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Trichloroethylene (TRI) and tetrachloroethylene (TETRA) are solvents that have been widely used in a variety of industries, and both are widespread environmental contaminants. In order to provide a better basis for understanding their toxicokinetics at environmental exposures, seven human volunteers were exposed by inhalation to 1 ppm of TRI or TETRA for 6 h, with biological samples collected for analysis during exposure and up to 6-days postexposure. Concentrations of TRI, TETRA, free trichloroethanol (TCOH), total TCOH (free TCOH plus glucuronidated TCOH), and trichloroacetic acid (TCA) were determined in blood and urine; TRI and TETRA concentrations were measured in alveolar breath. Toxicokinetic time courses and empirical analyses of classical toxicokinetic parameters were compared with those reported in previous human volunteer studies, most of which involved exposures that were at least 10-fold higher. Qualitatively, TRI and TETRA toxicokinetics were consistent with previous human studies. Quantitatively, alveolar retention and clearance by exhalation were similar to those found previously but blood and urine data suggest a number of possible toxicokinetic differences. For TRI, data from the current study support lower apparent blood-air partition coefficients, greater apparent metabolic clearance, less TCA production, and greater glucuronidation of TCOH as compared to previous studies. For TETRA, the current data suggest TCA formation that is similar or slightly lower than that of previous studies. Variability and uncertainty in empirical estimates of total TETRA metabolism are substantial, with confidence intervals among different studies substantially overlapping. Relative contributions to observed differences from concentration-dependent toxicokinetics and interindividual and interoccasion variability remain to be determined.

Objectives-To estimate dermal absorption of vaporous and liquid 2-methoxyethanol (ME) and in volunteers. Methods-Five volunteers (two men and three women) were dermally exposed to vaporised and liquid ME and EE. Dermal exposure on an area of about 1000 cm2 (forearm and hand) to vapours ofME and EE (4000 mglm' ME and 3700 mglm' EE) lasted for 45 minutes. Duration of exposure to liquid ME and EE on an area of 27 cm2 (forearm) was 15 minutes. Dermal uptake was assessed by measurement of the main metabolites in urinary methoxyacetic acid (MAA) and ethoxyacetic acid (EAA). For each volunteer, excretion of metabolites was compared with a reference inhalatory exposure. Results-Mean (SD) absorption rates of ME and EE vapour were 36 (11) and 19 (6) cmlh respectively. The mean (SD) absorption rates of the liquid ME and EE amounted to 2-9 (2.0) and 0-7 (0.3) mglcm'.h. Conclusions-Vaporised and liquid ME and EE are readily absorbed through the skin. In the combined inhalatory and dermal exposure when whole body surface is exposed to vapour, the uptake through the skin is estimated to be 55% of the total uptake of ME and 42% of EE. Dermal uptake resulting from skin contact ofboth hands and forearms (about 2000 cm?) with liquid ME and EE for 60 minutes would exceed inhalatory uptake ofthe eight hour occupational exposure limit by 100 times at 16 mg/iM3 of ME and 20 times at 19 mg/mi of EE. The substantial skin uptake of ME and EE indicates that in assessing the health risks biological monitoring and use of biological exposure indices are preferable to environmental monitoring. (Occup Environ Med 1997;54:38-43) Keywords: 2-methoxyethanol; 2-ethoxyethanol, dermal exposure Although often comprising < 10% of the final product, 2-methoxyethanol (ME) and (4 7) hours.3The main concern for human exposure is the occupational environment. The occupational exposure limits (OEL) of ME and EE are set in The Netherlands5 and United States6 at 5 ppm (16 and 19 mg/M3, respectively). A skin notation assigned to ME and EE in these OEL documents implies that skin absorption might be an important route of entry.Despite hard evidence that both glycol ethers as liquids are readily absorbed through human skin in vitro7 there are few human data on skin absorption of ME and EE in the liquid as well as in the vapour phase. Human data for skin uptake of another glycol ether 2-butoxyethanol have been published,8 9 reporting that dermal exposure to 2-butoxyethanol, both liquid and vapour, was even more important than respiratory uptake. The purpose of this study was, therefore, to estimate the percutaneous absorption of ME and EE in volunteers under controlled experimental conditions. Subjects and methods SUBJECTSThe volunteers (two men and three women) ranged in age from 22 to 25. All were without a history of serious diseases and their skins appeared normal. None of them took medicines or alcohol from at least 12 hours before exposure until the end of collection of urine. The experimental protocol was submitted to and approved by the med...

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This study gives additional data which indicate that glutathione-mediated metabolism is of minor importance in humans exposed to TRI. In spite of indications to the contrary, significant metabolism of the cysteine conjugate via beta-lyase, which could result in a toxic metabolite, cannot be ruled out completely.