Final Report: Inhalation and Dermal Exposure to Disinfection By-Products of Chlorinated Drinking Water

EPA Grant Number: R825953
Title: Inhalation and Dermal Exposure to Disinfection By-Products of Chlorinated Drinking Water
Investigators: Weisel, Clifford P. , Laskin, Jeffrey
Institution: Environmental and Occupational Health Sciences Institute , University of Medicine and Dentistry of New Jersey
EPA Project Officer: Nolt-Helms, Cynthia
Project Period: October 1, 1997 through September 30, 2000
Project Amount: $539,069
RFA: Drinking Water (1997) RFA Text |  Recipients Lists
Research Category: Drinking Water , Water


The overall objective of this research project was to determine the potential inhalation and dermal exposure to haloacetic acids, haloketones, haloacetonitriles, and chloral hydrate from showering and bathing. Drinking water has multiple uses that can result in exposure to disinfection byproducts (DBPs) by ingestion, inhalation, and dermal contact. To properly evaluate the risk associated with DBPs in drinking water, it is important to assess the magnitude of dose associated with each potential exposure route. To date, the only DBP that has been well characterized is chloroform. This research determined the potential exposure and dose to the targeted DBPs through a combination of in vivo and in vitro experiments. The in vitro studies included: (1) measurement of aerosol particle size and number distributions from showers; (2) DBP air concentrations in particle and vapor phases resulting from showers; and (3) dermal fluxes determined using excised skin tissue placed in a Franz cell. The in vivo studies were based on measurements of urinary and breath levels of DBPs, or their metabolites, following exposures to known DBP water concentrations during showering and bathing.

Summary/Accomplishments (Outputs/Outcomes):

Aerosol number distribution was determined during and following showering. An exponential increase in particle numbers was observed while the shower stream was on, followed by an exponential decline once the shower water was turned off. The majority of the particles generated were less than 0.2 micrometers. The bulk of the mass (339 µg/m3) was in particles greater than 2.0 micrometer range, based on the mass distribution calculated by assuming unity density for water and spherical particles. Haloacetic acids (HAAs) and haloketone (HK) concentrations were measured in the shower aerosol derived from water containing 200 µg/L and 25 µg/L, respectively. The aerosols were collected using an opened face filter, which collects all particle size ranges and represents the upper limit of the inhalation exposure from aerosols. The aerosol HAA and HK air concentrations were 6.3 and 0.13 µg/m3, respectively. The estimate of the dose from inhalation exposure of aerosolized DBPs was less than one percent of the ingestion dose. Thus, inhalation is not expected to be an important exposure route to non-volatile water contaminants or the portion of volatile DBPs that stay in the aerosol phase, unless the lung is the target organ. The vapor phase levels of volatile DBPs, haloketones (HKs), chloral hydrate (CH), and haloacetonitriles (HANs) were in the tens to hundreds of µg/m3 range, significantly higher than the aerosol concentrations, and can contribute greater than 10 percent of the ingestion dose during a shower. Risk assessments to the volatile DBPs need to consider the inhalation route.

A series of in vitro skin studies were conducted for HAAs, HKs, HANs, CH, and trihalomethanes (THMs) to determine their percutaneous absorption. HAAs were not found to penetrate the skin significantly at pH 7, presumably because they are completely ionized at neutral pH and the skin is an efficient barrier for ionic species. The other compounds were found to penetrate the skin within minutes of contact, indicating that dermal penetration occurs within the time frame of showering and bathing. The permeability coefficients calculated using steady state methods for THMs, HKs, HANs, CH, and HAAS were about 0.2 cm/hour, about 0.03 cm/hour, about 0.1 cm/hour, about 0.04 cm/hour, and 0.002 cm/hour, respectively. Thus, it is predicted, as previously has been reported for chloroform, that dermal absorption from showering for 10 minutes would be important for THMs and for the HANs, (in excess of 30 percent of the ingestion dose) and to some extent HKs and CH (about 10 percent of the ingestion dose).

The initial in vivo experiments were conducted to evaluate whether the proposed biomarkers were proportional to the exposure and excreted or expired in sufficient quantities following each exposure route to be measurable above background levels. A variety of biomarkers in urine and breath, were examined. For the HAAs, urinary HAAs were measured by gas chromatography/electron capture detection (GC/ECD) after methylation with sulfuric acid/methanol. Only trichloroacetic acid and dichloroacetic acid were found routinely in background or post-exposure urine samples. No consistent increase in the urinary levels of any of the HAAs was observed following either dermal exposure during a 30-minute bath or from a combined dermal and inhalation exposure during a 10 minute shower using water concentrations up to 200 µg/L. The lack of an increased excretion of HAAs could be due to either the lack of dermal absorption or an inhalation dose, or from complete metabolism of the HAAs prior to excretion. The in vitro studies suggested that the HAA dose from showering or bathing would be small. However, ingestion studies also found limited increases in the excretion dichloroacetic acid and trichloroacetic acid, with no increase in monochloroacetic acid or the brominated species. The ingestion studies indicated that metabolism of the monochloroacetic acid and the brominated species is rapid. However, ingested compounds though, go directly to the liver (i.e., first pass) where they efficiently are metabolized, while compounds entering the body through other routes can be removed by the kidneys or expired through the lungs prior to reaching the liver, so more rapid metabolism is expected for ingested compounds than from other exposure routes. Although the in vivo experiments on HAA did not conclusively rule out dermal and ingestion exposure, they are highly supportive of the in vitro studies that suggest these exposure routes are not important for the HAAs.

