.

Response rates were excellent. Amongst Ranch Handers

1,174 (97%) participated in the questionnaire and 1,145

(87%) participated in the physical examination. The

response rates amongst controls were somewhat less.

Despite some initial difficulties the control group was

adequate for the study's purposes, particularly in view of

the large number of comparisons which were available.


The following findings are relevant for present

purposes: The Commission's conclusions or remarks in

relation to certain findings are set out.

1. On a total fertility index the Ranch Hand group scored

higher than the control group;

VI1-4 5

2. On a married fertility index 60% of Ranch Hand couples

had the number of children they desired as compared

with 58.6% of the original controls and 58.2% of the

added controls.

The Commission concludes that the Ranch Hand group did

not suffer any relative loss of fertility, the only

probable outcome in the unlikely event of a chemically

induced mutagenic effect on gonads.

3. No significant difference was found in the sperm

counts of Ranch Handers and non Ranch Handers. Nor

was there any difference in the sperm morphology of

the two groups. This provides no evidence for any

effect of chemicals on spermatogenesis in the Ranch „ , 48

Hand group.

4. The Ranch Hand group and controls were compared in

relation to miscarriage and stillbirth. Such

comparison was made both pre- and post-South East

Asian service. In relation to miscarriage although

there was some excess in the miscarriage rate

post-South East Asia for the Ranch Hand group it was

nearly equivalent to a similar excess existing between

the two groups pre-South East Asia. In the overall 4 9

analyses there was no significant difference.


Similarly there was no significant difference in

stillbirth rates and the rates against both parameters

were found to be comparable to observed rates in the

general United States population. The increase in

both Ranch Handers and comparisons post South East

Asia is appropriately attributed to increasing

* n 50 maternal age.

Once again there was no evidence for any chemically

induced effects on the rates of stillbirths and


The finding of a slight statistical increase in

miscarriage rate amongst the sub group of officers is

an anomaly. The same effect was not found either

amongst enlisted flying crew or enlisted ground 51 crew.

5. A smaller percentage of Ranch Hand personnel reported

children with birth defects than did the comparisons.

When the relative situations were compared, pre-South 52

East Asia and post-South East Asia there was no

statistically significant difference between the two

groups in relation to birth defects.


6. A statistically significant difference between the two

groups was found in relation to neo-natal death. This

statistical significance flows not from any increase

in the rate of neo-natal deaths amongst the children

of Ranch Hand personnel, which remained constant at

1.5%, but by a diminution in the reported incidence of

neo-natal deaths amongst the comparisons. This

diminution was from 1.2% to .4% which was, in the view

of the investigators, a mere artefact arising out of

under-reporting on the part of the comparison group.

Professor John Mathews advises that a .4% neo-natal

death rate is well below the rate which might have

been expected from any general population. The other

three figures, 1.5, 1.5 and 1.2 are more approximate 53 to those one would expect.

The Commission is of the view that the relative risk

based on this artefact should be ignored.

7. When the broad category of birth defects was analysed,

after adjustments for maternal co-variables (smoking,

drinking and age) a statistically significant excess

was found for the Ranch Hand group in relation to post

South-East Asia live births.

VI1-4 8

However. when the results were further analysed after

omitting skin anomalies included in ICD Category 757

(these anomalies are of minor medical consequence, and

include what are usually called birthmarks, not birth

defects), no significant group differences remained.

Suggestive group differences however, could not be 54 excluded.

There appeared to be a small clustering of birth

anomalies in the skin of children of the Ranch

Handers. This suggests that those who were exposed

were, naturally, more alert in their examination of

their offspring and consequently found such birth


To date the analyses have relied in large measure on

unverified spouse reports. Amongst exposed people,

higher differential recording of conception and birth

outcomes is tu be expected and the study could not

measure its effect.

The omitting of the skin anomalies is an appropriate

epidemiological device. The suggestive association

that remains is readily explained by differential

reporting, and does not in the Commission's view

contradict the Australian Birth Defect Study.

VI1-4 9

8. The investigators themselves warn about the absence of

verification and the effect of differential


9. It is instructive to compare the cluster of ICD 757

defects (that is, skin anomalies) with corresponding

findings in the Australian Birth Defect Study, where

only one out of 32 cases with defects in this

classification was the child of a veteran. Thus, no

corresponding cluster is to be found in the Australian

Study which suggests that the Ranch Hand investigators

fear of over-reporting in relation to post-South East

Asia children may be justified. Note that the

Australian Study was not based on self reports.

10. Dr Stein (whose high qualifications are referred to

above) emphasises the objective parameters of

fertility, sperm count and sperm morphology which

argue strongly against the operation of what seems to

be the only plausible theoretical mechanism for the

production of adverse reproductive effects, namely,

mutagenic damage to the male germ cells.This makes a 5 5

skin or neo-natal death connection unlikely.


11. W A A called Dr Schneiderman to comment upon the Ranch

Hand II findings. He did not seek to place any stress

upon the artefactual increase in relative risk of

neo-natal death nor upon the suggestive excessive

birth defects in ICD 757 classification. Dr

Schneiderman sought rather to rely upon what he called

a trend of differences said to be evident in a number 5 6 of end-points.

4.2. WAA's Final Submission on Ranch Hand II

This matter is taken up by W A A in its final submission,

as follows:-

In looking at the data in Ranch Hand II in

respect of unfavourable birth outcomes it is seen that 10 items of data have been collected,

namely, childless marriages, abnormal sperm, miscarriages, stillbirths, non live births, learning disability, physical handicaps, infant

deaths, birth defects and neo-natal deaths. There is a statistically significant increase in neo-natal deaths in the children of Ranch Hand

personnel. What is more important is that out of 10 listed items there is an increase in 9


The submission continues that the likelihood of this

happening by chance is less than 1%. Dr Schneiderman,

whose proposition this was, was cross-examined.58 The

following points were made by the cross-examiner:-


1. The doctor took a list of twelve items and drew his

conclusion from only 10 of them. There is of course a

difference between 9 out of 10 and 9 out of 12. This

makes the 1% theory incorrect.

2. The list analysed by the doctor included both

stillbirths and non-live births. The doctor was

unable to draw a distinction between these 2


3. The doctor conceded that what he had counted as an

increase in respect of neo-natal deaths was not an

increase but a difference. He conceded that this

difference reflected a decrease in the comparison

group which was a result of either a protective

effect, improved neo-natal care or, most likely,


4. The doctor conceded that the physical handicap

classification was one where there was not an increase

or worsening but rather an improvement on the part of

the Ranch Hand group.

5. The doctor conceded that the live birth incidence

figure revealed no difference in real terms.


6. He further agreed that the miscarriage rate difference

was not significant. Indeed his own phrase was, "I

wrote it down for myself, the ratios have not changed

over time, one."

7. He conceded that the report showed that Ranch Handers

were more fertile.

8. He conceded that the report showed Ranch Handers

scoring higher on the test of having the desired

number of children.

9. He agreed that Ranch Handers were shown to be more

likely to marry post South-East Asia.

10. He agreed that sperm abnormalities were higher amongst

controls than amongst Ranch Handers.

Having regard to these matters, the Commission does not

regard the "trend of increases" argument as having any


The Commission accepts Dr Schneiderman as a witness of

truth. His speciality is as he readily conceded that of a


mathematician. He is not an epidemiologist, a geneticist

or an expert in reproductive outcomes. His conclusions

insofar as they are mathematical, have not been



The next study which requires consideration in the process

of assessing the consistency of data is the US Study of

Eriksson et al, called "Vietnam Veterans Risks for

Fathering Babies with Birth Defects" known as the CDC


The impetus for the study was the concern expressed by US

Vietnam veterans at the possibility of increased risks for

fathering babies with birth defects.

The concern was that the increased risk might stem from

exposure to herbicides, particularly Agent Orange. The

study was however designed to determine if Vietnam

veterans (in general) had been at increased risk. This

approach was taken because at the time when the study was

designed the investigators took the view that it might not

be possible to obtain any measure of exposure to

herbicides other than by questioning individual Vietnam


veterans. which, of course could lead to the criticism

that the cases would be likely to suffer recall bias.

This is because of the well-known phenomenon that those

who have the "outcome" are inclined to "remember" the

exposure in circumstances where there has been a great

deal of publicity connecting the one with the other.

Accordingly the basic design focused on that which could

be easily checked, namely, service in Vietnam.

5.1. Methods

Atlanta, Georgia, has a Congenital Defects Register

conducted by the Metropolitan Atlanta Congenital Defects

Program (MACDP). This program attempts to ascertain all

babies with defects diagnosed during the first year of

life born to mothers resident in the area.

The study chose births during the years 1968 through 1980

and registration in the register as "tickets of entry" to

the study. In all. about 13,000 babies qualified.

From the register of babies, only those who had defects

coded by ICD code-8 rubrics were chosen as cases. Such

classification usually signifies a serious or major birth



This selection process resulted in an initial choice of

7,529 babies as cases. The final number eligible for the

study was 7,133. This reduction occurred for various

reasons including the exclusion of babies thought to have

been given up for adoption, the random choice of one baby

from families with more than one registered baby, and the

selection of babies for a pilot study.

The control group was selected from amongst 323,421 live

born babies born in the Atlanta area during 1968 through

1980. These were selected with the aid of the State of

Georgia Vital Records Unit and matched to the babies in

the case group with respect to-

(a) Race;

(b) Year of Birth;

(c) Hospital of Birth;

Some of the babies thus chosen were babies from the case

group and these were deleted from the control group

although retained in the case group. The study was thus a

classical case-control epidemiological study and was

conducted with great care.


The Commission had the opportunity of two days detailed

discussion with Dr Eriksson. Dr Mulinare and their

associates. One could not fail to be impressed with their

professionalism. The study was a powerful one by any

epidemiological standard, having sufficient power to

detect an odds ratio of 1.2 for all types of birth defects

with 70% probability and power to detect odds ratios of

1.5 or greater on a 2 tailed test with confidence of

almost 100%.

The study used computer-assisted telephone interviewing

techniques. Great care was taken to preclude interviewer

bias and to this end tracing staff were not aware of the

case or control status of the families.

When the parents were contacted (and both mother and

father were interviewed where possible) they were asked to

participate in a study designed to help learn about the

causes of birth defects; no mention was made either of

Agent Orange or of service in Vietnam.

Each parent was interviewed twice. The first interviewer

for each parent asked about the parents' reproductive

history. Because such history would include a description

of the health of the index baby, the first interviewer


could usually not avoid knowing whether the baby belonged

to the case or control group. Accordingly, in order that

interview bias might be avoided, a second interviewer for

each parent asked questions about a wide variety of

exposures (that is to say, Vietnam service and Agent

Orange questions were interspersed with occupation,

chronic disease, drugs etc so as to remove bias flowing

from a small number of questions).

Answers about Vietnam service were verified as far as

possible from Army records and two measures of Agent

Orange exposure were designed. One was a "self-report"

exposure index where the veteran himself gave an

assessment of his likely exposure. As well, the Agent

Orange Task Force, Army, in Washington, under the

direction of Richard Christian provided indexes of

"exposure opportunity" from contemporaneous military

records including the HERBS tapes.60

The Commission's primary concern about the CDC study has

been the low response rates. Overall, only 69.9% of

eligible mothers and 56.3 of eligible fathers completed

interviews. Participation rates for parents of the white

race were substantially higher than those for parents of

other races. Statistical techniques showed that this


participation difference was of little concern insofar as

it might affect the inferences to be drawn regarding the

risks of Vietnam service.

Of course the difficulty with low response rates is that

those in the non-responding group may have fared worse or

differently from those in the responding group.

It is the practice in the United States to conduct

epidemiological research through outside contractors. In

the case of the CDC study contractors were employed to

trace and find the parents of the babies. It seems that

the contract provided for a flat fee per parent traced;

accordingly the profit was to be made in the tracing of

those most easily found. There was. the Commission feels.

a lesson to be learnt for those contracting for

epidemiological research in the future. It would be

advisable to allow for increases in fees payable as the

number traced increases so as to ensure enthusiasm in the

contractor for participation rates in the highly desirable

90 percentiles.

Having regard to the careful statistical analysis

performed, to the selection of the index babies from a

register without possibility of bias and to the careful


selection and matching of controls, the Commission is

satisfied that, notwithstanding the low response rates,

the study is an extremely valuable one for its primary


In general terms the study indicates that there is no

evidence that Vietnam veterans have any increased risk of

fathering babies with the measured defects. The relative

risk was found to be .97 which is suggestive of reduction

of risk but not significantly different from 1.00 with a

confidence level of 95%. This study is consistent with

and supportive of the negative findings in the Australian

Birth Defect Study. Each study reinforces the other.

Dr Zena Stein, whose qualifications have already been

discussed was a persuasive witness. She said, discussing

the Australian Study and the CDC Study together:

Quantitatively, one could rule out even a

moderately raised risk (say 1.5) with a high degree of certainty (say 80%) in either study. Taken together one would want to make an even stronger negative statement. In general, the two studies taken together support each other in the consistency with which 1 no effect1 is shown.61


One observes that the Ranch Hand Study was of a group

known to have been exposed, and heavily exposed, to Agent

Orange. The CDC study incorporated an index of exposure,

albeit of questionable validity. Neither Ranch Hand nor

CDC was limited to birth defects discovered in the first

week of life. Accordingly neither study is subject to the

two postulated limitations of the Australian study. All

three studies reach the same negative conclusion.

W A A 1 s submission relied upon three elevated risks in

sub-categories of birth defects found amongst the 96

selected for examination, from the ICD code.

The study tested 96 hypotheses. The significant level

chosen for deciding whether to accept or reject these

hypotheses was .05. That means that if there was in fact

no true difference in risk between the populations from

which the case and control group parents were drawn, a

false positive result would be expected to occur by chance

alone about 5 times in 100 (i. e. , 4 or 5 times in 96


Observe the following. Statistical reality is always in

the mind of the Casino owner, but usually forgotten by the

Casino client. If 7 heads in a row never came up the


Casino would always be empty. Because they sometimes do

the Casino is full. Because the overwhelming tendency is

towards 50%-heads, 50%-tails. in the long run the Casino

owner must win.

On the other hand, W A A makes no submission based upon the

following finding. Vietnam veterans were found to have a

significantly lower risk for fathering babies with complex

cardio-vascular defects.

Again, veterans (excluding Vietnam veterans) were found to

be at a lower risk for total sex organ defects.

5.2 Spina Bifida

Next, an association of spina bifida with a high score on

the Agent Orange exposure opportunity index was noted.

The authors note that the anencephaly scores suggest a

lower risk for this defect amongst men who had the higher

index scores. These two defects are aetiologically

related and indeed were described by experts in evidence

as the same defect presenting differently.

All of this suggests that the finding for spina bifida is

a chance phenomenon. This view is enhanced by comparison


with the Australian Birth Defect Study. Table 6.7 of that

study, where anencephaly and spina bifida were grouped

together, shows that it was more likely that the father of

a control was a Vietnam veteran than the father of the

case. The Commission is satisfied that no real

association exists.

5.3 Coloboma

The CDC study also indicates statistically significant

increases in the risks for exposed fathers in respect of

the defect. coloboma.

This is a very rare disease and there appear to have been

only 16 cases in the study. The authors point out that a

four-fold increase of* risk would still produce only about

.3 cases per 1,000 live births.

When one makes a comparison with the Australian study, one

finds not a single case of coloboma amongst the children

of Vietnam veterans. This too, the Commissioh finds is an

unreal association.


5.4 Cleft Lip

The study found a significant increase in the defect cleft

lip without cleft palate in association with the Agent

Orange exposure opportunity indices.

It should be noted that amongst non-Vietnam veterans an

odds ratio in respect of this defect of 1.4 was found;

this was statistically significant. The odds ratio for

Vietnam veterans is only 1.1, and statistically associated

only with the exposure opportunity index.

Second, there is actually a finding of decreased risk both

in non-Vietnam veterans and Vietnam veterans in the

aetiologically related defect of cleft palate.

Third, in the Australian Study, the item cleft lip and/or

palate, was analysed in Table 6.7. There were 10

occurrences in which a veteran was father of the case and

11 where a veteran was father of the control, suggesting

an absence of any association in relation to these

defects. As well Dr Schneiderman conceded62 that no

conclusion as to an association could be drawn from the

material contained in the CDC study. Professor Mathews in

his evidence was also of this view.63


The Commission concludes that this is a chance finding.

5.5 Congenital Neoplasms

Another "elevated" risk found in the CDC Study was that of

having babies with congenital neoplasms. This risk was

1.8 with 95% confidence limits of .99 to 3.29. The point

estimates of the risks found here are rather low - of such

a level that they could conceivably be the result of some

unknown bias or confounding factor, or they could be

chance results. The Commission inclines towards chance.

Certainly, on the balance of probabilities, this is a

chance finding. When one has regard to the conclusions

the Commission has drawn, later discussed, of the

feasibility of the mechanisms involved in production of

male-mediated birth defects the Commission has no

hesitation in finding that there is no real association.

