SAR Models for Estimating the Percutaneous Absorption of Polynuclear Aromatic Hydrocarbons

Abstract

A structure-activity relationship (SAR) of the in vitro percutaneous absorption of polycyclic aromatic hydrocarbons (PAH) is described. The data set consisted of 60 three to seven ring PAH. Over 50 numeric descriptors were generated from the modeled molecular structures. Computer aided methods were used to evaluate descriptors and develop linear expressions relating the percent of dermally applied PAH dose absorbed through skin (PADA) to PAH structure. Three regression models with one and two variables were developed. The log octanol/water partition coefficient (log P) was the most important variable in determining percutaneous absorption. An inverse relationship between log P and the skin penetration properties of the PAH was observed. Nearly 40 of 60 PAH tested had PADA-values within a factor of two of benzo[a]pyrene (BaP); well over 50 of 60 had PADA-values within a factor of three. The results lend support to the use of isotopically labeled BaP as a surrogate for measuring the dermal flux (in vivo and in vitro) and estimating the dermal bioavailability of PAH from complex mineral oil and coal-tar derived mixtures.

Key Words:

• SAR
• PAH
• log P
• percutaneous absorption
• dermal exposure
• molecular descriptors