title: Associations between hazard indices of di-n-butylphthalate and di-2-ethylhexylphthalate exposure and serum reproductive hormone levels among occupationally exposed and unexposed Chinese men.
abstract: The knowledge on the dose-response relationships between cumulative phthalate exposure and reproductive hormones in human are lacking. To assess the characteristics of the associations between hazard index (HI) of cumulative di-n-butylphthalate (DBP) and di-2-ethylhexylphthalate (DEHP) exposures and serum concentrations of free testosterone (fT), estradiol, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), we used restricted cubic spline function to characterize the dose-response curves between the HI values and reproductive hormones for 74 male workers occupationally exposed to high levels of DBP and DEHP, and 63 male construction workers as comparison group matched for age and smoking status. The median of HI value was 5.30 for exposed workers, 53.0-fold that of unexposed workers (0.10). 89.2% of exposed workers and 1.6% of unexposed workers have HI over 1.00. We observed a borderline significantly negative association between HI and fT in exposed workers (r=-0.195, p=0.096), but not in unexposed workers. The exposed workers showed inverted long-tailed J-shaped fT and FSH curves, and small changes in the LH curve, whereas unexposed workers had inverted and flattened-S-shaped fT and mirror-S-shaped LH and FSH curves. Both T production and hypothalamo-pituitary-testis (HPT) axis function were damaged in workers with high HI of phthalate exposures. HPT feedback function was activated in workers with both high and low HI, and plays an important role in preventing fT level from further decreasing with a rise in HI.
authors.affiliation: Department of Environmental Epidemiology, Liaoning Provincial Center for Disease Control and Prevention, Shenyang, China Bihoro Ryoiku Hospital, Hokkaido, Japan. panpgw@yahoo.com.cn
authors.forename: G
authors.initials: G
authors.lastname: Pan
authors.forename: T
authors.initials: T
authors.lastname: Hanaoka
authors.forename: L
authors.initials: L
authors.lastname: Yu
authors.forename: J
authors.initials: J
authors.lastname: Na
authors.forename: Y
authors.initials: Y
authors.lastname: Yamano
authors.forename: K
authors.initials: K
authors.lastname: Hara
authors.forename: M
authors.initials: M
authors.lastname: Ichiba
authors.forename: T
authors.initials: T
authors.lastname: Nakadate
authors.forename: R
authors.initials: R
authors.lastname: Kishi
authors.forename: P
authors.initials: P
authors.lastname: Wang
authors.forename: H
authors.initials: H
authors.lastname: Yin
authors.forename: S
authors.initials: S
authors.lastname: Zhang
authors.forename: Y
authors.initials: Y
authors.lastname: Feng
mesh_terms: D000328:Adult; D044466:Asian People; D003993:Dibutyl Phthalate / Q000633:toxicity*; D004051:Diethylhexyl Phthalate / Q000633:toxicity*; D004958:Estradiol / Q000097:blood*; D005640:Follicle Stimulating Hormone / Q000097:blood*; D015386:Hazardous Substances / Q000633:toxicity*; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D007986:Luteinizing Hormone / Q000097:blood*; D008297:Male; D016273:Occupational Exposure / Q000009:adverse effects*; D018570:Risk Assessment; D013737:Testis / Q000187:drug effects; D013739:Testosterone / Q000097:blood*
chemical_list: D015386:Hazardous Substances; D003993:Dibutyl Phthalate; D013739:Testosterone; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D004051:Diethylhexyl Phthalate