IOM has been asked to make recommendations concerning the need, if any, for additional scientific studies to resolve continuing scientific uncertainties about the health effects of the herbicides used in Vietnam and their contaminants. Great strides have been made over the past several years in understanding the health effects of exposure to the herbicides used in Vietnam and to TCDD and in elucidating the mechanisms that underlie the effects, but there are still subjects on which increased knowledge could be very useful.

This committee recommends that VA should more actively query its own medical databases to identify potential associations between Vietnam service and specific health outcomes, particularly for those outcomes that are less common. Moreover, if a perceived conflict of interest exists in surveying its own databases, it is recommended that an external advisory group be formed to determine the best mechanism for mining this information so that these medical databases could be available for external study.

The committee for Update 2008 concluded that it was plausible that exposure to the herbicides sprayed in Vietnam could cause paternally mediated effects in offspring as a result of epigenetic changes, and such potential would most likely be attributable to the TCDD contaminant in Agent Orange. There is a growing body of evidence that TCDD, and also arsenicals, can induce epigenetic changes in animal models, but there remains extremely limited data on the risk of paternal exposure to xenobiotics in general, and the VAO chemicals of interest in particular, resulting in adverse effects on their offspring. Consequently, this committee continues to recommend that laboratory research be conducted to characterize TCDD’s potential for inducing epigenetic modifications. Further, the committee recommends development of epidemiologic protocols to address the logistical challenge of determining whether adverse effects are being manifested in the adult children and grandchildren of Vietnam veterans as a result of paternal exposure. The best cohorts for revealing potential associations would be those with known, well-characterized exposure information. Another alternative would be to adopt a case–control approach and explore whether information about Vietnam exposure or specific herbicide exposure could be ascertained in any of the many birth cohorts that have been established in the past several decades. To hone in on a paternal effect, however, it will be necessary to establish that the mothers did not have the opportunity for exposure above background levels to the chemicals of interest.

As in previous years, this committee recommends the pursuit of additional research in toxicology. The development of animal models of various chronic health conditions and their progression would be useful for understanding the possible contributions of the chemicals of interest to compromise the health of aging Vietnam veterans. Specifically, determining the mechanism by which dioxin-like chemicals induce B cell cancers and how this exposure alters the sus-

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