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IN VITRO EMBRYOTOXICITY OF A SERIES OF PARA-SUBSTITUTED PHENOLS: STRUCTURE, ACTIVITY AND CORRELATION WITH IN VIVO DATA
Citation:
Oglesby, L., M. Ebron-McCoy, T. Logsdon, F. Copeland, P. Beyer, AND R. Kavlock. IN VITRO EMBRYOTOXICITY OF A SERIES OF PARA-SUBSTITUTED PHENOLS: STRUCTURE, ACTIVITY AND CORRELATION WITH IN VIVO DATA. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-92/371 (NTIS PB93107167).
Description:
The embryotoxicity of phenol and twelve para-substituted congeners on mid-gestation rat embryos was evaluated in vitro. hrough application of correlative procedures and stepwise regression, equation describing the relationship between physical-chemical properties and various measures of activity were developed. mbryotoxicity was quantified by the log of the reciprocal of the potency estimates for reduction in selected growth parameters and induction of four morphological defects. n general, co-cultured hepatocytes ameliorated embryotoxicity; only phenol-induced embryotoxicity was enhanced by the presence of hepatocytes. n the absence of hepatocytes, measures of growth retardation were positively correlated with molar refractivity of the phenols. ith hepatocytes, lipophilicity became important for describing the potential to induce growth deficits. he structural defects had varying correlation patterns in both culture systems. otencies of these congeners in vitro were also compared to maternal and developmental potencies observed in vivo (Kavlock, '90). wo of the congeners were very toxic in both systems. or the remaining congeners, one maternal toxicity measure was found to be positively correlated with embryotoxicity for growth and development in vitro without hepatocytes. ith hepatocytes, a broad spectrum of correlations, both positive and negative, were observed between in vivo developmental toxicity endpoints.