When one is dealing with a study in detail and analysing

small apparent increases in risks so as to decide whether

or not they are real, a reader may be distracted from the

overall conclusions. Vietnam veterans were shown to have

no increased risk of fathering babies with defects. Even

those Vietnam veterans who had upon their own estimation

greater opportunities for Agent Orange exposure were not


at greater risk for fathering babies with defects. These

conclusions are consistent with the Ranch Hand Study and

the Australian Birth Defect Study and therefore have great

scientific weight.

These three studies taken collectively, powerfully negate

the proposition that service in Vietnam and exposure to

the chemical agents used there increased the incidence of

birth defects.



6.1 Smith et al (1981)

This well-done New Zealand study compared the rates of

congenital malformations and spontaneous abortions

(ascertained by interview) in the families of agricultural

sprayers, with rates in families of agricultural workers

who did not use sprays.

No differences were observed between the two groups, nor

were confounding factors likely to have masked an effect.

The rates were similar to those expected from population

data which is corroborative.

VII-6 6

6.2 Smith et al (1982) 65

These investigators examined pregnancy outcomes of wives

of professional agricultural sprayers in New Zealand who

had sprayed 2,4.5-T during the same calendar year as, or

during the calendar year before that outcome. The

pregnancy outcomes were compared with those of a control

group of agricultural contractors who did not spray


Relative risk of 1.19 for congenital defects and of .89

for miscarriages were found. In each case the difference

was not statistically significant. The authors concluded

that the results should not raise concern for pregnancy

outcomes among wives of professional 2,4,5-T sprayers.

It may be noted that at least in some cases, the exposure

studied was not wholly paternal because wives may have

been exposed themselves by assisting their husbands in the

spraying activities, handling the chemicals or at least

by washing clothes wet with spray. The negative study is

made more convincing by this circumstance. This study,

carefully done, is quite consistent with the general

epidemiological picture, and supports the conclusions of

Ranch Hand II, CDC and the Australian studies.



7.1 General

The next group of studies to be considered in an

assessment of the consistency of data are the Vietnamese


The Commission had the advantage of journeying to Vietnam

and had an opportunity therefore to assess not only the

reports of the studies but also the facilities available

for the performance of the scientific work. As well, the

Commission was able to observe and sense the political and

emotional climate in which the work was done.

The Commission was accompanied on its journey to Vietnam

by its Senior Scientific Adviser, Professor John Mathews,

and also by Dr Fiona Stanley, an expert in the

epidemiology of birth outcomes. The qualifications and

standing of both have been discussed elsewhere in this


The Vietnamese Government made available to the Commission

all scientists with whom it wished to have contact, except

Professor Can who unfortunately was not available. The


party met with all those who had worked with Professor Can

in the preparation of his studies and although failure to

meet him was a disappointment, in view of the quality of

his work, nothing was lost.

All scientists spoke freely and frankly to those

Assisting, to the scientific advisers and indeed to the

Commissioner. Expert Vietnamese translators were made

available to the party and, additionally, by resorting to

French, the common language between the two groups,

communication was further facilitated.

Dr Fiona Stanley took a leading role in the detailed

questioning of the Vietnamese experts. She took this role

not only because the field was in a sense most

particularly hers or because her command of French was the

best of the Australian group, but most of all because her

flair for friendliness combined with direct and probing

questioning produced excellent results.

The Commission has nothing but admiration and respect for

the individual Vietnamese scientists. They were helpful,

frank, hospitable and intelligent. However, specialised

training in epidemiological techniques of the kind

necessary for the drawing of valid conclusions was

evidently lacking.


A number of other comments are necessary. There is in

Vietnam a strong Governmental commitment to the view that

the use of herbicides in Vietnam amounted to chemical

warfare as a matter of International Law. This view has

prevailed in that country since the early years of the

conflict and the passage of time apparently has done

nothing to diminish it.

Governmental commitment to that view includes a commitment

to the view that herbicides caused serious health problems

amongst the Vietnamese people. That strongly held belief

is carried through into effective propagation of the

idea. In particular. the Vietnamese Government is

committed to the notion that the use of herbicides caused

birth defects. This is displayed not only by commentary

in the state-owned newspapers, in radio programs and in

pamphlets distributed to all willing to read them, but

also by exhibitions such as the Museum of Atrocities. The

Exhibition of War Crimes is devoted to the

herbicides/birth defects connection.

The propagation of this viewpoint is expressed in highly

emotive terms and the exhibitions are regularly visited

by, inter alia, organised groups of school children.


A further example is that there is an official path along

which visiting journalists, scientists, politicians and,

indeed. Royal Commissioners are taken. All those who write

of a visit to Vietnam tell the story of the chromosomal

defects, the deformed babies in bottles, the conjoint

twins, the mothers of the molar pregnancies threatened

with cancer and the Exhibitions mentioned above.

It must also be said that it was apparent that the

scientific people themselves reflect, at a personal level,

the Government commitment. Two scientists actually said.

"I know this study does not prove it but I still believe

it is happening."

An examination of the work done by Vietnam scientists

displays conditions under which they worked were far from

ideal and in many cases totally inadequate. The

researchers did their work whilst carrying a full clinical

load. The research was done after hours with little staff

and no facilities. In addition, the public record keeping

has substantial gaps and at many levels is totally

unsatisfactory. Such records as are kept are on fine rice

paper in large storage boxes with only a primitive system

of indexing.


In Vietnam (as elsewhere) the bearing of a defective child

is a matter for shame. Early records obviously seriously

understate birth defect incidence. Stories of infanticide

abound and the Commission was told of concealment of

defective births in earlier times.

The Vietnamese studies are considered in two groups,

descriptive and analytical.

7.2 Descriptive Studies

(a) Tung et al 198066

These authors report a rather confusing set of studies on

North Vietnamese War veterans who went to fight in the

South and who were stated to be extensively exposed to

herbicides. In a population of 10,000 civilians, 700 were

veteran families and it was claimed that of 30 children

with malformations born in 1975-78, 15 were to veterans

and 15 were to civilians.

No denominators, (that is. numbers of births) were given.


In another province of 4,500 people. there were 30

veterans. Amongst 233 births between 1976 and 1978, the 9

children with malformations noted were all veterans'


These studies are poorly reported and cannot be judged due

to insufficient detail. It is obvious that observer bias

could be operating when veteran status is known as cases

are being ascertained. Exposed veterans in the Vietnamese

atmosphere are much more likely to bring forward malformed

children than either unexposed veterans or civilians who

have normal children.

The figures themselves are inherently unlikely. The study

is unhelpful.

(b) Ministry of Health/US Military Assistance Command.

Vietnam and US Department of Defense

In 1970, five years after spraying with defoliants had

commenced in Vietnam, and after the first reports of

possible teratogenicity of 2,4,5-T in rats,67 a study

was undertaken by the above bodies. This study collected

data on congenital malformation, stillbirths and

hydatidiform moles in the Republic of Vietnam before and

after the widespread use of defoliant chemicals.


Twenty-two public hospitals were in the study and provided

499,119 birth events, including 16,166 stillbirths, 2,866

hydatidiform moles and 2,355 congenital malformations.

The hospitals were located in both metropolitan Saigon and

in rural areas. Standard criteria were set for each

abnormal outcome but accuracy depended on the quality of

records kept which varied from hospital to hospital and

even within hospitals. Some hospitals had no records at

all for some periods.

The number of live births in these hospitals increased

steadily and markedly from 1960-69, particularly in

hospitals outside Saigon. Qualitative changes in the

maternal population (which could result in selection bias)

were not recorded, and thus any changing characteristics

of the sample are not known.

The overall stillbirth, hydatidiform mole and congenital

malformation rates fell during 1960-69. The rates are

roughly what would be expected (stillbirth rate 33.7 per

thousand and mole rate 6 per thousand) except for the

malformation rate which at 4.9 per thousand was very low.


The study concluded that meaningful correlation of

abnormal birth events to herbicide use was precluded

because the data were inadequate. However, if spraying

was causally associated with defects, a rise in rate would

have been expected because of the increased proportion of

rural births in the later years. No such rise was

demonstrated. The study is, if anything, negative.

(c) Huong and Phuonq (1983168

This study reports a rise in spontaneous abortions,

hydatidiform moles and congenital malformations from the

major obstetric hospital in South Vietnam between


Discussions with the authors of the study revealed that

there had been a change in the pattern of obstetric

practice between the early part of the period studied and

more recent times. As the decentralisation of obstetric

services occurred, establishment of midwifery clinics at a

local level developed and the major obstetric hospital

became increasingly a clearing house for the more

difficult cases.

Nonetheless, the claim made by the authors is that the

increases reflect real changes in the rates and that the

rise followed the war and the increases in spraying.


However the following should be noted:

(a) No data are presented which permit investigation of

the rises or the reasons for them.

(b) The reported rises in adverse pregnancy outcomes

occurred after the U.S. animal experiments

demonstrating the teratogenic effect of 2,4,5-T were

published in 1970.

(c) There are no reported rises in any Vietnamese study

before this date although spraying had been occurring

since 1964-65.

(d) The rates of spontaneous abortions. stillbirths and

congenital malformations in the 1960-65 period

reported in this study were lower than rates being

observed now in the most developed countries in the


(e) The rates are lower than those mentioned in the US

Ministry of Defense Survey (1970) reviewed above.


The Commission concludes that marked under-ascertainment

early, followed by better ascertainment together with the

selective referral of high-risk women account for the

stated rise in frequency.

(d) Tuven et al69

This is one of a group of studies investigating somatic

mutational effects. It examined chromosomal anomalies.

The authors suggest that structural chromosomal anomalies

were more frequent amongst South Vietnamese civilians and

their offspring than amongst North Vietnamese and

unexposed South Vietnamese. Note that:

(a) No evidence of exposure was provided.

(b) More samples were observed from exposed people than

from those not exposed and it is possible that this

reflects repeated (biased) sampling from exposed

individuals showing abnormalities.

(c) It was not clear that cells from exposed and unexposed

subjects were examined "blind".

(d) Samples were not examined on the same day.

Technique is very important in such studies. The study is

so flawed as to be totally inconclusive. Additionally,


the significance of such abnormalities as sister chromatid

exchanges has yet to be determined and may amount to 70 nothing. The Commission finds this study unhelpful.

(e) Truna et al


These two studies were carried out in 1983. The first

compared the peripheral blood lymphocyte chromosomes in 15

"exposed" adults and children with 5 controls (adults) and

found a larger number of sister chromatid exchanges in the

former than the latter.


The second was a study in areas documented as heavily

sprayed. Structural chromosomal anomalies were assessed

in 56 adults (men and women) and 10 controls and

significant differences were found in numerical and

structural chromosomal defects.

The methodology of these studies is unreliable. Both

studies selected exposed persons who were related to those

with defects or who had defects themselves. The controls

appear to have been chosen because they were genetically

healthy as well as unexposed I Thus chromosomal

abnormalities were much more likely to have been observed

in the "exposed" than in the "unexposed". The Commission

finds these studies unhelpful.


This study compared two areas of South Vietnam, one

sprayed and the other not. Whilst no details of how this

was documented were given, 100% of couples interviewed in

the former and only 8% interviewed in the latter reported

exposure. A health interview survey was conducted in

these areas in 1982 to ascertain the long term

reproductive effects of exposure. 1,249 exposed and 1,244

unexposed families were interviewed. Markedly higher

rates of congenital malformations, (no criteria or

definitions given), fetal deaths, spontaneous abortions,

molar pregnancies and new-born deaths were noted in the

exposed than the unexposed groups.

This study which is methodologically vague has a number of

obvious defects. The high percentages are per hundred

women interviewed and not per hundred pregnancies and thus

do not take parity into account. The outcomes are based

on recall and interpretation is therefore difficult. Most

importantly, the rates amongst the non-exposed group are

lower than expected. They are just too good to be true.

Material rebutting probable observer and selection bias is

not shown. The Commission cannot rely on this study one

way or the other.

(f) Phuonq & Huong (1983)73


These researchers collected data on spontaneous abortions

and birth defects in the families who lived in sprayed

areas in South Vietnam during the war and who have

remained there since. There may well have been selection

bias operating in those remaining in sprayed areas.

Data were collected in 1982 by informal interview, with

the potential for bias from knowledge of exposure by the


Before spraying, the spontaneous abortion rates were 5.2,

4.3 and 7.2 in three areas. After spraying, these rose,

it was said, to 12.2, 11.6 and 16% respectively.

The non-sprayed area remained unchanged at around 7.5%.

The malformation rate rose from .14% before spraying to

1.78% after. The recorded defects ranged from

hydrocephalus to speech deficiency and thus the criteria

for congenital malformations were very broad. This study

has serious design flaws and the "control" rates are

implausibly low. It does not provide evidence of an

association. The Commission finds it unhelpful.

(g) Trunq. Chien et al (1983)74


This descriptive study deals with three North Vietnamese

districts where no spray was used. Two groups were


(a) Neither parent exposed;

(b) Father exposed whilst in South Vietnam during conflict.

No actual documentation of exposure is given. Data

collection was by interview in 1982 „ (that is, by

retrospective recall of pregnancy outcomes) and validated

by checking abnormal outcomes against medical records

available in the area. Any abnormal children still alive

were examined and photographed.

There were 40,064 pregnancies in the 3 areas of which

11,023 were by fathers who had been in South Vietnam. The

rates for abortions, molar pregnancies, fetal deaths and

congenital malformations were calculated. They

demonstrated relative risks around unity (i.e. no

increased risk) for abortions, molar pregnancies and fetal

deaths in (b) groups compared to (a).

(h) Can et al (1983)75


Increased relative risks of 1.2 to 2.2 for congenital

malformations were reported. Poor recall of outcomes

(particularly abortions and molar pregnancies) occur in

retrospective studies and this makes interpretation


The malformation rates are much lower than one would have

expected and may be biased as a result of recall. Such

bias would include possible bias towards greater recall

amongst those exposed (and therefore worried) and poorer

recall amongst those unexposed.

Stillbirth rates seem the most consistent and these showed

no differences between the (a) and the (b) groups.

Other differences between groups (a) and (b) which may

have helped with interpretation, were not sought. For

example, social class and demographic variables are known

to be associated with both poor pregnancy outcomes and

with war service in the South. This study, which is of a

higher epidemiological standard, is essentially negative.


This rather poor series of studies showed a higher rate of

congenital malformation amongst veterans' children in

Vietnam compared with civilian (2.6% compared with .46%).

However, data collection was poor and these rates were low

compared with those expected.

Baseline data on certain pregnancy outcomes are reported

by Nguyen Ho Dang (1983) in Tay Ninh Province which was

sprayed from 1961-1970. Data from 1979-81 show neo-natal

death rates, of 20 per thousand. abortion rates at 25%,

premature delivery rates of over 20%, moles at 2% and low

malformation rates (1%). No control data are available.

Whilst these levels seem high they are perhaps not

unexpected in modern and poor rural Vietnam.

In general terms, descriptive studies are of less

assistance than analytical ones. The Commission has had

available to it highly qualified advice concerning these

descriptive studies. Overall they do not provide any

clear or consistent relationship between birth defects and

chemical exposure. Having regard to the advice given and

the methodological problems of these studies the

Commission is of the view these results are not

(j) Lang. Van and Tung (1983)76

VI1-8 3

susceptible of meaningful interpretation. With the

exception of Can et al (1983) (h) supra, they must be put


7.3 Analytical Studies

(a) Can et al (1983)77

From the three North Vietnamese areas of his earlier

survey Professor Can collected 61 cases of birth defects

with well-defined criteria and had the cases re-examined

by two observers. Controls (N = 183) were matched by

maternal age. parity, residential area with a live child

born within 2 years of the case. The level of exposure

was then ascertained by questionnaire amongst cases and

controls. Recall bias (more recall by cases than

controls) was not checked. The relative risk between

exposed and unexposed was calculated and found to be well

over one (3.6). The study included confidence limit

calculations, with good analytic technique.

A major worry about this study is that cases were stated

by the

v 78

researchers to have been selected by the

village midwives with knowledge of sprayed status. In

other words, selection bias might well have operated. In


addition, the types of defects chosen (cleft oalate, limb

defects. megacolon, congenital cataract, deafness and

blindness) include those associated with social and

demographic risk factors perhaps related to Army service

in South Vietnam and not chemical exposure.

The Commission observes that this is the only analytical

Vietnamese study which meets even the most basic

epidemiological standards.

The criterion for exposure was that the husband "had been

in South Vietnam on business during the war time". There

is also a somewhat oblique reference to using "the lots

drawing" method to choose the districts and the cases for


Dr Stanley closely questioned the colleagues of Dr Can

during the Commission's Vietnam visit and she gave the

following evidence:

.... whilst on paper this study looks good, one has this suspicion that in fact they were chosen with exposure status known. The controls were non-cases, again we do not know how exactly they were chosen. We hoped that they were not chosen

on non-exposure status. There again, we were not able to ascertain that clearly.79


The Commission's own recollection of this encounter was

that the questioning was vigorous and that the point of it

was well understood. Interpretation from Vietnamese into

English at this particular meeting became difficult

although the same interpreter was used as at other

meetings and when direct communication between the

Commission's party and the investigators in French began,

the interpreter displayed his restlessness and interrupted

in Vietnamese, effectively preventing continuance in


In view of the probability of selection bias, the

Commission cannot be strongly persuaded by this study

although it can be regarded as a solid scientific attempt.

