Exposure of farmers to phosmet, a swine insecticide.
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OBJECTIVES: The goal of this study was to measure dermal and inhalation exposures to phosmet during application to animals and to identify what determinants of exposure influence the exposure levels. METHODS: Ten farmers were monitored using dermal patches, gloves, and air sampling media during normal activities of applying phosmet to pigs for insect control. Exposures were measured on the clothing (outer), under the clothing (inner), on the hands, and in the air. Possible exposure determinants were identified, and a questionnaire on work practices was administered. RESULTS: The geometric mean of the outer exposure measurements was 79 microg/h, whereas the geometric mean of the inner exposure measurements was 6 microg/h. The geometric mean for hand exposure was 534 microg/h, and the mean air concentration was 0.2 microg/m3. Glove use was associated with the hand and total dermal exposure levels, but no other determinant was associated with any of the exposure measures. The average penetration through the clothing was 54%, which dropped to 8% when the farmers wearing short sleeves were excluded. The farmers reported an average of 40 hours a year performing insecticide-related tasks. CONCLUSIONS: Farmers who applied phosmet to animals had measurable exposures, but the levels were lower than what has been seen in other pesticide applications. Inhalation exposures were insignificant when compared with dermal exposures, which came primarily from the hands. Clothing, particularly gloves, provided substantial protection from exposures. No other exposure determinant was identified. (+info)
In vivo skin decontamination of methylene bisphenyl isocyanate (MDI): soap and water ineffective compared to polypropylene glycol, polyglycol-based cleanser, and corn oil.
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In the home and workplace, decontamination of a chemical from skin is traditionally done with a soap-and-water wash, although some workplaces may have emergency showers. It has been assumed that these procedures are effective, yet workplace illness and even death occur from chemical contamination. Water, or soap and water, may not be the most effective means of skin decontamination, particularly for fat-soluble materials. This study was undertaken to help determine whether there are more effective means of removing methylene bisphenyl isocyanate (MDI), a potent contact sensitizer, from the skin. MDI is an industrial chemical for which skin decontamination, using traditional soap and water and nontraditional polypropylene glycol, a polyglycol-based cleanser (PG-C), and corn oil were all tried in vivo on the rhesus monkey, over 8 h. Water, alone and with soap (5% and 50% soap), were partially effective in the first h after exposure, removing 51-69% of the applied dose. However, decontamination fell to 40-52% at 4 h and 29-46% by 8 h. Thus, the majority of MDI was not removed by the traditional soap-and-water wash; skin tape stripping after washing confirmed that MDI was still on the skin. In contrast, polypropylene glycol, PG-C, and corn oil all removed 68-86% of the MDI in the first h, 74-79% at 4 h, and 72-86% at 8 h. Statistically, polypropylene glycol, PG-C, and corn oil were all better (p < 0.05) than soap and water at 4 and 8 h after dose application. These results indicate that a traditional soap-and-water wash and the emergency water shower are relatively ineffective at removing MDI from the skin. More effective decontamination procedures, as shown here, are available. These procedures are consistent with the partial miscibility of MDI in corn oil and polyglycols. (+info)
Dermal transfer of chlorpyrifos residues from residential surfaces: comparison of hand press, hand drag, wipe, and polyurethane foam roller measurements after broadcast and aerosol pesticide applications.
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Indoor residential pesticide applications present the potential for human exposures, particularly for small children. Personal contact with target and nontarget surfaces can result in transfer of pesticides to the skin, but the magnitude of such transfer is uncertain. This research compared surface sampling techniques [wipe and polyurethane foam (PUF) roller] with the removal ability of human skin following broadcast and total aerosol release applications of Dursban (Dow Elanco, Midland, MI), a residential formulation containing the insecticide chlorpyrifos. Hands were washed immediately after surface contact, following a protocol that included a laboratory-generated adjustment factor to account for incomplete removal of chlorpyrifos from skin. Chlorpyrifos transfer was similar for hand press and hand drag techniques, averaging approximately 1-6 ng/cm2 of carpet contacted. These amounts represented < 1% of the amount of chlorpyrifos deposited on the surfaces 3.5 hr earlier. Chlorpyrifos transfer from carpet to skin was 23-24 times lower than for wipe sampling and 33-36 times lower than for PUF roller sampling (p = 0.0007 and p = 0.0006 for broadcast and aerosol applications, respectively). Hand press sampling removed approximately 4.5 times less chlorpyrifos from nontarget furniture surfaces (12 ng/cm2) than did wipe sampling (56 ng/cm2; p = 0.009). Chlorpyrifos residues on carpet were substantially higher after broadcast applications than after aerosol applications, but residues on such nontarget surfaces as furniture were substantially higher for the aerosol application. This study indicates that human skin removes substantially less residue from carpets and furniture than either conventional wipe or PUF roller sampling methods following residential pest control applications of chlorpyrifos. Although this paper focuses on quantifying residue transfer from surface to skin using different surface sampling techniques, no attempt is made to quantify the amount of chlorpyrifos residue that is subsequently absorbed. (+info)
Oral and dermal absorption of chlorpyrifos: a human volunteer study.
