Occupation and urinary phthalate metabolite concentrations in a national survey of adults in Canada.

Associations between urinary and follicular fluid concentrations of phthalate metabolites and reproductive outcomes in Brazilian women undergoing fertility treatment.

Preterm birth is a leading cause of neonatal mortality. Preterm birth is a public health burden, particularly in the United States, where approximately 10% of deliveries are preterm. Although the underlying cause of most preterm births is unknown, environmental chemical exposures (such as phthalates) possibly contribute. Phthalates are common in consumer products, and exposure can occur through diet, personal care products, and even household dust. Consequently, exposure is ubiquitous for pregnant individuals. Prenatal phthalate exposure has been associated with adverse neurodevelopment in children and disordered development of the male reproductive tract. This study reviewed 16 prospective studies conducted within the United States to pool individual-level data to examine prenatal urinary biomarkers of phthalate exposure and preterm birth. In addition, potential influence of exposure to overall phthalate mixture was assessed to determine the potential impact of reduced exposure on preterm birth. Results of the study indicated that of 6045 pregnant women, 539 (9%) delivered preterm. Overall, of the entire included cohort, 802 individuals were Black (13.3%), 2576 were White (42.6%), 2323 were Latina (38.4%), and 328 had other race identity (including Native Hawaiian, Alaskan Native, or American Indian). Characteristics of participants were similar between those who delivered preterm versus term. Some 96% of urine samples displayed detectable concentrations of urinary phthalate metabolites. As demonstrated by regression analyses, higher concentrations of most phthalate metabolites bore an association of slightly higher odds (12%–16% higher) for preterm birth. In addition, the study estimated that reducing the mixture of phthalate metabolite concentrations by 10%, 30%, or 50%, respectively, could prevent 1.8, 5.9, and 11.1 preterm births per 1000 live births. The study found a relationship between higher maternal pregnancy concentrations of urinary phthalate metabolites and preterm birth. The findings of this study identify a potential benefit of phthalate exposure reduction among pregnant individuals via either regulations or behavioral interventions. Because phthalate exposure can occur through many environments and sources, the US Consumer Product Safety Commission has attempted to pinpoint major sources of phthalate exposure and has determined that the predominate exposures appear to occur through food and medications, although uncertainty in the primary source of exposure remains. Phthalate exposure also widely varies in the United States based on several factors such as whether a person is at a disadvantaged socioeconomic status, is pregnant, or is of a marginalized race or ethnicity. Targeted interventions, such as altering personal care products, is made challenging as consumers are not readily able to access accurate ingredients lists. In the United States, for example, fragrance ingredient lists are not required to list phthalates when they are included in the product. Diet interventions intending to reduce phthalate exposure have had mixed results. Although federally mandated restrictions have limited the use of phthalates in products for children, few such restrictions exist for products intended for pregnant individuals. As 28 phthalates are currently allowed as food additives or in food contact materials, they are difficult to avoid. Mitigation of population-level health effects from phthalates through regulatory means would be most effective when considering phthalates not as individual chemicals, but rather as a class. This study found that higher concentrations of several urinary phthalate metabolites in pregnancy were associated with preterm birth, a consistent finding across 16 prospective US studies. Such findings emphasize the importance of the development of policy measures and public health around phthalate exposure reduction, especially among pregnant individuals.

Background/Aim: Quinolinic acid (QA), a neuroactive metabolite produced during tryptophan degradation, is implicated in the pathogenesis of several neurological disorders. Phthalates are structurally similar to QA, and exposure to phthalates has demonstrated increased QA production and excretion in rodent studies. We recently showed that very high exposure to dibutyl phthalate was associated with higher concentrations of urinary QA in men. However, no human studies examined the associations between background (low) phthalate exposures and QA. We examine the associations of urinary phthalate metabolite concentrations with QA. Methods: Female participants (N=126) who participated in a prospective cohort study at a Fertility Center in Boston provided 758 urine samples (273 during pregnancy and 485 during non-pregnancy). Concentrations of 11 phthalate metabolites and QA in urine were measured. We used multivariable linear mixed effect models to estimate the percent change in urinary QA concentrations associated with a doubling (100%) of phthalate metabolite concentration, and evaluated whether there was effect modification by pregnancy.Results: Women's mean (standard deviation) age was 34.2 (4.0) years with a body mass index of 23.5 (3.7) kg/m2. The women were primarily Caucasian (92%), had ≥a college degree (98%), and none were current smokers. In multivariable-adjusted models, the percent change in urinary QA concentrations was significantly higher for each doubling of several urinary phthalate metabolite concentrations. For example, each doubling of DBP metabolites was associated with a 13.7% (95%CI: 10.6, 16.9) higher QA. Associations between the low molecular weight phthalate metabolites and QA were stronger among samples collected during pregnancy as compared to non-pregnancy.Conclusions: Urinary concentrations of several phthalate metabolites were positively associated with QA among women. These findings, along with the known neurotoxicity of QA, warrant the need to examine whether QA concentrations may serve as a pathway for the adverse neurodevelopment outcomes found in children's health studies.

