TY - JOUR
T1 - Development of quantitative structure-activity relationship (QSAR) models for predicting risk of exposure from carcinogens in animals
AU - Singh, A. K.
PY - 2001/8/4
Y1 - 2001/8/4
N2 - 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.
AB - 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.
KW - Carcinogenesis
KW - Dibenzo-p-dioxin
KW - Polychlorinated hydrocarbons
KW - QSAR
UR - http://www.scopus.com/inward/record.url?scp=0034917466&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034917466&partnerID=8YFLogxK
U2 - 10.1081/CNV-100104289
DO - 10.1081/CNV-100104289
M3 - Article
C2 - 11486704
AN - SCOPUS:0034917466
SN - 0735-7907
VL - 19
SP - 611
EP - 620
JO - Cancer Investigation
JF - Cancer Investigation
IS - 6
ER -