Development of Quantitative Structure-Activity Relationship (QSAR) Models for Predicting Risk of Exposure from Carcinogens in Animals

Abstract

Quantitative structure-activity relationship (QSAR) modelscapable of predicting acute toxicity and carcinogen potency of polychlorinateddibenzo-p-dioxin (PCDD), polychlorinatedhydrocarbons, and chlorinated insecticides have been formulated. Median lethaldose (LD₅₀) for PCDD-exposed mice correlated negativelywith polarity and positively with (H acceptor × ²χ),whereas LD₅₀ for PCDD-exposed guinea pigs correlatedwith (H acceptor × density). Both (H acceptor × ²χ)and (H acceptor × density) exhibited parabolic relationship with logP (partition coefficient). Carcinogenic potency, determined from order ofmagnitude (OM) values, correlated negatively with log P and positively with(length × width). Thus, a hydrophobic mechanism plays a key role inthe lethal effects of PCDD in mice, whereas both hydrophobic and electronicmechanisms are involved in the lethal effects of PCDD in guinea pigs. However,the molecule's lipophilicity, length, and width may play important rolesin the carcinogenic effects of chlorinated compounds.

• Carcinogenesis
• dibenzo-p-dioxin
• Polychlorinated hydrocarbons
• QSAR