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- Ingestion, Inhalation, and Dermal Exposuresto Chloroform and Trichloroethene from Tap Water Clifford P. Weisel' and Wan-Kuen J d `Environmental and Occupational Health Sciences Institute, UMDNJ-Robert Wood Johnson Medical School, Piscataway. NJ 08854 USA; aepartment of Environmental Engineering, Kyungpook National University, Sankeok-dong, Bukgu, Taegu, South Korea Individuals are exposed to volatile compoundspresent in tap mter by ingestion, inhalation, and dermal absorption. Traditional risk assessments for water often only consider ingestion exposure to toxic chemicals, even thougb showering has been shown to increase the body burden of ccrtain chemicals due to inhalation exposure and dermal absorption. We collected and analyzed time-series samples of qird alvaolar breath to evaluate cbanges in concentrations of volatile organic compounds being expired, which reflects the rate of change in the bloodstream due to expiration, metabolism, and absorption into tissues. Analysis ofchloroform and trichloethene in expired breath, compounds regulated in water, was also used to determineuptake from tap water by each route (inhalation, ingestion, or absorption). Each route of exposure contributed to the total exposure of these compounds from daily water use. Further, the ingestion dose was complerdy metabolizedbefore entering the bloodsueun, whereas the dose from the other routes was dispersed throughout the body. Thus,di&renes in potential biologicdy e&ctivc doses depend on route, target organ, and wfKthcr the conurninant or metabolite is the biologically active agent. Kq worth chloroform, dermal eqosmes, drinking water, ingestion exposures, inhattion QKPOSLUCS, trichloroethene, volatile organic compounds. Environ He&h Pmpect 104:48-51 (19%f. Traditional approaches for evaluating exposure to and adverse health effects from cont- aminants in tap water have assumed that ingestion is the major route of exposure. Thus, when water contamination has occurred, federal guidance documents advised the avoidance of ingestion to protect public health, but did not necessarily warn against other water uses that result in inhalation and dermal exposures, which also increase the body burden of volatile water contaminants (1).Furthermore, the ingestion of 2 1 of water has been used to estimate the health risk associated with waterborne chemical contaminants and the establishment of drinking water standards (2) without quantifylng the doses received from other routes. This practice can lead to an underestimation of the potential health risk. Exposure assessment models, pharmacokinetic models, and experimental data measuring breath concentrations of chloroform associated with inhalation exposure and the dermal absorption associated with showering with chlorinated water suggest that inhalation and dermal absorption contribute a measurable dose to the body (3-7). These studies predicted that the dose of volatile compounds associated with showering is similar to the dose resulting from ingesting 2 1 of water, the exposure upon which regulations are based. Thus, it has been proposed that inhalation and dermal absorption need to be considered in the analysis of total human exposure analysis to volatile contaminants in tap water (3. Metabolism of environmental contaminants occurs in multiple organs, and the site of metabolism is an important deter- minant of a compound's toxicity. The route of exposure can alter the overall rate and site of metabolism and affect a compound's site-specifictoxicity. The concentration of a volatile compound in exhaled breath is related to its concentration in the bloodstream and can be used to determine changes in body bur- den with time (8-19.Exhaled breath con- centrations have also been used to infer the relative internal dose received, the exposure route, and to examine differences in overall metabolic rates (11-13). Physiologically based pharmacokinetic (PBPK) models are used to model the distribution of environmental contaminants and their metabolites in the body (14,15). An application of a PBPK model by Blancato and Chiu (15) examined the biologically effective dose resulting from exposure to contaminants in water and prediaed that for the same amount of interndized chloroform, ingestion exposure results in a higher dose of chloroform to the