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Toxicol Sci

Title:		Subchronic Exposure to Di(2-ethylhexyl) Phthalate and Diisononyl Phthalate During Adulthood Has Immediate and Long-Term Reproductive Consequences in Female Mice
Author(s):		Chiang C; Flaws JA;
Address:		"Department of Comparative Biosciences, University of Illinois at Urbana-Champaign, Urbana, Illinois"
Journal Title:		Toxicol Sci
Year:		2019
Volume:		168
Issue:		2
Page Number:		620 - 631
DOI:		10.1093/toxsci/kfz013
ISSN/ISBN:		1096-0929 (Electronic) 1096-6080 (Print) 1096-0929 (Linking)
Abstract:		"Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer used in a variety of consumer products. This is concerning because DEHP is an endocrine disruptor and ovarian toxicant. Diisononyl phthalate (DiNP) is a DEHP replacement that is a rising human toxicant due to its increased use as a DEHP substitute. However, little is known about the effects of DEHP or DiNP exposure during adulthood on female reproduction. Thus, this study tested the hypothesis that DEHP or DiNP exposure during adulthood has long-term consequences for female reproduction in mice. Adult female CD-1 mice (39-40 days) were orally dosed with vehicle control (corn oil), DEHP (20 microg/kg/day-200 mg/kg/day), or DiNP (20 microg/kg/day-200 mg/kg/day) for 10 days. Females were paired with untreated male mice for breeding trials immediately post-dosing and again at 3 and 9 months post-dosing. Immediately post-dosing, DEHP and DiNP did not affect fertility. At 3 months post-dosing, DiNP (20 and 100 microg/kg/day and 200 mg/kg/day) significantly disrupted estrous cyclicity, and DiNP and DEHP (20 microg/kg/day) significantly reduced the ability of females to get pregnant. At 9 months post-dosing, DiNP significantly disrupted estrous cyclicity (100 microg/kg/day), reduced time to mating (100 microg/kg/day-200 mg/kg/day), and borderline reduced percent of females who produced offspring (20 mg/kg/day). At 9 months post-dosing, DEHP (200 microg/kg/day and 200 mg/kg/day) and DiNP (100 microg/kg/day and 20 and 200 mg/kg/day) increased numbers of male-biased litters. These data show that DEHP and DiNP exposure has long-term consequences for female reproduction, even long after cessation of exposure"
Keywords:		"Animals Diethylhexyl Phthalate/*toxicity Dose-Response Relationship, Drug Endocrine Disruptors/*toxicity Estrous Cycle/drug effects Female Male Mice Mice, Inbred Strains Phthalic Acids/*toxicity Plasticizers/*toxicity Pregnancy Prenatal Exposure Delayed E;"
Notes:		"MedlineChiang, Catheryne Flaws, Jodi A eng T32 ES007326/ES/NIEHS NIH HHS/ R01 ES028661/ES/NIEHS NIH HHS/ R56 ES025147/ES/NIEHS NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't 2019/01/17 Toxicol Sci. 2019 Apr 1; 168(2):620-631. doi: 10.1093/toxsci/kfz013"