Phthalate exposure and semen quality in fertile US men.

Several experimental and observational studies have demonstrated the antiandrogenicity of several phthalates. However, there is limited evidence of an association between phthalate exposure in adult life and semen quality. The aim of this study was to examine phthalate exposure during adulthood in relation to semen quality in fertile US men. This multi-center cross-sectional study included 420 partners of pregnant women who attended a prenatal clinic in one of five US cities during 1999-2001. Nine phthalate metabolites [mono (2-ethylhexyl) phthalate (MEHP), mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono (2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono (2-ethyl-5-carboxypentyl) phthalate (MECPP)], as well as mono-n-butyl phthalate (MBP) and mono-isobutyl phthalate (MiBP), mono (three carboxypropyl) phthalate (MCPP), monobenzyl phthalate (MBzP), and monoethyl phthalate (MEP)] were measured in urine collected at the same time as the semen sample. We regressed natural log-transformed (ln) sperm concentration, ln(total sperm count), ln(total motile sperm count), percent motile spermatozoa, and percent spermatozoa with normal morphology on each of the nine natural log-transformed metabolite concentrations and on the molar-weighted sum of DEHP metabolites in separate models. We fit unadjusted models and models that adjusted for confounders determined a priori. In unadjusted models, ln(MiBP) was significantly and positively associated with motility and ln(MBzP) significantly negatively associated with ln(total sperm count). In adjusted linear models, urinary metabolite concentrations of DEHP, DBP, DEP, and DOP were not associated with any semen parameter. We found an inverse association between ln(MBzP) concentrations and sperm motility (β = -1.47, 95% CI: -2.61, -0.33), adjusted for ln(creatinine concentration), geographic location, age, race, smoking status, stress, recent fever, time from sample collection and time to complete analysis. Several sensitivity analyses confirmed the robustness of these associations. This study and the available literature suggest that impacts of adult exposure to phthalates at environmental levels on classical sperm parameters are likely to be small.

Thurston SW ，Mendiola J ，Bellamy AR ，Levine H ，Wang C ，Sparks A ，Redmon JB ，Drobnis EZ ，Swan SH ... -  《-》

The relationships between urinary phthalate metabolites, reproductive hormones and semen parameters in men attending in vitro fertilization clinic.

Evidence from previous studies has shown that phthalates may play a role in male reproductive function; however, results are still inconclusive, and the mechanism remains unclear. In this study, we first assessed whether exposure to phthalates is associated with altered reproductive hormones and semen parameters in 599 men attending an in vitro fertilization clinic. Secondly, we evaluated whether reproductive hormones could play a mediating role in the association between phthalates and sperm parameters. Eight phthalate metabolites were measured in two different spot urine samples: mono‑n‑butyl phthalate, mono-isobutyl phthalate (MiBP), monoethyl phthalate (MEP), monobenzyl phthalate, and four oxidative metabolites of di‑(2‑ethylhexyl) phthalate (DEHP) [i.e., mono‑(2‑ethylhexyl) phthalate (MEHP), mono‑(2‑ethyl‑5‑hydroxyhexyl) phthalate (MEHHP), mono‑(2‑ethyl‑5‑oxohexyl) phthalate (MEOHP), and mono‑(2‑ethyl‑5‑carboxypentyl) phthalate (MECPP)]. Semen parameters (concentration, volume, motility, and morphology) and reproductive hormones, i.e., follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroid-stimulating hormone, estradiol (E2), testosterone (TEST) and prolactin (PROL) were also determined and considered the main study outcomes. Separate multivariate linear regression was used to assess associations between levels of each urinary phthalate metabolite, molar sum of DEHP metabolites (∑DEHP), percentage of MEHP to ∑DEHP (%MEHP), and each outcome (natural log-transformed). Inverse associations were observed between TEST and MiBP (β = -0.099), FSH and MEHHP (β = -0.087), and PROL and MEOHP (β = -0.102), while a positive relationship was seen between E2 and MEP (β = 0.098). %MEHP was associated positively with FSH (β = 0.118) and LH (β = 0.099), but negatively with TEST/LH (β = -0.086) and TEST/E2 (β = -0.109). Sperm concentration was associated positively with MECPP (β = 0.131), MEHHP (β = 0.117), MEOHP (β = 0.107) and ∑DEHP (β = 0.111), but negatively with %MEHP (β = -0.135). All p-values were <0.05. Sobel's test indicated that FSH mediated significantly up to 60% of the positive relationship between sperm concentration and MEHHP, while FSH and LH mediated respectively 15 and 12% of the inverse association between sperm concentration and %MEHP. Further research on this topic is warranted.

Al-Saleh I ，Coskun S ，Al-Doush I ，Al-Rajudi T ，Abduljabbar M ，Al-Rouqi R ，Palawan H ，Al-Hassan S ... -  《-》

Biomonitoring of phthalate metabolites in the Canadian population through the Canadian Health Measures Survey (2007-2009).

