Urinary Phthalate Concentrations Research Articles

Effects of exposure to phthalate during early pregnancy on gestational diabetes mellitus: a nested case-control study with propensity score matching.

Owing to the complexity of phthalates (PAEs) components and the diversity of their sources, the health hazards of their metabolites to pregnant women remain unclear. This study aimed to explore the relationship between exposure to PAEs during early pregnancy and gestational diabetes mellitus (GDM) in rural pregnant women. We assessed pregnant women with (n = 338) or without (n = 3082) GDM from the ongoing Zunyi Birth Cohort. Participants' urine samples were collected to measure the levels of 10 metabolites of PAEs. GDM was diagnosed using the 75-g oral glucose tolerance test at 24-28weeks of gestation. We adopted propensity score matching based on GDM-related factors and pregnant women's backgrounds to establish two groups of 338 patients: those with or without GDM. In the cohort, we included 5734 pregnant women; 519 of them developed GDM, yielding a GDM incidence rate of 9.05%. Urinary concentrations of monooctyl phthalate (MOP), mono-benzyl phthalate (MBzP), mono(2-ethyl-5-oxyhexyl) phthalate (MEOHP), and mono(2-ethyl-5-carboxypentyl) phthalate (MECPP) during early pregnancy were significantly associated with GDM (P < 0.05). Logistic regression models revealed that MEOHP in the urine was positively associated with GDM (odds ratio [OR] = 1.55; 95% confidence interval [CI]: 1.00-2.39). Furthermore, restricted cubic spline models revealed that urine MEOHP concentrations greater than 15.6μg/L were positively associated with GDM, and approximately 23.5% pregnant women had urine MEOHP concentrations greater than 15.6μg/L. Thus, approximately 23.5% of pregnant women were at the risk of developing GDM due to MEOHP, which suggested that pregnant women should reduce the use of packaged food and cosmetics to reduce the risk of GDM. However, further molecular biology experiments are required to confirm these findings and to elucidate the underlying mechanisms.

The Joint Effect of Perceived Psychosocial Stress and Phthalate Exposure on Hormonal Concentrations during the Early Stage of Pregnancy: A Cross-Sectional Study.

Phthalates alter the hormonal balance in humans during pregnancy, potentially affecting embryonic and fetal development. We studied the joint effect of exposure to phthalates, quantified by urinary phthalate metabolite concentration, and perceived psychological stress on the concentration of hormones in pregnant women (n = 90) from the Nitra region, Slovakia, up to the 15th week of pregnancy. We used high-performance liquid chromatography, tandem mass spectrometry (HPLC-MS/MS), and electro-chemiluminescence immunoassay to determine urinary concentrations of phthalates and serum concentrations of hormones, respectively. We used Cohen perceived stress scale (PSS) to evaluate the human perception of stressful situations. Our results showed that mono(carboxy-methyl-heptyl) phthalate (cx-MiNP) and a molar sum of di-iso-nonyl phthalate metabolites (ΣDiNP) were negatively associated with luteinizing hormone (LH) (p ≤ 0.05). Mono(hydroxy-methyl-octyl) phthalate (OH-MiNP) and the molar sum of high-molecular-weight phthalate metabolites (ΣHMWP) were positively associated with estradiol (p ≤ 0.05). PSS score was not significantly associated with hormonal concentrations. When the interaction effects of PSS score and monoethyl phthalate (MEP), cx-MiNP, ΣDiNP, and ΣHMWP on LH were analyzed, the associations were positive (p ≤ 0.05). Our cross-sectional study highlights that joint psychosocial stress and xenobiotic-induced stress caused by phthalates are associated with modulated concentrations of reproductive hormones in pregnant women.

