Urinary Paraben Concentrations Research Articles

A large-scale survey of urinary parabens and triclocarban in the Chinese population as well as the influencing factors and health risks

Parabens and triclocarban are widely applied as antimicrobial preservatives in foodstuffs, pharmaceuticals, cosmetics, and personal care products. However, few studies have been conducted on large-scale biomonitoring of parabens and triclocarban in the Chinese general population. In the present study, there were 1157 urine samples collected from 26 Chinese provincial capitals for parabens and triclocarban measurement to evaluate the exposure levels, spatial distribution, and influencing factors, as well as associated health risks in the Chinese population. The median concentrations of Σparabens and triclocarban were 14.0 and 0.03 μg/L, respectively. Methyl paraben was the predominant compound. Subjects in western China were more exposed to parabens, possibly due to climate differences resulting in higher consumption of personal care products. Subjects who were female, aged 18–44 years, or had a higher education level were found to have higher paraben concentrations. The frequency of drinking bottled water was positively associated with paraben exposure. The assessment of health risk based on urinary paraben concentrations indicated that 0.8 % of the subjects had a hazard index exceeding one unit, while Monte Carlo analysis suggested that 3.6 % of the Chinese population exposure to parabens had a potential non-carcinogenic risk. This large-scale biomonitoring study will help to understand the exposure levels of parabens and triclocarban in the Chinese general population and provide supporting information for government decision-making.

Paternal and maternal preconception and maternal pregnancy urinary concentrations of parabens in relation to child behavior.

Epidemiologic studies of the effects of parental preconception paraben exposures on child behavior are limited despite emerging evidence suggesting that such exposures may affect offspring neurodevelopment. We investigated whether maternal and paternal preconception and maternal pregnancy urinary concentrations of parabens were associated with child behavior. We analyzed data from the Preconception Environmental exposure And Childhood health Effects Study, an ongoing prospective cohort of children aged 6-13 years and their parents. We estimated covariate-adjusted associations of loge -transformed urinary methyl, propyl, and butyl paraben concentrations (individually using linear regression models and as a mixture using quantile g-computation) collected prior to conception and during pregnancy with Behavioral Assessment System for Children-3 and Behavior Rating Inventory of Executive Function T-scores (higher scores indicate more problem behaviors). This analysis included 140 mothers, 81 fathers, and 171 children (25 sets of twins); parents were predominantly non-Hispanic white (88% for both mothers and fathers). In single paraben models, higher paternal preconception urinary propyl and methyl paraben concentrations were associated with higher Internalizing Problem T-scores (propyl paraben =1.7; 95% confidence interval: 0.6, 2.8, methyl paraben =2.2; 95% confidence interval: 0.5, 3.9) and higher Behavioral Symptom Index T-scores (propyl paraben =1.4; 95% confidence interval: 0.3, 2.5, methyl paraben =1.6; 95% confidence interval: -0.1, 3.3). Each quantile increase in the paternal mixture of three parabens was associated with a 3.4 (95% confidence interval: 0.67, 6.1) and 2.5 (95% confidence interval: 0.01, 5.0) increased internalizing problem and Behavioral Symptom Index T-scores respectively. Higher paternal preconception ( =1.0; 95% confidence interval: 0.04, 1.9) and maternal preconception ( =1.1 95% confidence interval: -0.1, 2.2) concentrations of propyl paraben were associated with higher Behavior Rating Inventory of Executive Function Metacognition Index T-scores in children, but the paraben mixtures was not. In this cohort, paternal preconception urinary concentrations of propyl and methyl paraben were associated with worse parent-reported child behaviors.

Urinary concentration of phenols and parabens, and biomarkers of oxidative stress in pregnant women

Urinary concentration of phenols and parabens, and biomarkers of oxidative stress in pregnant women

Urinary Paraben Concentrations and Associations with the Periconceptional Urinary Metabolome: Untargeted and Targeted Metabolomics Analyses of Participants from the Early Pregnancy Study.

