Absorption correction, dermal

Dermal/Inhalation Absorption Correction. Since it is generally presumed that 100% of the Inhaled pesticide dose is absorbed, little work is being done to refine this. It has also been shown that in most agricultural applicators the dermal route is the predominant route of exposure. However, the patch methods which are used only... 

Correct for body weight by dividing the TDE by 70 kg (theoretical weight of adult). Correct for dermal absorption of 3% for chlorpyrifos penetration of the skin. 

In vivo experiments on 4 human volunteers, to whom 0.0026 mg/cm2 of 14C-benzene was applied to forearm skin, indicated that approximately 0.05% of the applied dose was absorbed (Franz 1984). Absorption was rapid, with more than 80% of the total excretion of the absorbed dose occurring in the first 8 hours after application. Calculations were based on urinary excretion data and no correction was made for the amount of benzene that evaporated from the applied site before absorption occurred. In addition, the percentage of absorbed dose excreted in urine that was used in the calculation was based only on data from rhesus monkeys and may not be accurate for humans. In another study, 35-43 cm2 of the forearm was exposed to approximately 0.06 g/cm2 of liquid benzene for 1.25-2 hours (Hanke et al. 1961). The absorption was estimated from the amount of phenol eliminated in the urine. The absorption rate of liquid benzene by the skin (under the conditions of complete saturation) was calculated to be low, approximately 0.4 mg/cm2/hour. The absorption due to vapors in the same experiment was negligible. The results indicate that dermal absorption of liquid benzene is of concern, while dermal absorption from vapor exposure may not be of concern because of the low concentration of benzene in vapor form at the point of contact with the skin. No signs of acute intoxication due to liquid benzene dermally absorbed were noted. These results confirm that benzene can be absorbed through skin. However, non-benzene-derived phenol in the urine was not accounted for. 

The USEPA reviewed a number of registrant-submitted studies to assess exposure to handlers applying chlorpyrifos in agricultural and residential settings (USEPA, 2001). The biomonitoring studies measured urinary concentrations of the primary chlorpyrifos metabolite and back-calculated these to the absorbed dose of the parent. The passive dosimetry study results were corrected for 3 % dermal absorption from a human dosing study (Nolan et al 1984). The results of the studies are reported in Table 1.4 and demonstrate fairly close concordance between the two methodologies. 

If appropriate dermal penetration data are available for rats in vivo and for rat and human skin in vitro, the in vivo dermal absorption in rats may be adjnsted in light of the relative absorption throngh rat and human skin in vitro. The latter adjustment may be carried out because the permeability of human skin is often lower than that of animal skin (McDougal et al., 1990 Sato et al., 1991 Barber et al., 1992 Howes et al., 1996). A generally applicable correction factor for extrapolation to man can, however, not be derived, because the extent of overestimation appears to be agent- and animal-specific (Bronaugh and Maibach, 1987 ECETOC, 1993). 

Because these experiments illustrate the excretion differences between dermal. Intramuscular, and oral dose excretion, the excretion differences between compounds, and also problems about which urinary metabolite to monitor (see 44). a very comprehensive experimental design would be necessary to correctly model dermal exposure, absorption, and urinary metabolite levels. Statistical problems, centering around replicate variation and the resulting necessity for abnormally large numbers of replications, could drive the costs of such an experiment In small animals, and certainly in humans, to prohibitively high levels. 

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