PUBLIC HEALTH
October 4, 2012

Dioxin: The Toxin that Keeps on Giving

Dioxin persists in the environment, and the body, for a very long time. Genetic effects can last for generations.

The toxic chemical dioxin may not only harm the people who are exposed to it; it may also harm their descendents several generations down the road. In a study from Washington State University, when pregnant rats were exposed to dioxin, their offspring had increases in sexual abnormalities and other diseases that lasted for three generations, the length of the study.

Studies of the effects of toxic compounds on rats don't always accurately predict what those compounds will do to humans. If this one does, it means that the harm caused to people exposed to dioxin will extend to their children and great-grandchildren.

The researchers note that because dioxin persists for a long time in the body, with a half-life of up to 10 years, any woman becoming pregnant even 20 years after dioxin exposure runs the risk of transmitting dioxin's ill effects to her children and later generations.

Dioxin was a contaminant present in Agent Orange, a defoliant widely used during the Vietnam War from 1961 to 1971. Vietnamese officials estimate that 400,000 people were killed or maimed and 500,000 children born with birth defects resulting from exposure to Agent Orange. According to the Washington State study, that may only be the beginning of the story.

The researchers exposed pregnant rats to roughly 0.1% (one-thousandth) of the lethal dose of dioxin during days 8 to 14 of pregnancy. This dose is low enough that no toxic effects were observed in the exposed rats. The object of the study was to assess the effects on descendents of the exposed rats, particularly the third generation (great-grandchildren).

The pregnant rats exposed to dioxin were called the F0 generation. The fetal rats were the F1 generation, their progeny were the F2 generation and the next generation's rats, called F3, were the great-grandchildren of the pregnant rats used at the study's start.

Since the exposure of a pregnant F0 rat to dioxin also directly exposes the F1 generation fetus and the germ line (sperm or egg) that will produce the F2 generation, the F3 generation is the first generation without direct exposure to dioxin.

Both the F1 and F3 generations showed several different abnormalities. The F2 generation was not examined.

In females, both the F1 and F3 generation showed increases in polycystic ovarian disease and egg follicle loss. They also showed an increase in pubertal abnormalities, with 47% of the F3 generation experiencing early-onset puberty.

The F1 males had a 40% incidence of pubertal abnormalities, mostly delayed-onset puberty, and three-quarters also had prostate disease. Over one-quarter of the F3 males had kidney disease, more than double the incidence seen in males whose great-grandmothers had not been exposed to dioxin.

Taken together, these results show a number of different diseases and abnormalities occurring in the progeny of exposed rats, lasting for at least three generations.

The harm appears to be coming from a special type of mutation called an epigenetic mutation, in this case an alteration in the methylation of specific genes. The researchers found 50 such alterations in the sperm of F3 generation male rats, alterations that were not present in the great-grandchildren of rats not exposed to dioxin. These mutations are presumably permanent and are passed onto succeeding generations.

Whatever the exact mechanism is, the researchers note that because dioxin persists for a long time in the body, with a half-life of up to 10 years, any woman becoming pregnant even 20 years after dioxin exposure runs the risk of transmitting dioxin's ill effects to her children and later generations, at least if the study results prove to be as true for humans as they are for rats.

The study results are published in the journal, PLoS ONE.

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