Associations of urinary metabolite concentrations of legacy phthalates and their replacements with body composition from mid-childhood to early adolescence

Associations of urinary metabolite concentrations of legacy phthalates and their replacements with body composition from mid-childhood to early adolescence

Associations between phenols and phthalates and placental weight in a mother-child cohort with improved exposure assessment

Background and Aim: The placenta plays a key role in assuring a normal foetal development and growth. Few epidemiological studies have investigated the effects of phenols and phthalates on placental function. We aimed to explore whether maternal exposure to phenols and phthalates during the second and third pregnancy trimesters are associated with changes in placental weight at birth and placental-to-birth weight ratio (PFR). Methods: We relied on a subsample of 357 women from the French SEPAGES cohort with placental and birth weights assessed, and for whom 8 phenols (4 parabens, 2 bisphenols, triclosan and benzophenone-3), 13 phthalate metabolites and 2 non-phthalate plasticizer metabolites were measured in within-subject pools of repeated urine samples collected at second and third pregnancy trimesters (median= 21 samples/trimester). Adjusted linear regressions were used to evaluate the associations between each compound and placental weight or PFR. Results: Each ln-unit increase in urinary monobenzyl phthalate (MBzP) concentrations at the second and third trimesters was associated with a mean placental weight decrease of 19.67 g (95%CI: -37.94; -1.4) and 16.71 g (95%CI: -33.08; -0.33), respectively. A decrease in PFR was also observed with MBzP exposure at the second (β: -0.51; 95%CI: -0.99; -0.04) and third trimester (β: -0.46; 95%CI: -0.88; -0.03). Children born to mothers with detected/quantified bisphenol S (BPS) in the second trimester showed a significantly lower PFR compared to mothers with undetected BPS (β: -0.83, 95%CI: -1.57; -0.09). No associations were observed with the remaining compounds. Conclusions: This is the first study exploring the effect of BPS maternal exposure on placental function in humans. Our MBzP results are consistent with a previous study that found a similar negative association on placental function in girls, whereas three other studies relying on spot urine samples reported null associations. Keywords: placental weight, phenols, phthalates, pfr, prenatal exposure

P07-35 Time-trends in human urinary concentrations of phthalates and substitutes DEHT and DINCH in Asian and North American countries (2009–2019)

P07-35 Time-trends in human urinary concentrations of phthalates and substitutes DEHT and DINCH in Asian and North American countries (2009–2019)

Microbiome alterations associated with phthalate exposures in a US-based sample of Latino workers

Low-wage service sector jobs are largely occupied by racial/ethnic minority workers who often experience an increased risk of elevated chemical exposures, including chemicals like phthalates, compared to the general public. Phthalates have been linked with adverse health effects, including increased risk of atopy and asthma. An important etiological component in respiratory disease, including asthma, is the role of the upper respiratory microbiota in atopic disease development. However, it is unclear how the upper respiratory microbiome is affected by chemical exposures, and how this may impact respiratory outcomes. As Latino workers are often disproportionately exposed to increased concentrations of chemicals and Hispanics have higher rates of adverse respiratory health conditions such as asthma, the aim of this pilot study was to evaluate the effects of 10 unique phthalate urinary biomarkers on the 16S rRNA nasal microbiome. Nasal and urinary samples were collected from 20 facility workers (plumbers, landscapers, electricians) and 20 custodial workers. Our analysis revealed altered microbial composition and diversity according to phthalate urinary biomarker concentration within the two worker groups. Higher urinary biomarker concentrations of select phthalates (MBP, MBIP, and ∑DEHP) were associated with increased Moraxella relative abundance, which has been positively associated with asthma. Within-sample alpha diversity levels were decreased in facility workers and were generally inversely associated with most phthalate urinary biomarker concentrations. Our research suggests that exposure to chemicals in this vulnerable worker group may impact the respiratory microbiome, which may increase risk of development of adverse health conditions. Further research is warranted to refine the mechanistic pathways that underpin the relationships between phthalate exposures and respiratory microbial communities to provide key insights on respiratory pathologies and, most importantly, to identify modifiable risk factors that can be used to direct mitigation efforts aimed at ameliorating the harmful effects of chemical exposures in this understudied occupational population.

Urinary phthalate concentrations and mortality risk: A population-based study

Phthalates are widely used as plasticizers. Laboratory-based mechanistic and epidemiological studies suggest that phthalates are detrimental to human health. Here, we present prospective analyses on phthalate exposure and all-cause, as well as cause-specific, mortality from the National Health and Nutrition Examination Survey (NHANES), a population-based cohort. Between 1999 and 2018, urinary concentrations of 12 phthalate metabolites were measured by high-performance liquid chromatography-electrospray ionization tandem mass spectrometry in spot urine samples of 10,881 adults aged 40–85 years, of which 2382 died over a median duration of 8.9 years after sample provision. Multivariable Cox regression analyses adjusted for a wide range of lifestyle factors and comorbidities showed that higher concentrations of mono-benzyl phthalate (MBzP) and Mono-n-butyl phthalate (MnBP) were associated with increased mortality. The hazard ratios for participants in the highest quartiles of MBzP and MnBP concentrations were at 1.27 [95% confidence interval: 1.08, 1.49; p linear trend = 0.002] and 1.35 [1.13, 1.62; p linear trend = 0.005). These findings reinforce the need for monitoring of phthalate exposure in relation to health outcomes.

