Development of quantitative structure-activity relationship (QSAR) models for predicting risk of exposure from carcinogens in animals

Quantitative structure-activity relationship (QSAR) models capable of predicting acute toxicity and carcinogen potency of polychlorinated dibenzo-p-dioxin (PCDD), polychlorinated hydrocarbons, and chlorinated insecticides have been formulated. Median lethal dose (LD₅₀) for PCDD-exposed mice correlated negatively with polarity and positively with (H acceptor × ²χ), whereas LD₅₀ for PCDD-exposed guinea pigs correlated with (H acceptor × density). Both (H acceptor × ²χ) and (H acceptor × density) exhibited parabolic relationship with log P (partition coefficient). Carcinogenic potency, determined from order of magnitude (OM) values, correlated negatively with log P and positively with (length × width). Thus, a hydrophobic mechanism plays a key role in the lethal effects of PCDD in mice, whereas both hydrophobic and electronic mechanisms are involved in the lethal effects of PCDD in guinea pigs. However, the molecule's lipophilicity, length, and width may play important roles in the carcinogenic effects of chlorinated compounds.