Malathion, dermal absorption

The mass balance approach was used to develop an in vivo animal model for skin penetration of topically applied dmgs in hairless rats (Simonsen et al., 2002). Two dmgs, C-sahcylic acid and C-butyl salicylate were topically applied for the assessment of the model. Rapid and differentiated percutaneous absorption of both compounds was indicated by urinary excretion data. Total mass balance on the applied radioactivity was performed, and 90% recovery was achieved. Carver and Riviere (1989) conducted an extensive mass balance study with " C-labeled xeno-biotics after topical and intravenous administration to pigs. These authors reported that dermal absorption of C-benzoic acid, caffeine, malathion, parathion, progesterone, and testosterone was 25.7, 11.8, 5.2, 6.7, 16.2, and 8.8%, respectively, following topical administration to pigs. 

Although more predictive approaches may be possible in the future, with the ethical considerations of utilizing humans in studies with pesticides, currently the laboratory rat appears to be a suitable model. Dermal absorption studies with the rat allow the calculation of a penetration rate and hence, assist in the estimation of a potential body burden in man. Indeed, the extrapolation of a dermal penetration rate in the rat to man may represent a worst case approximation. Studies with one pesticide, malathion, in the rat and man have revealed the absorption/ penetration rate in the rat to be approximately 3-fold higher than man ( ). 

For some pesticides, in vivo and in vitro data are comparable. An excellent example is the dermal ab.sorption of malathion (6.8% dose at 24 hr and 8.2% dose at 5 days) in human volunteers (Feidmann and Maibach, 1974 Maibach and Feidmann, 1974), which is comparable to in vitro absorption (8.77% dose at 24 hr) in human skin (Wester et al., 1996), in vivo absorption of malathion in Yorkshire pigs (5.2% at 6 days) (Carver and Riviere, 1989), as well as predicted IPPSF absorption (5.9%) (Williams et al., 1990). 

To better define the role of blood flow in dermal pharmacokinetics, Williams et al. (1990) represented the skin vasculature as a three-compartment model with a fourth compartment for the skin surface (Figure 13.5). They then examined hypothetical changes in the absorption profile of the organophosphate pesticide malathion in the IPPSF fitted to the model as shown in Figure 13.6 (Rivirae and Williams, 1992). The amounts of solute in each compartment of this model are described by the following expressions (Equation 13.6 to Equation 13.9) (Williams etal., 1990) ... 

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