Associations of maternal urinary bisphenol and phthalate concentrations with offspring reproductive development

Fetal exposure to bisphenols and phthalates may influence development of the reproductive system. In a population-based, prospective cohort study of 1059 mother-child pairs, we examined the associations of maternal gestational urinary bisphenols and phthalates concentrations with offspring reproductive development from infancy until 13 years. We measured urinary bisphenol and phthalate concentrations in each trimester. We obtained information on cryptorchidism or hypospadias after birth from medical records. At 9.7 years, we measured testicular and ovarian volume by MRI. At 13.5 years, we measured child Tanner stages and menstruation through questionnaire. We performed linear or logistic regression models for boys and girls to assess the associations of maternal urinary average and trimester-specific bisphenols and phthalates with child reproductive outcomes. Next, to further explore potential synergistic or additive effects of exposures together, we performed mixed exposure models using a quantile g computation approach. Models were adjusted for maternal age, ethnicity, body-mass index, education, parity, energy intake, smoking and alcohol use, and child's gestational age at birth, birthweight and body-mass index. In boys, no associations of maternal gestational phthalate or bisphenol with offspring cryptorchidism and hypospadias were found. Higher maternal high-molecular-weight phthalate and total bisphenol, but not phthalic acid or low-molecular-weight phthalate, were associated with larger child testicular volume at 10 years. Higher maternal phthalic acid and total bisphenol were associated with earlier genital and pubic hair development at 13 years, respectively (p-values<0.05). In girls, we found no associations of maternal urinary bisphenol and phthalate with ovarian volume or menstrual age. Only higher maternal urinary high-molecular-weight phthalate was associated with earlier pubic hair development at 13 years (p-values <0.05). Higher mixture exposure was associated with earlier pubic hair development in both sexes. In conclusion, higher maternal gestational urinary bisphenol and phthalate concentrations were associated with alterations in offspring reproductive development, mainly in boys.

Associations of exposure to melamine, cyanuric acid, phthalates with markers of early kidney impairment, and their interactions in US adults: analyses of NHANES 2003-2004 data.

Melamine (MEL), cyanuric acid (CYA), and phthalates have kidney toxicity, respectively. Still, no study has explored whether there is an interaction of co-exposure to MEL, CYA, and phthalates on early kidney impairment, including cystatin C (CYST), beta 2-microglobulin (β2-MG), albumin creatinine ratio (ACR), and estimated glomerular filtration rate (eGFR). Urine samples were collected from 333 adults in the National Health and Nutrition Examination Survey (NHANES) 2003-2004, and urinary MEL, CYA, and ten metabolites of phthalates were quantified. The multiple markers of early kidney impairment were also measured, including serum CYST, β2-MG, urinary ACR, and eGFR. Their associations were explored by multiple linear and multivariate logistic regression models. Meanwhile, the interactions of co-exposure to MEL, CYA, and phthalates on early kidney impairment were analyzed by Wilcoxon rank-sum test combined with the LSD test. In the multiple linear regression model, urinary concentrations of monobenzyl phthalate (MBzP), mono(3-carboxypropyl) phthalate (MCPP), mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), and mono(2-ethylhexyl) phthalate (MEHP) were positively associated with urinary ACR, serum β2-MG, and CYST, respectively. Urinary concentrations of MBzP and MCPP were negatively associated with eGFR. In the multivariate logistic regression model, increased urinary CYA concentration was the risk factor of CYST abnormality with an odds ratio (OR) (95% confidence interval, 95% CI) of 2.38 (1.01, 5.60) (P = 0.047) and increased urinary MBzP concentration was the risk factor of ACR abnormality with an OR of 2.59 (1.41, 4.75) (P = 0.002). The co-exposure to MEL, CYA, and four phthalate metabolites (MEHP, MBzP, MCPP, and MECPP) presented significantly interactive effects on the markers of early kidney impairment, respectively. There were the independent and interactive effects of exposure to MEL, CYA, and specific phthalate metabolites on early kidney impairment. Due to co-exposure to multiple environmental chemicals in our daily life, more attention should be paid to the health damage raised by the synergistic effects of environmental chemicals.