(b) Huong & Phuona (1983)80

These investigators conducted a case control study in 1982

which was poor by epidemiological standards. Cases were

molar pregnancies (N = 100) and congenital malformations

(N = 15). It is odd tha t so few malformations were

included as they are much more common than molar

pregnancies. The method of case selection was not

detailed. Controls (N = 284) were chosen from the same

hospital (mother with genital infection). Maternal (not


paternal) exposure to herbicides was obtained by

questionnaire along with certain cultural and other

potentially confounding factors.

Exposure levels were 56% for moles, 33% for defects and

10% for controls. There were also differences in smoking

and alcohol (a trend, but not significant, to higher

exposure in cases than controls) and malnutrition (higher

in control parents than cases).

Methodological difficulties in case and control selection,

collection of exposure data and the lack of control for

confounding makes interpretation of this study impossible.

7.4 Conclusion

Overall there is nothing in the Vietnamese data that would

be regarded as sufficient to disturb the consistency of

the results obtained in the Ranch Hand, CDC and the

Australian studies.


The following studies are of inconsistent quality. The

Commission includes them with appropriate comment for the

sake of completeness.


(a) Field and Kerr (1979) 81

These investigators described a statistical correlation

between two poorly ascertained pieces of data namely,

neural tube defects in New South Wales (known to be rising

because of better ascertainment over time, particularly in

view of recent X-ray diagnostic techniques), and the

quantity of 2.4,5-T supplied for the whole of Australia

during a given period.

Thus the exposure was a very indirect measure. For

example, very few of the mothers in metropolitan Sydney

giving birth to the malformed babies would have been

exposed at all, but, if exposed, such exposure could have

resulted from only an extremely small percentage of the

Australia-wide 2,4,5-T supply.

In addition, the graph shown in the paper appears both to

the Commission and to other more expert observers to show

the line of correlation being more convincing than was


(b) Thomas (1980).82 Thomas and Czeizel (1982)83

These investigators presented a similar ecological

descriptive study on data from Hungary. Hungary has an


excellent congenital malformations register which has been

producing good population data for many years. Thus there

was no problem of changes in ascertainment over time.

Over 1969-75 national 2,4.5-T usage in Hungary rose from

46 to over 1,200 tonnes, mainly in rural areas. There was

no rise in rates of congenital malformations and in fact

the rate for neural tube defects fell during 1970-1976.

The authors noted that exposure in Hungary was more likely

than in New South Wales (or in the UK) as more Hungarians

live in rural areas than in metropolitan areas by

comparison with Australians who predominantly live in

major cities on the sea board (less than 30% live in rural


The authors also refer to a study of female agricultural

workers in Hungary who showed no increase in congenital

malformation rates amongst their offspring. (Thomas

1980). Rates of malformation, stillbirths and spontaneous

abortions were actually higher in metropolitan (ostensibly

lower exposure) than in rural areas.

Thus a better conducted ecological study contradicted the

conclusions of Field and Kerr.


(c) Nelson et al (1979)84

These investigators conducted an ecological study of cleft

lip and palate (CLP) incidence in relation to 2,4,5-T

usage in Arkansas between 1949 and 1976.

Rural areas of Arkansas were divided into high, medium or

low exposure based on types of crops and cultivation

(which indicated the amount of 2,4,5-T used). CLP cases

were obtained from only two sources with probable

resultant under-ascertainment. No association between CLP

incidence and 2,4,5-T exposure (as defined) was observed,

although a rising rate of CLP was noted with time and

attributed by the investigators to better case


(d) Hanifv et al (1981)85

This was a New Zealand ecological study. The rate of

malformations noted at birth was compared with

quantitative estimates of 2,4,5-T exposure in the same

areas. No spraying occurred in 1959-60 but was common in

1972-1976. Positive associations of some congenital

malformations with spraying in 1972-1976 were noted. the

relative risks of some being more than one (congenital

heart defects, talipes and hyperspadias) .


After further analysis of the data allowing for season and

other potential confounding factors. only talipes remained

statistically significantly associated with 2.4,5-T

spraying. The study was well done. It is nonetheless

only a descriptive study and the finding is probably due

to chance.

(e) Townsend et al86

This was an "in-house" study of Dow Chemical Company

employees. The Company as a manufacturer of 2,4.5-T,

known at times to be contaminated with dioxin, has an

interest in demonstrating a "no association" result.

The investigators identified employees exposed to dioxin

as a result of being assigned for at least one month to

specified jobs in the chlorophenol processes between

January 1939 and December 1975. A one for one control

group of employees not so exposed was also identified.

After some 930 employees were identified as exposed

attempts were made to trace the wives of both cases and

controls. The shortfall in numbers of wives resulted from

difficulties in the original location of cases and


controls, the limiting of the survey to those living

locally and, in particular, from wives declining to


As always, one must be concerned with such a low response

rate. Those who failed to respond may have had more

abnormal pregnancies than those who came for interview.

Reproductive outcomes were determined by interviewer

administered questionnaire.

No statistically significant associations were found

between exposure and pregnancy outcome. Techniques

included stratification by pertinent sets of up to nine

co-variables. Nor was there evidence of adverse outcomes

correlating with duration of exposure.

It is worth noting that the malformation rates observed

were slightly higher than expected on a population basis.

This could be related to over-reporting since husbands in

both groups were employed in chemical factories„

putatively a risk factor.

The study does not support a connection between TCDD

exposure and adverse reproductive outcomes.


(f) Balaiaran and McDowell87

These investigators reported upon congenital malformation

rates by occupational group in the United Kingdom. They

chose groups in whom occupational exposure to pesticides

such as 2,4,5-T would be expected to be high and compared

their rates with those for all occupational groups. No

actual documentation of exposure was attempted (for

example, by questionnaire or assessment of actual duties

performed by individuals).

An excess of spina bifida and cleft lip and palate was

found amongst the offspring of agricultural workers,

gardeners and groundsmen compared with other occupations.

The authors felt that this required further investigation.

It must be emphasised that many other factors could be

different in these groups of people and no allowances were

made for important confounding variables such as alcohol,

tobacco. social status, etc. The authors concede the

inconclusiveness of their observational study.

Two other descriptive studies - the Yusho bran oil and the

Korean rice oil investigations (Reggiani et al 1983)

contribute nothing to the reproductive debate.


(g) The Seveso Accident

In 1976 there was an accidental release of a cloud of TCDD

from a factory in Seveso, near Milan. Data have been

collected from three defined zones in the Seveso district

of varying exposure and exposure levels have been

carefully documented.88

Data on spontaneous abortions and congenital malformations

were not available for the exposed areas before the

accident. The data collected afterwards must be

interpreted in the light of significantly increased

awareness and diligent ascertainment by the authorities.

A large number of unrecorded, unreported induced abortions

were allegedly performed on Seveso women in other parts of

Europe, particularly in London. No numbers can be

ascertained but the anecdotal evidence of these inductions

is widespread.

The latest reports are from Dr Bruzzi of the Istituto

Superiore di Sanita, Some. These do demonstrate some

differences in malformation rates between the highest and

the lowest exposed zones. Few are statistically

significant and all are well within normal European


limits. The relative risks are small. 1.2 in the highest

zone, and easily explicable by increased ascertainment

amongst the exposed.

The Commission had the advantage of detailed examination

and cross-examination of Dr Bruzzi. in Rome. Afterwards,

informal discussion between the Commissioner and Counsel

and Dr Bruzzi occurred. Dr Bruzzi stated that he feels

that there is "Something in it".

However, the Commission feels that these inconclusive

studies do not demonstrate increased risk after a major

parental exposure of both males and females. It finds

comfort in that conclusion by its coincidence with the

view of the head of the Research Institute, Dr Pocchiari,

a most astute epidemiologist, who stated that there is

"Nothing in it".89

(h) Alsea II

This descriptive study has been criticised at an

international level. It compared three areas of Oregon,

one with supposedly high levels of exposure and two

control areas, one rural and one urban. The area with

high levels of exposure was later found to be an area of

very low population density.


Data in respect of spontaneous abortions was collected.

Higher levels were found in the high exposure area

compared with the two control areas.

The major deficiencies of this study include:

(a) differing methods of data collection in the three


(b) no control for confounding factors such as maternal

age and social condition.

(c) ignorance of the marked seasonal changes in


(d) poor exposure data,

(e) the abortion rates were much lower than expected.

No causal connection can be inferred from this study.

(j) Conclusion

The Commission concludes that many of the different sets

of data analysed above demonstrate no association between

exposure of the father to chemical agents and untoward

birth outcomes: the consistency is most persuasive.



The next question to be discussed in whether association

between a risk factor and a particular outcome is

specific. It follows from the lack of association above

demonstrated that no specific outcome is found in

association with the risk factor. This would always be

significant but it is more significant than usual in the

particular case.

One of the postulated mechanisms. of which more later. for

the paternally mediated effect is the suggestion that,

following exposure of the male to chemicals, some chemical

or contaminant constituent is absorbed by the male into

his system. This finds its way into the seminal fluid and

then at the time of fertilisation, or during the pregnancy

as a result of later intercourse, the fertilised ovum or

the embryo is exposed to the chemical carried by the

seminal fluid with toxic results. Without dealing for the

moment with all the arguments against such a mechanism, if

it were operating one would certainly expect a specific

and characteristic response, such as occurred in the

thalidomide tragedy.

It follows that the lack of any specific outcome negates

the postulation of WAA.



None of the studies indicate any association between

unfavourable birth outcomes and dose. In particular, the

Australian Study shows no association between birth

outcome and (a) numbers of tours to Vietnam, (b) length of

time in Vietnam, and (c) the time since the soldier

departed for or returned from Vietnam. The lack of any

dose response relationship is highly significant.


The next step in the process of assessment is a

consideration of the biological plausibility of the

outcome being associated with the exposure.

As has been observed in the Exposure Chapter of this

Report, Chapter IV, no evidence exists of Australian

personnel having been exposed to Agent Orange or to other

chemicals to an extent likely to give rise to any

long-term toxic effects.

A mere possibility (as opposed to actuality) of exposure

to Agent Orange spray has been demonstrated in the same


chapter. This was shown as a possibility only in relation

to a very limited number of Australian personnel.

So far as the evidence discloses, only one female amongst

the Australian personnel became pregnant whilst in

Vietnam. Her daughter is well and attending school in

Victoria. Few women performed Special Overseas Service as

part of the Australian contingent.

Accordingly, the postulate must be that exposure of the

male to chemicals in Vietnam caused untoward pregnancy

outcomes amongst their offspring. Those offspring must of

necessity have been conceived after exposure ceased and

within women themselves unexposed. That this is the claim

is made clear by the final submission on behalf of



That submission,

mechanisms. At p



112 of the

cryptically, postulates

submission the following

The first question which must be asked is whether it is biologically feasable (sic) to have

paternally mediated birth defects.

It is submitted that clearly the answer is in the affirmative. Several witnesses have spoken of the possibilities and types of birth defects, they are:


1. Mutation; 2. Germ cell damage; 3. Teratogenic effects by the release of

chemicals in the seminal fluid.

Dr Stanley expresses the hypotheses somewhat differently.

She says:

The most likely hypotheses being tested by those who suggest that Agent Orange in the father is the cause of congenital malformations in his offspring are:

(a) a mutation in his germ cells has been

transmitted and is evident as a defect in organ development • (b) a mutation in his germ cells has been

transmitted as a marked increase in genetic susceptibility to some environmental teratogen;

(c) a less likely hypothesis is that the

chemical remained in the sperm/seminal fluid until conception (months/years after exposure) and then the developing embryo was exposed during sexual intercourse (after conception)-that is a teratogenic effect.91

Whilst maternal exposures and the possible teratogenic

effects of drugs, viruses and radiation have received much

attention, paternal exposures and possible mutagenic 92

effects have been relatively neglected. Agent Orange

has become an exception to this but attention has mostly

been caught by unscientific and sensational media articles

rather than by reports of epidemiological studies.



The next factor that must be considered is the timing of

exposure before conception. The development of mature

sperm in the human male takes approximately 74 days. Only

mature sperm can impregnate the ? female ovum. About

mid-way in the development of the mature sperm is a step

called meiosis.

This is a maturation process of the gametes, consisting of

chromosome conjunction and two cell divisions in the

course of which the diploid chromosome number becomes

reduced to the haploid. This process is important in that

it weeds out damaged sperm cells in which there are broken

chromosomes or other types of structural damage. Such

cells with damaged criromosomes cannot "make it over the

bridge." Thus. it is seen that the whole process of

spermatogenesis in the male is one of protecting the

species by ensuring that mature sperm is as good as


The result of all this is that if there is exposure even

to a most powerful mutagen causing mutagenic damage to the

DNA of the sperm, either all of the damaged sperm would be

eliminated at the meiotic stage or it would simply pass


through the system and be disposed of by replacement with

normal sperm after a maximum of 90 days. The 90 days

assumes a slowing down of the process as a result of toxic

response. The time span for the normal maturation process

is about 74 days.

Since the case for the veterans is that there is an

increase in birth defects amongst children of veterans

generally and not only amongst those children who were

conceived within 90 days of their father's return from

Vietnam, one must postulate a mutagen of sufficient power

to damage spermatogonial cells. One notes that the

Australian Birth Defects Study found no association

between the date of conception of the cases and the

proximity of that date with the date when the father

returned from Vietnam.

In animal models only two mutagens have been found to be

of sufficient, power to damage spermatogonial cells. One

is tri-ethylene melamine, the other is mitomycin C. These

are compounds which are used in cancer therapy and are

amongst the most powerful alkylating agents. Another

known mutagen is radiation. Even exposure to high doses

of radiation following the explosion of the atomic bombs

at Hiroshima and Nagasaki has not been proven to increase


mutation frequency. As a mutagen, radiation was powerful

enough to be responsible for increases in malignancies but

did not increase birth defects.

In his evidence Dr John Poliak postulated a mechanism

which involved the binding of 2,4-D and/or 2,4,5-T to DNA

so as to cause mutation in the spermatogonial cells. His

only warrant for this theory was research by


Bamberger . indicating a potential for these herbicides

to bind to DNA in plant cells. Dr Brusick suggests that

DNA binding in plant cells seems to be irreversible

covalent binding, whereas in animal cells it has been 94 found to be reversible: it follows that the

extrapolation made by Dr Poliak is quite unreliable.

The result of these considerations is that one must seek

for a powerful mutagen, a mutagen of a type never before

found to have operated in human populations: one must

seek it by an examination, not of human populations, but

of necessity by an examination of laboratory experiments

in animals and in cell cultures.

If this issue was not of such concern to veterans and

their families. one might not embark upon such analysis.


W A A pointed to no particular chemical nor, indeed, to any

particular data as supporting the biological proposition

other than the very late presentation of the W A A

collected Tasmanian data dealt with as an addendum to this

chapter of the Report.

Accordingly, it has been necessary for those assisting the

Commission to collect, collate and investigate all data in

relation to every chemical listed by W A A and/or known to

have been used in Vietnam. This was necessary to assess

whether or not there was any basis for a conclusion that

there was exposure to such a powerful mutagen.

From the evidence. it is clear that human beings and

indeed all mammals have evolved a system which is

extremely protective of the species from mutagenic agents.

Dr Fiona Stanley, consultant to the Commission, confirms

that a powerful mutagen would be necessary to damage 9 5 germinal cells.

The Commission will turn then to those studies which have

examined the question of chemical exposure of the male and

the mutagenic effect on male cells. It will also deal

with the theory of a male mediated teratogenic mechanism


operating by way of the seminal fluid or perhaps by the

sperm itself.


Mutagenesis is the process by which an agent (e . g .,

chemical, viral. physical etc.) causes a genetic change in

a cell. There are two kinds - somatic mutations and

germinal mutations.

Somatic mutations are changes to the genetic material in

somatic cells and may occur to those cells within either

the formed embryo (teratogenically) or within an

individual after birth. In the latter case, such mutation

may cause problems in the individual, e.g. neoplasia, but

the problem is not transmissible to that individual's

future offspring. Similarly, the problems suffered by an

affected embryo are not transmissible to any future

propagation of that embryo. In both cases, because the

germinal cells are not involved, the problems are not

transmissible to the next generation.

Germinal mutations are changes to the genetic material in

germinal cells which result in permanent transmissible

change in the genetic material. They occur in either


maternal or paternal germ cell lines (ova or sperm) and

will be transmitted to the embryo (maybe lethally) if the

fertilised ovum acquires a chromosome carrying a mutation

from a germ cell of either the father or the mother.