liver, but inhalation and dermal absorption exposures result in more chloroform being circulated throughout the body and to other organs, such as the bladder. Epidemiological studies examining the health effects of chlorinated water have found that populations exposed to chlori- nation by-products have elevated bladder cancer rates (1617)and have suggested an association between exposure to chlorination by-products in water and adverse reproductive outcomes (1819. The present research was conducted to determine the dose of water contaminants resulting from the three common routes associated with water use: ingestion (drinking), inhalation (during showering), and dermal contact (showering, bathing). The results were based on measurements of human breath concentrations of chloroform and trichloroethene following ingestion, inhalation, and dermal exposures to residential tap water. Chloroform is contained in municipal water supplies that are disinfected by chlorination, the most common disinfection process in the United States (20).Trichloroethene is a common contaminant in groundwater, particularly near National Priority List or Superfund sites (21).To obtain the incremental dose, each experiment was limited to examining a single exposure route. Methods Exposure to a single route at a time was accomplished by imposing a control on the routes of exposure not being studied while performing normal activities (drinking, showering, and bathing) (4). During an inhalation exposure, the subject wore waterproof clothing while showering to minimize dermal contact. For dermal exposure, the subject breathed purified air whde showering or bathing. The compounds were then measured in a rime series of exhaled breath samples to monitor their expiration rate. We performed 25 experiments using i 1 subjects (6 males and 5 females between the ages of 20 and 50 years old). Eight 10-min dermal-only "showers" and four 60-min dermal-only baths were taken to evaluate the effect of the dermal exposure route on the elimination rates of volatile organic compounds (VOCs). Nine 10-min inhala- Address correspondence to C.P. Weisel, Environmental and Occupational Health Sciences Institute, UMDNJ-Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854 USA. This work was supported by the Risk Science Institute-ILSI, NIEHS Superfund Basic Research Program (project Es-05955), and an NIEHS center grant (EsO5022-06). Received 18 July 1995; accepted 1 1 October. 48 Volume 104, Number I , January 19% Environmental Health Perspectives ! Articles Multiroute exposure to VOCs in drinking water tion-only showers were taken to evaluate The chloroform and trichloroethene the effect of the inhalation exposure route concentrations in the exhaled breath were on elimination rates of VOCs. Four experi- elevated in each subject after both inhala- 9 ments were performed for ingestion of 0.5 1 tion and dermal exposures during shower- water. Informed consent was obtained ing, demonstrating that chemicals in the from each subject. water entered the body by both routes Water samples were collected into clean (Figures 1 and 2). Breath concentrations glass vials with teflon-lined enclosures. were also elevated after dermal exposure via During collection, care was taken to ensure bathing (Fig. IC). In contrast to ingestion, that no bubbles formed in the water. The after inhalation and dermal exposure, the ! water was analyzed for chloroform and exhaled breath had elevated levels for trichloroethene by purge and trap followed extended time periods, implying that the by GC/MS or GC/electron capture detec- compounds were distributed throughout tion (ECD). The air was sampled during the enure inhalation exposure by drawing an air sample through a 0.25-inch ID stainless-steel the bloodstream before being metabolized. These observations support the predictions of a PBPK model for chloroform exposures 0 50 1w 150 Mo 250 300 350 Time (min) trap packed with a multilayered, adsorbent from tap water (IS). trap containing Carboxen 563 (Supelco Co., One previous study measured elevated Belleforte, Pennsylvania), Tenax TA (Mtech levels of chloroform in blood and breath C o p , Deerfield, Illinois), and Carbosieve following a bolus ingestion of 5 x 105 pg SI11 (Supelco).Breath sampleswere collected (0.5 g) of chloroform (22). Our present using a sampler designed to collect