Parabens, found in everyday items from personal care products to foods, are chemicals with endocrine-disrupting activity, which has been shown to influence reproductive function. This study investigated whether urinary concentrations of methylparaben, propylparaben, or butylparaben were associated with the urinary metabolome during the periconceptional period, a critical window for female reproductive function. Changes to the periconceptional urinary metabolome could provide insights into the mechanisms by which parabens could impact fertility. Urinary paraben concentrations were measured in paired pre- and postconception urine samples from 42 participants in the Early Pregnancy Study, a prospective cohort of 221 women attempting to conceive. We performed untargeted and targeted metabolomics analyses using ultrahigh-performance liquid chromatography quadrupole time-of-flight mass spectrometry. We used principal component analysis, orthogonal partial least-squares discriminant analysis, and permutation testing, coupled with univariate statistical analyses, to find metabolites associated with paraben concentration at the two time points. Potential confounders were identified with a directed acyclic graph and used to adjust results with multivariable linear regression. Metabolites were identified using fragmentation data. Seven metabolites were associated with paraben concentration (variable importance to projection score , false discovery rate-corrected ). We identified four diet-related metabolites to the Metabolomics Standards Initiative (MSI) certainty of identification level 2, including metabolites from smoke flavoring, grapes, and olive oil. One metabolite was identified to the class level only (MSI level 3). Two metabolites were unidentified (MSI level 4). After adjustment, three metabolites remained associated with methylparaben and propylparaben, two of which were diet-related. No metabolomic markers of endocrine disruption were associated with paraben concentrations. This study identified novel relationships between urinary paraben concentrations and diet-related metabolites but not with metabolites on endocrine-disrupting pathways, as hypothesized. It demonstrates the feasibility of integrating untargeted metabolomics data with environmental exposure information and epidemiological adjustment for confounders. The findings underscore a potentially important connection between diet and paraben exposure, with applications to nutritional epidemiology and dietary exposure assessment. https://doi.org/10.1289/EHP12125.

Associations between urinary parabens and lung cancer.

Parabens are a family of endocrine-disrupting chemicals. Environmental estrogens may play a vital role in the development of lung cancer. To date, the association between parabens and lung cancer is unknown. Based on the 189 cases and 198 controls recruited between 2018 and 2021 in Quzhou, China, we measured 5 urinary parabens concentrations and examined the association between urinary concentrations of parabens and lung cancer risk. Cases showed significantly higher median concentrations of methyl-paraben (MeP) (2.1 versus 1.8ng/mL), ethyl-paraben (0.98 versus 0.66ng/mL), propyl-paraben (PrP) (2.2 versus 1.4ng/mL), and butyl-paraben (0.33 versus 0.16ng/mL) than controls. The detection rates of benzyl-paraben were only 8 and 6% in the control and case groups, respectively. Therefore, the compound was not considered in the further analysis. The significant correlation between urinary concentrations of PrP and the risk of lung cancer (odds ratio (OR)adjusted = 2.22, 95% confidence interval (CI): 1.76, 2.75; Ptrend < 0.001) was identified in the adjusted model. In the stratification analysis, we found that urinary concentrations of MeP were significantly associated with lung cancer risk (OR = 1.16, 95% CI: 1.01, 1.27 for the highest quartile group). Besides, comparing the second, third, and fourth quartile groups with the lowest group of PrP, we also observed urinary PrP concentrations associated with lung cancer risk, with the adjusted OR of 1.52 (95% CI: 1.29, 1.65, Ptrend = 0.007), 1.39 (95% CI: 1.15, 1.60, Ptrend = 0.010), and 1.85 (95% CI: 1.53, 2.30, Ptrend = 0.001), respectively. MeP and PrP exposure, reflected in urinary concentrations of parabens, may be positively associated with the risk of lung cancer in adults.

