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Environmental Epigenetics: Potential Application in Human Health Risk Assessment
Perumal-Kuppusamy, S., Jonathan-P Kaiser, AND S. Wesselkamper. Environmental Epigenetics: Potential Application in Human Health Risk Assessment. Presented at Society of Toxicology (SOT) Annual Meeting, Phoenix, AZ, March 23 - 27, 2014.
Although previous studies have shown a significant involvement of epigenetic dysregulation in human diseases, the applicability of epigenetic data in the current human health risk assessment paradigm is unclear. The goals of this study are to compare the relative sensitivities of epigenetic alterations (DNA methylation) with tumor incidence data and to explore the possibility of incorporating epigenetic data into the hazard identification step of human health assessments. DNA methylation alterations and tumor incidences in laboratory animal studies were analyzed from various toxicological databases for the following chemicals: di(2-ethylhexyl) phthalate, bromodichloromethane, dibromochloromethane, chloroform, hydrazine, trichloroethylene, benzidine, and trichloroacetic acid. All analyses involved conversion of animal doses to human equivalent doses. Benchmark dose values for tumor incidences were compared to no-observed-adverse-effect levels (NOAELs) for DNA methylation changes. In the absence of a NOAEL, a 10-fold uncertainty factor was applied to the lowest-observed-adverse-effect level (LOAEL) to approximate a NOAEL. This analysis revealed that DNA methylation is 1.2- to 25-fold more sensitive than the corresponding tumor incidence for all chemicals, except for trichloroacetic acid, where there is no difference in sensitivity. The predominant DNA methylation alteration was hypomethylation of either whole DNA or the promoter region of various oncogenes, and the exposure duration of epigenetic studies was shorter compared to a 2-year carcinogenicity study. This study shows that DNA methylation changes are more sensitive than tumor incidences and could potentially be considered as an alternative point of departure in human health assessments of suspected carcinogens. However, more research is needed to ascertain how epigenetic data can be applied in human health risk assessment. [The views expressed in this abstract are those of the authors and do not necessarily reflect the views or policies of the U.S. EPA]
There is a growing concern that epigenetic events may be involved in adverse health outcomes due to chemical exposures. The objective of this research is to determine the influence of epigenetic programming on human health effects following exposure to environmental stressors and its applicability in human health risk assessment. The result from this project is anticipated to improve human health risk assessment by providing a scope of incorporating epigenetic screening in the hazard identification of chemicals.
Record Details:Record Type: DOCUMENT (PRESENTATION/POSTER)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL CENTER FOR ENVIRONMENTAL ASSESSMENT