Disposition of Bromodichloromethane in Humans Following Oral and Dermal Exposure

Abstract

Exposure to bromodichloromethane (BDCM), one of the most prevalent disinfection byproducts in drinking water, can occur via ingestion of water and by dermal absorption and inhalation during activities such as bathing and showering. The objectives of this research were to assess BDCM pharmacokinetics in human volunteers exposed percutaneously and orally to (13)C-BDCM and to evaluate factors that could affect disposition of BDCM. Among study subjects, CYP2E1 activity varied fourfold; 20% had the glutathione S-transferase theta 1-1 homozygous null genotype; and body fat ranged from 7 to 22%. Subjects were exposed to (13)C-BDCM in water (target concentration of 36 mug/l) via ingestion and by forearm submersion. Blood was collected for up to 24 h and analyzed for (13)C-BDCM by solid-phase microextraction and high-resolution GC-MS. Urine was collected before and after exposure for mutagenicity determinations in Salmonella. After ingestion (mean dose = 146 ng/kg), blood (13)C-BDCM concentrations peaked and declined rapidly, returning to levels near or below the limit of detection (LOD) within 4 h. The T(max) for the oral exposure ranged from 5 to 30 min, and the C(max) ranged from 0.4 to 4.1 ng/l. After the 1 h dermal exposure (estimated mean dose = 155 ng/kg), blood concentrations of (13)C-BDCM ranged from 39 to 170 ng/l and decreased to levels near or below the LOD by 24 h. Peak postdose urine mutagenicity levels that were at least twice that of the predose mean level occurred in 6 of 10 percutaneously exposed subjects and 3 of 8 orally exposed subjects. These results demonstrate a highly significant contribution of dermal absorption to circulating levels of BDCM and confirm the much lower oral contribution, indicating that water uses involving dermal contact can lead to much greater systemic BDCM doses than water ingestion. These data will facilitate development and validation of physiologically based pharmacokinetic models for BDCM in humans.

DNA methylation levels and long-term trihalomethane exposure in drinking water: an epigenome-wide association study

“…Given the different molecular weights and polarity of the DBPs, potential exposure routes include not only ingestion but also inhalation and/or dermal absorption during showering and water related activities (cleaning, swimming, flushing the toilet, etc.). [37][38][39][40][41] These routes, plus the subject water handling and consumption behaviors, may produce differential internal doses and partially explain why subjects apparently exposed to similar THM levels had a wide range of changes in DNA methylation levels in our sample. Exposure misclassification due to unaccounted nonresidential exposure (e.g., workplace) is expected to be low, only affecting the ingested THM fraction.…”

Overview of Disinfection By-products and Associated Health Effects

“…Given that THMs (as well as other DBPs) are volatile and skin permeable, the exposure pathways are numerous, and include ingestion of water, inhalation and skin absorption while showering, bathing, swimming in treated pools, and hand dish-washing [36]. Pharmacokinetics differs among exposure routes [37]. Experimental studies in volunteers have shown a larger internal dose and longer duration in the bloodstream from activities involving inhalation and dermal absorption compared to ingestion [36,37].…”

“…Pharmacokinetics differs among exposure routes [37]. Experimental studies in volunteers have shown a larger internal dose and longer duration in the bloodstream from activities involving inhalation and dermal absorption compared to ingestion [36,37]. As such, a proper exposure assessment should include ingestion and noningestion activities involving water contact in order to ascertain the relevant exposure window (Table 1).…”

Drinking Water Disinfection By-products, Genetic Polymorphisms, and Birth Outcomes in a European Mother–Child Cohort Study

“…5 Only two studies have examined whether genetic variation may affect risk of birth outcomes associated with exposure to trihalomethanes. 6,7 Exposure assessment has been a major limitation of most studies that have used predominantly ecologic estimates of trihalomethane exposures in water supply zones.…”