Urinary concentrations of bisphenols and parabens and their association with attention, hyperactivity and impulsivity at adolescence

BackgroundNeurobehavioural disorder diagnoses have been increasing over the last decades, leading to heightened interest in the aetiological factors involved. Endocrine disrupting chemicals, such as parabens and bisphenols, have been suggested as one of those factors. It is unknown whether exposure during adolescence may affect neurobehavioural development. ObjectiveTo determine whether urinary concentrations of parabens and bisphenols are associated with attention and concentration in adolescents, in general and sex-specific. MethodsWe invited 188 adolescents (13–15 years old) for the follow-up birth cohort-study. Concentrations of five parabens and three bisphenols (BPA; BPF; BPS) were measured in morning urine after overnight fasting, using a validated LC-MS/MS method. Attention and concentration were assessed at the clinic with subtests of the Test of Everyday Attention in Children and the Dutch Attention Deficit Hyperactivity Disorder questionnaire (AVL), the latter being filled in by parents. Linear regression analyses were performed, adjusting for urine creatinine concentrations and potential confounding factors. Results101 (54%) adolescents participated (46 girls; 55 boys). Urinary paraben concentrations were higher in girls than in boys. Methylparaben was positively associated with attention in girls (p ≤ .05; B= −2.836; 95%CI= −5.175;−.497), ethylparaben negatively with hyperactivity (p ≤ .05; B= −1.864; 95%CI= −3.587;−.141). Butylparaben was associated with more optimal scores on parent reported attention. Propylparaben was negatively associated with scores on sustained auditory attention in girls (p ≤ .10; B=.444; 95%CI= −.009;.896). Bisphenol concentrations were not associated with scores on attention and concentration after adjusting for confounders. ConclusionIn 13–15-year-old Dutch adolescents, urinary concentrations of methylparaben and ethylparaben were associated with better attention and less hyperactivity, whereas a trend toward significance was found between higher urinary propylparaben concentrations and poorer attention. Bisphenol concentrations were not associated with attention and concentration after adjusting for confounders.

Within-day variability, predictors, and risk assessments of exposure to parabens among Chinese adult men

BackgroundParabens, as suspected endocrine disruptors, are widely used in personal care products and pharmaceuticals. However, variability, predictors, and risk assessments of human exposure to parabens are not well characterized. ObjectiveTo evaluate within-day variability, predictors, and risk assessments of exposure to parabens among Chinese adult men. MethodsWe measured four parabens including methylparaben (MeP), ethylparaben (EtP), propylparaben (PrP), and butylparaben (BuP) in repeated urine samples from 850 Chinese adult men. We examined the variability by intraclass correlation coefficients (ICCs) and identified the predictors by multivariable linear mixed models. We assessed risks of paraben exposures based on the estimated daily intake (EDI). ResultsThe four parabens were detected in >76% of urinary samples. We observed fair to good to high reproducibility (ICCs: 0.71 to 0.86) for urinary paraben concentrations within one day. Use of facial cleanser was associated with higher four urinary paraben concentrations. Increasing age, taking medicine, intravenous injection, and interior decoration in the workplace were related to higher urinary concentrations of specific parabens. Smoking and drinking were associated with lower urinary concentrations of specific parabens. The maximum EDIs for the four parabens ranged from 13.76 to 848.68 μg/kg bw/day, and 0.9% of participants had the hazard quotient values > 1 driven by PrP exposure. ConclusionsUrinary paraben concentrations were less variable within one day. Several lifestyle characteristics including use of facial cleanser and pharmaceuticals may contribute to paraben exposures.

Associations between urinary paraben concentrations and measures of cardiometabolic risk in pre-school children of the ENVIRONAGE birth cohort

