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DOI | 10.1093/toxsci/kfv196 |
Dose Addition Models Based on Biologically Relevant Reductions in Fetal Testosterone Accurately Predict Postnatal Reproductive Tract Alterations by a Phthalate Mixture in Rats | |
Howdeshell, Kembra L.1; Rider, Cynthia V.1; Wilson, Vickie S.2; Furr, Johnathan R.2; Lambright, Christy R.2; Gray, L. Earl, Jr.2 | |
发表日期 | 2015-12-01 |
ISSN | 1096-6080 |
卷号 | 148期号:2页码:488-502 |
英文摘要 | Challenges in cumulative risk assessment of anti-androgenic phthalate mixtures include a lack of data on all the individual phthalates and difficulty determining the biological relevance of reduction in fetal testosterone (T) on postnatal development. The objectives of the current study were 2-fold: (1) to test whether a mixture model of dose addition based on the fetal T production data of individual phthalates would predict the effects of a 5 phthalate mixture on androgen-sensitive postnatal male reproductive tract development, and (2) to determine the biological relevance of the reductions in fetal T to induce abnormal postnatal reproductive tract development using data from the mixture study. We administered a dose range of the mixture (60, 40, 20, 10, and 5% of the top dose used in the previous fetal T production study consisting of 300 mg/kg per chemical of benzyl butyl (BBP), di(n)butyl (DBP), diethyl hexyl phthalate (DEHP), di-isobutyl phthalate (DiBP), and 100 mg dipentyl (DPP) phthalate/kg; the individual phthalates were present in equipotent doses based on their ability to reduce fetal T production) via gavage to Sprague Dawley rat dams on GD8-postnatal day 3. We compared observed mixture responses to predictions of dose addition based on the previously published potencies of the individual phthalates to reduce fetal T production relative to a reference chemical and published postnatal data for the reference chemical (called DA(ref)). In addition, we predicted DA (called DA(all)) and response addition (RA) based on logistic regression analysis of all 5 individual phthalates when complete data were available. DA (ref) and DA (all) accurately predicted the observed mixture effect for 11 of 14 endpoints. Furthermore, reproductive tract malformations were seen in 17-100% of F1 males when fetal T production was reduced by about 25-72%, respectively. |
英文关键词 | dose addition;phthalates;postnatal developmental toxicity;male reproductive tract;endocrine disruptors;mixture models |
语种 | 英语 |
WOS记录号 | WOS:000367195500013 |
来源期刊 | TOXICOLOGICAL SCIENCES |
来源机构 | 美国环保署 |
文献类型 | 期刊论文 |
条目标识符 | http://gcip.llas.ac.cn/handle/2XKMVOVA/58743 |
作者单位 | 1.NIEHS, Div Natl Toxicol Program NTP, Res Triangle Pk, NC 27709 USA; 2.US EPA, Off Res & Dev, Natl Hlth & Environm Effects Res Labs, Toxicol Assessment Div TAD,Reprod Toxicol Branch, Res Triangle Pk, NC 27711 USA |
推荐引用方式 GB/T 7714 | Howdeshell, Kembra L.,Rider, Cynthia V.,Wilson, Vickie S.,et al. Dose Addition Models Based on Biologically Relevant Reductions in Fetal Testosterone Accurately Predict Postnatal Reproductive Tract Alterations by a Phthalate Mixture in Rats[J]. 美国环保署,2015,148(2):488-502. |
APA | Howdeshell, Kembra L.,Rider, Cynthia V.,Wilson, Vickie S.,Furr, Johnathan R.,Lambright, Christy R.,&Gray, L. Earl, Jr..(2015).Dose Addition Models Based on Biologically Relevant Reductions in Fetal Testosterone Accurately Predict Postnatal Reproductive Tract Alterations by a Phthalate Mixture in Rats.TOXICOLOGICAL SCIENCES,148(2),488-502. |
MLA | Howdeshell, Kembra L.,et al."Dose Addition Models Based on Biologically Relevant Reductions in Fetal Testosterone Accurately Predict Postnatal Reproductive Tract Alterations by a Phthalate Mixture in Rats".TOXICOLOGICAL SCIENCES 148.2(2015):488-502. |
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