Accordingly, where male chemical exposure and its possible

effect on his subsequent offspring is to be examined (as

is the case here) then germinal mutations are those that

are most likely to be relevant.

At the outset, it should noted and clearly understood that

no chemical human mutagen has been definitely


13.1 Summary of Dr Pearn's Background Report to the

Senate (1982) re Birth Anomalies and Chemicals

The Commission is grateful to Dr John Pearn, Head of the

Department of Child Health at the Royal Childrens'

Hospital. Brisbane. who acted as a consultant to the

Commission from time to time. His "Congenital Defects and 97

Exposure to Militarily Used Herbicides" was presented

to the Senate Standing Committee on Science, and the

Environment in April 1982 and has been a valuable source

document to this Commission. The following summary has

been prepared from this source material.


1. 2,4-D and 2,4,5-T are relatively non-toxic in acute

dosage. The LD5Q for Rodentia is in the range of

480-940 mg,'kg.

2. The dioxin is extremely toxic to mammals

both in acute dosage, and in lesser doses administered

chronically. There are considerable species

differences in susceptibility to its toxic effects.

The LD50 for guinea pigs is approximately 1

microgram/kg, and the LD5Q for primates is

approximately 70 micrograms/kg. TCDD binds to

specific cell receptors and modifies the synthesis of

a range of critical enzymes within cells.

3. The acute toxic effects of TCDD include chloracne,

hyperkeratosis, hepatocellular mecrosis and immune

depression. Effects are dose-related. The long-term

clinical effects of significant exposure to herbicides

remain unresolved. TCDD is stored preferentially in

fat with a mammalian half-life (in that tissue) of

several months. The risk of angiosarcomas may be

relatively increased following chronic exposure, but

absolute risks remain low. Cohort studies of factory

workers from trichlorophenol and herbicide plants have


not demonstrated any greater mortality from neoplasms.

or from circulatory or other diseases. The

carcinogenicity of 2,4-D and 2,4,5-T is low.

4. Teratogenic chemicals act via the transplacental

route, act for only a critical period during

embryogenesis, are dose-dependent, depend on genetic

factors relating to both the mother and fetus (and

hence, also relate to the genotype of the father) and

may or may not produce specific dysmorphogenetic


5. 2,4-D and 2.4.5-T are teratogenic in mice if

administered either by the oral or subcutaneous route

to the pregnant mother, at critical stages of


6. The "no-effect teratogenic dose" for 2,4,5-T is 20


7. There is a positive dose-response curve for 2,4,5-T

with respect to the induction of cleft palate in

susceptible mouse strains. It is probable that there

is also a dose-response curve for the qualitative

severity of soft tissue lesions which involve the


kidney as well. The anatomical defects produced

(cleft palates and renal lesions) have not been

described in detail.

8. In the case of 2,4,5-T, the genotype of the mother,

the father, and the offspring are all important in the

question of susceptibility to the effects of the

teratogen, when it is administered to the mother.

9. No worker has reported being able to produce

teratogenic effects in rodentia other than mice, or in

other vertebrate species including primates, using

2,4,5-T and 2,4-D.

10. The dioxin TCDD is a potent teratogen in Rodentia.

Mice, rats and hamsters have all been shown to be

susceptible. TCDD produces defects with the smallest

effective dose of any known chemical teratogen in

mammals. The 50 per cent teratogenic dose in strains

of susceptible mice is 6.5 micrograms/kg given orally,

continuously over nine days of pregnancy.

11. Experimental results to date have not demonstrated

that TCDD is teratogenic in primates.


12. TCDD is excreted in mammalian milk, and has been shown

to be capable of abnormal enzyme induction in neonatal

Rodentia following prior administration to the

pregnant mother.

13. TCDD is toxic to embryos and fetuses exposed to it via

the transplacental route, in both rodents and in

primates, as evidenced by small fetal weight and

reduced litter size.

14. There are no experimental reports of fetotoxicity in

cases where maternal dosage with 2,4,5-T or TCDD was

insufficient to cause clinical signs of poisoning in

the mother.

15. A major review of all possible associations between

herbicide exposure and teratogenic effects in man has

been undertaken. There are to date no examples where

there is acceptable evidence that herbicides may have

caused congenital abnormalities, by a direct effect on

the pregnant mother.

16. There are a number of proven teratogens in rodents

which do not affect man. By contrast, all the proven

human chemical teratogens produce lesions in


experimental animals (these include 4-pteroylglutamic

acid, high-dose progesterone, anti-metabolites used as

anti-cancer drugs, tetracycline, thalidomide and


17. There is no evidence to indicate that the baseline

rate of congenital malformations is increased in women

exposed to TCDD (the Seveso accident), or to

herbicides used in agriculture or forestry. In all

cases where individual questions linking possible

maternal herbicide exposure and congenital

malformations have been studied, no cause-and-effect

suspicions have remained.

18. There is no satisfactory evidence of any clustering of

congenital malforma tions in time and space, with a

link to real or suspected maternal herbicide

exposure. Epidemiological studies in the United

Kingdom, Hungary, Italy, the United States. New

Zealand. and in Australia (the Yarram study) have all

failed to demonstrate any clustering of congenital



19. There is no evidence (in the world's literature) of

any new or unusual dysmorphogenetic syndrome

clustering in time and place, which could be related

to herbicide exposure.

20. In Australia in the last eight years, two reports have

highlighted demographic patterns of neural tube

defects (in New South Wales) and of cleft lip defects

(in Western Australia) which show variations from

previously established secular trends. In each case

there has been no direct cause-and-effect association

between such defects and herbicide exposure.

21. Questions of miscarriage and stillbirth rates relating

to herbicide exposure remain unresolved; there is

however, no positive evidence from any of the

international studies, or from the Australian

experience, to indicate a significant degree of

suspicion in this area.

22. There are no reports in the world's literature of

teratogenic effects in the children of groups of women

who have been exposed to high levels of herbicides and

where there has been an exposure-free period before

the subsequent conception of children.


23. A full analysis of all experimental and clinical data

concerning the effects of possible teratogens acting

through the male, is contained in Exhibit 877. In

particular, the question of toxic changes acting prior

to the subsequent conception of offspring is

addressed. There is unequivocal evidence that toxic

exposure of the male may result in temporarily-reduced


24. Toxic agents such as lead, carbaryl and vinyl chloride

are known to reduce fertility in humans acutely

exposed, to such agents. Teratospermia is a feature of

such toxicity in the human male. Toxic

paternally-mediated effects on fetal outcome have now

been positively detected in at least six vertebrate

species. The poor reproductive performance of such

males maybe reflected in an increased rate of

miscarriages noted both among wives of such workers

(in the case of humans). or the dams of experimental

sires who conceive during the period when the sire is

poisoned. An increased rate of congenital

malformations is not a part of this syndrome either in

human, clinical or epidemiological studies, nor has it

been reported in any experimental studies involving



25. Reproductive outcome may be compromised by at least

three mechanisms if the male is exposed to acute or

chronic toxic agents - a direct effect on higher

physiological function, a direct effect on the sperm

itself, or changes in the seminal fluid modifying

sperm motility or function. It is known on

theoretical and empirical grounds that abnormal sperms

are selected against, in the competition to fertilise

a mammalian ovum.

26. Male Rodentia acutely poisoned with TCDD may produced

litters of reduced size and with small offspring. In

no case has TCDD administered to a male experimental

animal resulted in a raised congenital malformation

rate in offspring, even when the male shows clinical

features of acute dioxin poisoning.

27. An analysis of all available experimental data

indicates that if a poisoned male animal is allowed to

recover, and is tested subsequently following a

significant toxin- free interval. the effects of

initial reduced fertility can no longer be



28. Exposure of male experimental animals to either acute

or chronic toxic doses of 2,4-D or 2,4,5-T does not

increase the rate of congenital malformations among

offspring. Male animals exposed in utero to

herbicides do not themselves show significant changes

in reproductive performance. Male mice experimentally

poisoned with replicated high-dioxin Agent Orange

cocktail are known to manifest acute toxic signs

clinically, but there is no increase in teratospermia,

or a reduction in reproductive capacity, or an

increase in the rate of congenital malformations.

29. Primates fed a long-term high-dioxin diet manifest

reduced spermatogenesis and altered testicular

histology, but no reports of congenital deformities in

offspring have yet appeared.

30. A full review of appropriate literature has

demonstrated that there is no evidence to link

herbicide exposure in human males with an increased

abnormality rate in their children, either (a) during

periods of acute or chronic exposure which have

resulted in clinical signs, or (b) after an

exposure-free interval prior to the conception of a



31. The interpretation of suspected clustering of

congenital abnormalities depends on an assessment of

the baseline or background rate. A review of the

rates for several countries is presented, and an

anlysis of disease-specific rates for individual

malformations is presented. Major congenital

malformations occur with a frequency of 2 to 3 per

cent, and minor malformation with a further rate of 5

to 8 per cent for the general population. Social

class, parental age, race, season of conception, and

drug-taking modify the rate of congenital

malformations and other unfavourable outcomes of

pregnancy, in sub-groups within society. These

influences are reviewed in the context of questions

concerning possible herbicide-malformations links.

32. In the absence of any specific teratogenic agent. a

group of 40,000 young males would be expected to

produce 1,000 children with major malformations, and a

further 2,400 with minor cosmetically-obvious but

functionally insignificant malformations, at a

conservative estimate. In addition, even in the

absence of any defined teratogenic influence, 800 of

their children would manifest significant intellectual



33. A personal series of 17 Veterans and their wives have

presented for genetic advice following concern about

exposure to Agent Orange. These have presented as

part of the more general case load of 800 families

seen in the Genetic Cline at the Department of Child

Health in Brisbane. In three of these cases there

were major congenital malformations present. Six of

the presenting families came for advice only; in the

remaining 11 families there were no features which

would specifically distinguish these from the pattern

of families who attend genetic clinics generally.98

13.2 Genetic Toxicology - Mutagenicity - Dr Brusick

That it is with the genetic activity of the various

chemicals that this Commission must be concerned is made

abundantly clear by the evidence of Dr David Brusick. He

is a most eminent genetic toxicologist, and the author of

one of the standard texts, "The Principles of Genetic

Toxicology".99 He is a member of the American

Association for the Advancement of Science, the American

Society for Microbiology, the Environmental Mutagen

Society, the Genetic Society of America and the Society of



He conducts a program on mutagenicity testing in his

capacity as a Director of the Biological Safety Evaluation

Division of Litton Bionetics, Inc.

Before becoming Vice-President of that organisation he had

extensive teaching experience including professorial

status in both Virginia and Washington.

Dr Brusick began his evidence by describing the origins of

congenital malformations. The overall average of

congenital malformations, he said, is of the order of 2.5

per hundred live births. Of these approximately 10% are

non-genetically related, and result from what are usually

teratogenic agencies which would include viral infection,

dietary deficiencies, hormonal imbalances consequent upon

drugs, chemical exposure and the like. These are not

inheritable, and result from female exposure only.

Accordingly for the Commission's purposes they may be put

to one side. The rest are genetically related. These are

of three types:

1. Somatic cell mutagen. Such mutations occur in utero,

result from female "exposure" only, are not

inheritable and are of environmental origin. For

present purposes these too may be put aside.


2. Single gene and chromosome traits, maintained in the

population. This group includes about 10% of

congenital malformations. A single gene trait means

that the inheritance pattern. or the congenital

malformation, is the result of an aberration or damage

to a single gene. Once that gene is damaged the

malformation can be expressed. There are

approximately 50,000 individual genes in the human

genome, i.e. within the DNA of one cell there are

located 50,000 genes. The genome represents the total.

These single gene malformations account for about 10%

of the total and can be traced back through a family

tree. The particular trait will appear, not in every

generation, but from time to time.

3. Mutiple gene traits. 80% of all congenital

malformations are maintained in the human population

through multiple gene traits.

A good example of a multiple gene trait is height. Height

in an individual is the consequence of many genes working

together in concert. An average person may have an equal

number of tall genes and short genes and therefore be of


average height. Two average height individuals could

conceivably give all of their short genes to their progeny

resulting in an extremely short child or alternatively

they could give all of their tall genes to one child and

have a very tall child.

The same is true for congenital malformations. All human

beings carry genes which contribute to the formation of

normal bone structure, normal organ structure and so on.

Malformations caused by multiple gene traits are of course

extremely difficult to study because there is no way to

determine how many of each kind of gene will be given to a

particular offspring. It is totally random. One cannot

do a family tree and look for cleft palate in families

where only one individual may, within recordable history,

show it.

It follows therefore that if one is dealing with male-only

exposure there is only one source of congenital

malformation left open, that is, a source which would

affect the DNA because in the fertilisation process only

one male cell is involved and the exposure must affect it.

Thus if a chemical is going to cause a congenital

malformation by male-only exposure it must be genetically


active; that means it must be able to produce a single

gene mutation, a chromosomal mutation, or a mutation in

one or more of the various genes which would contribute to

a multiple gene trait.

A single gene mutation may be either dominant or

recessive. A developing embryo gets chromosomal material

from both the mother and the father. If the mutation

occurs in only one of the parents then the mutation must

be dominant if it is to appear in his or her child. That

is to say, a dominant mutation will be expressed when it

is transmitted irrespective of what the other parent

contributes. So single gene mutations of the dominant

type will appear in the very first generation, and this

then must be the type with which this Commission is


Recessive gene mutations are those which are not

necessarily expressed even though transmitted to the

offspring. If a recessive mutation occurs in the male and

is transmitted then, unless the mother is also carrying

the very same mutation and transmits it. the mutation will

only be transmitted in a single dose and will not be

expressed. The chances of the same mutation occurring in

the female are small, and for practical purposes, amongst

V I 1-121

the Vietnam Veteran cohort of 45,000, a recessive gene

mutation is unlikely to be a cause of a birth defect.

Thus for practical purposes it is only relevant to look

for a chemical which is not only genetically active but

one which is an extremely powerful mutagen.


As the Commission is dealing with a purely theoretical

model it seems appropriate to examine the mutagenic

potential of all of the chemicals as disclosed by the

standard tests.

Methods of testing for mutagenicity are of various types

and complexity. The animal teratogenicity or reproduction

studies show that there are no teratogenic effects arising

from male only exposure. They also provide a foundation

for believing that there are no mutagenic effects

operating by male only exposure. Such studies were not

designed to look for mutagenic activity in either the

short term or the long term but the results tend to show

no such activity.


Nonetheless, since the animal studies are not capable of

completely closing the door on the mutagenic effect

argument, the Commission has considered the mutagenicity

studies. These extensive examinations are not reported in

detail herein. They do however permit the following

reliable conclusions to be drawn as to the particular

chemicals used in Vietnam.


The Commission concludes that 2,4-D may be a very weak

mutagen. Such mutagenicity as it might have is without

significance in the context of exposure in Vietnam.

The most substantial bases for the conclusion are as


(i) Dr Frank Dost reviewed the data in detail and said:

2,4-D has been extensively evaluated for mutagenic potential, using a wide range of test systems. ... The lack of positive

response in most tests and the very high dosage requirements in the positive assays indicate that 2,4-D may be a very weak

mutagen, but it is without significance as an environmental mutagenic hazard.100


Dr Ian Munro, a toxicologist of high repute101 also gave

evidence and, although in slightly more complicated terms,


The International Agency for Research into Cancer said:

2,4-D in the range of 50-500 micrograms per millilitre had a dose dependent inhibitory effect on cell growth of L929 cells in monolayer

cultures. With 350 to 500 micrograms per

millilitre complete inhibition of growth occurred after 24 hours incubation. On removal of 2,4-D a rapid resumption of cell multiplication took place.102

J.P. Silar in "The Genetic Toxicology of Phenoxy Acids

Other Than 2.4,5-T" pointed out that except in yeast 103

testing there was no strong mutagenic activity.

Dr Brusick summed the matter up as follows:

Studies in Drosophila, tissue culture cells and yeast have es tablished a very limited potential of phenoxy herbicides to induce mutation and chromosome aberrations. Yet when evidence for expression of these phenomena in vivo (either rodent or human) is sought the results are

essentially negative. Animal studies with 2,4-D. 2,4,5-T and TCDD have not shown evidence of somatic cell chromosome damage and more

importantly no evidence of genetic damage in the male germ cells (negative dominant lethal test) .... Thus in my opinion there is no evidence

supporting a concern that phenoxy herbicides pose a substantial genetic risk to the germ cells of exposed humans.^·04



In the United Kingdom the Government's Advisory Committee

on Pesticides has reviewed the safety for use in the

United Kingdom of the herbicide 2,4,5-T on three separate

occasions, in March 1979,105 December 1980106 and

December 1982. 107

The most extensive review was conducted in 1980. The

later review makes no qualification. The Committee


It is known that physical radiation is the most powerful mutagen in the laboratory. However, in some human populations exposed to high doses of physical radiation from atomic bombs, no

significant effects have been observed in progeny. (Grosch and Hopwood 1979). Thus even if Dioxin and 2,4,5-T were, at most, weak mutagens it is exceedingly unlikely they could give rise

to any observable increase in the incidence of congenital malformations.