Background and Aim: Parabens are widely used as antimicrobial preservatives in personal care products. Endocrine-disrupting effects have been described previously, but studies investigating obesogenic or cardiovascular effects have shown discordant results. Cardiometabolic changes associated with paraben exposure and predictive for later life health conditions may already be visible in early life. Methods: Paraben concentrations [methyl (MeP), ethyl (EtP), propyl (PrP), and butyl (BuP)] were measured by ultra-performance liquid chromatography/tandem mass spectrometry in 300 urinary samples from 4-6-year-old children of the ENVIRONAGE birth cohort. Values below the limit of quantification (LOQ) were imputed by censored likelihood multiple imputation. The association with anthropometric and cardiovascular measurements (BMI z-scores, waist circumference, blood pressure and retinal microvasculature) was analyzed in multiple linear regression models with a priori selected covariates. Effect modification by sex was investigated by including interaction terms. Results: The geometric means (geometric SD) of urinary MeP, EtP, and PrP levels above the LOQ were 32.60 (6.64), 1.26 (3.50), and 4.82 (4.11) µg/L respectively. For BuP 97% of all measurements were below the LOQ. In adjusted models with log-transformed paraben values MeP was associated with central retinal venular equivalent (β = 1.33, p = 0.029) and inversely associated with BMI z-scores (β = -0.065, p = 0.019). PrP was associated with the retinal tortuosity index (β = 0.0018, p = 0.0034). Additionally, EtP was significantly associated with BMI z-scores in boys (β = 0.12, p = 0.012). Conclusions: The inverse association between MeP and BMI z-scores could illustrate underlying biological mechanisms related to endocrine-disrupting properties of parabens. Associations between parabens and retinal microvasculature in pre-school children may indicate adverse effects on cardiometabolic health even at a young age and provide a starting point for further research on paraben-related modes of action. Keywords: Parabens, BMI z-scores, blood pressure, retinal microvasculature, ENVIRONAGE birth cohort

Maternal diet quality moderates associations between parabens and birth outcomes

Background/objectiveMaternal paraben exposure and diet quality are both independently associated with birth outcomes, but whether these interact is unknown. We assessed sex-specific associations of parabens with birth outcomes and differences by maternal diet quality. MethodsIllinois pregnant women (n = 458) provided five first-morning urines collected at 8–40 weeks gestation, which we pooled for quantification of ethylparaben, methylparaben, and propylparaben concentrations. We collected/measured gestational age at delivery, birth weight, body length, and head circumference within 24 h of birth, and calculated sex-specific birth weight-for-gestational-age z-scores and weight/length ratio. Women completed three-month food frequency questionnaires in early and mid-to-late pregnancy, which we used to calculate the Alternative Healthy Eating Index (AHEI)-2010. Linear regression models evaluated sex-specific associations of parabens with birth outcomes, and differences in associations by average pregnancy AHEI-2010. ResultsIn this predominately non-Hispanic white, college-educated sample, maternal urinary paraben concentrations were only modestly inversely associated with head circumference and gestational length. However, methylparaben and propylparaben were inversely associated with birth weight, birth weight z-scores, body length, and weight/length ratio in female, but not male newborns. For example, each 2-fold increase in methylparaben concentrations was associated with −46.61 g (95% CI: −74.70, −18.51) lower birth weight, −0.09 (95% CI: −0.15, −0.03) lower birth weight z-scores, −0.21 cm (95% CI: −0.34, −0.07) shorter body length, and −0.64 g/cm (95% CI: −1.10, −0.19) smaller weight/length ratio in females. These inverse associations were more prominent in females of mothers with poorer diets (AHEI-2010 < median), but attenuated in those with healthier diets (AHEI-2010 ≥ median). In newborn males of mothers with healthier diets, moderate inverse associations emerged for propylparaben with gestational length and head circumference. ConclusionsMaternal diet may moderate associations of parabens with birth size in a sex-specific manner. Additional studies may consider understanding the inflammatory and metabolic mechanisms underlying these findings.

