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IN UTERO EXPOSURE TO AN AR ANTAGONIST PLUS AN INHIBITOR OF FETAL TESTOSTERONE SYNTHESIS INDUCESCUMULATIVE EFFECTS ON F1 MALE RATS
HOTCHKISS, A. K., J. R. FURR, C. V. RIDER, K. HOWDESHELL, C. BLYSTONE, V. S. WILSON, AND L. E. GRAY. IN UTERO EXPOSURE TO AN AR ANTAGONIST PLUS AN INHIBITOR OF FETAL TESTOSTERONE SYNTHESIS INDUCESCUMULATIVE EFFECTS ON F1 MALE RATS. REPRODUCTIVE TOXICOLOGY. Elsevier Science Ltd, New York, NY, 30(2):261-270, (2010).
Risk assessments are typically conducted on a chemical-by-chemical basis; however, many regulatory bodies are developing frameworks for assessing the cumulative risk of chemical mixtures of chemicals. The current investigation examined how chemicals that disrupt rat sex differentiation via two diverse mechanisms disrupt Fl male rat reproductive development, when administered together orally on days 14-18 of gestation. Study 1 used a mixture of 50 rng/kg/d procymidone and 500 mg/kg/d dibutyl phthalate (DBP), whereas Study 2 used 150 mg/kg/d procymidone and 1125 mg/kg/d DBP (top dose), or 0, 4.17,8.33,16.7,33.3,50,66.7, and 83.3% of the top dose. When we compared the dose and response addition predictions to the observed effects we found that dose addition models were more accurate than response addition models, indicating that compounds that act by different mechanisms of toxicity produce cumulative dose additive effects.
This research describes how regulatory agencies like the USEPA should broaden their frameworks for conducting cumulative risk assessments beyond one based chemicals within the same class sharing a common mechanism of toxicity to include chemicals from other classes that disrupt development of common tissues.
Record Details:Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LAB
TOXICOLOGY ASSESSMENT DIVISION
REPRODUCTIVE TOXICOLOGY BRANCH