Urinary phthalate concentrations are associated with total fat mass in Thai children.

Phthalate is one of the endocrine-disrupting chemicals found in many daily consumer products. Chronic exposure to phthalate may associate with obesity and metabolic abnormalities. However, there is limited information showing a direct relationship between phthalate and body compositions. The aim of the study was to determine the association between urinary phthalate concentration and body composition measure among Thai children. A cross-sectional analytic study on urinary phthalate concentrations and body composition in elementary school children, aged 6-13years in Bangkok, was conducted during October 2019 to 2020. Urinary phthalate metabolites; (mono-methyl phthalate-MMP, mono-ethyl phthalate- MEP, mono-buthyl phthalate-MBP, and mono-ethylhexyl phthalate-MEHP), in early morning spot urine samples were measured by liquid chromatography tandem mass spectrometry (LC-MSMS) with a quantitation limit of 1ng/mL. Phthalate exposures were identified through questionnaires. Body composition was measured by Tanita BC-418®. Multivariate logistic regression analysis was performed to determine significant associations. A total of 364 children were enrolled in the study (boy 51.4%). After adjusting for confounders (sex, caregiver educations, family income, BMI-SDS: Body mass index-standard deviation score, TV watching, and exercise frequency), total urinary phthalate concentrations were associated with fat mass 8.24 (0.94, 15.53), trunk percent fat7.69 (3.26, 12.12), arm percent fat 3.69 (0.47, 6.91), arm fat mass 72.88 (1.08, 144.67), and leg fat mass 17.79 (2.37, 33.22). Higher urinary phthalate concentrations were significantly associated with elevated total fat mass among Thai school-aged children. These findings were not mediated through the degree of obesity defined by BMI. These finding emphasized to be careful when being use phthalate-containing products.

Urinary concentration of endocrine-disrupting phthalates and breast cancer risk in Indian women: A case-control study with a focus on mutations in phthalate-responsive genes

BackgroundPhthalates are known endocrine-disrupting chemicals used indiscriminately as constituents in consumer products including food processing, and packaging, cosmetics, personal care and household items. Although, few studies have assessed the risk of breast cancer on exposure to phthalates, their association with breast cancer risk in Indian women have not yet been evaluated. MethodsWe conducted a case-control study involving 171 participants. Urinary concentrations of six phthalate dieters; DMP (Dimethyl phthalate), DEP (Diethyl phthalate), DBP (Dibutyl phthalate), BBP (benzyl butyl phthalate), DEHP (Di-2-ethyl-hexyl phthalate), DINOP (Di-n-octyl phthalate) were estimated by GC-MS and geometric means were calculated. Univariate and multivariable logistic regression was performed to assess breast cancer risk on exposure to phthalates. Genes responsive to phthalates were identified through literature search and matched with NGS data, and gene-enrichment analysis was performed. ResultsSignificant associations were observed between urinary phthalate concentrations and increased risk of breast cancer for di-butyl phthalate (OR=1.5, 95% CI; 1.06, 2.11, p = 0.002) and di-2-ethyl-hexyl phthalate (>median vs ≤ median; OR=2.97, 95% CI; 1.18, 7.47, p = 0.005) in multivariable analyses. We also found several phthalate-responsive gene mutations in paired breast tumor tissues, which include PTPRD (76.19%), AR (42.86%), CYP1A1 (42.86%), CYP19A1 (23.81%), AHRR (19.05%), PIK3CA (19.05%), CYP1B1 (9.52%), RB1 (9.52%) and MMP9 (9.52%). Gene-enrichment analysis revealed that these genes form a major part of ER/PR, PPAR and HIF-1α-TGF-β signaling cascades involved in breast cancer ConclusionAlthough the sample size is small, in this first case-control study from India, DBP and DEHP were found to be associated with increased risk of invasive breast cancer and tumor tissues revealed mutations in several phthalate-responsive genes. It is, therefore suggested that human biomonitoring in India and larger studies evaluating the early life genetic and epigenetic alterations on phthalates exposure are required to establish their role in breast carcinogenesis.