Urinary paraben concentrations of adult women by fasting status: Comparison between Korea and the United States

Personal care products (PCPs) are considered as a major source of paraben exposure; however, the dietary contribution is not well known. We compared the urinary levels of methyl-, ethyl-, and propyl-paraben (MeP, EtP, and PrP), and investigated their associations with fasting status and contacts with other potential exposure sources among Korea and the US adult women.A group of fasting, non-pregnant adult women (n = 469) was recruited from Seoul, Ansan/Incheon, and Jeju, Korea in 2015–2016, and their urine was measured for parabens. Non-fasting Korean women of matching age (25–45 years) were chosen from the Korean National Environmental Health Survey (KoNEHS) Cycle 3 (n = 579). For the US women, both fasting (n = 154) and non-fasting (n = 201) females were chosen from the NHANES 2015–2016 participants.In fasting Korean women, the urinary MeP, EtP, and PrP concentrations (median) were measured at 47.30, 17.90, and 2.30 ng/mL, respectively. Urinary EtP and PrP levels in fasting Korean women were significantly lower than those in non-fasting women (EtP and PrP median of 26.40 and 3.57 ng/mL). On average, the difference in urinary EtP levels by fasting status was greater among the highly exposed groups. In the US population, EtP levels were significantly lower (median ranged 1.55–1.80 ng/mL depending on fasting status), but MeP levels were higher (67.90–84.35 ng/mL) than those of the Korean population. When only fasting women were considered, the median EtP levels of Korean women were 11.5-fold greater than those of US women, suggesting that the non-dietary contributions of EtP exposure could not be ignored among Korean women. Regardless of fasting status, MeP and PrP were significantly correlated, and their urinary levels in fasting Korean women were correlated with the use of several personal care products. The major dietary and non-dietary sources that may explain EtP exposure in Korean women warrant further investigation.

Paraben exposures and their interactions with ESR1/2 genetic polymorphisms on hypertension

The widely used paraben preservatives have been frequently detected in human urine, and shown to disrupt the endocrine system. Recently, several epidemiologic studies have investigated the associations between paraben exposures and hypertension risk, but findings are inconsistent. Genetic susceptibility variation may contribute to the conflicting results. This study aimed to explore the associations of paraben exposures and their interactions with estrogen receptor genes 1 and 2 (ESR1 and ESR2) polymorphisms with hypertension. We conducted a hospital-based case-control study involving 396 hypertension cases and 396 controls in Wuhan, China. The urinary paraben concentrations were determined using a liquid chromatography-quadrupole time of flight mass spectrometer. The genotyping of ESR1 and ESR2 was performed using the Applied Biosystems 3730 XL sequencer. Multivariable logistic regression models were applied to examine the associations between urinary paraben concentrations and hypertension risk. Gene-environment interactions were estimated on both multiplicative and additive scales. The results showed that urinary ethylparaben (EtP), propylparaben (PrP), and ∑parabens (∑PBs) levels were positively associated with the risk of hypertension (Ptrend<0.05). Compared with their reference groups, subjects in the highest tertile of EtP, PrP, and ∑PBs had a 4.05-fold (95% CI: 2.56, 6.41), 2.72-fold (95% CI: 1.76, 4.20), and 1.60-fold (95% CI: 1.08, 2.36) increased risk of hypertension, respectively. When stratified by sex, the hypertensive effect of EtP was more pronounced in males (Pinteraction = 0.012). Furthermore, interaction analysis showed that PrP exposure interacted with ESR1 rs2234693 polymorphism on hypertension risk, with the significance of multiplicative (Pinteraction = 0.043) and additive (RERI = 1.27, AP = 0.52). Our results suggested that paraben exposure was positively related to hypertension risk, and that ESR1 rs2234693 polymorphism might modify the parabens exposure-related hypertensive effect.

Concentrations of urinary parabens and reproductive hormones in Iranian women: Exposure and risk assessment