As appears above. Dr Brusick and Dr Dost agree with this

conclusion. Dr Tuchmann-Duplessis also agrees. The

Commission concludes that 2,4,5-T is at worst a very weak




The eminent toxicologist. Dr Ernest McConnell, reviewed

the toxicity of the dioxins in 1980 and said:

In summary, it appears that the mutagenic

potential of these chemicals is equivocal, at most, they would be considered weak


The United Kingdom's major review, referred to above,


It is impossible to come to any firm conclusion, except that, like 2,4,5-T, TCDD cannot be

considered as a powerful mutagen.109

In 1981 The Canadian National Research Council said, "The

available data on mutagenicity of TCDD indicate that this

compound is not mutagenic". The Committee also referred

to certain chromosomal abberrations and then said, "The

data on these effects are equivocal, but the majority of

the more carefully conducted studies have produced

negative results."110

This conclusion is one with which Dr Brusick agrees.111

Dr Alistair Hay, who gave evidence for W A A said:


The only evidence of chromosomal damage in humans arising from exposure to TCDD is from Vietnam. Vietnamese scientists claim that there is higher incidence of chromosome breaks and gaps in

individuals exposed to the herbicide Agent Orange when it was used as a defoliant in Vietnam.

However, the level of chromosomal damage reported as abnormal by Tung et al is considered normal in the West.... No chromosome abnormalities have been reported in workers engaged in the

manufacture of 2.4.5-T at Dow Chemicals in the United States or men exposed to TCDD as a result of industrial accidents in West Germany and Britain.112

The IARC in its cancer review of TCDD said, "Extensive

studies on workers and on adults, children and fetuses

exposed to TCDD in the Seveso incident have not revealed 113

any increase in chromosomal aberration frequencies."

The conclusion to which the Commission has come is that

the constituents of Agent Orange are at worst weakly

mutagenic and most unlikely to cause the kind of germinal

damage required to produce increases in unfortunate

reproductive outcomes amongst the offspring of those who

served in Vietnam.

These compounds are those which have taken up most of the

time of the Commission and indeed are those which gave

rise to the controversy. Nonetheless, many other

chemicals were used in Vietnam and the Commission's

conclusions about their mutagenicity are set out below.



The Commission. having reviewed all the material, is


content to adopt the evidence of Dr Munro in respect

of this compound and concludes that diquat is neither

carcinogenic nor mutagenic.


The Commission concludes that paraquat has no significant

mutagenic, carcinogenic or teratogenic effect in 115 mammals. The mutagenic potential of both diquat and

paraquat has been explored in vivo and in vitro. They

failed to demonstrate mutagenicity in the murine dominant

lethal test.116 The International Program on Chemical

Safety concluded, "Paraquat has been found to have minimal

to no genotoxic activity when evaluated in a variety of in


vitro and in vivo test systems."


The Commission concludes that picloram is not mutagenic,

adopting the opinion of Dr Ian Munro118. The Commission

reviewed the literature extensively, particularly that



W A A . 119

to by Dow Chemical (Australia) Limited and


The Commission concludes that dalapon is not mutagenic.

It has reviewed the literature and notes negative results


in all four bio-assays by Anderson et al and in three 121 by Carere et al.


Diuron was found to be negative for mutagenicity in four

assay tests. In the Commission's opinion it is not

mutagenic in man or animal. The literature was

extensively reviewed and the Commission reaches its


conclusion notwithstanding Seiler's work.


Monuron also gave negative results in all four assay

systems. The Commission finds that monuron is at most a

very weak mutagen. adopting Dr Brusick's opinion 123

notwithstanding some conflicting data.



Bromacil gave negative results in four assays and the

Commission finds that it is not mutagenic, as did the N.H.

& M.R.C. and the Pesticides & Agricultural Chemicals 124 (Standing) Committee.

Cacodvlic Acid

This compound presents a somewhat more difficult problem.

There is both negative and positive data in respect of its

mutagenicity and one must say that looking carefully at

the evidence and acknowledging some negative studies the

compound must be regarded as a candidate mutagen.

Certainly the negative testing suggests that if it is a

mutagen it is not a particularly powerful one.

Nonetheless the Commission finds that cacodylic acid is a

candidate mutagen Dr Munro points out that the compound

induces birth defects in laboratory animals only when

administered to the mothers at toxic or near toxic (i.e.


very high) doses. Thus even if mutagenic it is not

the kind of powerful mutagen that must be postulated.126



Dr Munro concludes that creosote is not mutagenic for 127

animal cells or for animals. Creosote/distillate is

however a mixture of polycyclic hydrocarbons and must be a

candidate mutagen at least in theory, as the

salmonella/microsome assay suggests. Again however it is 128

not the powerful mutagen that must be postulated.


No material has been discovered which suggests that

borate/chlorate is relevantly mutagenic and the Commission

finds accordingly.


This insecticide has been tested extensively for

mutagenicity and although there is some conflicting data

the Commission concludes that it is not mutagenic. The

Commission has reviewed the conflicting data in detail and

has no hesitation in adopting the conclusion of Dr

D . .129 Brusick.



Malathion data is substantially negative for mutagenicity

but there are some positive results. Notwithstanding

reports of chromosomal damage at very high exposure levels

which have been unreliably reported, the Commission has no

hesitation in finding that malathion has no relevant

mutagenic activity at the exposure levels likely to have

been experienced in Vietnam. Van Bao et al is

difficult to evaluate. The US Department of Health notes 131

several negative studies in conflict with this work.


The Commission adopts the conclusions of Dr Brusick 133 and Dr Ian Munro. See also I ARC 1982 June 30th Vol 30

and Malathion Research, June 1984 American Cyanamid.


There are mixed test outcomes in some systems but the

Commission concludes that dieldrin has no relevant

mutagenic activity. This coincides with the views of WHO


Expert Groups on Pesticide Residues and IARC.



Notwithstanding the work of Ahmed et al, the negative Ames

test and a review of the whole of the material leads the

Commission to the conclusion that chlordane is not

relevantly a mutagen. It poses no risk for heritable 135

genetic activity. The view is shared by I ARC and

IPCS.136 The Commission adopts Dr Brusick1s

. 137



The Commission concludes that this compound

mutagenic, adopting Dr Brusick1s opinion.138 , 140

and WHO agree.


Notwithstanding one positive in vitro test on human 141 lymphocytesj. the Commission comfortably concludes

that diazinon is not mutagenic in the relevant sense and

that there is no evidence of any mutagenic effects in

animals or man. Dr Brusick agrees142 as does the

14 3

Australian Department of Health.

is not





The conclusion to be drawn from the whole of the extensive

testing conducted on these compounds is that they are not 144

mutagenic, as Dr Brusick deposed. The Department of 145 Health agrees.

Diethyl-m-Toluamide (DEET)

The material in relation to this insect repellent is

sparse. No evidence has been led by anybody suggesting

that it is mutagenic and the Commission's own

investigations reveal only the work of Swentzel et al

which was negative.146 The Commission concludes that it

is not mutagenic.

Dimethyl-Phthalate (DMP) Insect repellent

These compounds are used widely as insect repellents and

also as perfume diluents. In some tests they were found

to be weakly mutagenic and in others to be non-mutagenic.

No contention that it is mutagenic or powerfully mutagenic

has been made on behalf of W A A and the Commission

concludes that it is either non mutagenic or so weakly

mutagenic as to be irrelevant in the present context.


There is some conflicting data but it is only of weak 147 responses.

Di-n-Butyl Phthalete (DBP) (Tick and Mite Repellent)

The Commission reaches the same conclusion as that reached

in respect of DMP, that is to say it is either not

mutagenic or it is so weakly mutagenic as to be non

mutagenic for present purposes. Dr Brusick is of the view

that it is not mutagenic.148

Dapsone. Chloroquine. Primaquine and Paludrin

No material has been put before the Commission which

suggests that any of these drugs are mutagenic. They have

been widely used over many years in malaria control.

Dapsone has been studied and found to be non mutagenic in

the normal test systems. The Commission finds no reason

for concluding other than that these four widely used and

internationally accepted drugs are anything other than non 149

mutagenic. IARC found Dapsone to be non-mutagenic.



The International Program on Chemical Safety recently

reviewed the toxicity of selected petroleum products.

Benzene, diesel fuel and jet fuel were found to produce

positive cell transformations. DMSO, Dimethyl Sulphoxide,

has been said to be a solvent which induces quicker

absorption, but nothing has been said to suggest that it

is mutagenic. The solvents are accepted by the Commission

as potentially capable of causing cell transformations but

unlikely to be genetic mutagens.


From the above it must be concluded that none of the

chemicals relied upon by W A A fall into the category of

"powerful mutagen". This makes the hypotheses relied upon

biologically most implausible.


A further suggestion which seemed to be made by W A A is

that, although none of the chemical compounds used in

Vietnam is itself mutagenic, a mutagenic effect was

possible as a result of some synergistic or additive


effect between many different chemicals used in different

ways in Vietnam. The matter was specifically put by

WAA's Counsel to Dr Frank Dost as follows:

MR MCINNES— But if a person is exposed to other chemicals. has been subjected to them before a toxic chemical is applied, you may expect to see an increased effect of the last

applied chemical?--- It is not likely at the levels of exposure that we are talking about in this kind of situation.150

Later in his evidence Dr Dost was asked by Senior Counsel

Assisting about the issue of synergism. Among other

things, he said:

To begin with the prospect that any group of these kinds of chemicals, pesticides of any kind, virtually, will interact within the environment to form new compounds is virtually nil. These

are substances that are from the point of view of the chemist, reasonably stable. They have to be or they could not be used as a product because by the time they were used they would be something other than that which they were when they were produced.151

And later:

There is no magic in chemistry and the rules, the basic rules that govern reactions in the

environment or for that matter in the body, would really militate against the formation of strange and wonderful compounds with enormous power. It just does not happen.152

Dr Munro in respect to the question of synergism said:


Of course the whole question of the level of exposure needs to be considered, when one thinks about the probabilities of interaction. My feeling would be that given the nature of

conditions we are talking about here, the

probability of interactions would probably be quite remote.

And further:

But I think in general the totality of exposure to these chemicals would not lead me to the

conclusion that this matter (the suggestion of synergistic effects) warrants study in any way.

The Commission itself then asked:

And the remoteness of the probability leads you to the conclusion that study of the

suggestion of synergism is not

warranted?--- No.

Yes. well if I could put this to you. Is there a real possibility that it may happen?--- No.

Dr Munro was further asked on this question:

Under conditions of daily use of malathion for vector control and the use of 2,4-D and

2,4,5-T contaminated at 2 parts per million with TCDD as a herbicide?-- 1 would not expect any synergistic effects at those levels".15^

Dr Phillipe Shubik in his written statement to

Commission said:



I have been asked to speculate on the matter of possible synergism between the various

herbicides, pesticides, drugs and possible environmental factors on any potential cancer producing (mutagens) effects that may have occurred. I can only respond that I have no

knowledge of any studies that would suggest that any of the agents involved have ever been

evaluated in any combination to examine this possibility. Neither am I familiar with any studies that would suggest theoretically that

such a possibility exists.154

Dr Bernard Stewart in his written statement to

Commission said:

There is no adequate experimental data to provide a basis for predicting the possible carcinogenic or mutagenic consequences to experimental animals of exposure to low doses of the suspect chemicals

in combination. Predicting such consequences for humans on the basis of experimental data must be regarded as speculation. If speculation upon the worst possible, but nonetheless credible,

scenario is made, then it would be predicted that some increase in environmentally determined promotional influence might be experienced by the exposed population. Nonetheless such a

prediction must be qualified. To be biologically effective, exposure to the promoters normally involves a long period (that is a significant

proportion of the individual's life time). Despite promotional activity being possible it is most likely that it would be impossible to

demonstrate such an effect amongst those who served in Vietnam. Either there will, in fact there would have been no effect or the effect would have been so minor as to be undetectable by

current investigative procedures. (emphasis added)155


V I 1-139

WAA's case on synergism is a bald statement of the

generality that chemicals can work in a potentiating or

accumulative way. The evidence satisfies the Commission

that as far as the chemicals being discussed are concerned

there is no synergistic or potentiating effect which would

translate the chemicals from non-mutagens or marginal

mutagens to the kind of potent mutagens required for the

dramatic effect relied upon by those contending for the

unfavourable outcome thesis.

returning then to the main argument.

The Commission assumes for the purposes of argument that

it is theoretically possible that exposure of a male to a

chemical substance can cause a mutation of the male

germinal cells.

Not only has it not been demonstrated that either TCDD or

the primary herbicide components of Agent Orange nor

indeed any of the other chemicals upon which W A A broadly

bases its claim can effect a mutagenic change in human

germ cells, but as well no human chemical mutagen has yet

been definitely identified. This is deposed to by Dr

Fiona Stanley.156


Further, in the studies specifically directed to the

question of whether exposure of veterans in Vietnam gave

rise to any excess of chromosome breaks or sister

chromatid exchanges, no differences were found between a

group of self selected Australian veterans and a group of 157 non veterans.

Similarly, in the pilot study by Newell et ai158 no

differences were found in the comparison between 50

Vietnam veterans and 50 matched controls in:

(i) the % of cells with chromosome breaks;

(ii) the number of breaks per cell;

(iii) the number or appearance of sperm;

(iv) the % of fluorescent bodies of sperm.

This study although carefully done and 159

investigators was subject to limitations

by its authors. It is nonetheless a useful

to the debate.

On the basis of the Commission's assumption postulated

above, what kind of reproductive outcomes would one expect?

by "blind"

referred to





The view was consistently expressed by expert witnesses

giving evidence before the Commission that the most likely

reproductive outcomes of a male exposure giving rise to a

germinal mutation are infertility, miscarriage or

spontaneous abortion and peri-natal death. Putting it at

its highest, structural congenital malformations are an

unlikely outcome, as Dr Stanley deposed.160

Dr Jacobs, Professor of Anatomy and Reproductive Biology,

University of Hawaii, an eminent cytogeneticist, expressed

the following view in her evidence:

Well if any of the pesticides that we used in Vietnam caused an increase in the level of

chromosome abnormalities these could be either of number or of structure. This increase could be present in the somatic cells of the exposed

individual, that is the non-germ cells, and/or the germ cells. If it were to be present in the germ cells it could result in an increase in the number of chromosomally abnormal conceptuses. Now the majority of these chromosomally abnormal

conceptuses would miscarry so one would find an excess of miscarriages due to this particular situation of having chromosome abnormality and a minority would probably present as congenitally abnormal live births.16^ ·

Dr Stanley, in her oral evidence, said:


Most of the literature suggests that the expected reproductive abnormalities are more likely to be infertility - I use the words spontaneous

abortion, you probably know it better as

miscarriage - spontaneous abortions in animals anyway. peri-natal death; actual structural congenital malformations are not reported very often and the general literature says that if you're going to look for the effects of germinal mutations you really need to look at infertility, miscarriage as your major outcomes, and

chromosomal anomalies. Now that is not to say that point mutations could not result in birth defects. We do not know what causes birth

defects, but from the literature it is less likely, put it that way, but we really do not know about the cause of birth defects ... A

germinal mutation causes either infertility because the sperms are just so abnormal that they cannot fertilise the egg, or that they are normal

and can fertilise the egg but the egg is so

abnormal that it will be miscarried early. ... These germinal mutations that end up in

chromosomal anomalies - I mean the vast majority of those are aborted well before 12 weeks. Very few of those get through to live birth, the

chromosomal anomalies. The only really major one that does is Downs' Syndrome which is Trisomy 21.162

Even in animals, there is an absence of evidence of

congenital malformations consequent upon the

administration of drugs or chemicals to the male parent.

In Dr Joffe's review paper, "Influence of Drug Exposure of

the Father on Peri-natal Outcome"163 the author sets out

in Table 1 a summary of adverse effects of drugs and

chemicals administered to male mammals prior to mating, on

their progeny. In only two of the studies cited are

malformations noted as an outcome, those studies being two

of the studies of Lutwak-Mann, reported in 1964 and 1967


respectively. A further study by the same author was

reported in 1965.

None of these three studies in fact justifies the

conclusion that malformations in the offspring of male

animals to which a chemical substance was administered

prior to conception were produced as a consequence of that


In the first of her three studies (1964) Dr Lutwak-Mann

reported experiments involving the mating of 6

thalidomide-treated male rabbits with 40 untreated does.

From the matings, 291 offspring were born.166 Two of

those offspring had gross malformations. The

malformations were not the same, one being spina bifida,

and the other involving the absence of a tail. Both

malformed pups were sired by the same male. Dr

Lutwak-Mann reports that "the incidence in our colony of

gross congenital malformations arising spontaneously is

low (1%)".167 The incidence in the experiments was even

lower and accordingly there is no basis for any suggestion

that the experimental drug was causing the malformations

observed. The study certainly does not provide evidence

that by a process of mutagenesis or otherwise male

exposure to a chemical can produce malformations in

offspring sired by that male.



