Abstract
OBJECTIVES AND METHODS—Chlorination has been the major disinfectant process for domestic drinking water for many years. Concern about the potential health effects of the byproducts of chlorination has prompted the investigation of the possible association between exposure to these byproducts and incidence of human cancer, and more recently, with adverse reproductive outcomes. This paper evaluates both the toxicological and epidemiological data involving chlorination disinfection byproducts (DBPs) and adverse reproductive outcomes, and makes recommendations for future research. RESULTS AND CONCLUSIONS—Relatively few toxicological and epidemiological studies have been carried out examining the effects of DBPs on reproductive health outcomes. The main outcomes of interest so far have been low birth weight, preterm delivery, spontaneous abortions, stillbirth, and birth defects— in particular central nervous system, major cardiac defects, oral cleft, and respiratory, and neural tube defects. Various toxicological and epidemiological studies point towards an association between trihalomethanes (THMs), one of the main DBPs and marker for total DBP load, and (low) birth weight, although the evidence is not conclusive. Administered doses in toxicological studies have been high and even though epidemiological studies have mostly shown excess risks, these were often not significant and the assessment of exposure was often limited. Some studies have shown associations for DBPs and other outcomes such as spontaneous abortions, stillbirth and birth defects, and although the evidence for these associations is weaker it is gaining weight. There is no evidence for an association between THMs and preterm delivery. The main limitation of most studies so far has been the relatively crude methodology, in particular for assessment of exposure. RECOMMENDATIONS—Large, well designed epidemiological studies focusing on well defined end points taking into account relevant confounders and with particular emphasis on exposure characterisation are ideally needed to confirm or refute these preliminary findings. In practice, these studies may be impracticable, partly due to the cost involved, but this is an issue that can be put right—for example, by use of subsets of the population in the design of exposure models. The studies should also reflect differences of culture and water treatment in different parts of the world. To identify the specific components that may be of aetiological concern and hence to fit the most appropriate exposure model with which to investigate human exposure to chlorinated DBPs, further detailed toxicological assessments of the mixture of byproducts commonly found in drinking water are also needed. Keywords: disinfection byproducts; chlorination; reproductive health
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- Arbuckle T. E., Sherman G. J., Corey P. N., Walters D., Lo B. Water nitrates and CNS birth defects: a population-based case-control study. Arch Environ Health. 1988 Mar-Apr;43(2):162–167. doi: 10.1080/00039896.1988.9935846. [DOI] [PubMed] [Google Scholar]
- Aschengrau A., Zierler S., Cohen A. Quality of community drinking water and the occurrence of late adverse pregnancy outcomes. Arch Environ Health. 1993 Mar-Apr;48(2):105–113. doi: 10.1080/00039896.1993.9938403. [DOI] [PubMed] [Google Scholar]
- Beech J. A., Diaz R., Ordaz C., Palomeque B. Nitrates, chlorates and trihalomethanes in swimming pool water. Am J Public Health. 1980 Jan;70(1):79–82. doi: 10.2105/ajph.70.1.79. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bove F. J., Fulcomer M. C., Klotz J. B., Esmart J., Dufficy E. M., Savrin J. E. Public drinking water contamination and birth outcomes. Am J Epidemiol. 1995 May 1;141(9):850–862. doi: 10.1093/oxfordjournals.aje.a117521. [DOI] [PubMed] [Google Scholar]