Parabens are antimicrobial preservatives in a variety of processed foods and beverages, cosmetics, pharmaceuticals, and personal care products. Parabens may be associated with reproductive and endocrine disorders among women of reproductive age. The first objective of this study was to examine the association between urinary parabens concentrations and follicle-stimulating hormone(FSH), luteinizing hormone (LH), and prolactin disorders. The second objective of this study was to calculate the Hazard Quotient (HQ) and Margin of Exposure (MOE) to assess the potential risk for endocrine disrupts for each woman based on urinary paraben concentrations. To address these two objectives, a cross-sectional study was designed in the Imam Reza Hospital in Kermanshah. The association between early morning urinary paraben concentrations and the serum of fasting blood specimens was analyzed using multivariable linear regressions adjusted for confounding variables (i.e., creatinine, age, body mass index, and time spent on physical activity). Among the 96 women who participated in the study, those with BMI> 25 and aged 18–40 years showed higher levels of total urinary parabens. The highest sum of urinary parabens (54,955.16 µg/L) was observed among the women who were using toothpaste several times per day. Almost all the parabens such as methyl paraben(MeP), ethyl paraben(EtP), propyl paraben(PrP), butyl paraben(BuP) had a positive and negative significant association with serum concentrations of FSH and LH (p-value < 0.05). However, no significant association was found between any of the four parabens and serum prolactin hormone (p-value > 0.05). The Margin of Exposure (MOE) approach calculated for all parabens (<10000) showed a potential risk in the studied population. The results suggested that parabens could adversely affect reproductive and endocrine systems in women. Further studies relying on long-term exposure to parabens are necessary to better understand the potential risk of the association between urinary parabens concentrations with reproductive hormones.

Variability of Urinary Concentrations of Phenols, Parabens, and Triclocarban during Pregnancy in First Morning Voids and Pooled Samples.

Urinary concentrations of phenols, parabens, and triclocarban have been extensively used as biomarkers of exposure. However, because these compounds are quickly metabolized and excreted in urine, characterizing participants' long-term average exposure from a few spot samples is challenging. To examine the variability of urinary concentrations of these compounds during pregnancy, we quantified four phenols, four parabens, and triclocarban in 357 first morning voids (FMVs) and 203 pooled samples collected during the second and third trimesters of 173 pregnancies. We computed intraclass correlation coefficients (ICCs) by the sample type (FMV and pool) across two trimesters and by the number of composite samples in pools, ranging from 2 to 4, within the same trimester. Among the three compounds detected in more than 50% of the samples, the ICCs across two trimesters were higher in pools (0.29-0.68) than in FMVs (0.17-0.52) and the highest ICC within the same trimester was observed when pooling either two or three composites. Methyl paraben and propyl paraben primarily exposed via cosmetic use had approximately 2-3 times higher ICCs than bisphenol A primarily exposed via diet. Our findings support that within-subject pooling of biospecimens can increase the reproducibility of pregnant women's exposure to these compounds and thus could potentially minimize exposure misclassification.

Increased Prevalence of Atopic Dermatitis in Children Aged 0-3 Years Highly Exposed to Parabens.

The prevalence of allergic diseases, such as bronchial asthma, atopic dermatitis, nasal allergies (pollinosis), and food allergies, has been increasing in many countries. The hygiene hypothesis was recently considered from the perspective of exposure to antimicrobial agents and preservatives, such as parabens (CAS number, 94-13-3). It currently remains unclear whether parabens, which are included in many daily consumer products such as cosmetics, shampoos, and personal care products as preservative antimicrobial agents, induce or aggravate allergies. Therefore, the aim of the present study was to examine the relationship between exposure to parabens and the prevalence of allergic diseases in Japanese children. The cross-sectional epidemiology of 236 children aged 0–3 years who underwent health examinations in Shika town in Japan assessed individual exposure to parabens using urinary concentrations of parabens. The results obtained showed that the prevalence of atopic dermatitis was significantly higher in children with high urinary concentrations of parabens than in those with low concentrations (p < 0.001). This relationship remained significant after adjustments for confounding factors, such as age, sex, Kaup’s index, and passive smoking (p < 0.001). In conclusion, the present results from a population study suggested a relationship between atopic dermatitis and exposure to parabens. A longitudinal study using a larger sample number and a detailed examination of atopic dermatitis, including EASI scores and exposure to parabens, will be necessary.

Urinary concentrations of phenols and parabens and incident diabetes in midlife women: The Study of Women's Health Across the Nation.

