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Permethrin absorption not detected in single-pass perfused rabbit ear, and absorption with oxidation of 3-phenoxybenzyl alcohol.

Bast GE, Taeschner D, Kampffmeyer HG.

Walther-Straub-Institute for Pharmacology and Toxicology, Faculty of Medicine, Ludwig-Maximilians-University, Munich, Germany.

Isolated rabbit ears were single-pass perfused with a protein-free medium. Permethrin (0.05-23.5%, w/w) was applied in four distinct ointments. Permethrin, 3-phenoxybenzyl alcohol, 3-phenoxybenzaldehyde, and 3-phenoxybenzoic acid were analysed by HPLC. Permethrin was not detected in the effluent. The permeation coefficient, calculated from the detection limit was < 7.3 x 10(-12) (cm/sec). The appearance rate of the 3-phenoxybenzyl moieties in the effluent agreed with the absorption of the corresponding impurities in the various ointments. In supernatant of homogenised skin, the hydrolysis rate of permethrin was linear; about 4 pmol/min per cm2 at 10 microM substrate concentration. The proportion of 3-phenoxybenzoic acid, a further metabolite of 3-phenoxybenzyl alcohol increased when an oxidizing co-factor system was added. The appearance rate in the effusate of 3-phenoxybenzyl alcohol following the lipophobic ointment was five times faster than from isopropyl myristate. The formation rate of 3-phenoxybenzoic acid followed saturation kinetics. Occupational systemic poisoning by dermal absorption of permethrin seems very unlikely since humans bear more epithelial cell layers than rabbits. These experiments do not contradict, however, possible paraesthesia during systemic poisoning after inhalation or ingestion of the pyrethroid-containing aerosols used in agriculture.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9049055&dopt=Abstract permethrin Elimite



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[Effects of renovation measures on the health status of persons, exposed to pyrethroids through carpets and flooring]

[Article in German]

Boge KP, Brokof H, Prohl A, Alsen-Hinrichs C.

Umweltambulanz Lubeck.

80 clients of a mobile unit for environmental quality testing were contacted after monitoring for potential toxic substances in their homes or places of work. Elevated concentrations of pyrethroids (in all cases at least permethrin) were found in these 80 cases in dust or materials, mainly because of pyrethroid treated carpetings. The clients were questioned whether they removed one or all of the contaminated carpets. Furthermore, they were questioned as to their state of health and the period of time which had passed since the carpets were removed. 75 of the 80 contacted clients had initially called the mobile unit for environmental quality testing because of health impairments, whereas 5 clients had done this only for preventive reasons. 47 (59%) of the contacted clients had removed all carpetings which were contaminated with permethrin. 8 (10%) clients had got rid of a part of the contaminated carpets and 25 (31%) clients did not remove any carpet. 39 (83%) of the clients who had removed all contaminated carpetings, described a complete or at least partial improvement of their complaints. The complaints of 6 (13%) clients did not improve despite removal of their carpets. The lowest concentration of permethrin that was assessed at the homes of clients, who, after removing all contaminated carpet floorings, described complete recovery, were 10-15 mg/kg dust and 15 mg/kg carpet, respectively. The effect of removing all contaminated carpetings on health improvement in comparison with the results of not removing any carpet was statistically significant (test: chi 2, p < 0.0001). The corrected contingency coefficient amounted to 0.71. In 3 cases, where the contaminated carpets had already existed for 5, 7 and 10 years in the homes of clients, there were still permethrin-concentrations of 115, 100 and 150 mg per kg dust. This result indicates that indoor contamination of permethrin is highly persistent.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9081512&dopt=Abstract permethrin Elimite



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Inheritance of larval resistance to permethrin in Aedes aegypti and association with sex ratio distortion and life history variation.

Mebrahtu YB, Norem J, Taylor M.

Department of Entomology, and Center for Insect Science, University of Arizona, Tucson 85721, USA.

The genetic mechanisms that confer larval permethrin resistance were investigated in two strains of Aedes aegypti, vectors of yellow fever and dengue hemorrhagic fever. Larval resistance to permethrin in an Ae. aegypti field-collected resistant Couva (R) strain was associated with the sex-determining locus by analysis of backcrosses to the susceptible Rockefeller (S) strain. The median lethal concentrations (LC50s) of these strains were 23.1 (95% confidence interval = 22.0-24.3) and 2.2 (2.0-2.3) parts/billion of permethrin, respectively. The estimated resistance ratio (RR) for the R strain was 10.8 (10.3-11.4) compared with the S strain. Resistance was inherited as partly recessive (dominance [D] = -0.31) with an estimated RR of 2.3 (2.1-2.4) in the F1 hybrids when the R parent was male. There were also significantly male-biased sex ratios for this cross. In contrast, inheritance was slightly dominant (D = 0.19) with an estimated RR of 4.1 (3.8-4.4) when the R parent was female, and no significant sex ratio bias of progeny was observed. Analysis revealed a strong paternal-strain effect in bioassay mortality, sex ratio, egg hatch, and fecundity. A maternal-strain effect was also evident for bioassay mortality. Similarly, a strong maternal by paternal strain interaction was also evident for sex ratio. Progeny of single-family backcrosses of F1 hybrids to R were statistically homogeneous for sex ratio, duration of oviposition, fecundity, and hatch rate. A significant increase in male bias was found for only one backcross to R, after treatment with permethrin. In contrast, complex patterns of inheritance of life histories were observed among backcrosses to S. Backcrosses to S had greater mean fecundities, shorter mean times to the start of oviposition, and shorter mean oviposition periods than did backcrosses to R. Hatch rates were statistically homogeneous among backcrosses, but all strikingly reduced relative to the parental generation. Times of start and duration of oviposition were highly negatively correlated with fecundity (first gonotropic cycle only) and rate of egg hatch. Females with lower fecundities had lower hatch rates, and there was a threshold of approximately 80 eggs per female, below which no eggs hatched. Generally all backcrosses had higher LC50s than expected from single-locus inheritance. Association between sex bias and inheritance of resistance was apparent, but no single genetic linkage model based on current understanding of sex chromosome genetics was consistent with these observations. These results may have epidemiologic importance considering that permethrin-soaked bed nets are being used in many countries to control the biting activity of disease vectors.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9158058&dopt=Abstract permethrin Elimite



