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TOXICOKINETICS AND STRUCTURE-ACTIVITY RELATIONSHIPS OF NINE PARA-SUBSTITUTED PHENOLS IN RAT EMBRYOS IN VITRO
Citation:
Fisher, H., L. Hall, M. Ebron-McCoy, F. Copeland, R. Kavlock, M. Sumler, S. Shrivastava, B. Edwards, AND L. Oglesby. TOXICOKINETICS AND STRUCTURE-ACTIVITY RELATIONSHIPS OF NINE PARA-SUBSTITUTED PHENOLS IN RAT EMBRYOS IN VITRO. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-94/063 (NTIS PB94143740), 1993.
Description:
The purpose of this study was to examine the pharmacokinetics of embryo uptake following exposure to a variety of related chemicals in rodent embryo culture. he uptake of nine radiolabeled para-substituted phenols by day 10 (9-13 somite stage) rat embryos in vitro was determined from I to 42 hours after being placed in culture media which had been dosed with compound. ptake was rapid, having a half-life of 3 hours or less, with 7 of the nine compounds having uptake half-times of less than one hour. he equilibrium concentration in the embryo ranged from 53 to 136% of the media concentration indicating only a factor of two in maximum discrimination against the compound for any of the phenols studied. he fraction of radioactivity remaining unbound in the media decreased with increasing log P (octanol/water partition coefficient). he binding was calculated to be 50% for log P-1.77 from the fitted regression equation and decreased by a factor of 5.9 for every decade increase in P. When hepatocytes were also present in the media the equilibrium concentration in the embryo was less than when hepatocytes were not present. ith the limited data, four of the phenols appeared to have no (i.e. zero) equilibrium level when hepatocytes were present. hus the metabolites produced by hepatocytes appear to have less affinity for the embryo than the original phenol. harmacodynamic information as given by the effective dose of the phenol in the embryo to cause somite or tail teratological effects was best predicted by the measured unbound fraction.