Health Effects of Permethrin-Impregnated Army Battle-Dress Uniforms (1994) / Chapter Skim
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3 PHARMACOKINETICS OF PERMETHRIN
3 PHARMACOKINETICS OF PERMETHRIN
Pages 27-42
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From page 27... ...
j amen ~SO~11ON OF ~~1H~ 6~s~-o~ icily Tom macaw unions are me oral a~ demo routes. Consider~ion of oral Motion of peering in annals is necessary to estate the Bosomed dose in carcinopenichy studies, which were co^cted by oral Savage.
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From page 28... ...
Based on these studies, a dermal absorption rate of 2% was assumed for humans by the Medical Toxicology and Worker Health and Safety Branches of the Department of Pesticide Regulation of CEPA in their
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From page 29... ...
was at a maximum over the first 48 hr but continued at a low rate for at least 14 days, suggesting continued elimination of absorbed permethrin. Estimates of permethrin absorption derived from metabolite excretion studies in healthy individuals suggested that the maximum absorbed by any one individual over the first 48 hr after application of 16 g of cream (800 mg of permethrin)
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From page 30... ...
The interspecies difference supports the finding of higher permeability of rat skin demonstrated previously with other pharmaceutical compounds and underscores the Importance of using caution in extrapolating the results of pesticide dermal absorption studies in nonpr~mate species to humans. Migration of permethrin from clothing to the skin surface is important for assessing the toxicity of permethrin when Impregnated into uniforms.
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From page 31... ...
This report indirectly suggests that the use of DEET in combination with a pyrethroid insecticide increases the toxic response possibly by facilitating fenvalerate absorption (Dorman, 1990~. The possibility for enhancement of permethrin absorption by DEET is supported by a study on the use of DEET to enhance transdermal delivery of drugs.
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From page 32... ...
However, the observed potentiation of permethrin toxicity by DEET is consistent with a facilitated absorption of permethrin by DEET across the gastrointestinal surfaces. Additional studies are recommended to assess the potential interactive effect on absorption (see "Recommendations" in this chapter for more details)
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From page 33... ...
33 o ._ Cal Cal ._ ·3 .
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From page 34... ...
As with other pyrethroids, bans isomer metabolism is dominated by hydrolysis and cis isomer metabolism is dominated by oxidation (Hutson, 1979~. HYDROLYSIS The major pyrethroid hydrolyzing esterase is located in mammalian liver microsomes and is probably a carboxy!
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From page 35... ...
Oxidative reactions occur at the cyclopropane carboxylic acid moiety, at the alcohol moiety, and also probably in the prox~mity of the ester bond so that its cleavage is catalyzed. This later process might be very important for cis isomers, which are more resistant to hydrolysis.
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From page 36... ...
These facts suggest that hydrolysis and oxidation are important in limiting acute toxicity, although they are not the only factors controlling acute toxicity (Hutson, 1979~. In summary, all of what is known about the metabolism of pyrethroids comes from studies conducted in laboratory animals and from in vitro studies using hepatic tissues.
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From page 37... ...
Radioactivity from the cis isomers tended to be retained longer than that from the bans isomers and that from the alcohol label longer than that from the acid label. The most striking difference was that only 45-54% of the radiocarbon from the cis isomer appeared in the urine, whereas Si-90% of that from the bans isomer appeared in the urine.
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From page 38... ...
However, they probably also reflect greater excretion of the cis residues via the fecal route or greater retention of the cis isomer in body tissues. DISTRIBUTION Tissue Concentrations 11 Pyrethroids are lipophilic molecules that generally undergo rapid absorption and distribution following ingestion by mammals (Hutson, 1979~.
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From page 39... ...
Protein Binding The amount of the permethrin in the tissues is of some importance even at concentrations that are lower than the concentrations necessary to produce neurotoxicity. Studies using human skin fibroblast androgen receptors have demonstrated that nonsteroidal compounds, including permethrin, can interact competitively with human androgen receptors and the sex hormone binding globulin (Ei!
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From page 40... ...
Research specifically on the interaction of DEET and pe~n~ethrin has not been conducted and represents an area of uncertainty regarding the dermal absorption of permethrin. Facilitated absorption of permethrin by DEET is a possible concern for the military personnel assigned to combat areas in which DEET applied to the skin is used in combination with permethrin-treated military uniforms.
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From page 41... ...
Military personnel should consider minimizing areas of skin that are covered by both DEET and the permethrin-treated uniforms to reduce potential interactive effects of DEET on permethrin absorption. In other words, the interactive effects could probably be minimized if the areas of the body covered by uniforms were not covered by DEET.
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