DEHP对大鼠睾丸氧化应激和血清睾酮水平影响

目的 探讨邻苯二甲酸二乙基己酯（DEHP）对青春期雄性大鼠睾丸及性激素的影响及潜在机制。方法 18日龄SD大鼠24只,按体重随机分为4组（对照组、低、中、高剂量DEHP组）,每组6只。DEHP染毒剂量分别为250、500和750 mg/kg,经口连续染毒30 d;颈部脱臼处死,收集血清,分离睾丸组织;测定血清睾酮、黄体生成素（LH）和卵泡刺激素（FSH）等性激素水平及睾丸组织中谷胱甘肽过氧化物酶（GSH-Px）、超氧化物歧化酶（SOD）、丙二醛和5α-还原酶（5α-R）活性。结果 DEHP处理组,大鼠睾丸和附睾脏器系数降低,睾丸曲精小管管腔缩小,结构坍塌,部分细胞膜破裂,细胞排列紊乱;与对照组比较,高剂量DEHP组大鼠血清睾酮和LH水平[分别为（115.04±14.21） pg/mL、（23.42±3.12） mIU/mL]降低,中、高剂量DEHP组大鼠血清FSH水平[分别为（5.49±0.42）、（4.63±0.51） IU/L]下降,差异有统计学意义（P<0.05）;与对照组比较,高剂量DEHP组大鼠睾丸组织中GSH-Px和SOD活力[分别为（728.3±95.3）、（835.8±151.2） U/mg pro]降低,而中、高剂量DEHP组大鼠睾丸组织中丙二醛含量[分别为（79.6±13.9）、（90.6±4.0） nmol/mg pro]和5α-R2活性[分别为（415.9±112.7）、（415.9±147.8） IU/mg pro]升高,差异有统计学意义（P<0.05）。结论 DEHP暴露后,大鼠睾丸发生氧化应激,并通过诱导5α-R2活性降低血清睾酮水平。     

Maternal and infant urinary phthalate metabolite concentrations: are they related?

Background

Phthalates are synthetic chemicals that are ubiquitous in our society and may have adverse health effects in humans. Detectable concentrations of phthalate metabolites have been found in adults and children, but no studies have examined the relationship between maternal and infant phthalate metabolite concentrations.

Objective

We investigated the relationship between maternal and infant urinary phthalate metabolite concentrations.

Methods

We measured nine phthalate metabolites in urine samples from 210 mother/infant pairs collected on the same study visit day (1999-2005) and obtained demographic history from questionnaires. Using multivariate linear regression analyses, we examined the degree to which maternal urine phthalate metabolite concentration predicted infant phthalate metabolite concentration. All analyses were adjusted for infant age, creatinine concentration, and race.

Results

Correlation coefficients between phthalate metabolite concentrations in the urine of mothers and their infants were generally low but increased with decreasing age of infant. In multivariate analyses, mother's phthalate metabolite concentrations were significantly associated with infants’ concentrations for six phthalate metabolites: monobenzyl phthalate, monoethyl phthalate, monoisobutyl phthalate, and three metabolites of di(2-ethylhexyl) phthalate: mono(2-ethylhexyl) phthalate, mono(2-ethyl-5-hydroxy-hexyl) phthalate, and mono(2-ethyl-5-oxo-hexyl) phthalate (p-values for all coefficients <0.05).

Discussion

Mother's urine phthalate metabolite concentration is significantly associated with infant urine phthalate metabolite concentration for six phthalate metabolites. It is plausible that shared exposures to phthalates in the immediate surrounding environment accounted for these relationships, but other unidentified sources may also contribute to infants’ phthalate exposures. This study indicates the importance of further identifying infant phthalate exposures that may be distinct from maternal exposures in order to decrease overall infant phthalate exposures.     

Maternal urinary phthalate metabolites during pregnancy and thyroid hormone concentrations in maternal and cord sera: The HOME Study

Background

Phthalates, endocrine-disrupting chemicals that are commonly found in consumer products, may adversely affect thyroid hormones, but findings from prior epidemiologic studies are inconsistent.

