Occlusive dermal absorption

Table II Occlusive Dermal Absorption in the Rats of 2-ethy1-6-methyl aniline...

Table IV Non-Occlusive Dermal Absorption of Methidathion in Rat vs. Mouse (72 hrs.)...

Dermal absorption was also studied in rats. [ C]Diethanolamine was applied to 19.5 cm of the dorsal skin (20 mg/cm, 1500 mg/kg bw) and covered for 48 h (no washing) or for 6 h before it was removed by washing. Absorbed [ Qdiethanolamine was determined in 48-h urine and faeces and from sampled tissues. FInwashed rats absorbed 1.4% and washed animals 0.64% of the dose, while the majority of [ C]diethanolamine was recovered in the occlusive wrappings (80%) and in skin of the dose site (3.6%). The radioactivity was found in carcass, liver or kidneys but very little in urine (0.11%), faeces or blood (Waechter etal., 1995, cited by Knaak etal, 1997). 

Dermal absorption is influenced by several factors, e.g. the physico-chemical properties of the substance, vehicle, occlusion, concentration, exposure pattern and skin site of the body (ECETOC, 1993 Howes et al., 1996 Schaefer and Redelmeier, 1996). Despite the fact that guidance exists for the conduct of dermal absorption studies (USEPA, 1998, 2004 OECD, 2004a,b,c), there continues to be discussion on some experimental details. In order to harmonize the use of dermal absorption data in human risk assessment within the EU, a guidance document was prepared by the Commission (EC, 2002). 

This chapter provides an overview of factors affecting dermal absorption. Factors influencing absorption are among others related to the skin (e.g. anatomical site, difference between species, metabolism, etc.) and the exposure conditions (e.g. area dose, vehicle, occlusion and exposure duration). In order to provide relevant information for the risk assessment of pesticides, dermal absorption studies should take these aspects into account. With respect to the methods being used nowadays for the assessment of dermal absorption, it is important to realize that neither in vitro nor in vivo animal studies have been formally validated. Available data from various in vitro studies, however, indicate that the use of the total absorbed dose (i.e. the amount of test substance in the receptor medium plus amount in the skin) could be used in a quantitative manner in risk assessment. Tape stripping of the skin can be adequate to give a good indication of test chemical distribution, and hence its immediate bioavailability. 

Occlusion is a primary experimental variable that may impact the magnitude of dermal absorption fluxes seen. Comparing fluxes for pesticides dosed under occluded versus nonoccluded conditions, or at different sites from the same species, doe.s not necessarily provide data on the comparative absorption of different compounds but, rather, on the overarching effect of application methods. 

As can be clearly appreciated from the previous presentation, there arc numerous experimental variables that have a major impact on the assessment of dermal absorption of pesticides. This was clearly seen with studies involving different methods (in vitro vs in vivo), different species, different doses, or application conditions such as occlusion. 

Qiao, G. L., Brook.s, J. D., and Riviere, J. E. (1997). Pcntachlorophcnol dermal absorption and di.sposition from soil in swine. Effects of occlusion and skin microorganism inhibition. To.xicol. Appl. Pharmacol. 147, 234-246,... 

With emphasis on safety evaluation applications, the use of radiotracers in rat and mouse dermal absorption studies are discussed. A multi-tiered experimental strategy is proposed containing judgement points providing akin absorption, tissue depletion and animal excretion rates in a cost effective manner. Techniques described include occlusive and non-occlusive treatments, sample preparations and data collection. Typical data is shown for herbicides and insecticides. 

E. The degree of occlusion (in fact, the tightness of the wrap over the test site) also alters percutaneous absorption and therefore irritation. One important quality control issue in the laboratory is achieving a reproducible degree of occlusion in dermal wrappings. 

Hexanone is also absorbed after dermal application. The excretion of C in the breath and urine of two human volunteers was measured after a 60-minute occlusive application of C-2-hexanone to their shaved forearms (DiVincenzo et al. 1978). Calculated skin absorption rates were 4.8 and 8.0 p g/min/cm however, the fraction of 2-hexanone that was absorbed was not calculated. 

Human deaths involving dermal exposure to 1,1,1-trichloroethane have not been reported. Such an occurrence is extremely unlikely in view ofthe high volatility of 1,1,1-trichloroethane, which would limit the amount of 1,1,1-trichloroethane in contact with the skin, and the relatively slow rate of percutaneous absorption. Animal deaths were observed only when extremely high doses (15,000 mg/kg) were applied to the skin for prolonged period (e.g., 24 hours) under occlusive dressings (Torkelson et al. 1958). 

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