primariiy study used a total ingestion of only 10 pg alveolar air (11). The subject breathed of chloroform (0.5 1 water containing 20 through a new mouthpiece into a one-way &I) and 10 or 20 pg of trichloroethene valve that directed the inspired air from a (0.5 I water containing 20 or 40 pg/l), charcoal purifier into the subject and the common environmental levels. The 0.5-g expired air into a temporary storage tube ingestion exposure probably exceeded the (0.64 an x 8 m) fiom which the breath was metabolic capacity of the liver. Thus, a continually withdrawn onto an adsorbent portion of the chloroform was not metabo- trap using a personal samplingpump set at a lized during the first pass through the liver flow rate of 1 Ymin. A series of breath sam- and entered the circulatory system, whereas ples were collected after exposure at times ranging from between 1 min and several hours to determine the relative body burden the ingestion of environmentally relevant concentrations are unlikely to have saturated metabolic enzymes. These data imply lime (min) \ of chloroform or trichloroethene resulting that for common environmental levels, if from each exposure. The air and breath sam- the target organ of a waterborne contami- ples were analyzed by thermal desorption nant is the liver or i f a long-lived metabo- coupled with GC/MS or GC/ECD. During lite is the toxic agent, then an ingestion the inhalation and dermal exposures, the exposure delivers the largest biologically *shower and bath water was maintained at a effective dose via the three routes studied. temperature of 40 2"C, a typical water However, if a different organ is the target, temperature for bathing. and either the parent compound or a short Results and Discussion lived metabolite is the biologically active agent, then inhalation and dermal expo- Only the breath samples collected seconds sures would deliver a larger biologically to minutes after ingesting residential well effective dose than ingestion. For example, water containing trichloroethene had ele- for chloroform, the reactive metabolite vated concentrations of trichloroethene. phosgene is suspected to be the biological Following ingestion of chlorinated munici- active agent (23);thus, inhalation and derpal water, none of the breath samples had mal absorption exposures to chlorinated Time (min) measurable levels of chloroform. The initial water will result in a larger chloroform dose elevation of breath concentrations for trichloroethene is most likely due to off- and may present a greater risk than ingestion to organs other than the liver, such as Figure 1. Exhaled chloroform breath time profiles after (A) inhalation exposure during a shower, (B) gassing of VOCs from the residual water present within the oral cavity, rather than reflecting blood-air exchange in the alveolar sacs because no continued elevation was detected. One explanation for this observa- the bladder where elevated cancer rates have been suggested (16,17),and for adverse reproductive outcomes (I&,?@. The amount of chloroform expired per microgram of the compound in 1 1 of water dermal exposure during a shower, and (C) dermal exposure during a bath. Each symbol represents a different experiment run. The normalized concentration was calculated by dividing the breath concentration by the water concentration. The shower water concentrations ranged from 10 to 50 pg/l tion is that the internal dose received from was calculated from the expired breath pro- for the inhalation exposure experiments and from ingestion is completely metabolized during a first pass through the liver, thus there was no measurable elevation in VOC concentration in the exhaled breath, which would reflect elevated blood concentrations. files, assuming a respiration rate of 0.01 m3/min. These values ranged from 0.02 to 0.05 pg for the inhalation-only exposure (Fig. lA), from 0.02 to 0.13 pg for the dermal-only shower exposure (Fig. 1B) and t 1 0 to 41 pg/l for the dermal exposure experiments; the bath water concentration ranged between 11 and 15 pg/I for the dermal exposure experiments. Four different subjects were used in each shower study; two different subjects participated twice in the bathing study. Environmental Health Perspectives Volume 104,Number I , January 1996 49 Articles Weisel and Jo -. .1.0 2 -m 0.8 Q .-J 8 0.6 Ic 0.4 0e E.