Dermal absorption and metabolism

Ford RA, Hawkins DR, Mayo BC, and Api AM (2001) The in vivo dermal absorption and metabolism of [d- C] coumarin by rats and by human volunteers under simulated conditions of use in fragrances. Pood and Chemical Toxicology 39 153-162. 

Dermal Absorption and Metabolism of Xenobiotics in Food-Producing Animals... 

Factors which might alter dermal absorption and metabolism of xenobiotics will be presented. This work will hopefully provide a framework for the systematic investigation of comparative dermal absorption across the diverse species of food-producing animals. 

Hotchkiss, S.A., Dermal metabolism, in Dermal Absorption and Toxicity Assessment. Drugs and the Pharmaceutical Sciences, Vol 91, Robberts, M.S. and Walters, K.A., eds., New York, Marcel Dekker, 43-101 (1998). 

Absorption, Distribution, Metabolism, and Excretion. Human data indicate that chloroform absorption from the lungs is rapid and fairly complete (Smith et al. 1973). The data also indicate that absorption after oral exposure is fairly complete for both animals and humans (Brown et al. 1974a Fry et al. 1972 Taylor et al. 1974). Although there are no experimental data regarding dermal absorption in humans, some data have been extrapolated from mouse studies (Tsumta 1975). The rate of absorption following oral or inhalation exposure is rapid (within 1-2 hours). Additional animal studies investigating the rate of dermal absorption would be useful to quantitate dermal absorption and to compare information from oral and inhalation studies. 

Further data on the effects of chronic inhalation exposure to 1,4-dichlorobenzene would be useful, especially because chronic exposures to 1,4-dichlorobenzene in the air, in the home, and the workplace are the main sources of human exposure to this chemical. Any further testing of the effects of chronic exposure to 1,4-dichlorobenzene via the oral route should probably be done at lower levels of 1,4-dichlorobenzene than those that have already been used in the NTP (1987) bioassay, and should focus on dose-response relationships involving the hepatic, renal, hematopoietic, central nervous system, and metabolic pathways. Data on the effects of chronic dermal exposure to 1,4-dichlorobenzene may be useful if dermal absorption and systemic distribution of 1,4-dichlorobenzene can be demonstrated from toxicokinetic studies, since chronic dermal exposure to 1,4-dichlorobenzene occurs as a result of bathing and showering in drinking water that contains low levels of this chemical in many U.S. communities. 

Martinez TT, Jaeger RW, deCastro FJ, et al A comparison of the absorption and metabolism of isopropyl alcohol by oral, dermal and inhalation routes. Vet Hum Toxicol 28 233-236, 1986... 

Martinez et al. (1986) compared the absorption and metabolism of isopropanol in rabbits after oral, dermal and inhalation exposure. The highest blood levels were seen after oral dosing, lower after inhalation and lowest after dermal application. Blood levels after doses of 4 mL/kg were approximately twice those seen after 2 mL/kg, but concentrations of acetone were the same after both doses, regardless of the route of administration. 

Results from a study of rats, guinea pigs, and monkeys under nonoccluded dermal exposure conditions indicated that evaporation from the skin was a major disposition route (Jeffcoat et al. 1983). Additional animal studies of absorption, distribution, and metabolism under occluded conditions of dermal exposure would provide information regarding maximal rates of dermal absorption and local tissue metabolism, and may help to confirm that distant-site effects from dermal exposure are imlikely. 

Hotchkiss, S. A. M. 1998. Dermal metabolism. In Dermal absorption and toxicity assessment, edited by M. S. Roberts, and K. A. Walters. New York Marcel Dekker, pp. 43-101. 

Absorption, Distribution, Metabolism, and Excretion. Studies in laboratory animals indicate that di- -butyl phthalate given orally is readily absorbed, mainly as the metabolite mono- -butyl phthalate, and subsequently, is rapidly excreted. Limited data exist regarding inhalation and dermal absorption. Studies on the absorption and metabolism of di- -butyl phthalate by the inhalation and dermal routes are needed to evaluate human health risk by these routes of exposure. 

Inhibits several metabolic enzyme systems. Dermal absorption occurs. Metabolized to cyanide (see p 177) fatalities have resulted. Symptoms Include headache, nausea, vomiting, weakness, and stupor. Limited evidence for adverse effects on fetal development in test animals given large doses. 

Absorption, Distribution, Metabolism, and Excretion. Evidence of absorption comes from the occurrence of toxic effects following exposure to methyl parathion by all three routes (Fazekas 1971 Miyamoto et al. 1963b Nemec et al. 1968 Skiimer and Kilgore 1982b). These data indicate that the compound is absorbed by both humans and animals. No information is available to assess the relative rates and extent of absorption following inhalation and dermal exposure in humans or inhalation in animals. A dermal study in rats indicates that methyl parathion is rapidly absorbed through the skin (Abu-Qare et al. 2000). Additional data further indicate that methyl parathion is absorbed extensively and rapidly in humans and animals via oral and dermal routes of exposure (Braeckman et al. 1983 Flollingworth et al. 1967 Ware et al. 1973). However, additional toxicokinetic studies are needed to elucidate or further examine the efficiency and kinetics of absorption by all three exposure routes. 

Absorption, Distribution, Metabolism, and Excretion. There are no data available on the absorption, distribution, metabolism, or excretion of diisopropyl methylphosphonate in humans. Limited animal data suggest that diisopropyl methylphosphonate is absorbed following oral and dermal exposure. Fat tissues do not appear to concentrate diisopropyl methylphosphonate or its metabolites to any significant extent. Nearly complete metabolism of diisopropyl methylphosphonate can be inferred based on the identification and quantification of its urinary metabolites however, at high doses the metabolism of diisopropyl methylphosphonate appears to be saturated. Animal studies have indicated that the urine is the principal excretory route for removal of diisopropyl methylphosphonate after oral and dermal administration. Because in most of the animal toxicity studies administration of diisopropyl methylphosphonate is in food, a pharmacokinetic study with the compound in food would be especially useful. It could help determine if the metabolism of diisopropyl methylphosphonate becomes saturated when given in the diet and if the levels of saturation are similar to those that result in significant adverse effects. 

Human populations are likely to be exposed to a pollutant through more than one exposure route at a time. Total exposure may combine intake through ingestion of different substances, dermal absorption from surface water and water supply, and inhalation at different locations in the study area (e.g., work, home, recreational areas, commuting routes). Calculation of total exposure requires that the pharmacokinetics (absorption, metabolism, storage, excretion) for different exposure routes are understood for the pollutant of concern. Otherwise, only exposures by route can be combined. 

Absorption, Distribution, Metabolism, and Excretion. Metabolism and excretion in animals exposed to acrylonitrile by the inhalation and oral routes have been studied extensively. However, only limited data on absorption and distribution are available. Some data on humans exposed by inhalation are available. No data are available on the toxicokinetics of acrylonitrile when the exposure route is dermal. More extensive information on absorption and distribution of acrylonitrile would be valuable to fully understand the toxicokinetics of acrylonitrile. Some data on the toxicokinetics of acrylonitrile... 

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