title: Urinary concentrations of cyclohexane-1,2-dicarboxylic acid monohydroxy isononyl ester, a metabolite of the non-phthalate plasticizer di(isononyl)cyclohexane-1,2-dicarboxylate (DINCH), and markers of ovarian response among women attending a fertility center.
abstract: Di(isononyl)cyclohexane-1,2-dicarboxylate (DINCH), a non-phthalate plasticizer, was introduced commercially in 2002 as an alternative to ortho-phthalate esters because of its favorable toxicological profile. However, the potential health effects from DINCH exposure remain largely unknown. We explored the associations between urinary concentrations of metabolites of DINCH on markers of ovarian response among women undergoing in vitro fertilization (IVF) treatments. Between 2011 and 2015, 113 women enrolled a prospective cohort study at the Massachusetts General Hospital Fertility Center and provided up to two urine samples prior to oocyte retrieval. The urinary concentrations of two DINCH metabolites, cyclohexane-1,2-dicarboxylic acid monohydroxy isononyl ester (MHiNCH) and cyclohexane-1,2-dicarboxylic acid monocarboxyisooctyl ester (MCOCH), were quantified by isotope dilution tandem mass spectrometry. We used generalized linear mixed models to evaluate the association between urinary metabolite concentrations and markers of ovarian response, accounting for multiple IVF cycles per woman via random intercepts. On average, women with detectable urinary MHiNCH concentrations, as compared to those below LOD, had a lower estradiol levels (-325 pmol/l, p=0.09) and number of retrieved oocytes (-1.8, p=0.08), with a stronger association among older women. However, urinary MHiNCH concentrations were unrelated to mature oocyte yield and endometrial wall thickness. In conclusion, we found suggestive negative associations between urinary MHiNCH concentrations and peak estradiol levels and number of total oocyte yields. This is the first study evaluating the effect of DINCH exposure on human reproductive health and raises the need for further experimental and epidemiological studies to better understand the potential effects of this chemical on health.
authors: Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, United States. Electronic address: lminguez@hsph.harvard.edu.
authors: Lidia
authors: L
authors: Mínguez-Alarcón
authors: Vincent Obstetrics and Gynecology, Massachusetts General Hospital and Harvard Medical School, Boston, United States.
authors: Irene
authors: I
authors: Souter
authors: Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, United States.
authors: Yu-Han
authors: YH
authors: Chiu
authors: Department of Epidemiology, and Harvard T.H. Chan School of Public Health, Boston, United States; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, United States.
authors: Paige L
authors: PL
authors: Williams
authors: Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, United States.
authors: Jennifer B
authors: JB
authors: Ford
authors: National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, United States.
authors: Xiaoyun
authors: X
authors: Ye
authors: National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, United States.
authors: Antonia M
authors: AM
authors: Calafat
authors: Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, United States; Department of Epidemiology, and Harvard T.H. Chan School of Public Health, Boston, United States; Vincent Obstetrics and Gynecology, Massachusetts General Hospital and Harvard Medical School, Boston, United States.
authors: Russ
authors: R
authors: Hauser
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D015415:Biomarkers / Q000652:urine; D003509:Cyclohexanecarboxylic Acids / Q000493:pharmacokinetics* / Q000633:toxicity / Q000652:urine*; D003998:Dicarboxylic Acids / Q000493:pharmacokinetics* / Q000633:toxicity; D004717:Endometrium / Q000187:drug effects; D005260:Female; D005307:Fertilization in Vitro; D006801:Humans; D008423:Maternal Age; D008875:Middle Aged; D054315:Oocyte Retrieval / Q000706:statistics & numerical data; D009865:Oocytes / Q000187:drug effects*; D010062:Ovulation Induction / Q000379:methods; D010968:Plasticizers / Q000493:pharmacokinetics* / Q000633:toxicity; D011446:Prospective Studies; D060728:Reproductive Health; D055815:Young Adult
chemical_list: D015415:Biomarkers; D003509:Cyclohexanecarboxylic Acids; D003998:Dicarboxylic Acids; D010968:Plasticizers; C000619439:cyclohexane-1,2-dicarboxylic acid monohydroxy isononyl ester; C558012:diisononyl 1,2-cyclohexanedicarboxylic acid
keywords: DINCH metabolites; Epidemiology; Markers of ovarian response; Phthalates; Reproductive health