Abstract  N-methyl-2-pyrrolidone is a solvent that is increasingly used in a variety of industries, including petroleum refining, microelectronics, pesticide formulation, and veterinary medicine. Animal studies have demonstrated fetotoxic effects after maternal exposure to doses that have minimal to no adverse effect on the mothers. The fetotoxicity comprises resorption, stillbirth, and low birthweight and delayed ossification in surviving young. We report a human case of intrauterine growth retardation followed by fetal demise at 31 weeks gestation. The mother was a laboratory worker with no other apparent risk factors, who sustained occupational exposure to N-methyl-2-pyrrolidone throughout the first trimester of pregnancy. Laboratory work and solvent exposure have both previously been associated with adverse reproductive outcomes. Laboratories and other industries that use suspected reproductive toxins should have reproductive health policies in place that allow for decision-making based on toxicologic review, exposure assessment, and medical evaluation. These policies should allow for voluntary removal of prospective parents until environmental assessment and controls are instituted.

Abstract  OBJECTIVES: The dermal absorption of the solvent N-methyl-2-pyrrolidone (NMP) and its elimination in urine was investigated in an experimental study.

METHODS: Seven volunteers were exposed to 1045 mg of liquid NMP under occlusive conditions for 2 h. Urine was collected before, during and up to 72 h after the exposure and analysed for NMP by GC/MS after liquid-liquid extraction. Additionally, the remaining NMP in the pads was determined to estimate the total dermal uptake.

RESULTS: The concentration of NMP in urine increased rapidly after beginning of the exposure up to 1 h after the exposure was completed. A peak concentration of 1,836+/-863 microg/l was observed, the half-life in urine was 3.2 h. About 0.5% of the absorbed dose was excreted metabolically unchanged. An average dermal absorption of 5.5 mg cm(-2) h(-1) was calculated.

CONCLUSIONS: The results of this study show that the percutaneous absorption of NMP may contribute significantly to the overall uptake of the solvent, e.g. in the workplace. Therefore, a biological monitoring of NMP exposed workers is essential for occupational-medical surveillance.

Abstract  OBJECTIVES: N-Methyl-2-pyrrolidone (NMP) is a versatile solvent used in various industrial processes and applications. Apart from its mildly irritating effects on the eyes, the mucous membranes and the skin, NMP has revealed prenatal toxicity in animal experiments after the oral administration of high doses. The dermal absorption of NMP and the urinary elimination of its main metabolites were investigated within an experimental exposure study.

METHODS: Four male volunteers were exposed to liquid NMP under occlusive conditions on the back of one hand with varying exposure times and solvent concentrations. Urine was collected before, during and after the exposure and analysed for the main NMP metabolites 5-hydroxy-N-methyl-2-pyrrolidone (5-HNMP) and 2-hydroxy-N-methylsuccinimide (2-HMSI).

RESULTS: The urinary concentration of the metabolites upon exposure to undiluted NMP for 2 h increased rapidly with 5-HNMP reaching a maximum at 4-5 h and 2-HMSI after 26-29 h. The application of aqueous NMP solutions resulted in a delay of the peak time for 5-HNMP of approximately 6 h as compared with the undiluted solvent. An average dermal absorption of 5.4+/-1.5 mg NMP cm(-2) h(-1) was calculated for a 2 h exposure to undiluted NMP (6.5+/-2.0 mg NMP cm(-2) h(-1) for a 30 min exposure). Aqueous dilution of NMP to 50% was followed by a decrease of the absorption to 0.9+/-0.5 mg NMP cm(-2) h(-1). NMP metabolite concentrations in the range of the detection limits were found only in isolated urine samples after exposure to 10% NMP in aqueous dilution.

CONCLUSIONS: NMP is rapidly absorbed across the skin and the dermal route may contribute significantly to the uptake of the solvent. Therefore, a biomonitoring of NMP exposed workers is essential for occupational-medical surveillance. Both urinary metabolites reflect the internal dose after a dermal absorption of NMP and thus qualify as suitable biomarkers for NMP exposure.