Association of Urinary Phthalate and Phthalate Replacement Metabolite Concentrations with Serum Lipid Biomarker Levels among Pregnant Women Attending a Fertility Center.

We examined whether urinary concentrations of phthalate and phthalate replacement metabolites were associated with lipid biomarker levels among pregnant women. This cross-sectional study included 175 women who enrolled in the Environment and Reproductive Health (EARTH) Study (2005–2017). We used linear regression models to assess the relationship between urinary phthalates and lipid biomarkers [triglycerides, total cholesterol, high density lipoprotein (HDL), non-HDL, and low-density lipoprotein (LDL) cholesterol] levels while adjusting for confounders. Pregnant women in the highest quartile of urinary mono(2-ethyl-5-carboxypentyl) phthalate (MECPP) had, overall, 14% [31 (95% CI = 6.56) mg/dL], 21% [33 (95% CI = 9.57) mg/dL] and 25% [30 (95% CI = 8.53) mg/dL] higher serum total, non-HDL and LDL cholesterol, respectively, compared to women in the lowest quartile of MECPP. Similar positive associations were found for urinary concentrations of other metabolites of di(2-ethylhexyl) phthalate, mono(2-ethylhexyl) phthalate, and mono(2-ethyl-5-oxohexyl) phthalate. Pregnant women with urinary mono-n-butyl phthalate (MBP) in the highest quartile had higher triglycerides and non-HDL cholesterol compared to women with MBP in the lowest quartile. Women with detectable concentrations of two phthalate replacement metabolites had lower HDL cholesterol compared to women with non-detectable concentrations. Gestational urinary concentrations of certain phthalate and phthalate replacement metabolites were associated with lipid levels among these women.

Time-trends in human urinary concentrations of phthalates and substitutes DEHT and DINCH in Asian and North American countries (2009–2019)

BackgroundMany phthalates are environmental pollutants and toxic to humans. Following phthalate regulations, human exposure to phthalates has globally decreased with time in European countries, the US and Korea. Conversely, exposure to their substitutes DEHT and/or DINCH has increased. In other countries, including China, little is known on the time-trends in human exposure to these plasticizers.ObjectiveWe aimed to estimate time-trends in the urinary concentrations of phthalates, DEHT, and DINCH metabolites, in general population from non-European countries, in the last decade.MethodsWe compiled human biomonitoring (HBM) data from 123 studies worldwide in a database termed “PhthaLit”. We analyzed time-trends in the urinary concentrations of the excreted metabolites of various phthalates as well as DEHT and DINCH per metabolite, age group, and country/region, in 2009–2019. Additionally, we compared urinary metabolites levels between continents.ResultsWe found solid time-trends in adults and/or children from the US, Canada, China and Taiwan. DEHP metabolites decreased in the US and Canada. Conversely in Asia, 5oxo- and 5OH-MEHP (DEHP metabolites) increased in Chinese children. For low-weight phthalates, the trends showed a mixed picture between metabolites and countries. Notably, MnBP (a DnBP metabolite) increased in China. The phthalate substitutes DEHT and DINCH markedly increased in the US.SignificanceWe addressed the major question of time-trends in human exposure to phthalates and their substitutes and compared the results in different countries worldwide.ImpactPhthalates account for more than 50% of the plasticizer world market. Because of their toxicity, some phthalates have been regulated. In turn, the consumption of non-phthalate substitutes, such as DEHT and DINCH, is growing. Currently, phthalates and their substitutes show high detection percentages in human urine. Concerning time-trends, several studies, mainly in Europe, show a global decrease in phthalate exposure, and an increase in the exposure to phthalate substitutes in the last decade. In this study, we address the important question of time-trends in human exposure to phthalates and their substitutes and compare the results in different countries worldwide.

