Utilization of quantitative structure-activity relationships (QSARs) in risk assessment: Alkylphenols
- Gradient Corporation, Cambridge, MA (United States)
Alkylphenols are a class of environmentally pervasive compounds, found both in natural (e.g., crude oils) and in anthropogenic (e.g., wood tar, coal gasification waste) materials. Despite the frequent environmental occurrence of these chemicals, there is a limited toxicity database on alkylphenols. The authors have therefore developed a 'toxicity equivalence approach' for alkylphenols which is based on their ability to inhibit, in a specific manner, the enzyme cyclooxygenase. Enzyme-inhibiting ability for individual alkylphenols can be estimated based on the quantitative structure-activity relationship developed by Dewhirst (1980) and is a function of the free hydroxyl group, electron-donating ring substituents, and hydrophobic aromatic ring substituents. The authors evaluated the toxicological significance of cyclooxygenase inhibition by comparison of the inhibitory capacity of alkylphenols with the inhibitory capacity of acetylsalicylic acid, or aspirin, a compound whose low-level effects are due to cyclooxygenase inhibition. Since nearly complete absorption for alkylphenols and aspirin is predicted, based on estimates of hydrophobicity and fraction of charged molecules at gastrointestinal pHs, risks from alkylphenols can be expressed directly in terms of 'milligram aspirin equivalence,' without correction for absorption differences. They recommend this method for assessing risks of mixtures of alkylphenols, especially for those compounds with no chronic toxicity data.38 references.
- OSTI ID:
- 5752119
- Journal Information:
- Regulatory Toxicology and Pharmacology; (United States), Vol. 14:3; ISSN 0273-2300
- Country of Publication:
- United States
- Language:
- English
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PHENOLS
TOXICITY
MAN
OXIDOREDUCTASES
RISK ASSESSMENT
STRUCTURE-ACTIVITY RELATIONSHIPS
ANIMALS
AROMATICS
ENZYMES
HYDROXY COMPOUNDS
MAMMALS
ORGANIC COMPOUNDS
PRIMATES
PROTEINS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology