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DISPOSITION OF BROMODICHLOROMETHANE IN HUMANS FOLLOWING ORAL AND DERMAL EXPOSURE
Citation:
Leavens, T L., M W. Case, R A. Pegram, R A. Pegram, D M. DeMarini, M. C. Madden, J. L. Valentine, AND B. C. Blount. DISPOSITION OF BROMODICHLOROMETHANE IN HUMANS FOLLOWING ORAL AND DERMAL EXPOSURE. Presented at Society of Toxiocology Annual Meeting, Nashville, TN, March 17-21, 2002.
Description:
DISPOSITION OF BROMODICHLOROMETHANE IN HUMANS FOLLOWING ORAL AND DERMAL EXPOSURE. TL Leavens1, MW Case1, RA Pegram1, BC Blount2, DM DeMarini1, MC Madden1, and JL Valentine3. 1NHEERL, USEPA, RTP, NC, USA; 2CDC, Atlanta, GA, USA; 3RTI, RTP, NC, USA.
The disinfection byproduct bromodichloromethane (BDCM) is found in drinking water treated by chlorination. Two routes of exposure to BDCM are ingestion of water and skin absorption from activities such as bathing and showering. The objective of this research was to measure blood concentrations in human volunteers exposed dermally and orally to 13C-BDCM. The subjects (9 males/1 female) were characterized according to their cytochrome P450 2E1 in vivo activities, glutathione-S-transferase theta genotype, and percentage body fat, factors which could affect disposition of BDCM. Cytochrome P450 2E1 activity was measured by chlorzoxazone metabolism, the glutathione-S-transferase theta genotype was determined from DNA amplified from buccal cells, and the percentage body fat was estimated from skin-fold thickness. There was a 4-fold difference in lowest to highest cytochrome P450 2E1 activity among subjects. Two of the subjects were glutathione-S-transferase theta negative. Body fat of the subjects ranged from 7% to 22%. For the exposures, the subjects drank approximately 250 mL of water or submerged their forearm for one hour in 37?C water containing 36 g/L 13C-BDCM. Blood was collected during and after exposure for up to 24 hours, and 13C-BDCM was quantitated by solid phase microextraction and high resolution GC-MS. After ingestion, the blood concentration increased rapidly and returned to baseline within 4 hrs. The Tmax for the oral exposure ranged from 5 to 30 min, and the Cmax ranged from 0.4 to 4.1 ng/mL. With dermal exposure, blood concentrations of 13C-BDCM increased rapidly and returned to baseline by the 24 hour timepoint. Peak concentrations ranged from 39 to 170 ng/mL. The data generated in this study will ultimately be used to develop a physiologically based pharmacokinetic model for BDCM in humans. (This is an abstract of a proposed presentation and does not reflect official US EPA policy.)