ABSTRACT
Cancer development from in utero exposure has been documented for a variety of agents with the most commonly studied compounds exhibiting mutagenic and genotoxic carcinogen properties. Age-dependent adjustment factors (ADAFs) are applied by the US Environmental Protection Agency to many such carcinogens when assessing cancer risk from early postnatal (PN) exposures; however, this approach has not been widely considered for transplacental (TP) exposure. To explore this question and further evaluate prenatal susceptibility a database of early life animal studies developed by California Office of Environmental Health Hazard Assessment (OEHHA) enhanced with additional literature searching was evaluated. Nine genotoxic carcinogens and one mixture (cigarette smoke) have data available via TP only, PN only and adult-only protocols. Potency comparisons across these lifestages displayed similarly greater potency in male liver and brain compared to adult-only exposure. Both TP and PN exposures were not markedly different than adult-only for other targets such as female liver and blood-borne tumors. Similarity in TP and PN targets and potency for carcinogen action suggests that a 10-fold ADAF may be applied for TP exposure as is currently applied to PN exposure. A similar conclusion was reached by OEHHA. The implications of this heightened TP vulnerability are greatest for less-than-lifetime exposure and this approach might be used to assess the level of cancer risk from exposures during pregnancy. A case example employing a mutagenic flame retardant was used to exemplify application of a TP ADAF for evaluating risks during pregnancy.
Acknowledgments
We appreciate the review provided by Lauren Zeise, Office of Environmental Health Hazard Assessment of the California Environmental Protection Agency and John Rogers, USEPA Toxicity Assessment Division of the National Health and Environmental Effects Research Laboratory. Project funded in part by US EPA Contract Number EP-15-H-000022 to the Partnership in Pediatric and Environmental Health (PIPEH).
Disclaimer
The views expressed in this manuscript are solely of the authors themselves and do not necessarily reflect the views and policies of the U.S. Environmental Protection Agency, the California Environmental Protection Agency’s Office of Environmental Health Hazard Assessment, Yale University or the Partnership in Pediatric and Environmental Health.
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Correction Statement
This article has been republished with minor changes. These changes do not impact the academic content of the article.