{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T19:18:48Z","timestamp":1790968728685,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T00:00:00Z","timestamp":1736121600000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Epidemiological studies report associations of drinking water disinfection byproducts (DBPs) with adverse health outcomes, including birth defects. Here, we used a rat model susceptible to pregnancy loss (full\u2010litter resorption; FLR) and eye malformations (anophthalmia, microphthalmia) to test 11 DBPs, including trihalomethanes, haloacetic acids (HAAs), and nitrogen\u2010containing DBPs (N\u2010DBPs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Timed\u2010pregnant F344 rats received gavage doses of chloroform, chlorodibromomethane, iodoform, chloroacetic acid, bromoacetic acid, dibromoacetic acid (DBA), diiodoacetic acid (DIA), trichloroacetic acid (TCA), dibromonitromethane, and iodoacetonitrile on gestation days (GD) 6\u201310. Bromonitromethane and TCA were administered via drinking water on GD 6\u201311. Litters were examined on postnatal days 1 and 6.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>All trihalomethanes tested caused FLR. The di\u2010 and tri\u2010halogenated HAAs, but not the mono\u2010HAAs, caused eye malformations. N\u2010DBPs caused neither effect at the dosages tested. TCA by gavage caused both FLR and eye defects, whereas drinking water exposure only caused eye defects. Potency rankings for causing FLR were chloroform\u2009\u2265\u2009iodoform\u2009&gt;\u2009chlorodibromomethane and the rankings for causing eye defects were DIA\u2009&gt;\u2009TCA\u2009=\u2009DBA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We confirmed that trihalomethanes caused pregnancy loss and that di\u2010 and tri\u2010HAAs were teratogenic. The N\u2010DBPs induced neither effect. Potency rankings were inconsistent with rankings seen in\u00a0vitro.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdr2.2427","type":"journal-article","created":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T06:03:11Z","timestamp":1736229791000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Developmental Toxicity of Disinfection Byproducts in <scp>F344<\/scp> Rats: Effects on Pregnancy Maintenance and Eye Development"],"prefix":"10.1002","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0515-4618","authenticated-orcid":false,"given":"Michael G.","family":"Narotsky","sequence":"first","affiliation":[{"name":"U.S. Environmental Protection Agency, Office of Research and Development, Center for Public Health and Environmental Assessment  Research Triangle Park North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie S.","family":"Fuentes","sequence":"additional","affiliation":[{"name":"Oak Ridge Institute for Science and Education  Oak Ridge Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oluwabusola","family":"Ola","sequence":"additional","affiliation":[{"name":"Student Services Contractor  Raleigh North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"TaCriasha L.","family":"Willoughby","sequence":"additional","affiliation":[{"name":"Oak Ridge Institute for Science and Education  Oak Ridge Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Lucas","sequence":"additional","affiliation":[{"name":"Oak Ridge Institute for Science and Education  Oak Ridge Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,1,6]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jea.7500098"},{"key":"e_1_2_9_3_1","first-page":"229","article-title":"Cumulative Effects of Thiram and Amitraz on Pregnancy Maintenance and Development in the Rat","volume":"84","author":"Best D. S.","year":"2005","journal-title":"Toxicological Sciences"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/59.2.309"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfh017"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhazmat.2023.133035"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/15287398209530275"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/109158101750408064"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.22541"},{"issue":"234","key":"e_1_2_9_10_1","first-page":"63798","article-title":"Guidelines for Developmental Toxicity Risk Assessment","volume":"56","author":"EPA","year":"1991","journal-title":"Federal Register"},{"issue":"2","key":"e_1_2_9_11_1","first-page":"388","article-title":"National Primary Drinking Water Regulations: Stage 2 Disinfectants and Disinfection Byproducts Rule; Final Rule","volume":"71","author":"EPA","year":"2006","journal-title":"Federal Register"},{"key":"e_1_2_9_12_1","unstructured":"EPA.2020. \u201cBenchmark Dose Software (BMDS) (Build 3.2) [Computer Software].\u201dhttps:\/\/www.epa.gov\/bmds\/download\u2010bmds."},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdr2.1755"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/biolre\/ioac079"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/tcm.1770070111"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9926(199606)54:2<57::AID-TERA1>3.0.CO;2-1"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.98106s4995"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdr2.2370"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/JOM.0000000000001191"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/EE9.0000000000000081"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41370-023-00595-1"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/tcm.1770070104"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2024.105673"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2021.105024"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jes.2022.04.016"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfm190"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1006\/taap.1998.8405"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdr2.2391"},{"key":"e_1_2_9_29_1","first-page":"166","volume-title":"Journal Biology of Reproduction","author":"Narotsky M.","year":"2004"},{"key":"e_1_2_9_30_1","first-page":"472","article-title":"Full\u2010Litter Resorptions Caused by Low\u2010Molecular Weight Halocarbons in F\u2010344 Rats","volume":"45","author":"Narotsky M.","year":"1992","journal-title":"Teratology"},{"issue":"5","key":"e_1_2_9_31_1","first-page":"376","article-title":"Comparison of Birth\u2010 and Conception\u2010Based Definitions of Postnatal Age in Developmental and Reproductive Rodent Toxicity Studies: Influence of Gestation Length on Measurements of Offspring Body Weight and Puberty in Controls","volume":"91","author":"Narotsky M. G.","year":"2011","journal-title":"Birth Defects Research Part A, Clinical and Molecular Teratology"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0890-6238(00)00111-8"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reprotox.2010.08.002"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9926(199710)56:4<252::AID-TERA4>3.0.CO;2-0"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1080\/15287399509531987"},{"issue":"13","key":"e_1_2_9_36_1","first-page":"15","article-title":"In Vivo Assessment of Prenatal Developmental Toxicity in Rodents","volume":"13","author":"Narotsky M. G.","year":"2003","journal-title":"Current Protocols in Toxicology"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1006\/faat.1997.2376"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1006\/faat.1995.1125"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.20585"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.1c04640"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/tcm.1770060503"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1420400506"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0892-0362(98)00008-7"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1186\/1476-069X-13-46"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ede.0000121380.02594.fc"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.envint.2021.106873"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jes.2017.04.021"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdr2.1348"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/tcm.1770070110"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1289\/EHP103"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph17249564"}],"container-title":["Birth Defects Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bdr2.2427","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T05:36:05Z","timestamp":1738647365000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/bdr2.2427"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1]]},"references-count":50,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,1]]}},"alternative-id":["10.1002\/bdr2.2427"],"URL":"https:\/\/doi.org\/10.1002\/bdr2.2427","archive":["Portico"],"relation":{},"ISSN":["2472-1727","2472-1727"],"issn-type":[{"value":"2472-1727","type":"print"},{"value":"2472-1727","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1]]},"assertion":[{"value":"2024-06-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2427"}}