Gestational and childhood phthalate exposures and adolescent body composition: The HOME study

BackgroundEarly life phthalate exposures may disrupt metabolism but results from human studies are inconsistent and few have examined body composition during adolescence. We investigated associations of gestational and childhood urinary phthalate biomarker concentrations with body composition at age 12 years. MethodsWe used data from 206 mother-child pairs in a prospective pregnancy and birth cohort enrolled in Cincinnati, OH from 2003 to 2006. We measured nine phthalate metabolites in spot urine samples collected twice from mothers during pregnancy and up to seven times from children at 1, 2, 3, 4, 5, 8, and 12 years. At age 12 years, we assessed fat and lean mass of the whole body and android and gynoid subregions, and visceral fat area with dual x-ray absorptiometry, and calculated android to gynoid %fat ratio and age- and sex-standardized fat and lean mass index z-scores. Using a multiple informant model, we estimated covariate-adjusted associations between urinary phthalate biomarker concentrations at each time period and outcomes at age 12 years. We assessed effect measure modification by child sex using stratified models. ResultsGenerally, urinary mono-benzyl phthalate (MBzP) concentrations were modestly associated with lower fat and lean mass. Each 10-fold increase in urinary MBzP concentrations during gestation and at ages 5 and 8 years was associated with a −0.34 (95%CI: −0.72, 0.05), −0.44 (95% CI: −0.83, −0.05), and −0.35 (95% CI: −0.71, 0.00) z-score difference in lean body mass index, respectively. Urinary monoethyl phthalate, mono-(3-carboxypropyl) phthalate, and summed di(2-ethylhexyl) phthalate metabolites were associated with greater lean mass at some exposure periods. Slightly weaker but similar patterns of association were found with other body composition measures; associations did not differ by child sex. ConclusionWhile most associations were weak, exposure to certain phthalates during gestation and childhood may be associated with adolescent body composition, particularly lean mass.

Maternal Phthalate and Bisphenol Urine Concentrations during Pregnancy and Early Markers of Arterial Health in Children.

Background:Fetal exposure to endocrine-disrupting chemicals such as phthalates and bisphenols might lead to fetal cardiovascular developmental adaptations and predispose individuals to cardiovascular disease in later life.Objectives:We examined the associations of maternal urinary bisphenol and phthalate concentrations in pregnancy with offspring carotid intima-media thickness and distensibility at the age of 10 y.Methods:In a population-based, prospective cohort study of 935 mother–child pairs, we measured maternal urinary phthalate and bisphenol concentrations at each trimester. Later, we measured child carotid intima-media thickness and distensibility in the children at age 10 y using ultrasound.Results:Maternal urinary average or trimester-specific phthalate concentrations were not associated with child carotid intima-media thickness at age 10 y. Higher maternal average concentrations of total bisphenol, especially bisphenol A, were associated with a lower carotid intima-media thickness [differences standard deviation score and 95% confidence interval (CI): , and (95% CI: , ) per interquartile range (IQR) increase in maternal urinary total bisphenol and bisphenol A concentration]. Trimester-specific analysis showed that higher maternal third-trimester total bisphenol and bisphenol A concentrations were associated with lower child carotid intima-media thickness [differences (95% CI: , ) and (95% CI: , ) per IQR increase in maternal urinary bisphenol concentration]. Maternal urinary bisphenol or phthalate concentrations were not associated with child carotid distensibility.DISCUSSION:In this large prospective cohort, higher maternal urinary bisphenols concentrations were associated with smaller childhood carotid intima-media thickness. Further studies are needed to replicate this association and to identify potential underlying mechanisms. https://doi.org/10.1289/EHP10293

Urinary Phthalate Biomarkers during Pregnancy, and Maternal Endocrine Parameters in Association with Anthropometric Parameters of Newborns.

Adverse birth outcomes present risk factors resulting in neonatal morbidity and mortality. Sufficient maternal hormonal concentrations are crucial for normal foetal development. Previous studies have shown a relationship between phthalate exposure and maternal hormonal levels during pregnancy. This study aims to investigate if neonatal anthropometric parameters are associated with maternal endocrine parameters during the ≤15th week of gestation and the third trimester of pregnancy concerning phthalate exposure in pregnant women from Nitra, Slovakia. We used high-performance liquid chromatography, tandem mass spectrometry (HPLC-MS/MS), and electro-chemiluminescence immunoassay to quantify urinary concentrations of phthalates and serum concentrations of hormones and sex hormone-binding globulin (SHBG), respectively. We observed a mostly positive correlation between neonatal anthropometric parameters (gestational age, birth length, birth weight, head circumference) and maternal concentration of phthalate metabolites (p ≤ 0.05). The hierarchical multivariate regression results showed a statistically significant association between Apgar score at 5 min after delivery, gestational age, birth weight, head circumference, and maternal endocrine parameters during pregnancy (p ≤ 0.05), adjusted to phthalate metabolites. To the best of our knowledge, our study is the first to indicate that prenatal exposure to phthalates may also affect birth outcomes through interaction with the maternal endocrine system.