Urinary excretion and exhaled breath concentrations of the HKs were evaluated as potential biomarkers of dichlorophenol (DCP) and trichlorophenol (TCP). The exhaled breath concentrations were more consistent, had fewer chromatographic interferences, and provided greater time resolution than the urinary measurement, so breath analyses were used to evaluate both dermal and inhalation exposures from bathing and showering. During exposure to water containing 25 µg/L, the air concentration was between 35 and 50 µg/m3 for DCP and TCP. Breath concentrations during the inhalation exposures were less than 10 µg/m3. The air to breath concentration ratio during exposure was higher for the HKs than for chloroform, indicating that the HKs are absorbed across the lungs more efficiently than chloroform. The post-exposure breath concentration for DCP and TCP were less than 1 µg/m3 following both inhalation and dermal exposures, again values less than measured for chloroform for similar exposure levels. The lower breath concentrations for the HKs than for chloroform are consistent with their greater solubility in liquids (blood) than air (lower Henry's Law constant). Their breath concentration decay appears to be more rapid than chloroform, possibly indicating a more rapid metabolism. The breath concentration following inhalation exposure was greater than the concentration following dermal exposure, suggesting that inhalation is a more important exposure route during showering for these compounds, but that both routes contribute to the total dose.

Urinary excretion of HANs and their urinary metabolites, haloacetamides, thiocyanide, and urinary CH and its metabolites, dichloroacetic acid, and trichloroacetic acid, along with exhaled breath concentrations of HANs and CH, were evaluated as biomarkers. No consistent increase in urinary HAN or haloacetamides was observed in the urine samples after exposure. Background levels of urinary thiocyanide were greater than would be produced from the HAN dose from drinking water. Expired breath levels of HANs and CH were elevated following inhalation exposures. Urinary dichloroacetic acid and trichloroacetic acid consistently were elevated above their background variability following inhalation and dermal exposure to CH. The elevated levels of the HANs and CH biomarkers after inhalation, and dermal exposures to these compounds in water, confirmed these routes of exposure as being important in elevating the body burden of these compounds.

Inhalation and dermal exposure were found to contribute significantly to the total exposure for HKs, HANs, and CH, but not for HAAs. The main property that distinguishes the DBPs contributing to inhalation exposure from those that do not is the volatility of the compounds, because aerosols do not contribute to inhalation exposures. Differences in dermal contribution are a function of the skin permeability of the compound at neutral pH. None of the biomarkers measured could be used to assess inhalation or dermal exposures in field studies because their biological residence times are too short and their concentrations are too low to be measured following exposures at environmental levels, except immediately after the exposure.

Journal Articles on this Report : 4 Displayed | Download in RIS Format

Other project views: All 13 publications 5 publications in selected types All 5 journal articles
Type Citation Project Document Sources
Journal Article Xu X, Mariano TM, Laskin JD, Weisel CP. Percutaneous absorption of trihalomethanes, haloacetic acids, and haloketones. Toxicology and Applied Pharmacology 2002;184(1):19-26. R825953 (Final)
  • Abstract from PubMed
  • Full-text: Science Direct PDF
  • Journal Article Xu X, Weisel CP. Inhalation exposure to haloacetic acids and haloketones during showering. Environmental Science & Technology 2003;37(3):569-576. R825953 (Final)
  • Abstract from PubMed
  • Abstract: Environmental Science & Technology
  • Journal Article Xu X, Weisel CP. Human respiratory uptake of chloroform and haloketones during showering. Journal of Exposure Analysis and Environmental Epidemiology 2005;15(1):6-16. R825953 (Final)
  • Abstract from PubMed
  • Abstract: Journal of Exposure Analysis and Environmental Epidemiology
  • Journal Article Xu X, Weisel CP. Dermal uptake of chloroform and haloketones during bathing. Journal of Exposure Analysis and Environmental Epidemiology 2005;15(4):289-296. R825953 (Final)
  • Abstract from PubMed
  • Abstract: Journal of Exposure Analysis and Environmental Epidemiology
  • Supplemental Keywords:

    exposure, dermal exposure, disinfection by-products, DBPs, chlorinated drinking water, risk., RFA, Scientific Discipline, Health, Air, ENVIRONMENTAL MANAGEMENT, Water, air toxics, Environmental Chemistry, Health Risk Assessment, Epidemiology, Chemistry, Risk Assessments, Drinking Water, Risk Assessment, dermal exposure, monitoring, public water systems, microbial risk assessment, human health effects, trihalomethanes, exposure and effects, chemical byproducts, disinfection byproducts (DPBs), dose response, exposure, community water system, residential water usage, chlorine-based disinfection, human exposure, inhalation, treatment, urinary biomarkers, chloramines, metabolism, drinking water contaminants, DBP exposure, drinking water system, exposure assessment, human health risk

    Relevant Websites: Exit

    Progress and Final Reports:

    Original Abstract
  • 1998 Progress Report
  • 1999 Progress Report