FACTORS AFFECTING THE BIOAVAILABILITY OF BENZO[A]PYRENE FROM OILS IN MOUSE SKIN - OIL VISCOSITY, GROOMING, ACTIVITY AND ITS PREVENTION

In the main study, tritium-labelled benzo[a]pyrene ([H-3]BaP) was added to oils of a wide range of viscosity (from 13.5 to ca. 8000 cSt at 40 degrees C) and these were applied once to mouse skin under conditions where grooming was either allowed or prevented. The binding of [H-3]BaP to epidermal protein and DNA was assessed, In addition, some studies were conducted to investigate the effect of prior oil exposure on binding levels and to compare binding levels following single and multiple application. It was found in the main study that the binding of [H-3]BaP to both DNA and protein was increased as the viscosity of the oil vehicle decreased. Whereas only a twofold difference in DNA binding was found between the lowest and highest viscosity oil vehicle if grooming was allowed, a 14-fold difference was seen if grooming was prevented. This was due to much higher binding levels with low viscosity oils when grooming was prevented. Protein binding showed similar results, although the difference between the grooming and nongrooming situations was slightly less. Whether grooming was prevented or not, both DNA and protein binding of [H-3]BaP were found to be inversely proportional to the logarithm of viscosity of the oil vehicle, but when grooming was prevented, the slope for DNA binding was 10 times steeper than when it was permitted. Exposure of the skin to either high or low viscosity oils prior to the application of [H-3]BaP in the same oil inhibited the binding to DNA but not to protein. In experiments where multiple applications of [(3)]BaP in oil were given, the difference in DNA binding between low and high viscosity oils was similar to that after a single application. This implied that the relative bioavailability of polycyclic aromatic hydrocarbons from oils of differing viscosity, as assessed following single application, is reasonably predictive of that following multiple applications. In considering the relevance of the findings of the main study to long-term animal studies and to human hazard, it is suggested that the situation where grooming was permitted is likely to be most relevant to animal studies, whereas that where grooming is prevented is more likely to represent human exposure. Hence, borderline positive findings in long-term mouse skin painting studies with low-viscosity oils should be regarded more seriously than similar findings with viscous oils, The findings should also be of assistance in making predictions of carcinogenicity from analytical data.