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RECORD NUMBER: 15 OF 27

OLS Field Name OLS Field Data
Main Title In vivo and In vitro Structure-Dosimetry-Activity Relationships of Substituted Phenols in Developmental Toxicity Assays.
Author Kavlock, R. J. ; Oglesby, L. A. ; Hall, L. L. ; Fisher, H. L. ; Copeland, F. ;
CORP Author Health Effects Research Lab., Research Triangle Park, NC.
Publisher c1991
Year Published 1991
Report Number EPA/600/J-91/133;
Stock Number PB91-213645
Additional Subjects Toxicity ; Teratogens ; Phenols ; In vivo analysis ; In vitro analysis ; Structure-activity relationships ; Embryo ; Cultured cells ; Metabolic activation ; Liver ; Reprints ;
Holdings
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Status
NTIS  PB91-213645 Most EPA libraries have a fiche copy filed under the call number shown. Check with individual libraries about paper copy. NTIS 11/26/1991
Collation 7p
Abstract
Structure-dosimetry-activity relationships (SDARs) of a series of substituted phenols were evaluated following exposure of gestation day 11 rats in vivo and in comparable stage embryos in vitro. In the in vivo study, 27 congeners were assayed and log P and Hammett sigma values (a measure of the electronic withdrawing ability of the substituent) were shown to correlate with maternal toxicity; however, no relationships between these parameters and developmental effects were observed. In the in vitro system, 13 congeners were evaluated and molar refractivity and/or lipophilicity were shown to correlate with the ability of the phenols to induce embryonic growth retardation and structural defects in the absence of the hepatocytes. In contrast, when a metabolic activating system (primary hepatocytes) was present in the in vitro system, the potential to induce growth retardation was inversely related to lipophilicity, although the relationships were weaker than the positive relationship seen without the hepatocytes. The binding of the phenols to macromolecules in the culture medium was highly correlated with log P. In summary, a systematic study of the response of in vivo and in vitro embryos to a series of structural analogues was conducted, and it attempted to relate the potency of the congeners to specific physicochemical properties. While different conclusions were reached about the potency of the phenols in the two systems, the assessment of pharmacokinetic parameters provided insight into the deposition and activity of these congeners in the embryo and have pointed us in the direction of determining the reason(s) for the differences that were observed.