Estimated daily phthalate exposures in a population of mothers of male infants exhibiting reduced anogenital distance.

Phthalate diesters have been shown to be developmental and reproductive toxicants in animal studies. A recent epidemiologic study showed certain phthalates to be significantly associated with reduced anogenital distance in human male infants, the first evidence of subtle developmental effects in human male infants exposed prenatally to phthalates. We used two previously published methods to estimate the daily phthalate exposures for the four phthalates whose urinary metabolites were statistically significantly associated with developmental effects in the 214 mother-infant pairs [di-n-butyl phthalate (DnBP) , diethyl phthalate (DEP) , butylbenzyl phthalate (BBzP) , diisobutyl phthalate (DiBP) ] and for another important phthalate [di-2-ethylhexyl phthalate (DEHP) ]. We estimated the median and 95th percentile of daily exposures to DBP to be 0.99 and 2.68 microg/kg/day, respectively ; for DEP, 6.64 and 112.3 microg/kg/day ; for BBzP, 0.50 and 2.47 microg/kg/day ; and for DEHP, 1.32 and 9.32 microg/kg/day. The U.S. Environmental Protection Agency (EPA) reference doses for these chemicals are 100 (DBP) , 800 (DEP) , 200 (BBzP) , and 20 (DEHP) microg/kg/day. The median and 95th percentile exposure estimates for the phthalates associated with reduced anogenital distance in the study population are substantially lower than current U.S. EPA reference doses for these chemicals and could be informative to any updates of the hazard assessments and risk assessments for these chemicals

Urinary Metabolites of Di(2‐ethylhexyl) Phthalate Are Associated With Decreased Steroid Hormone Levels in Adult Men

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/96413/1/jandrol.108.006403.pd

Maternal urinary bisphenol a during pregnancy and maternal and neonatal thyroid function in the CHAMACOS study.

BackgroundBisphenol A (BPA) is widely used in the manufacture of polycarbonate plastic bottles, food and beverage can linings, thermal receipts, and dental sealants. Animal and human studies suggest that BPA may disrupt thyroid function. Although thyroid hormones play a determinant role in human growth and brain development, no studies have investigated relations between BPA exposure and thyroid function in pregnant women or neonates.ObjectiveOur goal was to evaluate whether exposure to BPA during pregnancy is related to thyroid hormone levels in pregnant women and neonates.MethodsWe measured BPA concentration in urine samples collected during the first and second half of pregnancy in 476 women participating in the CHAMACOS (Center for the Health Assessment of Mothers and Children of Salinas) study. We also measured free thyroxine (T4), total T4, and thyroid-stimulating hormone (TSH) in women during pregnancy, and TSH in neonates.ResultsAssociations between the average of the two BPA measurements and maternal thyroid hormone levels were not statistically significant. Of the two BPA measurements, only the one taken closest in time to the TH measurement was significantly associated with a reduction in total T4 (β = -0.13 µg/dL per log2 unit; 95% CI: -0.25, 0.00). The average of the maternal BPA concentrations was associated with reduced TSH in boys (-9.9% per log2 unit; 95% CI: -15.9%, -3.5%) but not in girls. Among boys, the relation was stronger when BPA was measured in the third trimester of pregnancy and decreased with time between BPA and TH measurements.ConclusionResults suggest that exposure to BPA during pregnancy is related to reduced total T4 in pregnant women and decreased TSH in male neonates. Findings may have implications for fetal and neonatal development

Personal Care Product Use Predicts Urinary Concentrations of Some Phthalate Monoesters

Phthalates are multifunctional chemicals used in a variety of applications, including personal care products. The present study explored the relationship between patterns of personal care product use and urinary levels of several phthalate metabolites. Subjects include 406 men who participated in an ongoing semen quality study at the Massachusetts General Hospital Andrology Laboratory between January 2000 and February 2003. A nurse-administered questionnaire was used to determine use of personal care products, including cologne, aftershave, lotions, hair products, and deodorants. Phthalate monoester concentrations were measured in a single spot urine sample by isotope dilution–high-performance liquid chromatography coupled to tandem mass spectrometry. Men who used cologne or aftershave within 48 hr before urine collection had higher median levels of monoethyl phthalate (MEP) (265 and 266 ng/mL, respectively) than those who did not use cologne or aftershave (108 and 133 ng/mL, respectively). For each additional type of product used, MEP increased 33% (95% confidence interval, 14–53%). The use of lotion was associated with lower urinary levels of monobutyl phthalate (MBP) (14.9 ng/mL), monobenzyl phthalate (MBzP) (6.1 ng/mL), and mono(2-ethylhexyl) phthalate (MEHP) (4.4 ng/mL) compared with men who did not use lotion (MBP, 16.8 ng/mL; MBzP, 8.6 ng/mL; MEHP, 7.2 ng/mL). The identification of personal care products as contributors to phthalate body burden is an important step in exposure characterization. Further work in this area is needed to identify other predictors of phthalate exposure

Evidence of Interaction between Polychlorinated Biphenyls and Phthalates in Relation to Human Sperm Motility