Environmental phenols have been suggested as diabetogens but evidence from prospective cohort studies is limited. We examined associations between urinary concentrations of phenols and parabens, assessed at two time-points, and incident diabetes in the Study of Women's Health Across the Nation (SWAN). We examined 1,299 women, aged 45-56 years, who were diabetes-free at baseline of the SWAN Multi-Pollutant Study (MPS) (1999-2000) and were followed through January 2017. Urinary concentrations of bisphenol-A, bisphenol-F, triclosan, 2,4-dichlorophenol, 2,5-dichlorophenol, benzophenone-3, methyl-paraben, ethyl-paraben, propyl-paraben, and butyl-paraben were measured twice at MPS baseline and 3 years later (2002-2003), and the two average concentrations were used as exposure variables. Associations of incident diabetes with individual phenols and parabens were examined using Cox regression. We evaluated the overall joint effects using quantile-based g-computation. Adjusted hazard ratios (HRs) for incident diabetes of the third tertile compared with the first tertile of urinary concentrations were 0.40 (95% confidence interval [CI] = 0.29, 0.56) for methyl-paraben; 0.42 (0.30, 0.58) for propyl-paraben; 0.53 (0.38, 0.75) for 2,5-diclrorophenol; and 0.55 (0.39, 0.80) for benzophenone-3. Nonlinear associations were found for bisphenol-A and 2,4-dichlorophenol (significant positive associations in the second tertile but no associations in the third tertile compared with the first tertile). No significant associations were observed for the other individual chemicals or the joint effect of mixtures. Our findings do not support diabetogenic effects of urinary parabens which were inversely associated with incident diabetes among mid-life women. Epidemiologic findings for biomarkers with short half-lives and high within-person variability need to be interpreted with caution.

Higher quality maternal diet attenuates negative associations of maternal paraben concentrations with newborn weight and length

BACKGROUND AND AIM: We and others previously observed sex-specific negative associations of maternal paraben concentrations with birth weight (BW) and length (BL). Here, we evaluated whether maternal diet quality modifies these associations. METHODS: Pregnant women ages 18-40 years from Champaign-Urbana, IL provided 5 first-morning urines across pregnancy, which we pooled for analysis of butylparaben, ethylparaben, methylparaben, and propylparaben concentrations. We collected BW and BL data within 24hrs of birth and calculated sex-specific BW-for-gestational-age z-scores (BWz). Women completed 3-month semi-quantitative food frequency questionnaires in early and mid-to-late pregnancy, which we used to calculate mean Alternative Healthy Eating Index 2010 (AHEI-2010) – reflecting foods predictive of chronic disease risk. Multivariable linear regression models evaluated whether associations of parabens with BWz (n=403) and BL (n=429) were modified by AHEI-2010 (dichotomized at the median) and whether the modification varied by fetal sex. We modeled ethylparaben, methylparaben, and propylparaben as continuous variables and butylparaben as zero/non-zero. RESULTS:This predominately non-Hispanic white, college-educated population had lower urinary paraben concentrations than other U.S. women. Median (range) AHEI-2010 was 55.8 (28.1–82.8) out of 110, while BW and BL were 3.5 kg (2.2–4.9) and 50.0 cm (43.9–55.9), respectively. Associations of parabens with birth size only emerged in female newborns whose mothers consumed a poorer diet (AHEI-2010median). In these newborns, each 2-fold increase in maternal methylparaben was associated with 0.1 (95%CI: 0.02, 0.2) lower BWz and 0.2 cm (95%CI: 0.02, 0.3) shorter BL, with similar associations observed for propylparaben. Similarly, female newborns of women who ate a poorer diet and had non-zero butylparaben concentrations had 0.4 (95%CI: 0.1, 0.8) lower BWz and 0.9 cm (95%CI: 0.1, 1.6) shorter BL than women with zero butylparaben concentrations. CONCLUSIONS:Healthier maternal diets may effectively minimize the negative associations between parabens and birth size in female newborns. Additional studies in more diverse populations are needed to confirm these findings. KEYWORDS: Birth outcomes, endocrine disrupting chemicals, phenols

Propylparaben concentrations in the urine of women and adverse effects on ovarian function in mice in vivo and ovarian cells in vitro.

