Exposure dose, calculation dermal contact

Pharmacokinetic calculations yielded estimates of chlorpyrifos intake of 0.05-1 pg/kg per day in the general population. The model estimates compare favorably with pathway analysis estimates of aggregate chlorpyrifos exposure from numerous dose routes, including indoor inhalation, dermal contact, and food ingestion (Shurdut et al. 1998 Pang et al. 2002). The calculated exposure doses ranged from 0.02 to 1 pg/kg per day. Further... 

The route of exposure is another aspect of exposure in which health-relevance must be considered. In Section One of this book, there is a detailed discussion of exposure assessment methodologies, including the importance of identification of the most prevalent route of exposure (dermal, inhalation or oral) and the necessity of knowing the absorption of the pesticide to allow calculation of the absorbed dose for risk assessment. For epidemiological purposes, exposure-assessment smdies are usually limited to assessing contact exposure levels. Since dermal absorption is not known for many pesticides or complex mixtures, uptake through the dermal route can often not be estimated and contact exposure data are a poor proxy of internal exposure (absorbed dose) (Schneider et al., 1999). 

Although there are dose-response data from an animal inhalation exposure study (McNamara et al., 1975, see Section 5.1.1), route-to-route extrapolation (from inhalation to oral, as calculated in Section 5.2.1) is not considered appropriate because the exposure protocol of McNamara et al. (1975) resulted in rat skin tumors which might have occurred, not a result of systemic uptake, but as a result of dermal contact with sulfur mustard vapor (perhaps trapped by the rat pelt). Therefore, there is no method for estimating the dermal dose of sulfur mustard, or for converting this to an oral dose. 

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. 

Two general types of methods are available for estimating human exposure to pesticides. First, direct entrapment methods involve the use of some mechanism to entrap the toxic material as it comes in contact with the person during an exposure period. The amount of entrapped toxicant, as determined by chemical analysis, is then a direct measure of the particular exposure under study. Further calculations using the kinetics of dermal absorption for the compound and formulation under study are required to arrive at the actual ateorbed dose. For the oral and inhalation routes, exposure and absorbed dose are more closely equivalent than for the dermal route. However, for precise data, absorption must be taken into account for these routes, also. Second, indirect methods are based on measurement of some effect of the compound on the exposed individual (such as blood... 

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