邻苯二甲酸二乙基己基酯对大鼠睾丸细胞DNA损伤和睾丸组织氧化应激影响

目的 探讨邻苯二甲酸二乙基己基酯(DEHP)对大鼠睾丸细胞DNA的损伤和睾丸组织氧化应激的作用.方法 雄性Wistar大鼠25只,随机分为5组,每组5只,通过灌胃的方法摄入DEHP,4个染毒组剂量分别为1 500、3 000、4 500、6000mg·kg-1 ·d-1,1个阴性对照组.用单细胞凝胶电泳技术检测大鼠睾丸细胞DNA的损伤,睾丸组织中活性氧(ROS)、丙二醛(MDA)的水平以及睾丸组织中谷胱甘肽过氧化物酶(GSH-Px)、超氧化物歧化酶(SOD)的活力.结果 各染毒组和阴性对照组大鼠睾丸细胞DNA损伤率分别为29.0％、71.0％、89.0％、95.0％和15.0％,各染毒组睾丸细胞DNA损伤程度与对照组比较,差异均有统计学意义(P＜0.05,P＜0.01),且大鼠睾丸细胞DNA损伤率与染毒剂量之间呈剂量-反应关系(r =0.930,P＜0.01);各染毒组大鼠睾丸组织的ROS、MDA的水平均较阴性对照组显著升高(P＜0.05,P＜0.01),而GSH-Px、SOD的活力又较阴性对照组明显下降(P＜0.05,P＜0.01).结论 DEHP可造成大鼠睾丸组织明显的氧化应激并引起睾丸细胞DNA的损伤.     

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.     

Estimating the contribution of inhalation exposure to di-2-ethylhexyl phthalate (DEHP) for PVC production workers,using personal air sampling and urinary metabolite monitoring

Because of troubling reports of high urinary metabolite levels and adverse reproductive health effects in workers exposed to di(2-ethylhexyl)phthalate (DEHP) in occupational settings, concern about exposure to DEHP in occupational settings is increasing. However, the contributions of different routes of exposure to DEHP are unclear. We used personal air sampling and biomonitoring to determine the contribution of inhalation exposure to the body burden of DEHP in the workplace. Eighty-nine workers (high-exposure group: 66 raw-materials workers; low-exposure group: 23 administrative workers) were recruited from three polyvinyl chloride (PVC) factories. Urinary levels of mono(2-ethylhexyl) phthalate (MEHP), (mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) were measured in pre-shift and post-shift samples. The geometric means of airborne concentrations of DEHP were 5.3 μg/m³ (low-exposure group) and 32.7 μg/m³ (high-exposure group) (P < 0.01). Correlation analysis showed a consistently significant association between airborne DEHP concentration and urinary DEHP metabolite levels in the high-exposure group. Calculating daily DEHP intake based on total urinary metabolite levels showed that the geometric means of total daily urinary metabolite levels of DEHP were 9.2 μg/kg/day (low-exposure group) and 15.5 μg/kg/day (high-exposure group) (P < 0.01). A quartile analysis of all workers showed a significant trend toward an association between the individual contribution of inhalation exposure to DEHP and urinary DEHP metabolite levels, for which the mean inhalation contribution was 46.7% in the highest quartile. We conclude that inhalation-absorbed airborne DEHP significantly increased the total body burden of DEHP in these occupationally exposed workers.     