- Burmaster D. E. Lognormal distributions for total water intake and tap water intake by pregnant and lactating women in the United States. Risk Anal. 1998 Apr;18(2):215–219. doi: 10.1111/j.1539-6924.1998.tb00933.x. [DOI] [PubMed] [Google Scholar]
- Cantor K. P. Water chlorination, mutagenicity, and cancer epidemiology. Am J Public Health. 1994 Aug;84(8):1211–1213. doi: 10.2105/ajph.84.8.1211. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chen A. T., Reidy J. A., Sever L. E. Re: "Public drinking water contamination and birth outcomes". Am J Epidemiol. 1996 Jun 1;143(11):1179–1180. doi: 10.1093/oxfordjournals.aje.a008704. [DOI] [PubMed] [Google Scholar]
- Dawson B. V., Johnson P. D., Goldberg S. J., Ulreich J. B. Cardiac teratogenesis of halogenated hydrocarbon-contaminated drinking water. J Am Coll Cardiol. 1993 May;21(6):1466–1472. doi: 10.1016/0735-1097(93)90325-u. [DOI] [PubMed] [Google Scholar]
- Deane M., Swan S. H., Harris J. A., Epstein D. M., Neutra R. R. Adverse pregnancy outcomes in relation to water contamination, Santa Clara County, California, 1980-1981. Am J Epidemiol. 1989 May;129(5):894–904. doi: 10.1093/oxfordjournals.aje.a115223. [DOI] [PubMed] [Google Scholar]
- Dodds L., King W., Woolcott C., Pole J. Trihalomethanes in public water supplies and adverse birth outcomes. Epidemiology. 1999 May;10(3):233–237. [PubMed] [Google Scholar]
- Elwood J. M., Coldman A. J. Water composition in the etiology of anencephalus. Am J Epidemiol. 1981 Jun;113(6):681–690. doi: 10.1093/oxfordjournals.aje.a113148. [DOI] [PubMed] [Google Scholar]
- Ershow A. G., Brown L. M., Cantor K. P. Intake of tapwater and total water by pregnant and lactating women. Am J Public Health. 1991 Mar;81(3):328–334. doi: 10.2105/ajph.81.3.328. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Exon J. H., Henningsen G. M., Osborne C. A., Koller L. D. Toxicologic, pathologic, and immunotoxic effects of 2,4-dichlorophenol in rats. J Toxicol Environ Health. 1984;14(5-6):723–730. doi: 10.1080/15287398409530621. [DOI] [PubMed] [Google Scholar]
- Fenster L., Windham G. C., Swan S. H., Epstein D. M., Neutra R. R. Tap or bottled water consumption and spontaneous abortion in a case-control study of reporting consistency. Epidemiology. 1992 Mar;3(2):120–124. doi: 10.1097/00001648-199203000-00009. [DOI] [PubMed] [Google Scholar]
- Gallagher M. D., Nuckols J. R., Stallones L., Savitz D. A. Exposure to trihalomethanes and adverse pregnancy outcomes. Epidemiology. 1998 Sep;9(5):484–489. [PubMed] [Google Scholar]
- Gordon S. M., Wallace L. A., Callahan P. J., Kenny D. V., Brinkman M. C. Effect of water temperature on dermal exposure to chloroform. Environ Health Perspect. 1998 Jun;106(6):337–345. doi: 10.1289/ehp.98106337. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hemminki K., Mutanen P., Saloniemi I., Luoma K. Congenital malformations and maternal occupation in Finland: multivariate analysis. J Epidemiol Community Health. 1981 Mar;35(1):5–10. doi: 10.1136/jech.35.1.5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hunter E. S., 3rd, Rogers E. H., Schmid J. E., Richard A. Comparative effects of haloacetic acids in whole embryo culture. Teratology. 1996 Aug;54(2):57–64. doi: 10.1002/(SICI)1096-9926(199606)54:2<57::AID-TERA1>3.0.CO;2-1. [DOI] [PubMed] [Google Scholar]