Risk of Nonalcoholic Fatty Liver Disease Is Associated with Urinary Phthalate Metabolites Levels in Adults with Subclinical Hypothyroidism: Korean National Environmental Health Survey (KoNEHS) 2012-2014.

Nonalcoholic fatty liver disease (NAFLD) is a condition of excess accumulation of fats in the liver. Thyroid dysfunction is commonly observed in adult populations with NAFLD. In subjects with thyroid dysfunction, phthalates, which are chemical compounds widely used to increase the flexibility of various plastic products, may increase the risk of NAFLD prevalence. Therefore, our study aimed to evaluate the relationship between the levels of urinary phthalate metabolites and the risk of NAFLD stratified by the levels of thyroid-stimulating hormone (TSH). Data (n = 2308) were obtained from the Korean National Environmental Health Survey II (2012–2014). Using the hepatic steatosis index, participants were classified into non-NAFLD (<30) and NAFLD (>36) groups. Participants with euthyroidism were defined as 0.45–4.5 mIU/L for serum TSH and normal thyroxine (T4) levels (n = 2125). Subclinical hypothyroidism (SCH) was defined as a higher TSH level (4.5–10 mIU/L) with normal total T4 levels in the serum (n = 183). A multivariate analysis was performed to assess the association of the urinary phthalate concentration with the risk of NAFLD after stratification based on the thyroid hormone levels. The levels of phthalate metabolites in urine were not significantly associated with NAFLD in adults with euthyroidism. However, a significant increased risk of NAFLD in those with SCH was observed in the fourth quartile of mono (2-ethyl-5-hydroxyhexyl) phthalate (odds ratio (OR) 13.59, 95% confidence interval (CI) 12.13–86.44), mono (2-ethyl-5-oxohexyl) phthalate (OR 8.55, 95% CI 1.20–60.53), mono-(2-ethyl-5-carboxypentyl) phthalate (OR 9.06, 95% CI 1.78–45.96), and mono-benzyl phthalate (OR 6.05, 95% CI 1.62–22.54) compared to those of the lowest quartile after being adjusted with covariates. In conclusion, the levels of phthalate metabolites in urine are positively associated with NAFLD in adults with SCH. More experimental studies are needed to clarify the risk of NAFLD caused by phthalate exposure in cases with poor thyroid function.

Low-level plasticizer exposure and all-cause and cardiovascular disease mortality in the general population

BackgroundPlasticizers, also called phthalates, are a group of chemicals widely used in daily life. A previous report showed no significant association between phthalate metabolite concentrations and mortality. We investigated the association of urinary phthalate levels and individual phthalate metabolite levels with all-cause and cardiovascular disease (CVD) mortality after standardizing the phthalate concentration.MethodsA total of 6,625 participants were recruited from a nationally representative sample of adults aged 40 years or older who were enrolled in the National Health and Nutrition Examination Survey (NHANES) between 2003 and 2014 and were followed up through December 31, 2015. Data were analyzed from January 2021 to June 2021. NHANES-linked updated National Death Index public access files were used to acquire information on mortality status and cause of death. The present study conducted extended follow-up of an earlier analysis. Cox proportional hazard models were performed to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) of covariate-adjusted creatinine standardization urinary phthalate concentrations with all-cause and CVD mortality after adjusting for demographics, lifestyle factors and comorbidity variables.ResultsThe mean ± standard deviation age of all participants in the final study was 59.9±12.6 years old, and 49.6% of the participants were male. The median follow-up time was 73 months (range 1-157 months). At the censoring date of December 31, 2015, 3,023 participants were identified as deceased (13.4%). A fully adjusted Cox model showed that a urinary di(2-ethylhexyl) phthalate (DEHP) concentration >= 83.4 ng/mL was associated with a slight increase in all-cause mortality (HR 1.27, 95% CI 1.03, 1.57, P for trend= 0.014) and CVD mortality (HR 2.19, 95% CI 1.35, 3.54, P for trend= 0.002). Similarly, urinary mono-2-ethyl-5-carboxypentyl phthalate (MECPP) levels >= 39.2 ng/mL were associated with increased CVD mortality (HR 2.33, 95% CI 1.45, 3.73, P for trend < 0.001). Restricted cubic spline analyses suggested linear associations of DEHP and MECPP levels with all-cause and CVD mortality.ConclusionIn this large nationally representative sample of American adults, high urinary DEHP and MECPP were significantly associated with all-cause and CVD mortality after adjusting for demographics, lifestyle factors and comorbidity variables.

