Structure-Activity Relationships in the Developmental Toxicity of Substituted Phenols: In vivo Effects

摘要

Hansch analysis, a quantitative approach relating the physical-chemical properties of molecules to biological effects, was applied to a series of substituted phenols tested for developmental toxicity. The physical-chemical properties included a hydrophobic parameter (log P), an electronic parameter (Hammett sigma) and a bulk parameter (molar refractivity (MR)). Biological activities were obtained for 27 congeners in a Chernoff/Kavlock Assay performed in Sprague-Dawley rats exposed on day 11 of gestation. The effects discussed in the report are: the dose to decrease maternal weight gain by 10 g at 24 and 72 hours after treatment (MTOX1 and MTOX2); the dose to increase post-implantation loss by one over the concurrent control value (PLOSS); and the dose required to decrease total litter weight by 10% on postnatal day 6 (BIO6). Overall, 14 of 27 congeners were classified as active in terms of maternal effects, but only 50% of these were active for developmental effects. Seven of the nine overall active developmental toxicants were active maternal toxicants. Two QSAR models were developed from the data, one relating to maternal toxicity for 22 para-phenols and the other for the postimplantation loss potency of the 8 most active para-phenols. The properties of these phenols which contribute to maternal toxicity are different from those inducing developmental effects.