Topical permethrin exposure inhibits antibody production and macrophage function in C57Bl/6N mice.

Permethrin was applied to the shaved dorsal interscapular region of C57Bl/6N mice at doses of 0.5, 1.5 or 5.0 microl/day. These doses corresponded to approximately 22-220 mg/kg/day topical insecticide. Mice were exposed to permethrin in this manner daily for 10 or 30 consecutive days, or every other day for 7 or 14 exposures. The splenic macrophage chemiluminescent response was depressed in a dose-dependent manner at 2 and 10 days post-exposure to permethrin. Phagocytic ability of macrophages was not inhibited. Antibody production as shown by plaque-forming cell (PFC) assay decreased significantly after 10 consecutive days of exposure to permethrin. These data indicate that topical permethrin exposure may produce systemic immune effects.

Dermal penetration of 14C-labeled diisopropyl methylphosphonate in swine.

Diisopropyl methylphosphonate (DIMP) has been identified as a groundwater contaminant on or near sites of former chemical warfare production facilities. The material is a by-product of GB (or Sarin) manufacture and does not occur naturally in the environment. The present study measured the dermal absorption of 14C-labeled DIMP in swine to establish the basis for estimating health risk from this portal of entry. Yorkshire cross swine were treated by sc injection of labeled DIMP to measure the efficiency of bioelimination. Additional pigs each received a single percutaneous (pc) exposure of 400, 40, or 4 micrograms/cm2 of labeled DIMP. Absorption through 7 d was measured by the appearance of 14C label in the urine and feces. Tissue specimens, collected at necropsy, were assessed for residual radioactivity. The results showed that between 3 and 7% of cutaneous DIMP was absorbed through 7 d. Urinary elimination accounted for about 95% of the absorbed dose in the first 24 h. No significant tissue deposition was observed. Pigs treated by the sc route excreted nearly 100% of the injected material demonstrating an extremely efficient metabolic process. It was concluded that humans may be expected to absorb less than 10% of an unoccluded single dermal exposure to DIMP. Absorbed dose would likely be metabolized to isopropyl methylphosphonic acid and excreted primarily in the urine within 24 h. Significant evaporation of the material from the open skin surface would be expected to occur.

Permethrin transfer from treated cloth to the skin surface: potential for exposure in humans.

Permethrin is an agricultural insecticide of great interest to the military because of its repellency toward disease-bearing insects when impregnated into uniforms. However, migration of the substance from clothing to the skin surface is of toxicological importance. To quantitate leaching from treated clothing, studies were performed in which swatches of fabric impregnated with 14C-labeled permethrin were applied to the backs of rabbits for 1 wk. Permethrin migration was quantitated by measuring the fate of the 14C label. Conditions that could affect leaching and/or absorption were also evaluated, that is, varying environments, the presence of sweat, different fabric types, and the effects of prelaundering. Results showed that fabric treated with permethrin at a rate of 0.125 mg/cm2 lost the substance to the skin surface at an average rate of 0.49%/d. At the end of the 7-d exposures in rabbits, about 3.2% of the available permethrin had reached the skin, 2% having been recovered from excreta (absorbed) and 1.2% remaining on the skin surface. Prelaundering the treated fabric had little effect on migration rate, nor did the other variables tested. Exposure dose to humans from wearing permethrin-treated (0.125 mg/cm2) military clothing is predicted to be 6 x 10(-4) mg/kg/d.

Dermal penetration and potential for placental transfer of the insect repellent, N,N-diethyl-m-toluamide.

N,N-Diethyl-m-toluamide (m-Det) is a widely used insect repellent readily available in various formulations. Radiolabeled (14C) m-Det was evaluated for rate and extent of skin penetration in three animal species. Absorption was quantitated in excreta for 7 days following a single dermal application and deposition monitored in tissues at necropsy. The potential for transplacental transfer and bioaccumulation of absorbed m-Det the fetus was also assessed following repeated applications to pregnant rabbits. Significant dermal absorption of the repellent was noted in all species, primarily in the first few hours, and was essentially complete after 3 days. No bioaccumulation of the labeled moiety was noted in tissues at 7 days. Pregnant rabbits receiving repeated dermal applications throughout gestation showed no evidence of bioaccumulation of the chemical in maternal tissue or individual fetuses. It is suggested that m-Det should not present a dermatoxic hazard to man and that topical absorption should be less than 10% of the applied dose.

Dermal penetration of three topical insect repellents in dogs and rabbits.

Three (14)C-labeled candidate insect repellents, cyclohexamethylene carbamide, n-butylsufonimidocyclohexamethylene and 2-hydroxyethylcyclohexane carboxylate were evaluated for skin penetration in dogs and rabbits. Absorption of the repellents was determined by monitoring excreted urine daily for seven days following topical application. Significant percutaneous absorption of all three repellents occurred within 24 hours. (14)C-cyclohexamethylene carbamide showed the greatest absorption. Measurable amounts of radioactivity persisted at the application site for both species after seven days.