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The influence of diethyl-m-toluamide (DEET) on the percutaneous absorption of permethrin and carbaryl.

Baynes RE, Halling KB, Riviere JE.

Cutaneous Pharmacology and Toxicology Center, College of Veterinary Medicine, North Carolina State University, Raleigh 27606, USA.

Simultaneous exposure to DEET and permethrin was recently proposed to be associated with the "Gulf War Syndrome." However, no studies have reported the percutaneous absorption of DEET and permethrin when applied simultaneously to the skin as a mixture, the relevant route of exposure in the Persian Gulf. The present study quantitates percutaneous absorption of DEET and permethrin after coadministration to rodent and pig skin in vitro. Dosing solutions were also prepared with either acetone, dimethyl sulfoxide (DMSO), or ethanol to compare vehicle effects on percutaneous absorption of permethrin and DEET. The influence of DEET on carbaryl absorption and dermal disposition was also assessed in pig studies to statistically demonstrate DEET effects in acetone or DMSO and different solvent concentrations. Topical application of permethrin + DEET resulted in absorption of DEET (1-20% dose), but no permethrin. Permethrin (1.2-1.7% dose) was detected only when mouse skin was dosed solely with permethrin, a finding suggesting that DEET decreased permethrin absorption. DEET also inhibited carbaryl absorption in acetone mixtures, but had no effect on DMSO mixtures. Irrespective of solvent, DEET did not enhance carbaryl penetration into skin. For DEET, absorption was greater in mouse skin (10.7-20.6% dose) than in rat skin (1.1-5.2% dose) and pig skin (2.8% dose). The extent of DEET absorption was greater with DMSO and acetone than with ethanol in rat and mouse skin. These studies support DEET, but not permethrin or carbaryl, as having sufficient systemic exposure to potentially cause signs of toxicity when simultaneously applied with pesticides. Furthermore, these studies demonstrated that DEET does not necessarily enhance dermal absorption of all toxicants as was originally hypothesized.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9194417&dopt=Abstract permethrin Elimite



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Induction of urinary excretion of 3-nitrotyrosine, a marker of oxidative stress, following administration of pyridostigmine bromide, DEET (N,N-diethyl-m-toluamide) and permethrin, alone and in combination in rats.

Abu-Qare AW, Suliman HB, Abou-Donia MB.

Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.

In this study, we determined levels of 3-nitrotyrosine in rat urine following administration of a single oral dose of 13 mg/kg pyridostigmine bromide (PB) (3-dimethylaminocarbonyloxy-N-methylpyridinum bromide), a single dermal dose of 400 mg/kg N,N-diethyl-m-toluamide (DEET) and a single dermal dose of 1.3 mg/kg permethrin, alone and in combination. Urine samples were collected from five treated and five control rats at 4, 8, 16, 24, 48, and 72 h following dosing. Solid-phase extraction coupled with high-performance liquid chromatography with ultraviolet detection at 274 nm was used for the determination of tyrosine and 3-nitrotyrosine. A single oral dose of PB and a single dermal dose of DEET or their combination significantly (P<0.05) increased levels of 3-nitrotyrosine starting 24 h after dosing compared with control urine samples. The maximum increase of 3-nitroytyrosine was detected 48 h after combined administration of PB and DEET. The ratio of 3-nitrotyrosine to tyrosine in urine excreted 48 h after dosing was 0.19+/-0.04, 0.20+/-0.05, 0.28+/-0.03, 0.32+/-0.04, 0.19+/-0.05, 0.42+/-0.04, 0.27+/-0.03, 0.36+/-0.04, and 0.48+/-0.04 following administration of water, ethanol, PB, DEET, permethrin, PB+DEET, PB+permethrin, DEET+permethrin, and PB+DEET+permethrin, respectively. The results indicate that an oral dose of PB and a dermal administration of DEET, alone and in combination, could generate free radical species, and thus increase levels of 3-nitrotyrosine in rat urine. Induction of 3-nitrotyrosine, a marker of oxidative stress, following exposure to these compounds could be significant in understanding the proposed enhanced toxicity following combined exposure to these compounds.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11325563&dopt=Abstract permethrin Elimite