Human exposure to phthalates occurs through multiple sources and pathways. In the Canadian Health Measures Survey 2007-2009, 11 phthalate metabolites, namely, MMP, MEP, MnBP, MBzP, MCHP, MCPP, MEHP, MEOHP, MEHHP, MnOP, and MiNP were measured in urine samples of 6-49 year old survey respondents (n=3236). The phthalate metabolites biomonitoring data from this nationally-representative Canadian survey are presented here. The metabolites MEP, MnBP, MBzP, MCPP, MEHP, MEOHP and MEHHP were detected in >90% of Canadians while MMP, MCHP, MnOP and MiNP were detected in <20% of the Canadian population. Step-wise regression analyses were carried out to identify important predictors of volumetric concentrations (μg/L) of the metabolites in the general population. Individual multiple regression models with covariates age, sex, creatinine, fasting status, and the interaction terms age×creatinine, age×sex and fasting status×creatinine were constructed for MEP, MnBP, MBzP, MCPP, MEHP, MEOHP and MEHHP. The least square geometric mean (LSGM) estimates for volumetric concentration (μg/L) of the metabolites derived from respective regression models were used to assess the patterns in the metabolite concentrations among population sub-groups. The results indicate that children had significantly higher urinary concentrations of MnBP, MBzP, MEHP, MEHHP, MEOHP and MCPP than adolescents and adults. Moreover, MEP, MBzP, MnBP and MEOHP concentrations in females were significantly higher than in males. We observed that fasting status significantly affects the concentrations of MEHP, MEHHP, MEOHP, and MCPP metabolites analyzed in this study. Moreover, our results indicate that the sampling time could affect the DEHP metabolite concentrations in the general Canadian population.

Saravanabhavan G ，Guay M ，Langlois É ，Giroux S ，Murray J ，Haines D ... -  《-》

Predictors of urinary bisphenol A and phthalate metabolite concentrations in Mexican children.

Exposure to endocrine disrupting chemicals such as bisphenol A (BPA) and phthalates is prevalent among children and adolescents, but little is known regarding important sources of exposure at these sensitive life stages. In this study, we measured urinary concentrations of BPA and nine phthalate metabolites in 108 Mexican children aged 8-13 years. Associations of age, time of day, and questionnaire items on external environment, water use, and food container use with specific gravity-corrected urinary concentrations were assessed, as were questionnaire items concerning the use of 17 personal care products in the past 48-h. As a secondary aim, third trimester urinary concentrations were measured in 99 mothers of these children, and the relationship between specific gravity-corrected urinary concentrations at these two time points was explored. After adjusting for potential confounding by other personal care product use in the past 48-h, there were statistically significant (p<0.05) positive associations in boys for cologne/perfume use and monoethyl phthalate (MEP), mono(3-carboxypropyl) phthalate (MCPP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), and in girls for colored cosmetics use and mono-n-butyl phthalate (MBP), mono(2-ethylhexyl) phthalate (MEHP), MEHHP, MEOHP, and mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), conditioner use and MEP, deodorant use and MEP, and other hair products use and MBP. There was a statistically significant positive trend for the number of personal care products used in the past 48-h and log-MEP in girls. However, there were no statistically significant associations between the analytes and the other questionnaire items and there were no strong correlations between the analytes measured during the third trimester and at 8-13 years of age. We demonstrated that personal care product use is associated with exposure to multiple phthalates in children. Due to rapid development, children may be susceptible to impacts from exposure to endocrine disrupting chemicals; thus, reduced or delayed use of certain personal care products among children may be warranted.

Lewis RC ，Meeker JD ，Peterson KE ，Lee JM ，Pace GG ，Cantoral A ，Téllez-Rojo MM ... -  《-》

Prenatal urinary phthalate metabolites levels and neurodevelopment in children at two and three years of age.

Previous studies suggest that prenatal phthalate exposure affects neurodevelopment and behavior during the first years of life. To evaluate the effect of maternal urinary concentrations of phthalate metabolites during pregnancy on mental and psychomotor development in children 24-36 months of age. This analysis was conducted on the first three years of life among a subsample of 136 mother-child pairs from the ELEMENT cohort studies conducted in Mexico City. Maternal urine samples collected during the third trimester of pregnancy were analyzed for 9 phthalate metabolites: Mono-ethyl phthalate (MEP), Mono-n-butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP), mono-benzyl phthalate (MBzP), Mono-3-carboxypropyl phthalate (MCPP), and four di-2-ethylhexyl phthalate (DEHP) metabolites [mono-2-ethylhexyl-phthalate (MEHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP)]. Among the 136 children, 135 (99.3%) completed the study period. Child neurodevelopment was assessed using mental and psychomotor development indexes (MDI and PDI) from a Bayley (BSID II) test at 24, 30, and 36 months of age. The effect of prenatal phthalate exposure on neurodevelopment was estimated using linear regression models for longitudinal data clustered at the individual level. No significant associations were observed among all children combined, but differential effects by gender were found. Among girls, there was a negative association between MDI and DEHP metabolites MEHP (β=-2.11 [95% CI: -3.73, -0.49]), MEHHP (β=-1.89 [95% CI: -3.64, -0.15]), MEOHP (β=-1.80 [95% CI: -3.58, -0.03]) MECPP (β=-2.52 [95% CI: -4.44, -0.61]), and ΣDEHP (β=-3.41 [95% CI: -5.26, -1.55]); there was no significant effect among boys. Male PDI was positively related to MBzP (β=1.79 [95% CI: 0.14, 3.45]) and MCPP (β=1.64 [95% CI: 0.15, 3.12]); there was no significant effect on PDI among girls. This study demonstrates that sex plays a role of an effect modifier in the association between prenatal phthalate exposure and neurodevelopment.

Téllez-Rojo MM ，Cantoral A ，Cantonwine DE ，Schnaas L ，Peterson K ，Hu H ，Meeker JD ... -  《-》