Unlike Vietnam veterans who complained of fluctuations in weight patterns, gains as well as losses, the monkeys did not regain weight they lost. “They just go down,” says McNulty, “although I did have one animal who lost a lot of weight over a period of about three and a half months, without showing any of the other characteristic signs of toxic poisoning. And then she began to regain her weight and is still alive today, and appears to be quite well. But usually if they are sufficiently poisoned that they lose a significant amount of weight, they don’t recover from it. It simply goes on and they become worse and then they die.”
Although TCDD, when given to rats and mice in minute doses, causes congenital abnormalities, including fetal deaths, cleft palate, and kidney abnormalities, McNulty’s research failed to indicate that TCDD acts as a teratogen in rhesus monkeys. McNulty did find, however, that TCDD is fetotoxic in rhesus monkeys. “The experiment,” says McNulty, “was designed to explore whether short-term exposure to dioxin, either in a single or a few closely spaced doses during that period in early pregnancy when the organs are forming, would result in malformations. At the highest dose it was very toxic to the mother, and since I wasn’t really interested in that, I did very little at that particular level. At the intermediate level there was a fairly high level of abortion, or loss of the fetus. But those which did not abort gave birth to normal offspring. We were unable to find any malformations. Also, at the level that TCDD caused a fair number of abortions there were some late toxicities and deaths among the mothers. But the number of animals was relatively small, and unlike experimenting with rats and mice, you can’t use the number you would like for statistical significance. Still, with the relatively small number of animals I used it seems extraordinarily likely that TCDD is toxic to the fetus, but I did not conclude that it causes malformations in the offspring of rhesus monkeys.”
Fetotoxic effects, which means the ability of TCDD to destroy developing fetuses, have been observed in three different mouse strains, two rat strains, and one species of monkey. In a study by Dow Chemical, rats fed on nanogram (billionth of a gram) of TCDD per kilogram body weight per day exhibited increased stillbirth and shortened life spans for surviving pups. Skeletal birth defects have also been observed in four different mouse strains as well as other types of defects in rats when pregnant females are exposed to TCDD.2
Dr. McNulty has not researched the possible mutagenic effects of TCDD on male monkeys because, he says, “there isn’t any reason to think it would be a good experiment. As you recall, I said there is no evidence that TCDD is a mutagen, and any reproductive failures in terms of abortions or malformations that are going to be transmitted through the father almost necessarily have to be due to the mutagenicity of his germ cells. So it’s not the kind of experiment that’s likely to get results. Now, I’m sure Vietnam veterans would raise the question: ‘How do you know if you haven’t done it?’ Well, with mature monkeys now running around a thousand dollars each, it becomes a matter of choosing experiments that one has some reason to assume will give one conclusive results. It’s always difficult to prove that something doesn’t exist. In other words, how many males would I have to expose and then breed with females before I could say with confidence that TCDD does not cause reproductive failures through the male? One sure wouldn’t be enough. Would ten be enough? Not likely. Would a hundred be enough? Well, maybe, but still a little bit doubtful. And that’s just an impossibly expensive experiment if you don’t have any good reason ahead of time to think that it’s going to pay off.”
But not all scientists would agree with McNulty’s conclusions regarding the mutagenicity of TCDD. In their paper “The Mutagenicity of Dioxin and Its Effects on Reproduction among Exposed War Veterans,” Vietnamese doctors Ton That Tung, Ton Duc Lang, and Do Duc Van suggest that scientists should at least consider the possibility that TCDD might act as a human mutagen. Comparing birth defects among children born to North Vietnamese soldiers who had served in the South to those among children of soldiers who remained in the North, and noting that “none of the wives of exposed or non-exposed veterans received any exposure themselves,” the doctors wrote:
The congenital malformations are of many types, with an increased frequency of anencephaly in the children of former soldiers… In spite of the limitations of the available data, it is striking to compare the absence of anencephaly among the births in the unexposed civilian population to the seven cases among the births to former soldiers. The excessive incidence of congenital malformations in the children of soldiers exposed to dioxin were discovered by interviewing each couple. In relation to national and international norms, the incidence of neural tube malformations is particularly elevated.
Likewise, the rate of abortion, premature births, and sterility is significantly higher in the group of exposed veterans from the South. Moreover, the number of molar pregnancies[18] in Hanoi seems abnormally high; the Institute for Mothers and Children (The National Ob-Gyn Institute) has just reported the hospitalization of nineteen cases of molar pregnancies or chorioepitheliomas, of which nine were diagnosed in woman married to former soldiers from the South.
A plausible explanation for the association established between exposure to dioxin and excessive congenital malformations in first-generation offspring is that exposure may affect the father’s genetic material. This association calls for a vigorous epidemiological study taking into account the various factors which could interfere with reproduction. It also indicates that a cytologic and biological study of sperm of both man and animal exposed to dioxin should be carried out.”
A scientific paper by David Kriebel, published by the Center for the Biology of Natural Systems, Washington University, also gives a number of reasons for considering the possibility that TCDD might act as a human mutagen.
Two points must be made about the significance of the experimental animal data to human health. First, bacteria, rats and people have very few things in common. But one of those few is a genetic code made of deoxyribonucleic acid (DNA). If TCDD can damage DNA in salmonella, and lacking evidence to the contrary, we must assume it can damage it in humans as well. Second, chemicals known to harm humans (benzene, vinyl chloride, cigarette smoke, to name a few) via mutational damage almost invariably do it to other organisms as well. With only one exception (arsenic) all the known human carcinogens cause cancer in laboratory animals as well.
Scattered evidence supports what experimental studies suggest—that TCDD is probably a human mutagen. There is often conflicting data, and room for different interpretations; however, there is much more evidence now that there was two years ago, and this trend will probably continue. Chromosome damage has been reported in Hungarian workers exposed to TCDD in a chemical plant, and in Vietnamese civilians sprayed with the herbicide Agent Orange, which contained TCDD in small amounts (parts per million).
Could the exposure of veterans to Agent Orange in Vietnam over ten years ago cause birth defects in their children born today? There is no direct proof, but a mechanism capable of causing this effect certainly exists. If TCDD is a human mutagen, and if it causes mutations in male germ cells, then children born of men exposed at any time in their life could develop abnormally. At least three other environmental pollutants have been shown to cause birth defects or other reproductive problems; most likely via mutations in male germ cells.4
18
A molar pregnancy is one characterized by the presence of a uterine mole, a fleshy mass formed in the uterus by the degeneration or abortive development of an ovum.