- Jo W. K., Weisel C. P., Lioy P. J. Routes of chloroform exposure and body burden from showering with chlorinated tap water. Risk Anal. 1990 Dec;10(4):575–580. doi: 10.1111/j.1539-6924.1990.tb00541.x. [DOI] [PubMed] [Google Scholar]
- Kallman M. J., Kaempf G. L., Balster R. L. Behavioral toxicity of chloral in mice: an approach to evaluation. Neurobehav Toxicol Teratol. 1984 Mar-Apr;6(2):137–146. [PubMed] [Google Scholar]
- Kanitz S., Franco Y., Patrone V., Caltabellotta M., Raffo E., Riggi C., Timitilli D., Ravera G. Association between drinking water disinfection and somatic parameters at birth. Environ Health Perspect. 1996 May;104(5):516–520. doi: 10.1289/ehp.96104516. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Klinefelter G. R., Suarez J. D., Roberts N. L., DeAngelo A. B. Preliminary screening for the potential of drinking water disinfection byproducts to alter male reproduction. Reprod Toxicol. 1995 Nov-Dec;9(6):571–578. doi: 10.1016/0890-6238(95)02007-1. [DOI] [PubMed] [Google Scholar]
- Klotz J. B., Pyrch L. A. Neural tube defects and drinking water disinfection by-products. Epidemiology. 1999 Jul;10(4):383–390. doi: 10.1097/00001648-199907000-00005. [DOI] [PubMed] [Google Scholar]
- Kramer M. D., Lynch C. F., Isacson P., Hanson J. W. The association of waterborne chloroform with intrauterine growth retardation. Epidemiology. 1992 Sep;3(5):407–413. doi: 10.1097/00001648-199209000-00005. [DOI] [PubMed] [Google Scholar]
- Leger A. S., Elwood P. C., Morton M. S. Neural tube malformations and trace elements in water. J Epidemiol Community Health. 1980 Sep;34(3):186–187. doi: 10.1136/jech.34.3.186. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Linder R. E., Klinefelter G. R., Strader L. F., Narotsky M. G., Suarez J. D., Roberts N. L., Perreault S. D. Dibromoacetic acid affects reproductive competence and sperm quality in the male rat. Fundam Appl Toxicol. 1995 Nov;28(1):9–17. doi: 10.1006/faat.1995.1140. [DOI] [PubMed] [Google Scholar]
- Linder R. E., Klinefelter G. R., Strader L. F., Suarez J. D., Dyer C. J. Acute spermatogenic effects of bromoacetic acids. Fundam Appl Toxicol. 1994 Apr;22(3):422–430. doi: 10.1006/faat.1994.1048. [DOI] [PubMed] [Google Scholar]
- Linder R. E., Klinefelter G. R., Strader L. F., Suarez J. D., Roberts N. L., Dyer C. J. Spermatotoxicity of dibromoacetic acid in rats after 14 daily exposures. Reprod Toxicol. 1994 May-Jun;8(3):251–259. doi: 10.1016/0890-6238(94)90009-4. [DOI] [PubMed] [Google Scholar]
- Linder R. E., Klinefelter G. R., Strader L. F., Suarez J. D., Roberts N. L. Spermatotoxicity of dichloroacetic acid. Reprod Toxicol. 1997 Sep-Oct;11(5):681–688. doi: 10.1016/s0890-6238(97)00031-2. [DOI] [PubMed] [Google Scholar]
- Linder R. E., Klinefelter G. R., Strader L. F., Veeramachaneni D. N., Roberts N. L., Suarez J. D. Histopathologic changes in the testes of rats exposed to dibromoacetic acid. Reprod Toxicol. 1997 Jan-Feb;11(1):47–56. doi: 10.1016/s0890-6238(96)00196-7. [DOI] [PubMed] [Google Scholar]
- Lindstrom A. B., Pleil J. D., Berkoff D. C. Alveolar breath sampling and analysis to assess trihalomethane exposures during competitive swimming training. Environ Health Perspect. 1997 Jun;105(6):636–642. doi: 10.1289/ehp.97105636. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lockitch G. Perspectives on lead toxicity. Clin Biochem. 1993 Oct;26(5):371–381. doi: 10.1016/0009-9120(93)90113-k. [DOI] [PubMed] [Google Scholar]
- Lévesque B., Ayotte P., LeBlanc A., Dewailly E., Prud'Homme D., Lavoie R., Allaire S., Levallois P. Evaluation of dermal and respiratory chloroform exposure in humans. Environ Health Perspect. 1994 Dec;102(12):1082–1087. doi: 10.1289/ehp.102-1567469. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Magnus P., Jaakkola J. J., Skrondal A., Alexander J., Becher G., Krogh T., Dybing E. Water chlorination and birth defects. Epidemiology. 1999 Sep;10(5):513–517. [PubMed] [Google Scholar]