- 1.0 3. Jo WK, Weisel CP, Lioy PJ. Roura of chloroform exposure and body burden from showering with chlorinated tap water. Risk Anal 10575-580 (1990). 4. Jo WK, Weixl CP, Lioy PJ. Chloroform exposure and the health risk and body burden from showering with chlorinated tap water. Risk A d 10~581-585(1990). 5. Andelman J. Inhalation exposure in the home to volatile organic contaminants of drinking water. Sci Total Environ 47:443460 (1985). 6. McKone TE. Human exposure to volatile organic compounds in household tap water: the indoor inhalation pathway. Environ Sci Techno1 21:1194-1201 (1987). ao 0.0 7. Maxwell NI, Burmaster DE, Ozonoff D. b e (min) Time (min) Trihalomethanes and maximum contaminant levels: the significanceof inhalation and d e d fiaure 2 Exhaled trichloroethene breath time profiles after {A) inhalation exposure during a shower and (B) dermal exposure during a shower. Each symbol represents a different experimental run. The water concentration ranged from 28 to 41 pg/l for the inhalation exposure experiments and 16 to 150 pg/l for the dermal exposure experiments. Five different subjects participated. exposures to chloroform in household water. Regul Toxic01 Pharmacol 14:297-3 12 (I991). 8. Brugnone F, Perbellin L, Faccini GB, Pasini F, Danzi B, Maranelli G, Romeo L, Gowi M, Zcdde A. Benzene in the blood and breath of from 0.33 to 0.56 pg after the dermal bathing study (Fig. 1C). The larger 30-300 pg and for chloroform of 10- 100 pg. Thus, for typical activities of drinking normal and occupationally exposed workers. Am J Ind Med 16:385-399 (1989). 9. Weisel CP, Jo WK, Lioy PJ. Utilization of amount expired after bathing is due to the and showering, each exposure route con- breath analysis for exposure and dosc estimates longer exposure time (60 min versus 10 tributes similar internal doses, and the total of chloroform. J Expos Anal Environ min for the shower) and a larger portion of the body surface being in constant contact in the water. The amount of trichloroethene expired per microgram of the com- internal dose from a 10-min shower or a 30-min bath is greater than that from ingesting 2 1 of water. In conclusion, approximately equiva- Epidemiol 1:55-69 (1992). 10. Petreas MX, Rappaport SM, Materna BL, Rempel DM. Mixeddaled air measurements to assess exposure to temchioroethylcne in dry cleaners. J Expos Anal Environ Epidemiol *pound in 1 1 of water d e r the inhalation exposure (Fig. 2A) was 0.074 0.080 pg lent amounts of volatile contaminants from water can enter the body by three different (SUPPI)1:25-39 (1992). 11. Raymer J H , Pellizzari ED, Thomas KW, and after dermal exposure (Fig. 2B) was exposure routes, inhalation, dermal absorp- Cooper SD. Elimination of volatile organic \ 0.030 i 0.01 1 pg. However, the amount of tion, and ingestion, for typical daily activitrichloroethene expired after one of the ties of drinking and bathing. However, the compounds in breath after exposure to m p tionat and environmental microenvironments. J Expos Anal Environ Epidemiol 1:439451 inhalation exposure experiments is an order exposure route affects the rates of metabo- (199 1). of magnitude higher than the other values. lism and therefore the compound's poten- 12. Gordon SM, Kenny DV, Kelly TJ.Continuous If that value is removed, the mean trichloroethene expired after inhalation exposure was 0.035 i 0.018 pg, which was equivalent to the dermal value. The expiration data directly demonstrate that dermal tial toxicity. The ingested VOCs were metabolized during the first pass through the liver, thus the parent compound was not measurable in the exhaled breath and would not be present in the bloodstream. real-time breath analysis for the measurement of half-lives of expired volatile organic compounds. J Expos Anal Environ Epidemiol 1:41-54 (1992). 13. Wallace L, Pellizzari ED, Gordon S. A linear model relating breath concentrations to envi- exposure contributes as much to the body However, chloroform and trichloroethene ronmental exposures: Application to a chamber burden of chloroform or trichloroethene as concentrations were measurable in the study of four volunteers exposed to volatile inhalation exposure while showering with water containing these contaminants. Extended bathing yields an even greater dermal dose. breath after inhalation and dermal expo- sure, indicating dispersion throughout the body. These results confirm the necessity of knowing the biologically active agent organic chemicals. J Expos Anal Environ Epidemiol375-102 (1993). 