Urinary excretion of phthalate metabolites,phenols and parabens in rural and urban Danish mother–child pairs

Some phthalates, parabens and phenols have shown adverse endocrine disrupting effects in animal studies and are also suspected to be involved in human reproductive problems. However, knowledge about exposure sources and biomonitoring data in different subsets of populations are still scarce. Thus, in this study first morning urine samples were collected from 6 to 11 years Danish children and their mothers. The content of seven parabens, nine phenols and metabolites of eight different phthalates were analysed by LC–MS/MS. Two parabens, six phenols and metabolites from six phthalate diesters were measurable in more than 50%, 75% and 90% of the participants, respectively. Thus the children and their mothers were generally exposed simultaneously to a range of phthalates, phenols and parabens. In general, the levels were low but for several of the compounds extreme creatinine adjusted concentrations 100–500-fold higher than the median level were seen in some participants. Children were significantly higher exposed to bisphenol A (BPA) and some of the phthalates (DiBP, DnBP, BBzP, DEHP and DiNP) than their mothers, whereas mothers were higher exposed to compounds related to cosmetics and personal care products such as parabens (MeP, EtP and n-PrP), benzophenone-3, triclosan and diethyl phthalate. However, a very high correlation between mothers and their children was observed for all chemicals. A high individual exposure to one chemical was often associated with a high exposure to other of the chemicals and the possibility of combination effects of multiple simultaneous exposures cannot be excluded.     

Prenatal exposure to phthalates and neuropsychological development during childhood

There is inconsistent evidence regarding the effects of prenatal phthalate exposure on children's neuropsychological development. We evaluate the association between prenatal phthalate exposure and the cognitive, psychomotor and behavioral development of 367 children at repeated ages in a prospective birth cohort study. We measured phthalate metabolites (sum of four DEHP metabolites – Σ₄DEHP, MBzP, MEP, MiBP and MnBP) in urine samples collected during the 1st and 3rd trimesters of pregnancy in women participating in the INMA-Sabadell birth cohort study. We assessed cognitive and psychomotor development of their children at 1 and 4 years, and social competence, ADHD symptoms and other behavioral problems at 4 and 7 years. No associations were observed between prenatal phthalate exposure and cognitive and psychomotor scores at the age of 1 year and at the age of 4 years, except for an association between MBzP and lower psychomotor scores (β = −1.49 [95% confidence interval (CI) = −2.78, −0.21]). Σ₄DEHP concentrations were associated with increased social competence scores at 4 years and with reduced ADHD symptoms at age 4 and 7 years. Increasing MEP concentrations were associated with a reduced risk of inattention symptoms at 4 years. No associations were observed for MBzP, MiBP or MnBP in relation to behavioral problems. This study, with multiple phthalate exposure measurements and measures of neuropsychological domains at different ages, suggest that prenatal phthalate exposure does not adversely affect children's cognitive, psychomotor or behavioral development.     

Comparisons of urinary phthalate metabolites and daily phthalate intakes among Japanese families

We measured urinary phthalate metabolites, including di-n-butyl phthalate (DnBP), di-isobutyl phthalate, benzyl butyl phthalate (BBzP), and di(2-ethylhexyl) phthalate (DEHP), from 178 school-aged children and their 284 family members using gas chromatography-mass spectrometry, and we calculated daily phthalate intakes. The highest median levels of phthalate metabolites were for mono-isobutyl phthalate in all participants except schoolchildren, where the highest levels were for mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP). Comparing the schoolchildren with their parents, the schoolchildren had significantly higher urinary metabolites for MEOHP, mono-(2-ethyl-5-carboxypentyl) phthalate, and ΣDEHP. Regarding daily intakes, the schoolchildren had significantly higher daily intakes of DnBP, BBzP, and ΣDEHP. All phthalate metabolite and sums of metabolite levels in the schoolchildren were positively correlated with their mothers’ levels, except for MEHP, whereas fathers were less correlated with their children. The DEHP intake in this study was higher than that of most other studies. Moreover, 10% of the children and 3% of the adults exceeded the Reference Dose (RfD) value (20 μg/kg/day) of the U.S. Environmental Protection Agency, which indicates that it is important to focus on children's DEHP exposure because the children exceeded the RfD more than adults among the same families who shared similar exposure sources. Our results will contribute to considerations of the regulations for some phthalates and the actual phthalate exposure levels in the Japanese population.