{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T22:31:08Z","timestamp":1759530668997},"reference-count":18,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2003,8,26]],"date-time":"2003-08-26T00:00:00Z","timestamp":1061856000000},"content-version":"vor","delay-in-days":25,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Birth Defects Research Pt B"],"published-print":{"date-parts":[[2003,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>BACKGROUND:<\/jats:bold> Polnoks R (poly\u20102,2,4\u2010trimethyl\u20101,2\u2010dihydroquinoline) is used as an antioxidant in elastomer processing. It is an embryotoxic and fetotoxic agent. This chemical given per os to female rats induces also teratogenic effect but only at doses toxic to the mother. The aim of the study was to evaluate prenatal development and tissue distribution in rats exposed to 2,2,4\u2010trimethyl\u20101,2\u2010dihydroquinoline (TMDHQ), a monomer of Polnoks R. <jats:bold>METHODS:<\/jats:bold> Females were exposed orally to unlabeled TMDHQ during organogenesis at doses 50\u2013400 mg\/kg to asses prenatal toxicity and to radiolabeled <jats:sup>14<\/jats:sup>C monomer at a dose 210 mg\/kg to evaluate tissues distribution. <jats:bold>RESULTS:<\/jats:bold> TMDHQ administered to pregnant females per os at doses 100 mg\/kg and higher produced teratogenic effect (cleft palate, wavy ribs, kyphoscoliosis, exencephaly, external hydrocephalus, hydronephrosis, and renal hypoplasia). Peak <jats:sup>14<\/jats:sup>C\u2010radioactivity was found in mothers' plasma about 10 hr after administration of this compound at dose 210 mg\/kg. The accretion of <jats:sup>14<\/jats:sup>C proceeded with a kinetic constant of 0.35 hr <jats:sup>\u22121<\/jats:sup> and a half\u2010life of 53.3 hr. Kidneys are the main organs of monomer excretion. The highest concentration of <jats:sup>14<\/jats:sup>C in maternal tissues 24 hr after oral dosing was found in adipose tissue, sciatic nerve, muscles, kidneys, and liver. Radiocarbon retention in fetuses was the highest in kidneys at all time points after dosing. <jats:bold>CONCLUSIONS:<\/jats:bold> This study has demonstrated that transplacental exposure to Polnoks R monomer is teratogenic in rats. <jats:sup>14<\/jats:sup>C retention in placenta, amniotic fluid, and fetal tissues indicates that this compound or its metabolites penetrate into placenta to the fetus. Birth Defects Res B 68:375\u2013382, 2003. \u00a9 2003 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/bdrb.10031","type":"journal-article","created":{"date-parts":[[2003,9,2]],"date-time":"2003-09-02T19:34:23Z","timestamp":1062531263000},"page":"375-382","source":"Crossref","is-referenced-by-count":5,"title":["Maternal\u2010fetal distribution and prenatal toxicity of 2,2,4\u2010trimethyl\u20101,2\u2010dihydroquinoline in the rat"],"prefix":"10.1002","volume":"68","author":[{"given":"Krystyna","family":"Sitarek","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrzej","family":"Sapota","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2003,8,26]]},"reference":[{"key":"e_1_2_6_2_1","volume-title":"Clinical, biochemical and hematological\nreference values in normal experimental animals","author":"Brij M","year":"1977"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.3109\/10520292609115636"},{"key":"e_1_2_6_4_1","volume-title":"Biostatistics. A methodology for the health sciences","author":"Fisher LD","year":"1993"},{"key":"e_1_2_6_5_1","unstructured":"G\u00f3rnyR J\u0229drychowskiR StetkiewiczJ TaszakowskiT BaranczewskiP \u015awierczR StetkiewiczI LaoI CzerskiB.1991.Assessment of acute and subacute toxicity of Polnoks R sulfonamide TS and N\u2010methylmorfoline [in Polish]. Report IMP 1.18. Lodz: Nofer Institute of Occupational Medicine."},{"key":"e_1_2_6_6_1","first-page":"367","article-title":"Absorption, distribution, metabolism and excretion of 1,2\u2010dihydro\u20102,2,4\u2010trimethylquinoline in the male F344 rat","volume":"15","author":"Ioannou YM","year":"1987","journal-title":"Drug Metab Dispos"},{"key":"e_1_2_6_7_1","first-page":"25","article-title":"A study of toxicity of certain rubber antioxidants and their hygienic assessment [in Russian].","volume":"2","author":"Kelman G","year":"1966","journal-title":"Hyg Sanit"},{"key":"e_1_2_6_8_1","volume-title":"Physiology of animals [in Polish]","author":"Krzymowski T","year":"1973"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(66)90233-8"},{"key":"e_1_2_6_10_1","unstructured":"National Toxicology Program.1997.Toxicology and carcinogenesis studies of 1 2\u2010dihydro\u20102 2 4\u2010trimethylquinoline (CAS No. 147\u201047\u20107) in F344\/N rats and B6C3F1 mice (dermal studies) and the dermal initiation\/promotion study in female Sencar mice. NIH Technical Report No. 456."},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0272-0590(91)90104-C"},{"key":"e_1_2_6_12_1","unstructured":"Official Journal.1997. No. 111 [in Polish] 3445\u20133453."},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.3181\/00379727-106-26222"},{"key":"e_1_2_6_14_1","first-page":"52","volume-title":"Methods in prenatal toxicology","author":"Palmer AK","year":"1977"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1520-6866(1996)16:2<75::AID-TCM1>3.0.CO;2-C"},{"key":"e_1_2_6_16_1","first-page":"25","volume-title":"Methods in prenatal toxicology","author":"Tuchmann\u2010Duplessis H","year":"1977"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1965.tb12260.x"},{"key":"e_1_2_6_18_1","first-page":"91","volume-title":"Occupational and environmental reproductive hazards. A guide for clinicians","author":"Working PK","year":"1993"},{"key":"e_1_2_6_19_1","volume-title":"Biostatistical analysis","author":"Zar JH","year":"1974"}],"container-title":["Birth Defects Research Part B: Developmental and Reproductive Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fbdrb.10031","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bdrb.10031","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T21:19:21Z","timestamp":1697059161000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/bdrb.10031"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,8]]},"references-count":18,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2003,8]]}},"alternative-id":["10.1002\/bdrb.10031"],"URL":"https:\/\/doi.org\/10.1002\/bdrb.10031","archive":["Portico"],"relation":{},"ISSN":["1542-9733","1542-9741"],"issn-type":[{"value":"1542-9733","type":"print"},{"value":"1542-9741","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,8]]}}}