Phthalate exposure and risk of diabetes mellitus: Implications from a systematic review and meta-analysis.

Epidemiologic studies indicated that phthalate exposure might be associated with diabetes mellitus (DM). However, discrepancies existed. The link between phthalate exposure and risk of DM remained unclarified. We conducted a meta-analysis to explore the association between phthalate exposure and risk of DM. Effects of phthalate exposure on insulin resistance were also evaluated by systematic review. Seven studies involving 12,139 participants were included in this meta-analysis. Our results showed that urinary concentrations of phthalates were positively associated with risk of DM. The pooled ORs were 3.11 (95% CI: 1.16-8.37) for monomethyl phthalate (MMP), 1.27 (95% CI: 1.03-1.56) for mono-n-butyl phthalate (MnBP), 2.59 (95% CI: 1.10-6.10) for mono-isobutyl phthalate (MiBP), 1.99 (95% CI: 1.52-2.61) for mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), 1.90 (95% CI: 1.40-2.57) for mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), 1.55 (95% CI: 1.10-2.20) for mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), and 2.39 (95% CI: 1.18-4.85) for mono-(3-carboxypropyl) phthalate (MCPP), respectively. Molar summation of di-2-ethylhexyl phthalate metabolites (∑DEHP) was also found to be correlated with risk of DM (OR 2.15, 95% CI: 1.48-3.13). No significant association with risk of DM was found regarding monoethyl phthalate (MEP), monobenzyl phthalate (MBzP) and mono(2-ethylhexyl) phthalate (MEHP). In literature review, most studies showed positive correlations of phthalates, especially ∑DEHP, with homeostasis model assessment of insulin resistance and fasting glucose. Exposure to phthalates, especially MMP, MnBP, MiBP, MCPP and DEHP metabolites, might be a risk factor of DM. Our results should be interpreted with caution due to heterogeneous design of enrolled studies.

Effect of the phthalates exposure on sex steroid hormones in the US population

BackgroundNew alternative phthalates have been increasingly substituted for certain phthalates in some consumer products due to safety concerns. However, research on the steroidal effect of exposure to the newer replacement phthalates in the general adult population is lacking. ObjectivesThis study aimed to examine the associations of exposure to the older generation and newer replacement phthalates with sex hormone levels in the U.S. general population. MethodsThe current cross-sectional study was based on the National Health and Nutrition Examination Survey (NHANES) 2015–2016. Sixteen urinary phthalates metabolites and three serum sex hormones were measured in 1768 adults. Gender-specific associations between urinary phthalate concentrations and sex hormones were estimated by using adjusted multiple linear regression. Logistic regression was performed to calculate the risk of phthalates exposure on hormones dysfunction. ResultsMost phthalates metabolites concentrations were lower than 50 ng/mL. MEP, MBP, MiBP, MECPP, MCOP, MEHHP, MEOHP were higher than others, suggesting that new alternative DEP, DBP, and DiNP were exposed at high levels in daily life while DINCH was at a low level. Phthalates exposure was associated with decreased testosterone levels and increased estradiol and SHBG in total samples. Testosterone level was negatively associated with MnBP (β: −0.05, 95% CI: −0.09, 0), MEOHP (β:−0.05, 95% CI:−0.09,−0.01), MEHHP (β:−0.04, 95% CI:−0.08,0), MECPP (β:−0.07, 95% CI:−0.11,−0.03), MEP (β: −0.03, 95% CI: −0.06, 0), MiBP (β: −0.05, 95% CI: −0.10, −0.01) in males; ln-transformed estradiol were increased by 0.18 pg/mL (95% CI: 0.05,0.31), 0.15 pg/mL (95% CI: 0.01,0.29) with each 1 ln-concentration increase in MEHP and MNP, respectively, in females. ConclusionsOur results suggest that phthalates exposure may disturb the hormone homeostasis in adults. The safe alternative should be used with caution in industrial production in the future and the need for further research into the safety of the new alternative replacements is necessary.