In her 1965 study168, 31 experimental matings were

reported without any "gross malformation" although the

author did find it necessary to report that in a litter of

12 resulting from a mating of one of the males done since

the termination of the experiments, one pup was born with

paralysed hind legs.

In her 1967 study Dr Lutwak-Mann reported 6 malformations

from 103 experimental matings without disclosing the

number of offspring born. The author had. in her first

study, regarded a litter of 5 or less as a reproductive

shortcoming, and upon this basis, it is reasonable to

infer that the rate of malformation in the third study was

not greater than the normal rate of 1%.

Professor Tuchmann-Duplessis in his oral evidence noted

that despite the very large number of male persons who

over many years have received chemotherapy treatment for

cancer by the administration of chemicals with known

mutagenic qualities, he knew of no cases of male mediated

birth defects arising out of such treatment:

Here again, the situation is the following - people who are treated, the sperm count is going down we get sterility and it is coming back. To my knowledge there has never been any

modification of the embryonic development.169



The one area in which there has been a suggestion of

congenital malformations in man associated with chemical

exposure of the father is in relation to anaesthetic

gases. but there is substantial inconsistency among the

results of the various studies and the suggestion has to

be regarded as doubtful at best. Dr Stanley said of these


These data on anaesthetic gases are just so inconsistent around the world that you really get quite worried about it. I mean, in terms of the anomalies, mainly because of the small numbers and so on. If you pooled them altogether it

might be that you would get absolutely no


The evidence is, the Commission feels, doubtful and

unconvincing even in relation to spontaneous abortion.

The relevant studies may be summarised as follows:


(a) Akrog and Anor. (1970) conducted a study in

Denmark directed to the effects of both male and

female exposure which included only 137 pregnancies of

wives of exposed male anaesthetists. A very

significant increase in miscarriages was found in this

group but a difference between the frequency of


congenital malformations in children conceived before

and during the employment periods could not be

demonstrated, although the authors noted that this was

possibly because of the small numbers involved.

(b) The American Society of Anaesthesiologists published

in 1974 the report of an ad hoc committee (Cohen et 172 al) on the effect of trace anaesthetics on the

health of operating room personnel based on

questionnaires completed by a total of nearly 50,000

exposed operating room personnel. That study found

"little evidence that male exposure results in

abortion in the spouse but found a statistically

significant difference in congenital abnormality rates

in children born to the wives of male physicians".

Other corresponding groups comprising nurses and

physicians also showed differences but they were not

statistically significant. The Committee did not

advance this as evidence of any causal connection but

rather as an unexpected finding which deserved further



(c) Knill-Jones et al (1975) reported a study of

7,949 male doctors in the United Kingdom which found

that "paternal exposure did not appear to influence


the overall abortion rate or the frequency of major

congenital abnormality and involuntary infertility".

The authors did find some increase in the frequency of

minor abnormalities but attributed that difference to

biased recall due to awareness of the suggestion of

possible occupational health hazards associated with

work in operating theatres.


(d) The same Cohen et al. (1975) conducted a mail

survey of 4,797 general dental practitioners and 2,642

oral surgeons exposed to various extents (20.2% in the

first group and 74.8% in the second group) to

anaesthetic gases. That study found a highly

significant increase in miscarriages in the wives of

exposed subjects and a slight and insignificant

increase in congenital abnormalities. Although the

results of the study appear to have been carefully

analysed to allow for age and other factors, the

possibility of recall bias cannot be excluded among

the study group having regard to previous publicity in

relation to male and female exposure within a

relatively small professional group, and having regard

to the form of questionnaire used which bore the

heading "Effects of Waste Anaesthetics on Health" and

was quite patently directed to the association under



Accordingly, of the four studies, two found

statistically significant associations between male

exposure and miscarriage, while two found none, one found

a statistically significant increase in malformations in

one group but not in others, while the other three found

no increase or a statistically insignificant increase,

which in one study was expressly attributed to recall bias.

Dr. Stanley quotes Rogers and Danks (1983)176 for the

proposition that it is now established that advanced

paternal age has effects on new autosomal dominant

mutations such as achondroplasia, Marfan's syndrome, and

fibrodysplasia ossificans progressiva and that males can

contribute the extra chromosome in cases of Trisomy 21

(Down's syndrome). She pointed out that each of these is

an extremely rare condition, Down's syndrome occurring in

one per thousand of births and the others constituting far

less than 1% of all congenital malformations which in turn 177

constitute less than 4% of all live births.

Accordingly, while there is demonstration of the

possibility of male contribution to congenital structural

malformation there appears to be no evidence of such

malformation due to male exposure to a chemical except

perhaps in the somewhat doubtful case of male exposure to

anaesthetic gases.



There are thus substantial reasons why it would be

surprising to find an excess of congenital malformations

among the children of Vietnam veterans, arising as a

consequence of the exposure of those veterans to Agent

Orange or the other chemical agents:

(i) As to Agent Orange there is an absence of evidence

that any or any more than a small number of

Australian veterans were exposed;

(ii) The only plausible mechanism for such an outcome

depends upon a mutagenic effect of the relevant

chemicals. but there is no convincing evidence that

any one of the chemical agents is mutagenic in

humans; and

(iii) There is no example (except perhaps the rather weak

suggestion in relation to anaesthetic gases),

either in animals or man, of male exposures to a

chemical giving rise to birth defects in the

children of the exposed male.

As far as Agent Orange is concerned, the second and third

of those reasons are reinforced by such conclusions as may

be drawn from an experimental study using mice, which


study was expressly designed to test the hypothesis that

male exposure to Agent Orange could give rise to birth

defects and other adverse reproductive consequences.

That was the study of J.C. Lamb et al.178 The authors

administered 2,4-D. 2,4,5-T and TCDD in proportions

corresponding to those present in Agent Orange as used in

Vietnam to four groups of mice which were then mated with

untreated females. No changes were reported in any

reproductive parameters for the treated groups when

compared with a control group given a diet supplemented

only with the corn oil used as a vehicle for the

experimental chemicals. Parameters measured were mating

frequency, average fertility, percent implantation and

resorption, fetal malformations, germ cell toxicity, sperm

concentration, sperm motility, sperm abnormalities,

survival of offspring and neo-natal development.

Despite the absence of any reproductive effects, toxicity

of the liver and thymus and decreased body weights were

observed in the treated males, those effects being

dose-related, and reversible after treatment had ceased.

In other words, in at least one species, actual exposure

of males to Agent Orange to an extent sufficient to give

rise to measurable toxic effects in the males treated, not


only failed to lead to the production of any congenital

malformations in their offspring, but did not produce any

adverse reproductive effects at all over the wide range of

reproductive parameters considered. The significance of

this negative study is perhaps enhanced by the fact that

cleft palate, decrease in fetal weight and fetal mortality

have been produced as teratogenic effects in the same

species when Agent Orange was administered to pregnant 179 females.


It is of assistance to have regard to the final

conclusions expressed by various expert witnesses who gave

evidence before the Commission, as to the existence of any

relationship between service in Vietnam and exposure to

Agent Orange, and the subsequent occurrence of adverse

reproductive outcomes. The following views were expressed

by various witnesses in their evidence:

Dr Stanley

Doctor, we have talked about the balance of probabilities. On the balance of

probabilities in your opinion is an

Australian Vietnam veteran more likely than any other member of this community to father a birth defected baby?--- No.


Should a Vietnam veteran or his spouse have any more anxiety than any other member of the community about reproduction?--- May I add a rider to that?

Yes?--- The only reason that they have is they have not got the data and they have not been able to interpret it properly because the media have been so emotive about it. I feel very strongly about that. The media have been so emotive about it, so a lot of them are anxious, extremely stressed about

their reproductive outcomes but based on data which is very flimsy indeed.

Doctor. if. a Vietnam veteran came to you and he had had a child with a birth defect and he asked you, was it likely to be connected with chemical exposure in Vietnam, what would your answer to him be?--- 1 think that

I would say that the cause of birth defects are unknown, that it - is unlikely - very unlikely that the chemical exposure in Vietnam of himself had anything to do with

the birth defect in that child.1®0

Dr Stein

... On the balance of probabilities, in your opinion, is an Australian Vietnam veteran more at risk of fathering a child with a

birth defect than any other member of the community?--- 1 would think not.

Has a Vietnam veteran, an Australian, any more reason to fear child-bearing or has his spouse any more reason to fear child-bearing than any other person?--- 1 would think not.1®1

Dr Jacobs

From a cytogeneticist's point of view, on the balance of probabilities, is a Vietnam veteran in your view more likely than any other member of the community to father a

birth defected child?--- 1 do not think he is any more likely to.


And has a Vietnam veteran or his spouse any more reason to be apprehensive about

reproduction, than anybody else?--- None at all.182

Dr Mathews

... On the balance of probabilities, in your opinion, is a Vietnam veteran, an Australian Vietnam veteran, more likely to father a birth defected child than any other

person?--- I think I would have to say no.

And on the same standard in your opinion is there any reason for a Vietnam veteran or his

partner to be more apprehensive about having children than any other member of the

community?--- It is easy to answer no to that question because any risk that might be there must be exceedingly small.183

Dr Brusick

Have you an opinion about that study (the Australian Birth Defects Study),

Doctor?--- 1 have read the study during the past few days and I obviously would state that I am not an epidemiologist and would not want to comment on the actual design of the study. I have looked at it and it

appears to have been careful in searching for any possible effects that might have arisen. It seems to be consistent with the conclusions that I generated on the basis of the discussion in that it would be unlikely in my opinion for an agent, which I consider to be non-mutagenic, to have been expected to produce any elevation (of) inheritable genetic effects which would have then

resulted in an increase in congenital

malformations in the offspring of women....

Are you saying. Doctor, that although you are not an epidemiologist the study got the answer you would have expected it to get?--- It did.184



The Commission concludes:

1. In considering whether the children of Australian

personnel serving in Vietnam have suffered adverse

reproductive outcomes as a result of chemical exposure

in Vietnam, a teratogenic mechanism for such effects

may be dismissed.

2. The only plausible theoretical mechanism is one

involving mutagenic effect of the male germ cells.

3. Such a mutagenic effect would require a most potent

mutagen and a significant degree of exposure, beyond

that of the mutagenic effect of radiation at Hiroshima

or Nagasaki.

4. The evidence is that none of the chemical agents to

which Australian personnel were exposed in Vietnam is

such a potent mutagen. Any exposure to those agents

was not of sufficient degree to be significant.

5. Even if one of the chemical agents could be said to be

a powerful mutagen the more likely reproductive


outcomes would be infertility or miscarriage. There

is no evidence that infertility levels or miscarriage

levels are in any way higher than normal amongst the

wives of Vietnam veterans.

6. The three major epidemiological studies relating to

service in Vietnam confirm the above expectations.

They are negative as to any overall association

between service in Vietnam and adverse reproductive

outcomes including infertility, miscarriage and

congenital malformations.

7. Earlier in this Chapter the Commission set out the

circumstances under which an inference of causation

might logically be made from studies of

epidemiological data.

The Commission finds that there is no association

between the risk factor, namely exposure to chemicals

in Vietnam and any untoward reproductive outcomes.

8. There is no consistency between the purportedly

positive studies.

9. No specific outcome has been identified.


10. No dose response relationship can be ascertained.

11. The mechanisms suggested are biologically implausible.

All that is left is the fanciful theory of male mediated

teratogenesis. The suggestion seems to be that following

the exposure of the male to chemicals„ one or more of the

chemicals is absorbed into the system and years later

finds its way by means of the sperm or seminal fluid into

the mother's vagina and thence to the embryo or fetus

transplacenta as a result of absorption into the mother's

blood stream. This happens, so the theory goes, either at

the time of insemination or after fertilisation during

subsequent intercourse. These postulated effects were

considered by a number of expert witnesses and each of

them rejected it out of hand.

Dr. Poliak was called by W A A to give evidence. In

discussing the studies of Lutwak-Mann in relation to

supposed male-mediated effects of thalidomide in the

offspring of exposed male rabbits he said:

In this study it was also found that appreciable amounts of thalidomide were present in the ejaculate, but there is no indication if any of the malformations and other deleterious effects were induced by the thalidomide carried by the

spermatozoa. The fact that all the malformations


were non-specific, instead of the highly specific effects caused by thalidomide, suggests that another mechanism was involved.185

Indeed. Dr Lutwak-Mann herself, at a symposium in 1965,

disclaimed any suggestion that this mechanism had operated

in studies carried out by her:

It was never suggested that in the type of

experiment described by me, thalidomide was actually transferred to the female reproductive tract and that the amount present in ejaculates could affect pregnancy.186

Dr. Fiona Stanley dealt with the theory as follows:

Virtually no seminal fluid, only the sperm swim up here (where the fetus is implanted). No

seminal fluid will get up there so it is not an effect directly on the developing fetus. What would have to happen is that the chemical would have to be absorbed into the blood stream from

the vagina or cervix. It would have to go into the bloodstream, circulate around the mother into the placenta, cross the placenta, get into the fetus as a teratogenic effect and that really is a very unlikely hypothesis ... It is biologically very implausible.18' 7

Dr. Brusick expressed the following view about the theory

insofar as it relied on transport of a chemical by sperm:

It is almost impossible to devise a mechanism by which exposed males could transmit teratogenic effects to unexposed females via sperm.188

That would be an extremely rare possibility simply because fertilisation occurs in the


fallopian tubes quite high up away from the site of insemination. Insemination occurs in the vagina of the female, the sperm then begin to swim and travel up into the fallopian tubes.

There is a very few number of sperm which reach the egg for fertilisation and the amount of semen material would have been quite diluted before the sperm reaches the egg. I think that would be an

extremely unlikely possibility.189

Dr. Stein in her oral evidence said of the theory:

Well it has been suggested that the actual

seminal fluid might be affected, but as Dr. Brusick and many other people have shown, the seminal fluid is protected quite strongly from many of the circulating substances and so we do not quite know how things get into the seminal

fluid and what kinds of chemicals get in and if they do get in we do not know how long they would have an effect either, so it is not a very viable theory and also not been demonstrated ... I have postulated this to biologists and they usually answer me that it is a far-fetched idea.190

Professor Tuchmann-Duplessis expressed a similar view.

especially in relation to the suggestion that contaminated

seminal fluid might accompany the sperm at the time of 1 q Ί fertilisation.

In the evidence taken in Zurich Professor Larsson rejected

the possibility of harm being caused by TCDD in seminal

fluid coating the sperm at the time of fertilisation,

having regard to the minute quantity which could

conceivably accompany the sperm. Professor Larsson's


evidence, based on calculations and the same principle of

dilution to which Dr. Brusick referred. was given upon the

hypothetical assumption that TCDD could find its way into

the seminal fluid of a male exposed in Vietnam.

There is no evidence of any TCDD having been found in the

seminal fluid of a human male exposed to Agent Orange or

some similar chemical.

Dr. Brusick in his oral evidence explained how unlikely it

was that a chemical such as TCDD should enter the testes

in a human:

Well, the blood testes barrier has been studied extensively in biochemistry and metabolism in humans as well as other animals. If you expose an animal or administer a chemical of any type to any animal you can follow the distribution of this throughout the body. In most cases you will find that where the circulatory system travels you will get a steady set-up in various organs

nearby the circulatory system. The exception to this - or one of the good exceptions - is in the testes whereby you will find gradients of

exposure, such that you will find high

concentration in the blood near the testes, but you will find very low concentrations if any in the testes itself and the reason for this is again believed to be an evolutionary protective device that is called ' the blood testes barrier1 and primarily it limits all except very small molecules from being transported from the circulatory system in the testes - small

molecules, low molecular weight, get transported back and forth. Ethanol for example is a good one which is not affected by the blood testes


barrier. ... I would think the TCDD would be one which probably would be prevented from entering the testes.19^

Having regard to the mass of evidence against the theory,

and the absence of any evidence to support it, the claim

of a male-mediated teratogenic mechanism is rejected. Such

a claim, in the Commission's view, is not only fanciful

but is one having no reasonable hypothesis to support it.

Accordingly, a tribunal could readily be satisfied beyond

reasonable doubt that there are insufficient grounds for

accepting such a claim.

Royal Commissions are not bound by precedent. Indeed they

need have no regard thereto. But the reasons for judgment

in two major decisions of Courts dealing with the same

subject matter have been read with interest. This

Commission is of the view that both are persuasive.

The first is that of the Supreme Court of Nova Scotia

(Trial Division) in Palmer et al v. Nova Scotia Forest

Industry 60 N.S.R. (2d) 271.

Broadly speaking, a group of environmentalists brought

action in Sydney, Nova Scotia before Mr. Justice Nunn for

an injunction restraining the use of phenoxy herbicides by


the defendant. The trial Judge came to the conclusion that

no injunction was warranted. In giving his reasons for

judgment he made the following findings:

591 I am satisfied that the overwhelming

currently accepted view of responsible scientists is that there is little evidence that, for humans either 2,4-D or 2,4,5-T is mutagenic or

carcinogenic and that TCDD is not an effective carcinogen, and further, that there are no-effect levels and safe levels for humans and wildlife for each of these substances.

