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Agent Orange Contaminant Linked to Autistic Traits in Vietnamese Kids

By Laura Macfarlane

NEW YORK - Half a century after the end of the war, Vietnamese infants exposed to high levels of a compound used in the herbicide 'Agent Orange' show a higher incidence of autistic traits that differ from the neurotoxicity found in children exposed to total dioxins, a recent study suggests.

Children who were primarily exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) "show specific alterations in higher brain functions, without changes to any aspects of general neurodevelopment" the study authors noted online March 18 in Molecular Psychiatry.

Agent Orange was manufactured for the U.S. Department of Defense and deployed by the military's herbicide program during the war in Vietnam from 1961-1971.

The 2,4,5-T used to produce Agent Orange was contaminated with TCDD, an extremely toxic dioxin compound.

In some areas of Vietnam, the TCDD concentrations in soil and water were hundreds of times greater than the levels considered safe by the U.S Environmental Protection Agency.

Indeed, the present study's authors cite previous data indicating levels of TCDD and polychlorinated dibenzo-p-dioxins/furans (PCDDs/F, also termed total dioxins), in the breast milk of mothers living in the study area - an abandoned US airbase - was three to four times higher than that of those living in unsprayed areas.

The older data showed substantial effects of perinatal dioxin exposure on the neurodevelopment of four month-old infants living in areas of Vietnam that had been contaminated by Agent Orange and other dioxin herbicides in the so-called "Rainbow Herbicides" range - including Agent Purple, Agent Green, and Agent Pink.

Moreover, they found that several furam isomers present in the breast milk of women in the contaminated areas were linked to test scores of social-emotional behavior in a survey of three-year olds.

Their present study took a breast milk sample from the mothers of around 150 Vietnamese babies born in the affected area in 2008 and 2009, one-month after giving birth, and assessed the behavioral development of their offspring at three years of age using the neurodevelopmental battery Bayley-III.

The high TCDD exposed groups (at least 3.5 picograms per gram of body fat) showed significantly higher Autism Spectrum Rating Scale (ASRS) scores for both boys and girls than the mild-TCDD exposed groups, without differences in neurodevelopmental scores.

In contrast, the high total dioxin-exposed group indicated by PCDDs/F (toxic equivalent (TEQ) levels of at least 17.9 pg-TEQ per gram of body fat), had significantly lower neurodevelopmental scores than the mild PCDDs/F-exposed group in boys only, but there was no difference in the ASRS scores.

The lead author of the study, Dr. Muneko Nishijo, an expert in toxicology from the Department of Public Health, Kanazawa Medical University, Ishikawa, Japan, told Reuters Health in an email that the effect of TCDD is mainly on the social emotional functions related to communication (including non-verbal communication), whereas the effects of PCDDs/Fs (total dioxins) is related to general neurodevelopment such as intelligence, language and motor function.

According to Dr. Nishijo, dioxins are well known as a teratogen linked to congenital anomalies both during and after the Vietnam War.

"However, no clear alteration of genes or DNA that will continue to affect their babies for generations was found in previous human studies. The effects of dioxin-related neurodevelopment including autistic traits are not caused by mutation (direct damage of DNA or gene), and may be by epigenetic change such as alteration of DNA methylation in babies (only exposed generation, not future next generation).

"We are interested in the mechanisms related to epigenetic changes of dioxin effects. These also need future studies," he writes.

Dr. Nishijo says that these mothers don't need to stop breast feeding because the infants are exposed to TCDD during pregnancy. Testing the breast milk was a way of assessing dioxin exposure.

Commenting on the study, Professor Andrew Whitehouse, Director of the Autism and Related Disorders research team, at the Telethon Kids Institute in Western Australia, says potential environmental links to autism are "a very hot research topic and this interesting study certainly adds to the debate.

"While this study links TCDD exposure with autism, there are two key points that people need to keep in mind. First, the researchers didn't diagnose autism in any child, but rather they asked parents to report on autistic traits. We can't be sure that any of the children in the study met full diagnostic criteria for autism. Second, this study found an 'association' between TCDD exposure and autistics traits. We can't be sure that the high-levels of TCDD actually caused the increase in autistic traits among the infants."

"Our current thinking is that TCDD may change the way that genes are expressed in the brain. In rats, TCDD exposure has been found to affect the development of certain neurons in the brain, which then leads to aberrant behavior," Professor Whitehouse told Reuters Health.

"The good news," writes Dr. Nishijo, "is the heavily contaminated environment where these mother-and-infant pairs are living will be improved in the near future, because the land of former US airbase is going to be treated by collaboration project between USA and Vietnam now".

SOURCE: https://bit.ly/PtOkEb

Molecular Psychiatry 2014.

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