Abstract  A procedure has been developed for measuring the steady state rate of permeation of commercial solvents through living human skin. To get the most consistent results, it was necessary with some solvents to normalize the solvent permeation rate of a given skin sample with its [3H]water permeation rate. For other solvents this was not necessary, so the un-normalized data were used. High [3H]water permeation rate also was used as a criterion for "defective" skin samples that gave erroneous permeability rates, especially for solvents having slow permeability. The linearity of the steady state data was characterized by calculation of the "percent error of the slope." The following permeability rates (g/m2h) of single solvents were measured: dimethyl sulfoxide (DMSO), 176; N-methyl-2-pyrrolidone, 171; dimethyl acetamide, 107; methyl ethyl ketone, 53; methylene chloride, 24; [3H]water, 14.8; ethanol, 11.3; butyl acetate, 1.6; gamma-butyrolactone, 1.1; toluene, 0.8; propylene carbonate, 0.7; and sulfolane, 0.2. The effect of [3H]water saturation on the shape of the presteady state portion of the permeation curve was determined and found to be very dependent on the solvent. The permeability of mixtures of DMSO and octyl acetate were measured. No octyl acetate was detected and the permeability of DMSO was proportional to its mole fraction in the mixture. The effect of two hours of solvent exposure on the viability of skin (based on DNA synthesis) was measured and found to be very dependent on the solvent.

Abstract  The emissions of two volatile organic compounds (VOCs) of concern from five building products (BPs) were measured in the field and laboratory emission cell (FLEC) up to 250 d. The BPs (VOCs selected on the basis of abundance and low human odor thresholds) were: nylon carpet with latex backing (2-ethylhexanol, 4-phenylcyclohexene), PVC flooring (2-ethylhexanol, phenol), floor varnish on pretreated beechwood parquet (butyl acetate, N-methylpyrrolidone), sealant (hexane, dimethyloctanols), and waterborne wall paint on gypsum board (1,2-propandiol, Texanol). Ten different climate conditions were tested: four different air velocities from ca. 1 cm s(-1) to ca. 9 cm s(-1), three different temperatures (23, 35, and 60 degrees C), two different relative humidities (0% and 50% RH), and pure nitrogen instead of clean air supply. Additionally, two sample specimen and two different batches were compared for repeatability and homogeneity. The VOCs were sampled on Tenax TA and determined by thermal desorption and gas chromatography (FID). Quantification was carried out by individual calibration of each VOC of concern. Concentration/time profiles of the selected VOCs (i.e. their concentration decay curves over time) in a standard room were used for comparison. Primary source emissions were not affected by the air velocity after a few days to any great extent. Both the temperature and relative humidity affected the emission rates, but depended strongly on the type of BP and type of VOC. Secondary (oxidative) source emissions were only observed for the PVC and for dimethyloctanols from the sealant. The time to reach a given concentration (emission rate) appears to be a good approach for future interlaboratory comparisons of BP's VOC emissions.(C) 1998 Elsevier Science Ltd. All rights reserved.

Abstract  The exposure to organic solvents among 12 graffiti removers was studied. Health effects were also assessed by structured interview and a symptom questionnaire. Blood and urine samples were collected at the end of the day of air sampling. The concentrations of dichloromethane, glycol ethers, trimethylbenzenes and N-methyl-2-pyrrolidinone in the breathing zone of each worker were measured during one working day. The 8-h time-weighted average exposure to dichloromethane ranged from 18 to 1200 mg/m3. The Swedish Permissible Exposure Limit value for dichloromethane is 120 mg/m3. The air concentrations of glycol ethers, trimethylbenzenes and N-methyl-2-pyrrolidinone were low or not detectable. No exposure-related deviations in the serum concentrations of creatinine, aspartate transaminase, alanine transaminase, gamma-glutamyl transpeptidase or hyaluronan or the urine concentrations of alpha 1-microglobulin, beta 2-microglobulin or N-acetyl-beta-glucosaminidase were found. Irritative symptoms of the eyes and upper respiratory tract were more prevalent than in the general population. This study demonstrates that old knowledge about work hazards is not automatically transferred to new professions. Another aspect is that the public is also exposed as the job is performed during daytime in underground stations. At least for short periods, bystanders may be exposed to high concentrations of organic solvent vapours. People with predisposing conditions, e.g. asthmatics, may risk adverse reactions.