© 1992 Oxford University Press
research-article |
Further Validation of an in Vitro Method to Reduce the Need for in Vivo Studies for Measuring the Absorption of Chemicals through Rat Skin
Metabolism and Pharmacokinetics Section, ICI Central Toxicology Laboratory Alderley Park, Near Macclesfield, Cheshire, SK10 4TJ, U.K.
Received December 2, 1991; accepted May 26, 1992
Current requirements for the registration of agrochemicals, particularly in the U.S.A., often require the provision of dermal absorption data. In this process the rat is often used and complex in vivo studies, using large numbers of animals, are performed. We have compared the data obtained from in vivo and in vitro dermal absorption studies using eight pesticides with a range of physicochemical properties. Measurements were made of the 14C-labeled pesticides which could be washed from the skin, were associated with (on/in) skin, or absorbed through the skin following dermal applications in vivo and in vitro at various time points over a 24-hr exposure period. Good agreement was found between the amounts washed from and associated with the skin in vivo and in vitro. Over the time period 4–24 hr after application the in vitro experiments predicted the in vivo absorption within a factor of 2–3. These results show that, with a range of pesticide molecules, the in vitro method accurately predicted in vivo absorption supporting the utilization of the in vitro method for risk assessment from exposure to pesticides and other chemicals.