Background: Previous studies have shown that women have higher urinary concentrations of several phthalate metabolites than do men, possibly because of a higher use of personal care products. Few studies have evaluated the association between phthalate metabolites, diabetes, and diabetes-related risk factors among women.Objective: We explored the association between urinary phthalate metabolite concentrations and diabetes among women who participated in a cross-sectional study.Methods: We used urinary concentrations of phthalate metabolites, analyzed by the Centers for Disease Control and Prevention, and self-reported diabetes of 2,350 women between 20 and 79 years of age who participated in the NHANES (2001–2008). We used multiple logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) and adjusted for urinary creatinine, sociodemographic characteristics, dietary factors, and body size. A secondary analysis was conducted for women who did not have diabetes to evaluate the association between phthalate metabolite concentrations and fasting blood glucose (FBG), homeostasis model assessment–estimated insulin resistance, and glycosylated hemoglobin A1c.Results: After adjusting for potential confounders, women with higher levels of mono-n-butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP), monobenzyl phthalate (MBzP), mono-(3-carboxypropyl) phthalate (MCPP), and three di-(2-ethylhexyl) phthalate metabolites (ΣDEHP) had an increased odds of diabetes compared with women with the lowest levels of these phthalates. Women in the highest quartile for MBzP and MiBP had almost twice the odds of diabetes [OR = 1.96 (95% CI: 1.11, 3.47) and OR = 1.95 (95% CI: 0.99, 3.85), respectively] compared with women in the lowest quartile. Nonmonotonic, positive associations were found for MnBP and ΣDEHP, whereas MCPP appeared to have a threshold effect. Certain phthalate metabolites were positively associated with FBG and insulin resistance.Discussion: Urinary levels of several phthalates were associated with prevalent diabetes. Future prospective studies are needed to further explore these associations to determine whether phthalate exposure can alter glucose metabolism and increase the risk of insulin resistance and diabetes.

Exposure to environmental pollutants, especially endocrine-disrupting chemicals, disproportionately affects vulnerable populations like pregnant women, lactating mothers, and preterm infants. This study aimed to assess the detection patterns of DiNP-, DEP-, and DEHP-related metabolites in maternal urine and breast milk, examine agreement between matrices, and explore maternal factors associated with phthalate exposure. Fifty-five mothers who delivered at ≤32 gestational weeks and whose infants were hospitalized in the Neonatal Intensive Care Unit (NICU) were enrolled. Breast milk and urine samples were analyzed using a validated isotope-dilution LC-MS/MS method. Urinary phthalate metabolite concentrations were adjusted for specific gravity. Linear mixed-effects models with a random intercept for mother were used to examine associations between urinary and breast milk phthalate metabolite concentrations, assess temporal changes, and evaluate the influence of breast milk lipid content. DEHP and DiNP metabolites were detected in nearly all maternal urine samples. Breast milk contained predominantly primary metabolites (MEHP and MiNP), while secondary oxidative metabolites were rarely detected. Urine concentrations consistently exceeded breast milk concentrations. Urinary and breast milk phthalate concentrations were not correlated across sampling periods, indicating limited matrix concordance. Mothers of very preterm infants experience sustained phthalate exposure in the postpartum period; however, limited metabolite transfer to breast milk indicates that maternal urine remains the preferred biomonitoring matrix for assessing systemic phthalate exposure. Breast milk phthalate profiles exhibit compound-specific temporal changes and appear largely independent of concurrent urinary exposure biomarkers.

Urinary phthalate monoesters and endometriosis in infertile Japanese women

Association of urinary concentrations of phthalate metabolites with quinolinic acid among women: A potential link to neurological disorders

Associations of urinary phthalate metabolites and lipid peroxidation with sperm mitochondrial DNA copy number and deletions

Toxicoanthropology: Phthalate exposure in relation to market access in a remote forager-horticulturalist population

Background:Personal care products (PCPs) are exposure sources to phthalates and parabens; however, their contribution to men’s exposure is understudied.Objectives:We examined the association between PCP use and urinary concentrations of phthalate metabolites and parabens in men.Methods:In a prospective cohort, at multiple study visits, men self-reported their use of 14 PCPs and provided a urine sample (2004–2015, Boston, MA). We measured urinary concentrations of 9 phthalate metabolites and methylparaben, propylparaben, and butylparaben. We estimated the covariate-adjusted percent change in urinary concentrations associated with PCP use using linear mixed and Tobit mixed regressions. We also estimated weights for each PCP in a weighted binary score regression and modeled the resulting composite weighted PCP use.Results:Four hundred men contributed 1,037 urine samples (mean of 3/man). The largest percent increase in monoethyl phthalate (MEP) was associated with use of cologne/perfume (83%, ) and deodorant (74%, ). In contrast, the largest percent increase for parabens was associated with the use of suntan/sunblock lotion (66–156%) and hand/body lotion (79–147%). Increases in MEP and parabens were generally greater with PCP use within 6 h of urine collection. A subset of 10 PCPs that were used within 6 h of urine collection contributed to at least 70% of the weighted score and predicted a 254–1,333% increase in MEP and parabens concentrations. Associations between PCP use and concentrations of the other phthalate metabolites were not statistically significant.Conclusions:We identified 10 PCPs of relevance and demonstrated that their use within 6 h of urine collection strongly predicted MEP and paraben urinary concentrations. https://doi.org/10.1289/EHP1374