593 Having reached this point it is appropriate to add that the evidence of risk assessments clearly indicates that any risk here in Nova Scotia, if, indeed, there is a risk at all, is

infinitesimally small and many, many times less than one in a million which level, apparently, is regarded as a safe and acceptable risk by most of the world's regulatory agencies. Putting this in

perspective, as indicated by Dr Wilson in his evidence, the risk of cancer to a smoker is 1 in 800 and for a non-smoker continuously in the same room with smokers it is 1 in 100,000, while the risk to a person drinking two litres of water per day from a stream immediately after being sprayed

(which will not happen with buffer zones) is 1 in 100,000 million or which itself is regarded as a "de minimus" risk.

594 To my mind, after hearing all the evidence and reading all the exhibits, there is no doubt that the weight of current responsible scientific opinion does not support the allegations of the plaintiffs. I feel it is my responsibility, in view of the nature of this matter, to add that, while I do not doubt the zeal of many of the

plaintiffs' scientific witnesses or their ability. some seemed at many times to be

protagonists defending a position, thereby losing some of their objectivity. There was a

noticeable selection of studies which supported their view and a refusal to accept any criticism of them or contrary studies. Where the study was


by anyone remotely connected with industry there was a tendency to leap to the "fox in the chicken coop" philosophy, thereby ruling out the value of

the study as biased. In my view a true

scientific approach does not permit such

self-serving selectivity, nor does it so readily decry a study on the basis of bias.

596 It would be a Herculean task to go through the evidence of each witness indicating which particular facts were accepted or rejected. However, it is not necessary, for reasons already

stated. I will say though, as a general point, that I accept the evidence of the defendant's witnesses as representing the generally accepted view of responsible scientists, and also as

indicative of the risks involved. Each of them categorically states that neither 2,4-D or 2,4.S-T, nor the concentration of TCDD presently

in 2,4,5-T, nor the mixture of 2,4-D and 2,4,5-T in the concentrations to be sprayed on Nova Scotia forests pose any health hazard

whatsoever. I am unable to accept that the

plaintiffs have proved any strong probability or a sufficient degree of probability of risk to health to warrant the granting of the remedy sought, a quia timet injunction.

The second decision was that of Chief Judge Weinstein

dealing with (inter alia) independent claims by veterans'

wives and children on a class action basis. His Honour

(although leaving open future claims on behalf of the

infant children on the basis that science may one day find

some connection to support a claim) dealt with the claims

that children were born with birth defects as a result of

their father's exposure to chemicals in Vietnam as follows:

Plaintiffs have produced no evidence of any probative value to contradict the Government's overwhelming showing of no present proof of causation.



The Commission finds that any untoward reproductive

outcomes amongst the offspring of Vietnam veterans did not

result from exposure of the father in Vietnam to any

chemical agent.

The claim that such outcomes are so associated is fanciful.

No reasonable hypothesis linking such outcomes with

chemical exposure in Vietnam can be postulated.

The hypotheses postulated by W A A have been overwhelmingly


The hypothesis of Dr Stanley that living with an unhappy

husband, particularly a heavy drinking one. might lead a

pregnant wife to expose herself to potential teratogens is 1 9 4 not fanciful.

Nor is the proposition that a disturbed family system

caused by a distraught father. may cause illness,

behavioural problems, learning difficulties and asthma in

the children of the family. There may well be an excess

of these problems among the offspring of disturbed Vietnam



It is for this reason, amongst others, that the Commission

recommends that the services of the W C S continue to be

available to all members of a Vietnam veteran's immediate



In view of the concern and apprehension of veterans and

their wives. the conclusions which the Commission has

reached in this area must be given the widest possible

publicity and the Commission so recommends.



WAA's Tasmanian Study

The Commission concluded its hearings on birth anomalies

on 5 September 1984. As early as December 1983 those

assisting the Commission were informed of a W A A proposal

to conduct an investigation into the reproductive outcomes

of Vietnam veterans who were residents of Tasmania.

During the year or more that followed, regular inquiries

were made of Senior Counsel for W A A as to the progress of

this study. These regular inquiries which were informal

and courteous became somewhat more insistent at the end of

the birth defects hearing in September 1984. At an open

hearing on 12 December 1984 Mr O'Keefe raised the question

of the appropriate report.

Mr Mclnnes said.

Your Honour, my latest information now is that whether it is Professor Kerr or Dr Field, (he or she) will not have that completed until


The Commission expressed its concern about the delay. Mr

Mclnnes responded:


It is what comes before Your Honour that counts and that is why we have been pressing for this to be completed.

By February 1985 insistence had become nagging. Contact

with Mr Phillip Thompson (which had replaced contact with

his legal advisers by this time) led eventually to a

direct contact between Senior Counsel Assisting and

Professor Kerr. This occurred in early April 1985.

Professor Kerr told Counsel that all the data had been

gathered, that it was in computer form but that he was

reluctant to produce any report before the data was

thoroughly analysed. Indeed he expressly said:

In view of what Dr Donovan has said about us. we must be sure of our analysis and its


Professor Kerr emphasised in that conversation that he was

personally extremely busy but that he hoped to be able

with Dr Field's assistance, to get the analysis to the

Commission by the end of the week of 18 April.

In the Sunday Telegraph of 21 April 1985, over the by-line

of John Dikkenberg. the following appeared:



There are more deaths among children of

Australian Vietnam veterans than among high-risk Aboriginal children. according to a report expected to be released shortly.

The report shows a sample group of veterans in unpolluted Tasmania had a higher mortality rate among their children than a comparable group of Aboriginals cut off from health services.

according to lawyers Orange inquiry. connected with the Agent

The Aboriginal child mortality rate was last publicly estimated at live births. about 30 deaths per 1000

The report, which is expected to stoke the

smouldering Agent Orange issue, has been compiled by geneticists Professor Charles Kerr of the Commonwealth Institute of Health and Dr Barbara Field of Sydney's Westmead Hospital.

Professor Kerr, formerly Professor of

Preventative Medicine at Sydney University headed the Ranger uranium inquiry and more recent Kerr Committee, which reported on British nuclear tests at Maralinga.

The two geneticists combined with Drs Peter Hall and Ben Selinger of the Australian National University in 1981 to compile a controversial preliminary report on the suspected links between Agent Orange and birth defects.

Agent Orange is the name given to a toxic

defoliant used in the Vietnam war. Its active ingredient is the chemical 2,4,5-T, which contains the dioxin molecule, one of the most potent poisons ever made.

According to the lawyers, the new report is based purely on a sample group of Vietnam veterans living in Tasmania, where the unpolluted

environment was most unlikely to introduce further complicating outside elements to the research.


It is believed more than 1000 veterans were used in the study and the outcome was worse than

anyone had feared.

The 1981 Kerr and Field report uncovered evidence which invalidated the $20M official Federal Government study into the effects of Agent Orange on the health of Vietnam veterans.

The study was referred to again in the National Times on

May 17 but in uninflamatory terms.

On 25 May 1985. the Australian published an article over

the by-line of Laurie Quinn which repeated the passage in

Mr Dikkenberg1s article concerning high-risk Aboriginal


The Editor of the Sunday Telegraph has informed the

Commission that its article was written after consultation

between Mr Dikkenberg and Mr Alun Hill formerly Junior

Counsel for WAA. Mr Hill concedes that he spoke with Mr

Dikkenberg but denies that he gave him the information

about the report contained in the article.

There is conflict between Dikkenberg and Hill. In this

regard. the Commission is not able to say whose imaginings

the statements in the Sunday Telegraph are. But it is of

serious concern that false information received widespread



A preliminary confidential report prepared by Professor

Kerr and Dr Field was delivered to the Commission under

cover of a letter dated 30 April 1985.

Having read the report the Commission set in train

inquiries as to the method by which the data had been

gathered. It became apparent that Professor Kerr and Dr

Field were really not able to help the Commission as to

the manner in which the data had been gathered.

Accordingly, the Commission's staff issued 3 summonses for

the production of the documents constituting the source

data for the confidential preliminary report.

Those summonses sought from WAA, Dr Field and Professor

Kerr the following documents 1 2 3 4

(1) The questionnaires;

(2) Any records of methods of tracing and selection of


(3) Any computer programs, disk records or print-outs

connected with the study;

(4) All clinical notes and records connected with the

study, including death certificates;


(5) All records from which incidence rates in the general

population were drawn;

(6) All correspondence connected with the study;

(7) All work sheets and calculations used in connection

with the study.

The relevant documents were produced by those who had them

on Monday, 27 May 1985.

The evidence of Professor Kerr and Dr Field confirmed the

Commission's belief that they were unable to assist as to

the manner in which the data was gathered.

It became clear that the investigation had been under the

control of one, Ms Andrea Shaw. Ms Shaw is an

Undergraduate in Arts and Science of the University of

Melbourne, a Graduand in Science, who had acted as

"para-scientist" advising Senior Counsel for W A A from

time to time and had also acted as assistant to Mr John

Evans. WAA's "scientific adviser".

Ms Shaw was unavailable to give evidence. It was said

that she was in hospital on the Friday prior to the

hearings of 27 and 28 May 1985. There seems also to have

been some failure of good relations between her and W A A

in about August 1984.


As became clear, Ms Shaw had travelled to Tasmania and

arranged for the data to be gathered and established a

method for its gathering.

In a statement given to Counsel Assisting Mrs Murtagh gave

the following account of the manner of collection of the

, - 197 data.


My husband, Kerry, was the President of the Tasmanian Branch of the Vietnam Veterans

Association of Australia.

During second half of 1983 Mr Phil Thompson told me that he had access to a nominal roll of

veterans who had been to Vietnam and who had enlisted in Tasmania.

I decided, at that stage not for the purpose of any study, to get names from the nominal roll and to check it against telephone books and electoral rolls so as to get together a list of Vietnam veterans in Tasmania. We were unable to get a

photocopy of the nominal roll and there was some delay but eventually Terry Loftus read the names, the service numbers and the units of Vietnam veterans who had enlisted in Tasmania to me over the phone.

There were between 1300 and 1400 names

transferred onto a list and my husband and I worked first with phone books matching names and initials and thus obtained a list of potential Vietnam veterans which I then checked against the

electoral rolls from the area where the phone book indicated the potential veterans last lived.


This list came to be called "Rose's list" and I added to it by carefully checking the actual electoral rolls (5) so as to pick out Vietnam veterans or potential Vietnam veterans who were not on the phone.

In January of 1984 I spoke to Thompson and he said to me that Andrea Shaw was interested in my list.

Later Andrea Shaw rang me and asked me to draw up a list of Vietnam veterans who were not members of the WAA.

I prepared such a list and as far as I can recall there were about 680 non members on the list. This list was created by highlighting out those who were members of the Association.

Andrew Shaw then asked me to get together

competent reliable people who could be trusted to conscientiously question people from a

questionnaire prepared by her. I gathered together six women I knew, some of whom were Vietnam veterans' wives but all of whom were competent and reliable.

Andrea then said that she wanted a random 200 selected from both members and non members. She applied some form of logarithmic selection process to the listed members and non members and

selected 200 names. I supplied the list of members and non members to Andrea and letters were sent out to all shown on it from Sydney

(i.e. from WAA's office and on its letterhead) which invited Vietnam veterans to co-operate in the study and suggested that they give an

appropriate time and telephone number where the questionnaire could be applied.

Andrea came to Tasmania and spent an afternoon training the people who were to ask the questions emphasising that the questions should be asked in the same way to both the veterans and to the

controls. We questioned a few people under her supervision and we always worked in two's so if a problem arose we could get advice and help.

The ones who responded (to the letter), about 316, we rang first. When we ran out of those who


had responded we also rang those who had not responded doing the best we could to contact everybody.

We found some non veterans on the list.

We would speak preferably to the veteran but we would also speak to a wife of a veteran if she wished to have contact with us or if the veteran was unavailable.

Sometimes the husbands and wives would consult with each other or the husband would suggest that we ask an obstetric or other guestion of the wife.

The guestioner nominated the next door neighbour to be a control. If the veteran did not want the next door neighbour to be a control he or his

wife was asked to nominate someone who did not go to Vietnam but who lived in the same area as the veteran and had children born since Vietnam time.

The same interviewer did both the case and the control. It was obvious that the interviewer knew veteran and/or non veteran status at the time of interview but we were careful to ask the questions in the same way. The questions

themselves of course told the interviewee what it was we were questioning about.

Amongst the 200 there were obviously people we were not able to contact. When a person who had been thrown up by the random selection process was unable to be contacted I provided the

substitute by the following method. I selected by a process of finding the nearest regimental number combined with the same year of service and as close as possible a match for age.

The evidence discloses that after the questioning process

had proceeded, the questionnaires were placed in files and

numbered. Those completed were forwarded to Sydney in

July 1984 and made available to Dr Barbara Field at WAA's

then headquarters at Newtown.


Dr Field went through these in detail and wrote to the

treating doctors on a paediatrician to paediatrician basis

to verify the major defects and serious medical conditions.

The verifications came in over a period of time.

Dr Field worked on 386 completed questionnaires and also

had a list of single veterans, non-parent veterans and

veterans who had children only pre-Vietnam. There were

also about 20 questionnaires in a different form. This

list and questionnaires totalled 100 veterans.

She then prepared the results in tabular form and she and

Professor Kerr wrote the preliminary report together. with

Professor Kerr physically writing the first versions.


In addition to general conclusions the report drew two

particular conclusions.

These were:


(1) The incidence of malformations of particular tissues

within this study of 885 children shows significant

increases by comparison to rates observed in the

general populations. There follows a table:


Open neural tube defects (3 cases) 3.4/1000 2/1000

Chromosome abnormality (4 cases) 4.5/1000 1.6/1000

Hydrocephalus (3 cases) 3.4/1000 1.6/1000

Congenital Heart Disease (10 cases) 11.7/1000 6-8/1000

(2) Under the Table the following appears:

In terms of coincidental occurrence in a

relatively small randomly selected population there appeared to be a concentration of rare syndromes diagnosed as cerebromandibular syndrome, Werdnig-Hoffmann disease and a degenerative central nervous system disease. These were recorded in addition to other some uncommon diseases viz. x-ichthyosis, diabetes -

(onset aged 2), and, in particular 7 neoplasms of childhood.

The report drew the following general conclusions:

(1) This study has identified a high peri-natal and infant

mortality rate among the children of Vietnam veterans


in Tasmania: the majority of lethal incidence

occurring in the years immediately following return to

civilian life.

(2) By comparison to the general population there were

significantly increased rates for major malformations

of the central nervous system, skeletal and

cardiovascular systems and certain childhood


(3) Accordingly the only plausible interpretation of the

observations in this study is that the increase in

offspring detriment is in some way related to events

that took place in Vietnam.

Each of the above five conclusions has been demonstrated

from the source documents and by cross-examination to be

totally unfounded.

Giving all the weight that can be given to the claimed

pressures of time, the presentation by trained people of a

report which disregards the most fundamental tenets of

science establishes in the Commission's view bias and

irresponsibility of a high order. The material could have

been presented without conclusions.


To present the material with numerical errors in favour of

the conclusions. with omission of necessary denominators,

with failure to compare like with like and with

misclassification of neoplasm is unforgiveable. If the

matter were not of such importance the Commission would

simply reproduce the answers that Professor Kerr gave

disavowing the conclusions in the preliminary report. The

circumstances however demand more.

Of the conclusions drawn, perhaps the most frightening

from a veteran parent point of view is the suggestion that

there were significantly increased rates of childhood

malignancies. The basis for this assertion was that there

were 7 neoplasms of childhood found amongst the offspring

of the alleged 500 veteran families examined.


Dr Field was asked in her evidence to nominate the 7 cases

of childhood neoplasm.198 She nominated the case

numbered on her sheet 59, a hydatidiform mole; case no. 60

a brain stem glioma; case no. 61 a lipoblastoma; case no.

62 an astrocytoma; case no. 63 a vascular hamartoma; case

no. 38 an arterio-venous malformation of brain; case no.


39 a porencephalic cyst; case no. 36 a giant hairy naevus

at base of spine and case no. 5 a teratoma of the brain.

The doctor conceded that the hydatidiform mole was

inappropriately placed amongst major malformations and

diseases in surviving children since the mole certainly

did not survive.

Similarly the teratoma of the brain was a case of

stillbirth and not a case of malformation or disease in a

surviving child.

Dr Field had available medical reports from the treating

doctors in respect of each of the rest.

(a) Case No. 60. the brain stem glioma (File No. 379).

This boy was admitted to hospital on 7 November 1977

with a history of gradual onset of diplopia and mild

ataxia. He suffered no change whilst in hospital, all

his investigations were found to be normal and he was

discharged on 6 December 1977 for review in

outpatients. A diagnosis of "?? brain stem glioma"

was made.