Previously, we reported evidence of inverse associations between exposure to some polychlorinated biphenyls (PCBs) and some phthalate monoesters in relation to semen parameters, specifically sperm motility. Because humans are exposed to both phthalates and PCBs and because experimental studies suggest that PCBs may interact with glucuronidative enzymes that are responsible for phthalate metabolism, we explored the potential interaction between phthalates and PCBs in relation to human semen quality. We studied 303 men who were partners in subfertile couples seeking infertility diagnosis from the andrology laboratory at Massachusetts General Hospital. Semen parameters were dichotomized based on World Health Organization reference values, and phthalate and PCB levels were dichotomized at their respective medians. After adjusting for age and abstinence time, for below reference sperm motility there was a greater than additive interaction between monobenzyl phthalate and PCB-153 [relative excess risk due to interaction (RERI) = 1.40; 95% confidence interval (CI), 0.41–3.22], sum of PCBs (RERI = 1.24; 95% CI, 0.15–2.94), and cytochrome P450 (CYP450)-inducing PCBs (RERI = 1.30; 95% CI, 0.21–3.06). For below-reference sperm motility, there was also a greater than additive interaction between monobutyl phthalate (MBP) and PCB-153 (RERI = 1.42; 95% CI, 0.09–3.76) and CYP450-inducing PCBs (RERI = 1.87; 95% CI, 0.56–4.52) and a suggestive interaction between MBP and sum of PCBs (RERI = 1.35; 95% CI, −0.11 to 3.48). In conclusion, because there are important risk assessment and public health implications of interactions between these two ubiquitous classes of compounds, further studies need to be conducted to confirm these results and identify potential mechanisms of interactions

Personal Care Product Use Predicts Urinary Concentrations of Some Phthalate Monoesters

Phthalates are multifunctional chemicals used in a variety of applications, including personal care products. The present study explored the relationship between patterns of personal care product use and urinary levels of several phthalate metabolites. Subjects include 406 men who participated in an ongoing semen quality study at the Massachusetts General Hospital Andrology Laboratory between January 2000 and February 2003. A nurse-administered questionnaire was used to determine use of personal care products, including cologne, aftershave, lotions, hair products, and deodorants. Phthalate monoester concentrations were measured in a single spot urine sample by isotope dilution–high-performance liquid chromatography coupled to tandem mass spectrometry. Men who used cologne or aftershave within 48 hr before urine collection had higher median levels of monoethyl phthalate (MEP) (265 and 266 ng/mL, respectively) than those who did not use cologne or aftershave (108 and 133 ng/mL, respectively). For each additional type of product used, MEP increased 33% (95% confidence interval, 14–53%). The use of lotion was associated with lower urinary levels of monobutyl phthalate (MBP) (14.9 ng/mL), monobenzyl phthalate (MBzP) (6.1 ng/mL), and mono(2-ethylhexyl) phthalate (MEHP) (4.4 ng/mL) compared with men who did not use lotion (MBP, 16.8 ng/mL; MBzP, 8.6 ng/mL; MEHP, 7.2 ng/mL). The identification of personal care products as contributors to phthalate body burden is an important step in exposure characterization. Further work in this area is needed to identify other predictors of phthalate exposure

Medications as a Source of Human Exposure to Phthalates.

Phthalates are a group of multifunctional chemicals used in consumer and personal care products, plastics, and medical devices. Laboratory studies show that some phthalates are reproductive and developmental toxicants. Recently, human studies have shown measurable levels of several phthalates in most of the U.S. general population. Despite their widespread use and the consistent toxicologic data on phthalates, information is limited on sources and pathways of human exposure to phthalates. One potential source of exposure is medications. The need for site-specific dosage medications has led to the use of enteric coatings that allow the release of the active ingredients into the small intestine or in the colon. The enteric coatings generally consist of various polymers that contain plasticizers, including triethyl citrate, dibutyl sebacate, and phthalates such as diethyl phthalate (DEP) and dibutyl phthalate (DBP). In this article we report on medications as a potential source of exposure to DBP in a man who took Asacol [active ingredient mesalamine (mesalazine)] for the treatment of ulcerative colitis. In a spot urine sample from this man collected 3 months after he started taking Asacol, the concentration of monobutyl phthalate, a DBP metabolite, was 16,868 ng/mL (6,180 micro g/g creatinine). This concentration was more than two orders of magnitude higher than the 95th percentile for males reported in the 1999-2000 National Health and Nutrition Examination Survey (NHANES). The patient's urinary concentrations of monoethyl phthalate (443.7 ng/mL, 162.6 micro g/g creatinine), mono-2-ethylhexyl phthalate (3.0 ng/mL, 1.1 micro g/g creatinine), and monobenzyl phthalate (9.3 ng/mL, 3.4 micro g/g creatinine) were unremarkable compared with the NHANES 1999-2000 values. Before this report, the highest estimated human exposure to DBP was more than two orders of magnitude lower than the no observable adverse effect level from animal studies. Further research is necessary to determine the proportional contribution of medications, as well as personal care and consumer products, to a person's total phthalate burden