Markov chain model for quantitating dermal absorption from complex mixtures.
Pitts-CS; Smith-CE; Baynes-RE; BrookS-JD; Riviere-JE
Toxicologist 2007 Mar; 96(1):433
Exposure to pesticides dosed in complex chemical mixtures is a common environmental and occupational health concern. Risk assessors need to know the rate at which a pesticide is absorbed in to the skin in order to predict the toxicity of exposure to the pesticide. However, experimentally obtaining the absorption rates for even a small number of possible pesticide mixtures are expensive and time consuming. The objective of this study is to create a Markov chain model to predict pesticide absorption rates through the skin. The model parameters were fit to absorption data collected in the isolated perfused porcine skin flap (IPPSF) for a mixture of ethyl-parathion in ethanol. The model was investigated both analytically and through simulations using Gillespie's algorithm and was fit to the data using least squares methods. A model with three internal states, two absorbing states plus a delay appears to describe these data adequately. The structure of this model was compared to classical modeling approaches commonly used in dermal absorption studies (e.g. compartmental models and their reduction, PBPK models). Future work will expand the number of pesticide mixtures analyzed as well as search for correlations between absorption parameters and the physical and chemical properties of the pesticides and the mixture components into which they are exposed. These correlations may enable risk assessors to predict absorption profiles after chemical exposures in complex mixtures or formulations based on mixture component physical and chemical properties.
Skin-absorption; Skin-disorders; Skin-irritants; Skin-sensitivity; Dermatitis; Dermatosis; Mathematical-models; Statistical-analysis; Skin-exposure; Pesticides-and-agricultural-chemicals; Physical-properties; Chemical-properties; Chemical-composition; Models
Work Environment and Workforce: Mixed Exposures
The Toxicologist. Society of Toxicology 46th Annual Meeting and ToxExpo, March 25-29, 2007, Charlotte, North Carolina
North Carolina State University, Raleigh, North Carolina