- Maxwell N. I., Burmaster D. E., Ozonoff D. Trihalomethanes and maximum contaminant levels: the significance of inhalation and dermal exposures to chloroform in household water. Regul Toxicol Pharmacol. 1991 Dec;14(3):297–312. doi: 10.1016/0273-2300(91)90032-q. [DOI] [PubMed] [Google Scholar]
- McKone T. E. Linking a PBPK model for chloroform with measured breath concentrations in showers: implications for dermal exposure models. J Expo Anal Environ Epidemiol. 1993 Jul-Sep;3(3):339–365. [PubMed] [Google Scholar]
- Morris R. D., Audet A. M., Angelillo I. F., Chalmers T. C., Mosteller F. Chlorination, chlorination by-products, and cancer: a meta-analysis. Am J Public Health. 1992 Jul;82(7):955–963. doi: 10.2105/ajph.82.7.955. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Munger R., Isacson P., Hu S., Burns T., Hanson J., Lynch C. F., Cherryholmes K., Van Dorpe P., Hausler W. J., Jr Intrauterine growth retardation in Iowa communities with herbicide-contaminated drinking water supplies. Environ Health Perspect. 1997 Mar;105(3):308–314. doi: 10.1289/ehp.97105308. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Murray F. J., Schwetz B. A., McBride J. G., Staples R. E. Toxicity of inhaled chloroform in pregnant mice and their offspring. Toxicol Appl Pharmacol. 1979 Sep 30;50(3):515–522. doi: 10.1016/0041-008x(79)90406-x. [DOI] [PubMed] [Google Scholar]
- Narotsky M. G., Pegram R. A., Kavlock R. J. Effect of dosing vehicle on the developmental toxicity of bromodichloromethane and carbon tetrachloride in rats. Fundam Appl Toxicol. 1997 Nov;40(1):30–36. doi: 10.1006/faat.1997.2376. [DOI] [PubMed] [Google Scholar]
- Nurminen T. Maternal pesticide exposure and pregnancy outcome. J Occup Environ Med. 1995 Aug;37(8):935–940. doi: 10.1097/00043764-199508000-00008. [DOI] [PubMed] [Google Scholar]
- Ruddick J. A., Villeneuve D. C., Chu I., Valli V. E. A teratological assessment of four trihalomethanes in the rat. J Environ Sci Health B. 1983;18(3):333–349. doi: 10.1080/03601238309372373. [DOI] [PubMed] [Google Scholar]
- Savitz D. A., Andrews K. W., Pastore L. M. Drinking water and pregnancy outcome in central North Carolina: source, amount, and trihalomethane levels. Environ Health Perspect. 1995 Jun;103(6):592–596. doi: 10.1289/ehp.95103592. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Savitz D. A., Sonnenfeld N. L., Olshan A. F. Review of epidemiologic studies of paternal occupational exposure and spontaneous abortion. Am J Ind Med. 1994 Mar;25(3):361–383. doi: 10.1002/ajim.4700250306. [DOI] [PubMed] [Google Scholar]
- Schwetz B. A., Leong B. K., Gehring P. J. Embryo- and fetotoxicity of inhaled chloroform in rats. Toxicol Appl Pharmacol. 1974 Jun;28(3):442–451. doi: 10.1016/0041-008x(74)90229-4. [DOI] [PubMed] [Google Scholar]
- Shalat S. L., Walker D. B., Finnell R. H. Role of arsenic as a reproductive toxin with particular attention to neural tube defects. J Toxicol Environ Health. 1996 Jun 28;48(3):253–272. doi: 10.1080/009841096161320. [DOI] [PubMed] [Google Scholar]
- Shimokura G. H., Savitz D. A., Symanski E. Assessment of water use for estimating exposure to tap water contaminants. Environ Health Perspect. 1998 Feb;106(2):55–59. doi: 10.1289/ehp.9810655. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smith M. K., George E. L., Zenick H., Manson J. M., Stober J. A. Developmental toxicity of halogenated acetonitriles: drinking water by-products of chlorine disinfection. Toxicology. 1987 Oct 12;46(1):83–93. doi: 10.1016/0300-483x(87)90140-5. [DOI] [PubMed] [Google Scholar]