Comparison of urinary exposure profiles to phthalates and bisphenol analogues in kindergartens in Korea: Impact of environmental choices on children’s health

Urinary phthalate metabolite concentrations are negatively associated with follicular fluid anti-müllerian hormone concentrations in women undergoing fertility treatment.

Urinary phthalate metabolites and anemia: Findings from the Korean National Environmental Health Survey (2015–2017)

BackgroundPhthalates are ubiquitous in the environment, but concentrations in multiple media from breast-feeding U.S. women have not been evaluated.ObjectivesThe objective of this study was to accurately measure and compare the concentrations of oxidative monoester phthalate metabolites in milk and surrogate fluids (serum, saliva, and urine) of 33 lactating North Carolina women.MethodsWe analyzed serum, saliva, urine, and milk for the oxidative phthalate metabolites mono(3-carboxypropyl) phthalate, mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono(2-ethyl-5-hydroxyhexyl) phthalate, and mono(2-ethyl-5-oxohexyl) phthalate using isotope-dilution high-performance liquid chromatography tandem mass spectroscopy. Because only urine lacks esterases, we analyzed it for the hydrolytic phthalate monoesters.ResultsWe detected phthalate metabolites in few milk (< 10%) and saliva samples. MECPP was detected in > 80% of serum samples, but other metabolites were less common (3–22%). Seven of the 10 urinary metabolites were detectable in ≥ 85% of samples. Monoethyl phthalate had the highest mean concentration in urine. Metabolite concentrations differed by body fluid (urine > serum > milk and saliva). Questionnaire data suggest that frequent nail polish use, immunoglobulin A, and fasting serum glucose and triglyceride levels were increased among women with higher concentrations of urinary and/or serum phthalate metabolites; motor vehicle age was inversely correlated with certain urinary phthalate concentrations.ConclusionsOur data suggest that phthalate metabolites are most frequently detected in urine of lactating women and are less often detected in serum, milk, or saliva. Urinary phthalate concentrations reflect maternal exposure and do not represent the concentrations of oxidative metabolites in other body fluids, especially milk.

Background: Within-person variations in urinary phthalate metabolite concentrations are substantial, but little is known about what predicts these variations. This knowledge is important to the design, analyses and interpretation of epidemiologic studies. We examined whether within-person change in urinary phthalate metabolite concentrations between 1999/2000 and 2002/2003 differed by population characteristics in a cohort of mid-life women. Methods: We measured 11 urinary phthalate metabolites (monoethyl phthalate (MEP), mono-n-butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP), monobenzyl phthalate (MBzP), mono(2-ethylhexyl) phthalate, mono(2-ethyl-5-hydroxyhexyl) phthalate, mono(2-ethyl-5-oxohexyl) phthalate, mono(2-ethyl-5-carboxypentyl) phthalate, mono-carboxyoctyl phthalate (MCOP), mono-carboxy-isononyl phthalate, and mono(3-carboxypropyl) phthalate (MCPP)) in 1221 women who had baseline demographics (age, race/ethnicity, study site, income, education) and dietary data (daily total calorie intake, dietary fat content), menopausal status and hormone therapy (HT) use at both time points. We used multiple linear regression to predict within-person change in metabolite concentrations, defined as the three-year difference in log-transformed metabolite concentrations, with baseline demographics and within-person changes in diet, menopausal status and HT use. Results: Over three years, concentrations of most metabolites significantly decreased, except for MiBP and di(2-ethylhexyl) phthalate (DEHP) metabolites. Income and education were associated with differential changes in MCOP, MCPP, MBzP and DEHP metabolites, but the associations were not monotonic. Increasing intake of dietary fat was significantly associated with smaller decreases in MnBP and MBzP. Compared to women who remained pre-menopausal with no HT use, women who started HT had greater decreases in MnBP and MCPP, while those who used HT at baseline had smaller decreases in MEP. Conclusion: Urinary phthalate metabolite concentrations changed differentially by population characteristics. Secular changes in sources of exposure may not apply uniformly to all socioeconomic groups. Changing behaviors may further alter metabolite concentrations. Given this, taking the mean or constructing trajectories of repeatedly sampled metabolite concentrations may better characterize phthalate exposure over an extended period.