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OBJECTIVES: To determine the kinetics of elimination of urinary dialkylphosphate metabolites after oral and dermally applied doses of the organophosphate pesticide chlorpyrifos to human volunteers and to determine whether these doses affected plasma and erythrocyte cholinesterase activity. METHOD: Five volunteers ingested 1 mg (2852 nmol) of chlorpyrifos. Blood samples were taken over 24 hours and total void volumes of urine were collected over 100 hours. Four weeks later 28.59 mg (81567 nmol) of chlorpyrifos was administered dermally to each volunteer for 8 hours. Unabsorbed chlorpyrifos was washed from the skin and retained for subsequent measurement. The same blood and urine sampling regime was followed as for the oral administration. Plasma and erythrocyte cholinesterase concentrations were determined for each blood sample. The concentration of two urinary metabolites of chlorpyrifos--diethylphosphate and diethyl-thiophosphate--was determined for each urine sample. RESULTS: The apparent elimination half life of urinary dialkylphosphates after the oral dose was 15.5 hours and after the dermal dose it was 30 hours. Most of the oral dose (mean (range) 93% (55-115%)) and 1% of the applied dermal dose was recovered as urinary metabolites. About half (53%) of the dermal dose was recovered from the skin surface. The absorption rate through the skin, as measured by urinary metabolites was 456 ng/cm2/h. Blood plasma and erythrocyte cholinesterase activity did not fall significantly during either dosing regime. CONCLUSION: An oral dose of chlorpyrifos was readily absorbed through the skin and almost all of the dose was recovered as urinary dialkylphosphate metabolites. Excretion was delayed compared with the oral dose. Only a small proportion of the applied dose was recovered during the course of the experiment. The best time to collect urine samples for biological monitoring after dermal exposure is before the shift the next day. The amounts of chlorpyrifos used did not depress acetyl cholinesterase activity but could be readily detected as urinary dialkylphosphate metabolites indicating that the urinary assay is a more sensitive indicator of exposure. (+info)
Estimation of the dermal absorption of m-xylene vapor in humans using breath sampling and physiologically based pharmacokinetic analysis.
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A physiologically-based pharmacokinetic model, containing a skin compartment, was derived and used to simulate experimentally determined exposure to m-xylene, using human volunteers exposed under controlled conditions. Biological monitoring was conducted by sampling, in exhaled alveolar air and blood, m-xylene and urinary methyl hippuric acid concentrations. The dermal absorption of m-xylene vapor was successfully and conveniently studied using a breath sampling technique, and the contribution to m-xylene body burden from the dermal route of exposure was estimated to be 1.8%. The model was used to investigate the protection afforded by an air-fed, half-face mask. By iteratively changing the dermal exposure concentration, it was possible to predict the ambient concentration that was required to deliver the observed urinary excretion of methylhippuric acid, during and following inhalation exposure to 50 ppm m-xylene vapor. This latter extrapolation demonstrates how physiologically-based pharmacokinetic modeling can be applied in a practical and occupationally relevant way, and permitted a further step not possible with biological monitoring alone. The ability of the model to extrapolate an ambient exposure concentration was dependent upon human metabolism data, thereby demonstrating the mechanistic toxicological basis of model output. The methyl hydroxylation of m-xylene is catalyzed by the hepatic mixed function oxidase enzyme, cytochrome P450 2E1 and is active in the occupationally relevant, (<100 ppm) exposure range of m-xylene. The use of a scaled-up in vitro maximum rate of metabolism (Vmaxc) in the model also demonstrates the increasingly valuable potential utility of biokinetic data determined using alternative, non-animal methods in human chemical-risk assessment. (+info)
Predicting vehicle effects on the dermal absorption of halogenated methanes using physiologically based modeling.
