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

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)611-620
Number of pages10
JournalCancer Investigation
Volume19
Issue number6
DOIs
StatePublished - Aug 4 2001

Fingerprint

Quantitative Structure-Activity Relationship
Carcinogens
Lethal Dose 50
Guinea Pigs
Chlorinated Hydrocarbons
Insecticides
Polychlorinated Dibenzodioxins

Keywords

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

Cite this

@article{61445a45660a445ba4f0e4b87401ee02,
title = "Development of quantitative structure-activity relationship (QSAR) models for predicting risk of exposure from carcinogens in animals",
abstract = "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.",
keywords = "Carcinogenesis, Dibenzo-p-dioxin, Polychlorinated hydrocarbons, QSAR",
author = "Singh, {Ashok K}",
year = "2001",
month = "8",
day = "4",
doi = "10.1081/CNV-100104289",
language = "English (US)",
volume = "19",
pages = "611--620",
journal = "Cancer Investigation",
issn = "0735-7907",
publisher = "Informa Healthcare",
number = "6",

}

TY - JOUR

T1 - Development of quantitative structure-activity relationship (QSAR) models for predicting risk of exposure from carcinogens in animals

AU - Singh, Ashok 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

VL - 19

SP - 611

EP - 620

JO - Cancer Investigation

JF - Cancer Investigation

SN - 0735-7907

IS - 6

ER -