- Smith M. K., Randall J. L., Read E. J., Stober J. A. Developmental toxicity of dichloroacetate in the rat. Teratology. 1992 Sep;46(3):217–223. doi: 10.1002/tera.1420460305. [DOI] [PubMed] [Google Scholar]
- Smith M. K., Randall J. L., Read E. J., Stober J. A. Teratogenic activity of trichloroacetic acid in the rat. Teratology. 1989 Nov;40(5):445–451. doi: 10.1002/tera.1420400506. [DOI] [PubMed] [Google Scholar]
- Smith M. K., Randall J. L., Stober J. A., Read E. J. Developmental toxicity of dichloroacetonitrile: a by-product of drinking water disinfection. Fundam Appl Toxicol. 1989 May;12(4):765–772. doi: 10.1016/0272-0590(89)90008-0. [DOI] [PubMed] [Google Scholar]
- Smith M. K., Randall J. L., Tocco D. R., York R. G., Stober J. A., Read E. J. Teratogenic effects of trichloroacetonitrile in the Long-Evans rat. Teratology. 1988 Aug;38(2):113–120. doi: 10.1002/tera.1420380203. [DOI] [PubMed] [Google Scholar]
- Susser M., Susser E. Preserving public health values. Epidemiology. 1999 Mar;10(2):204–205. doi: 10.1097/00001648-199903000-00028. [DOI] [PubMed] [Google Scholar]
- Swan S. H., Shaw G., Harris J. A., Neutra R. R. Congenital cardiac anomalies in relation to water contamination, Santa Clara County, California, 1981-1983. Am J Epidemiol. 1989 May;129(5):885–893. doi: 10.1093/oxfordjournals.aje.a115222. [DOI] [PubMed] [Google Scholar]
- Swan S. H., Waller K., Hopkins B., Windham G., Fenster L., Schaefer C., Neutra R. R. A prospective study of spontaneous abortion: relation to amount and source of drinking water consumed in early pregnancy. Epidemiology. 1998 Mar;9(2):126–133. [PubMed] [Google Scholar]
- Thompson D. J., Warner S. D., Robinson V. B. Teratology studies on orally administered chloroform in the rat and rabbit. Toxicol Appl Pharmacol. 1974 Sep;29(3):348–357. doi: 10.1016/0041-008x(74)90107-0. [DOI] [PubMed] [Google Scholar]
- Tibbetts J. What's in the water: the disinfectant dilemma. Environ Health Perspect. 1995 Jan;103(1):30–34. doi: 10.1289/ehp.9510330. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Toth G. P., Kelty K. C., George E. L., Read E. J., Smith M. K. Adverse male reproductive effects following subchronic exposure of rats to sodium dichloroacetate. Fundam Appl Toxicol. 1992 Jul;19(1):57–63. doi: 10.1016/0272-0590(92)90028-g. [DOI] [PubMed] [Google Scholar]
- Waller K., Swan S. H., DeLorenze G., Hopkins B. Trihalomethanes in drinking water and spontaneous abortion. Epidemiology. 1998 Mar;9(2):134–140. [PubMed] [Google Scholar]
- Weisel C. P., Jo W. K. Ingestion, inhalation, and dermal exposures to chloroform and trichloroethene from tap water. Environ Health Perspect. 1996 Jan;104(1):48–51. doi: 10.1289/ehp.9610448. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weisel C. P., Kim H., Haltmeier P., Klotz J. B. Exposure estimates to disinfection by-products of chlorinated drinking water. Environ Health Perspect. 1999 Feb;107(2):103–110. doi: 10.1289/ehp.99107103. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Windham G. C., Swan S. H., Fenster L., Neutra R. R. Tap or bottled water consumption and spontaneous abortion: a 1986 case-control study in California. Epidemiology. 1992 Mar;3(2):113–119. doi: 10.1097/00001648-199203000-00008. [DOI] [PubMed] [Google Scholar]
- Wrensch M., Swan S. H., Lipscomb J., Epstein D. M., Neutra R. R., Fenster L. Spontaneous abortions and birth defects related to tap and bottled water use, San Jose, California, 1980-1985. Epidemiology. 1992 Mar;3(2):98–103. doi: 10.1097/00001648-199203000-00006. [DOI] [PubMed] [Google Scholar]