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Occupational and environmental settings present opportunities for humans to come into contact with a variety of chemicals via the dermal route. The chemicals contacting the skin are likely to be diluted with a vehicle or present as a component of a mixture. In order to support risk assessment activities, we evaluated the vehicle effects on dermal penetration of two halogenated hydrocarbons, dibromomethane (DBM) and bromochloromethane (BCM). In vivo exposures to 15 combinations of of these in water, mineral oil, and corn oil vehicles were conducted, and blood was sampled for dibromomethane and bromochloromethane during the exposure at 0.5, 1, 2, 4, 8, 12, and 24 h. A physiologically based pharmacokinetic (PBPK) model was used to estimate the total amounts of dibromomethane or bromochloromethane that were absorbed during the exposure, and the dermal permeability coefficients were determined. While the permeability coefficients for dibromomethane and bromochloromethane were approximately 73- and 40-fold higher, respectively, in the water vehicle than in the corn oil, the permeability coefficient, when normalized for the skin:vehicle matrix partition coefficient, varied by less than a factor of 2. The permeability in an aqueous vehicle was then successfully used to predict the permeability coefficient for dibromomethane in a nonpolar vehicle, peanut oil. (+info)
In vitro test of nicotine's permeability through human skin. Risk evaluation and safety aspects.
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Permeability tests with Franz' diffusion cells and an in vitro test model were made to evaluate the importance of dermal absorption of nicotine as a pathway for intoxication. Studies were carried out to ensure that safety procedures, when spilling nicotine on skin, are sufficient to prevent poisoning. Pure nicotine and nicotine in various concentrations in water or ethanol were applied on human skin or gloves in Franz' cells. Washing was simulated by removing nicotine from skin after 3 or 5 min. Permeation rate (flux) and lag time were calculated and estimated for human skin. Different glove materials were tested for their nicotine breakthrough time. Flux depended on concentration in a non-linear way when nicotine-water solutions were tested. Highest flux was found in 50% w/w nicotine dissolved in water. Solutions with low concentration of nicotine (1% w/w) dissolved in water had a similar permeation rate to 100% nicotine. Flux was found to be low when using ethanol as a vehicle; flux was also pH-dependent. The nicotine-water solution containing acetic acid had the lowest flux. The tests where nicotine was washed away revealed that skin served as a possible nicotine depot, because nicotine concentration in the receptor compartment continued to increase after removing the nicotine from the surface. The length of contact time affected the amount of substance passing the skin, resulting in great difference between 3 and 5 min contact time, 5 min giving higher nicotine concentration and 3 min lower. This emphasizes the importance of washing away nicotine spilled on skin rapidly. Two glove types were tested and they were found to be appropriate in their use with nicotine if changed regularly. (+info)
Dermal application of JP-8 jet fuel induces immune suppression.
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Chronic exposure to JP-8 jet fuel induces lung toxicity, adverse neurological effects and some liver and kidney dysfunction. In addition, inhalation of JP-8 induces immune suppression. Besides the lung, the other major route of JP-8 exposure is via the skin. In this study we tested the hypothesis that dermal exposure to JP-8 is immune suppressive. JP-8 was applied to the skin of adult female C3H/HeN mice and various immune parameters were examined. Dermal exposure to JP-8, either multiple small exposures (50 microl for 5 days) or a single large dose (250-300 microl) resulted in immune suppression. The induction of contact hypersensitivity was impaired in a dose-dependent manner regardless of whether the contact allergen was applied directly to the JP-8-treated skin or at a distant un-treated site. In addition, the generation of a classic delayed-type hypersensitivity reaction to a bacterial antigen (Borellia burgdorferi) injected into the subcutaneous space was suppressed by dermal application of JP-8 at a distant site. The ability of splenic T lymphocytes from JP-8-treated mice to proliferate in response to plate-bound monoclonal anti-CD3 was also significantly suppressed. Interleukin-10, a cytokine with potent immune suppressive activity, was found in the serum of JP-8-treated mice, suggesting that the mechanism of systemic immune suppression may involve the upregulation of cytokine release by JP-8. These findings confirm the immunosuppressive effects of JP-8 and demonstrate that dermal exposure to JP-8 is immunotoxic. (+info)