14. McKone TE. Linking a PBPK model for chloroform with measured breath concentrationsin showers: Implications for dermal exposure The internal dose derived from inhala- (either the parent compound or a metabo- models. J Expos Anal Environ Epidemiol tion can be calculated from the air concentration, breathing rate, duration of the shower, and adsorption efficiency across the lung barrier (9).The calculated internal dose from inhalation exposure ranged lite of VOCs found in water) and the site of activity of a contaminant to accurately quantify the dose received from all significant exposure routes before forming public health policies related to contaminated 3:339-365 (1993). 15. Blancato JN, Chiu N. Predictive modeling for uptake and tissue distribution from human exposura. In: Safety of water disinf&on: balancing chemical and microbial risks (GF Craum, ed). Washington, DC:ILSI Press, between 60 and 250 pg for trichloroethene water supplies. 1993;303-316. and between 30 and 80 pg for chloroform. The amount of chloroform and trichloroethene expired after inhalation and dermal shower exposures were similar, suggesting nearly equivalent internal doses for these two exposure routes during showering. An ingestion of 2 1 of water containing the concentrations observed in this study and, assuming a 100% transfer across the gastrointestinal tract, yields maximum internal dose estimates for trichloroethene of REFERENCES 1. Vanderslice RR. Benefits of deriving drinking water standards based on comprehensiveassments of exposure. In: Water contamination and health (Wong R, ed). New York:Marcel Dekker, 1994;125-134. 2. U.S. EPA. Workshop on assessment and management of drinking water contamination. EPA/600/M-86/026. Washington, DC:Environmental Protection Agency, 1987. 16. Cantor KP, Hoover R, Hartge P, Mason TJ, Silverman DT, Altman R, Austin DF, Child MA,Key CR, Marrett LD, et al. Bladder cancer, drinking water source, and tap water con- sumption: a case-conuol study. J Nad Cancer 1-t 79~1269-1279(1987). 17. McGeehin MA, Reif JS, Becher JC, Mangione EJ. Case-control srudy of bladder cancer and water disinfection methods in Colorado. Am J Epidemiol 138:492-501 (1993). 18. Kramer MD, Lynch CF, Isacson P, Hanson JW.The association of waterborne chloroform 50 Volume 104, Number 1, January 1996 Environmental Health Perspectives Articles Multiroute exposure to VOCs in drinking water with intrauterine growth retardation. Epidemiology3:407-413 (1992). 19. Bove F, Fulcomer MC, Savrin JE. Public drinking water contamination and birth out- comes Am J Epidemiol 141:850-862 (1995). 20. Krasner SW, McGuire MI, Jacangelo JG, Patania NL, Reagan KM, Aieta EM. The occurrence of disinfection by-products in US drinking water. J Am Water Works Assoc 81:4 1-53 (1989). 21. ATSDR Toxicological profile for trichloroeth- ylene. TP-92/19.Atlanta, GA: Agency for Toxic Substances and Disease Registry, 1993. 22. Fry BJ, Taylor T, Hathway DE. Pulmonary elimination of chloroform and its metabolite in man. Arch Int Pharmacodyn 196:98-111 (1972). 23. Davidson IW, Summer DD, Parker IC. Chloroform: a critical review of its metabolism, teratogenic,mutogenic and carcinogenic potentid. DrugChemToxicol. 5:1-87 (1982). 47 st Annual Water Pollution Control Manhattan College Riverdale, N Y June3-7, 7996 Manhattan College's forty-first annual Institute in Water Pollution Control will take place on June 3-7, 1996 in the Manhattan College Leo Engineering Building, Riverdale, New York. Two courses, which run concurrently, will be offered: Modern Eutrophication Modeling, and Treatment of Municipal, Hazardous and Toxic Wastewaters. These weeklong courses have much to offer young engineers and seasoned professionals who have not been able to stay abreast of the rapidly changing field. Set in a classroom atmos- phere, the courses allow for dialog between lecturer and participants. The fee per course is $1,150 and includes a set of notes for each attendee. For a brochure of additional information, contact: Ms. Lucia Chiocchio, Program Coordinator Manhattan College Environmental Engineering Department Riverdale, NY 10471 Phone (718) 920-0277 FAX (718) 543-7914 Environmental Health Perspectives Volume 104, Number I , January 1996 51