||In vitro Embryotoxicity of a Series of Para-Substituted Phenols: Structure, Activity, and Correlation with In vivo Data.
Oblesby, L. A. ;
Ebron-McCoy, M. T. ;
Logsdon, T. R. ;
Copeland, F. ;
Beyer, P. E. ;
||Health Effects Research Lab., Research Triangle Park, NC. Perinatal Toxicology Branch. ;ManTech Environmental Technology, Inc., Research Triangle Park, NC.
Teratogenic compounds ;
Structure-activity relationships ;
In vivo analysis ;
In vitro analysis ;
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The embryotoxicity of phenol and twelve para-substituted congeners on mid-gestation rat embryos was evaluated in vitro. Through application of correlative procedures and stepwise regression, equations describing the relationship between physical-chemical properties and various measures of activity were developed. Embryotoxicity was quantified by the log of the reciprocal of the potency estimates for reduction in selected growth parameters and induction of four morphological defects. In general, co-cultured hepatocytes ameliorated embryotoxicity; only phenol-induced embryotoxicity was enhanced by the presence of hepatocytes. In the absence of hepatocytes, measures of growth retardation were positively correlated with molar refractivity of the phenols. Data from preliminary dosimetry studies suggest that phenol congeners may accumulate in embryos exposed in vitro more readily than with in vivo exposure. Potency calculations based on dosimetry information may demonstrate better correlations between data and allow additional relationships between chemical structure and activity to be developed.