An examination of the parental questionnaire shows

that the boy was investigated for a year. The

interview took place in June 1984 and he was then

still alive. A reading of the questionnaire indicates

that the problem simply went away.

(b) Case No. 61. a lipoblastoma (File No. 257). The

treating doctor removed a smooth round disc shaped

lump from the child's back. He was able to completely

excise the mass and histological examination revealed

that this was a benign lipoblastoma. Nothing in the

report suggests malignant neoplasm. Dr Field suggests

that this lipoblastoma recurred in 1984. She conceded 199

that there was no evidence of neoplasm. The

treating doctor's report indicates that he reviewed

the child on 4 June 1984 at his own request and that

he found no evidence of recurrence.

The parents' questionnaire dated 13 April 1984 refers

to a "benign foetal lypoma (sic) attached to spine."

(c) Case No. 62 is an alleged astrocytoma (File No. 156).

Pathology reports from the Royal Children's Hospital

refer to a biopsy and a micro examination of the

biopsy. The report of 26 September 1983 reads. "The

features suggest a low grade astrocytoma."


This report was reviewed on 6 October 1983 , by two

pathologists. They together wrote an amended report:

Further sections have been prepared from the last pieces of tissues. These show that the tissue previously thought to be astrocytoma is in fact stromal tissue from choroid plexus showing focal calcification and haemorrhage.

Therefore there is no evidence of astrocytoma in any of this material. Diagnosis: brain "no pathological diagnosis" (choroid plexus).

Dr Field equivocated but finally conceded the later . . . 200


(d) Case No. 63. a vascular hamartoma (File No. 246). In

1980 this boy had a lump under his right arm diagnosed

by the histo-pathologist as a vascular hamartoma.

There was no suggestion of neoplasm. Dr Field

vv.· 201 conceded this.

(e) Case No. 39. a porencephalic cyst (File No. 201).

This little girl had epilepsy. On a "cat" scan a

large right porencephalic cyst in communication with

her ventricle was discovered. The visiting

neuro-surgeon. Dr Duffy wrote:


There is nothing to suggest a tumour.

Almost certainly the appearances on cat scan now have been the situation for the whole of her life and I do not feel that any further investigation or change of management was needed.

There was nothing to suggest neoplasm, as Dr Field

, , 202


(f) Case No . 38 an arterio venous malformation of the

brain. (File No. 189) . This little girl had a mass

removed from her left frontal lobe in March 1983.

Pathological examination of the tissue showed that it

was a blood clot with some organisation: it probably

resulted from a vascular malformation or a

pseudo-aneurysm. The treating neurosurgeon

specifically found, "there was no evidence of a

neoplastic process".

(g) Case No. 36. a giant hairy naevus (File No. 83). This

naevus was removed over a period in three operations

between 1976 and 1979. The pathology reports a

compound hairy naevus. There was nothing to indicate

neoplasm. Dr Field also included this giant hairy

naevus as a neural tube defect. She concedes that

there was no neoplasm in this case.


The result of this analysis is that far from there being

seven there is one genuine childhood neoplasm in a

surviving child amongst the group. One could expect

amongst a cohort of this size as many as four to six

neoplasms; accordingly the true rate of neoplasms amongst

this cohort was lower than expected. The conclusion that

the rates were significantly increased is quite untenable.

Selection Bias Potential

It must be said that the selection process is fraught with

potential for bias. From an original list of 1,390

veterans less than 500 were subjected to questionnaires.

The recovery rates are low. The selectors were Vietnam

Veteran Association officials or their wives. The

selectees were likely to have been influenced by the

controversy. The questionnaire itself is unsatisfactory

from an epidemiological stand-point.

Thus reliable conclusions from the data were unlikely.

Mortality Rates

Conclusion 4 was, "This study has identified a high

peri-natal and infant mortality rate amongst the children


of Vietnam veterans in Tasmania; the majority of lethal

incidents occurring in the years immediately following

return to civilian life."

The majority of the births also occurred in the years

immediately following return to civilian life and one

would expect the majority of lethal incidents to so

occur. Omission of the denominator is a classical

epidemiological error.

The study did not identify high peri-natal and infant

mortality rates when like was compared with like. The

study indentified 13 neo-natal deaths. (that is death

after a live birth up to age 28 days) and 9 stillbirths.

Amongst the stillbirths are included File No. 164, a

miscarriage in the 22nd week, which in 1971 would not have

been included in the Tasmanian or National statistics as a

stillbirth. Also included is File No. 117, a miscarriage

at 18 weeks which would at no relevant time have been

regarded as a stillbirth. The "true" stillbirth number

disclosed by the study is 7.

This produces a peri-natal death rate of 24.9 per thousand

which compares favourably with the West Australian rate


for 1968-70, of 27 per thousand and also with the

Tasmanian rates for the relevant period (1972, 20.2 per

thousand; 1973, 24.4 per thousand; 1974, 21 per thousand;

1975, 23.5 per thousand).

As to infant mortality, the rates thrown up by the study

are statistically indistinguishable from the Tasmanian

rates for the relevant period. The rate shown by the

study was 18.1 per thousand compared with Tasmanian rates

for 1972 of 16.2 per thousand; 1973, 18.7 per thousand;

1974 of 16.6 per thousand.

Dr Field and Professor Kerr both conceded that there was

nothing significant in 3 cases of open neural tube defect

from a population of 885 births by comparison with general

population figures for Tasmania. The general population

figure for Tasmania is 2.34 per thousand.

In each of the other categories the Professor and the

Doctor made similar concessions.

As far as the totality is concerned Professor Kerr

conceded that the study showed no difference between the

rates of those studied and the Australian and the

Tasmanian statistics.


Dr Field, in a quite extraordinary display, sought to

withdraw the report. She was questioned by

Commission. The following exchange occurred.

What do you mean, if it is necessary? I would only accept that if you said that, that is what you really feel after listening to some of the evidence given by Professor Kerr this afternoon and realizing, after the questions

that have been asked, that perhaps the study was done too quickly, the report was done too quickly, and it is not really worth the paper that it is written on. You see, it is very difficult if that is so, because I have been sitting here now for something like two years, and those who are assisting me and I, myself, have read literally hundreds and hundreds of reports done by people

throughout the world on relevant matters, and at the heel of the hunt this study has got a great deal of publicity in the press of this country. You see there are parents

in this country who are very, very

distressed about having children with abnormalities, or anomalies as you people call them. Now, they are not told that that is normal in this human race, that there are a percentage of children born each and every day throughout this world with defects. The general public are not told; the press will not say that. They grab hold of this study of yours and it has got wide publicity over Australia now, alleging that in Tasmania the

children of Vietnam veterans are giving birth - the fathers are begetting children with defects which are in excess of the

norm?-- 1 hope your Honour is - - -And it has been demonstrated to me - I have not heard all the evidence yet on it - that up to this stage it has been demonstrated that

that is not so?-- 1 agree, your Honour.203



The study has many deficiencies not the least of which is

its potential for selection bias. Its conclusions are

patently ill-founded. It provides no support for the

proposition that Vietnam veterans are fathering children

with birth anomalies or bringing about other untoward

pregnancy outcomes by reason of service in Vietnam as a

result of exposure to chemical agents or otherwise.

Indeed the rates discovered by the study suggest normal

birth outcomes amongst such veterans. It would however be

as unwise for anyone to draw negative conclusions from the

study as it was for Professor Kerr and Dr Field to draw

positive ones.

Nothing in this flawed and deceptive study leads the

Commission to change any of its final conclusions set out




1. See Ch 1 pp 1-4.

2. Exhibit 1040 p 62.

3. Ibid p 65.

4. Exhibit 1879.

5. Exhibit 1879 at p 122.

6. Exhibit 1427.

7. Exhibit 1391.

8. Exhibit 1248.

9. See Ch II Standard of Proof.

10. Exhibit 1040 p 62.

11. Bradford Hill. 1977, Adopted by Dr Stanley,

Exhibit 1422, pp 17-20.

12. "Handbook of Teratology" Wilson and Fraser (1977) Plenum Press p 310.

13. Donovan et al Exhibit 1248.

14. See Ch 1 Introduction.

15. See Ch VI "The Proposed Morbidity Study" at pp 5 et seq.

16. Ex 1248 1 p 1.

17. E.g. Dr Brusick, Transcript p 3900 et seq.

18. Transcript p 2006.

19. Transcript p 3931.

20. Transcript p 4353.

21. Transcript p 4501.

22. Transcript pp 4502-3.


23 .

24 .

25 .

26 .


28 .

29 .




33 .

34 .









43 .

44 .

45 .


Exhibit 1879.

Exhibit 1398.

Ibid p 388.

Exhibit 1398.

Transcript p 5434.

Exhibit 1673.

Transcript at p 5434.

Exhibit 1398.

See Table 6.7 Exhibit 1248.

part of Exhibit 1398 pp 194-5.

"Vietnam Service and the Risk of Congenital Anomalies" - part of Exhibit 1398 p 397.

Exhibit 1398 p 397.

Letter, Medical Journal of Australia on 4 August„ 1984, p 195 part of Exhibit 1398.

See Ch IV "Exposure".

Exhibit 1879 supra p 122.

Exhibit 1394.

Exhibit 1391.

Exhibit 1284P.

Exhibit 1431.

Exhibit 1233.

Exhibit 1394, p 1-2.

Exhibit 1121 Paragraph 7.

Exhibit 1122 p 16.

Exhibit 1398 pp 388-9.


47. Exhibit 1394 table Xl-1.

48 .





53 .















6 8 .

69 .

Exhibit 1394 Figure Xl-2.

Exhibit 1394. table Xl-5 p Xl-12.


Exhibit 1394 Xl-8.

Exhibit 1394 Table Xl-12.

Exhibit 1394 Table Xl-12.

Exhibit 1394 p XI-29.

Transcript p 4495. '

Transcript p 5493 et seq.

Exhibit 1879 at p 124.

Transcript p 5493-5508.

Exhibit 1391=

As to which see Ch IV "Exposure".

Transcript p 4520 - Exhibit 1434 p 9.

Transcript p 5462.

Transcript pp 4073-9.

Exhibit 1540.

Exhibit 1233.

Exhibit 1284P.

Bionetics Research Laboratories, Inc. 1968. Evaluation of Carcinogenic. Teratogenic and Mutagenic Activities of Selected Pesticides and Industrial Chemicals, see also endnote 32 in Ch 1.

Exhibit 1284H.

Exhibit 1284C.





73 .






79 .




83 .



86 .


8 8.

89 .



See Bloom "Guidelines for Studies of Human

Populations Exposed to Mutagenic and Reproductive Hazards" March of Dimes Birth Defects Foundation 1981. Hook. E.B.. 1983. Exhibit 1905 at p 393.

Exhibit 1284N.

Exhibit 1284B.

Exhibit 1284J.

Exhibit 1284K.

Exhibit 1284L.

Exhibit 1284F.

Exhibit 1284M.

Personal communication to the Commission. March 1984.

Transcript at p 4352.

Exhibit 1284H.

Exhibit 67.

Exhibit 608.

Letter to Nature 295 (5847) p 276.

Exhibit 424.

Exhibit 1244A.

Exhibit 1431.

Letter to Lancet (1983) i (833 ):1112-3.

Bisanti et al cited in Exhibit 1257 . see also

Exhibit 1265.

Informal Discussions between Dr Pocchiari and the Commissioner. Counsel Assisting and Counsel for W A A and Monsanto in Rome in October 1984.

Exhibit 1879.

Exhibit 1422 p 9.


92. Exhibit 1428.

93 .

94 .




98 .




102 .







109 .


111 .


113 .

Exhibit 1295.

Transcript p 3919.

Transcript p 4334.

See Huffier P.A. & Aase J.M. (1982) J. Occup. Med. 24(4):305-314.

Exhibit 877.

Exhibit 877, I - XIII.

Plenum Press (1980) New York.

Exhibit 1268, pp 31-33.

The Canadian Government's Senior Adviser on herbicides and environmental hazards.

(IARC), Monograph Volume 15 (1977) at pp 125-126.

pp 218-221.

Exhibit 1377 p 17.

Exhibit 706.

Exhibit 777.

Exhibit 1363.

See Halogenated Byphenyls . . . And Related Products, edited R.D. Kimbrough. Topics in Environmental Health 1980, Amsterdam.

Exhibit 777 (1980) at p 49.

Polychlorinated Dibenzo-p-Dioxins, Criteria for their effects on Man and his Environment, NRCC No 18574 p 125.

Transcript p 3919.

Exhibit 1283 p 46.

Exhibit 1351 at p 240.


114 .


116 .

117 .

118 .

119 .



122 .

123 .


125 .

126 .



129 .




133 .


Exhibit 1288.

Exhibit 828 p 11.

Exhibit 1895.

Exhibit 1245, p 14.

Exhibit 894. Exhibit 1288. Exhibit 934.

Exhibit 894, Vol 1 Ch. 9. p 15.

Exhibit 894. Vol 1 Ch. 9 p 16.

Exhibit 894. p 15 & 16. Exhibit 1288. p 12.

Transcript p 3929. Exhibit 1379. Exhibit 1288. Exhibit 894.

Exhibit 894, Vol 1, Ch 9 p 15-16. NH&MRC meeting 11 November 1982 and Pesticide and Agricultural Chemical Committee. February 1983.

Transcript p 2376.

Exhibit 1379, Exhibit 1379A. Exhibit 894. Vol 3. Ch. 7. p 1-4.

Transcript p 3929.

Exhibit 1379, see also Bos et al (1983) Mutation Research 119 21-25. and Wood Preservatives. Technical Bulletin 1981, No 1658.

Transcript p 3 9 28. [cf WHO, Exhibit 1898 , Exhibit 1379, IARC Exhibit 1351].

Exhibit 704.

Exhibit 672, p 71-73.

Transcript p 3928.

Transcript p 2379/80.

Exhibit 1351, p 112.113 and Monograph. 1977 Geneva 6-15 December, WHO/FAO Panel of Experts on Pesticide Residues and Environment.

Exhibit 1245, p 15.


135. Exhibit 1351.

136. Exhibit 1666.

137. Transcript p 3926.

138. Transcript p 3931.

139. Exhibit 1351.

140. WHO, the Monographs Geneva, 1974, p 307.

141. WHO Data Sheets on Pesticides No. 45.

142. Transcript pp 3927-8.

143. Exhibit 1288.

144. Transcript p 3929.

145. Exhibit 1288.

146. US Army Hygiene Agency Report ISS



147. Kozumbo et al, Env. Health Persp. Vol 45.

103-109; Zeiger et al, Env. Health Persp . Vol 45, 99-101; Seed et al Env. Health Persp. 111-114. Vol 45.

148 . Transcript pp 392-930.

149. Exhibit 861. p 68 and Exhibit 1351, p 105 •

150. Transcript at p 2765.

Ιβί. Transcript p 2792.

152. Transcript p 2793.

153. Transcript pp 2431-32.

154. Exhibit 1354 p 17.

155. Exhibit 1349 p 16.

156. P 11 of her written statement Exhibit 1422 citing and relying upon Buff let & Aase (1982) Genetic Risks and Environmental Surveillance. J Med. 24(4):305-314.

. Occup.








163 .









172 .

173 .

174 .


176 .


178 .

179 .


Exhibit 1966.

Ibid (cf p 344).

Exhibit 1422 p 12; see also Figure 1 prepared by Dr Brusick and appearing after p. 1 of Exhibit 1377.

Transcript p 4563.

Transcript pp 4331-2.

Exhibit 1427.

Exhibits 1252 and 1252A.

Exhibit 1483.

Table. Exhibit 1252 p. 1091.

Exhibit 1252 p 1091.

Exhibit 1483.

Transcript at p 4792.

Transcript p 4401.

Nord. Med. 83:498-500.

Anaesthesiology 41 No 4 321-340.

Lancet: p 807-809. 25 Oct 1975.

1975. JADA Vol 90, June 1291-1296.

Which together form Exhibit 1967.

Exhibit 1571.

Transcript p 4333.

Exhibit 1383.

Exhibit 36.

Transcript p. 4356.

Exhibit 833.



















198 .

199 .




203 .

Transcript p. 4512.

Transcript p 4573.

Transcript p. 4085.

Transcript pp 3931-2.

Exhibit 1312 p 33.

Exhibit 1483 p 155.

Transcript pp. 4328-9.

Exhibit 1379 p. 3.

Transcript pp. 3911-2.

Transcript at p 4510-11.

Transcript p 4790.

Transcript pp 3935-6.

Ford v. United States. CV-79-747.

Transcript p 4357.

Transcript p 6452.

cf Dr Donovan's evidence Transcript p 4176 et seq.

Exhibit 1968. This Exhibit was circulated to the parties and no party sought leave to

cross-examine Mrs Murtagh.

Transcript pp 6837-6838.

Transcript p 6839.

Transcript p 6839.

Transcript p 6839.

Transcript p 6839.

Transcript at p 6834.