{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T17:51:17Z","timestamp":1787507477341,"version":"build-2736575974"},"reference-count":25,"publisher":"American Chemical Society (ACS)","issue":"6","license":[{"start":{"date-parts":[[2017,12,29]],"date-time":"2017-12-29T00:00:00Z","timestamp":1514505600000},"content-version":"vor","delay-in-days":1044,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Trihalomethanes (THMs) and haloacetic acids (HAAs) are regulated disinfection by-products (DBPs); their joint reproductive toxicity in drinking water is unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>We aimed to evaluate a drinking water mixture of the four regulated THMs and five regulated HAAs in a multigenerational reproductive toxicity bioassay.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Sprague-Dawley rats were exposed (parental, F1, and F2 generations) from gestation day 0 of the parental generation to postnatal day (PND) 6 of the F2 generation to a realistically proportioned mixture of THMs and HAAs at 0, 500\u00d7, 1,000\u00d7, or 2,000\u00d7 of the U.S. Environmental Protection Agency\u2019s maximum contaminant levels (MCLs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Maternal water consumption was reduced at \u2265 1,000\u00d7; body weights were reduced at 2,000\u00d7. Prenatal and postnatal survival were unaffected. F1 pup weights were unaffected at birth but reduced at 2,000\u00d7 on PND6 and at \u2265 1,000\u00d7 on PND21. Postweaning F1 body weights were reduced at 2,000\u00d7, and water consumption was reduced at \u2265 500\u00d7. Males at 2,000\u00d7 had a small but significantly increased incidence of retained nipples and compromised sperm motility. Onset of puberty was delayed at 1,000\u00d7 and 2,000\u00d7. F1 estrous cycles and fertility were unaffected, and F2 litters showed no effects on pup weight or survival. Histologically, P0 (parental) dams had nephropathy and adrenal cortical pathology at 2,000\u00d7.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>A mixture of regulated DBPs at up to 2,000\u00d7 the MCLs had no adverse effects on fertility, pregnancy maintenance, prenatal survival, postnatal survival, or birth weights. Delayed puberty at \u2265 1,000\u00d7 may have been secondary to reduced water consumption. Male nipple retention and compromised sperm motility at 2,000\u00d7 may have been secondary to reduced body weights.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Citation<\/jats:title>\n                    <jats:p>Narotsky MG, Klinefelter GR, Goldman JM, DeAngelo AB, Best DS, McDonald A, Strader LF, Murr AS, Suarez JD, George MH, Hunter ES III, Simmons JE. 2015. Reproductive toxicity of a mixture of regulated drinking-water disinfection by-products in a multigenerational rat bioassay. Environ Health Perspect 123:564\u2013570;\u2002http:\/\/dx.doi.org\/10.1289\/ehp.1408579<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1289\/ehp.1408579","type":"journal-article","created":{"date-parts":[[2015,2,19]],"date-time":"2015-02-19T12:01:31Z","timestamp":1424347291000},"page":"564-570","source":"Crossref","is-referenced-by-count":44,"title":["Reproductive Toxicity of a Mixture of Regulated Drinking-Water Disinfection By-Products in a Multigenerational Rat Bioassay"],"prefix":"10.1021","volume":"123","author":[{"given":"Michael G.","family":"Narotsky","sequence":"first","affiliation":[{"name":"National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary R.","family":"Klinefelter","sequence":"additional","affiliation":[{"name":"National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerome M.","family":"Goldman","sequence":"additional","affiliation":[{"name":"National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony B.","family":"DeAngelo","sequence":"additional","affiliation":[{"name":"National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah S.","family":"Best","sequence":"additional","affiliation":[{"name":"National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"McDonald","sequence":"additional","affiliation":[{"name":"National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lillian F.","family":"Strader","sequence":"additional","affiliation":[{"name":"National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley S.","family":"Murr","sequence":"additional","affiliation":[{"name":"National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan D.","family":"Suarez","sequence":"additional","affiliation":[{"name":"National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael H.","family":"George","sequence":"additional","affiliation":[{"name":"National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"E. Sidney","family":"Hunter","sequence":"additional","affiliation":[{"name":"National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane Ellen","family":"Simmons","sequence":"additional","affiliation":[{"name":"National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2015,2,19]]},"reference":[{"key":"2026080606013089600_micit1","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1080\/10915810252866097","article-title":"Oral (drinking water) two-generation reproductive toxicity study of bromodichloromethane (BDCM) in 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Athens, GA:U.S. Environmental Protection Agency.Available: http:\/\/www.epa.gov\/athens\/publications\/DBP.html [accessed 7 May 2015]."}],"container-title":["Environmental Health Perspectives"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/evhpaz\/article-pdf\/123\/6\/564\/66431282\/ehp.1408579.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/evhpaz\/article-pdf\/123\/6\/564\/66431282\/ehp.1408579.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T13:48:21Z","timestamp":1786628901000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/evhpaz\/article-lookup\/doi\/10.1289\/ehp.1408579"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,2,19]]},"references-count":25,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2015,2,19]]},"published-print":{"date-parts":[[2015,6,1]]}},"URL":"https:\/\/doi.org\/10.1289\/ehp.1408579","relation":{},"ISSN":["0091-6765","1552-9924"],"issn-type":[{"value":"0091-6765","type":"print"},{"value":"1552-9924","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,2,19]]}}}