Female reproduction is precisely regulated by hormones, and the ovary is easily affected by environmental endocrine disruptors (EDCs), which are ubiquitous in industrialized societies. Parabens are EDCs that are used as antibacterial preservatives in cosmetics, personal care products (PCPs), medicines, and food. We used ultrahigh-performance liquid chromatography-mass spectrometry to quantitatively detect methyl-, ethyl-, butyl-, and propylparaben (PP) concentrations in urine samples from 74 women of childbearing age. Balb/c mice were subcutaneously injected with 100 mg/kg/day of PP for 21 consecutive days or 100 or 1,000 mg/kg/day of PP during superovulation. Various concentrations of PP (ranging from 1 to 1,000 nM) were added to a human ovarian granulosa tumor-derived cell line (KGN) culture for 24 h. The urinary paraben concentrations of women who used cosmetics and other PCPs within 48 h prior to sample collection were significantly elevated, and the PP concentration was significantly positively correlated with the basal estradiol concentration. After PP injection, the mouse serum estradiol concentrations were significantly increased, estrus cycles were disordered, corpus luteum number was reduced, and number of oocytes retrieved was significantly reduced. In in vitro experiments, PP treatment increased estradiol synthesis and the expression levels of aromatase enzyme (CYP19A1) and steroidogenic acute regulatory protein. This study demonstrates the adverse effects of PP on ovarian estradiol secretion and ovulation, further evaluates the safety of PP as a preservative, and provides guidance for the use of PCPs and cosmetics by women of childbearing age.

Urinary concentrations of phenols, parabens, and triclocarban in relation to uterine leiomyomata incidence and growth

To examine the association of urinary concentrations of phenols, parabens, and triclocarban with incidence and growth of uterine leiomyomata (UL; fibroids). Case-cohort study, nested within the Study of Environment, Lifestyle, and Fibroids, a prospective cohort study. Clinic visits at baseline and every 20 months for 60 months. 754 Black women aged 23-35 years residing in the Detroit, Michigan area (enrolled during 2010-2012). None. At each study visit, women underwent transvaginal ultrasound for measurement of UL incidence and growth and provided urine specimens in which we quantified concentrations of seven phenols, four parabens, and triclocarban. We used Cox proportional hazards regression to estimate hazard ratios and 95% confidence intervals (CIs) characterizing the relation of urinary biomarker concentrations with UL incidence during the 60 months of follow-up. In a subset of UL detected and measured at multiple time points, we used linear regression to assess the associations between biomarker concentrations and UL growth. Urinary biomarker concentrations were generally inversely associated with UL incidence, but the associations were weak and nonmonotonic. For example, hazard ratios comparing concentrations ≥90th with <50th percentile were 0.77 (95% CI: 0.46, 1.27) for bisphenol A, 0.72 (95% CI: 0.40, 1.28) for bisphenol S, and 0.76 (95% CI: 0.43, 1.33) for methylparaben. Biomarker concentrations were not strongly associated with UL growth. In this study of reproductive-aged Black women, urinary phenols, parabens, and triclocarban biomarkers were neither strongly nor consistently associated with UL incidence and growth.

Exposure to Parabens Through The Use of Personal Care Products Among Iranian Men.

Despite the widespread use of parabens as antimicrobial preservatives in personal care products (PCP) and foodstuffs, recent studies have shown that exposure to parabens can play a role in the endocrine disruption process. In the present study, the urinary concentrations of methylparaben (MP), ethylparaben (EP), propylparaben (PP), and butylparaben (BP) were measured among 125 men, and their relationship with the use of 13 distinct PCPs was examined. MP, EP, PP, and BP were detected with a median concentration of 60.12, 8.40, 9.74, and 7.19μg/L, respectively. The difference of urinary MP and PP between three groups of users of PCPs (low, medium, and high users) was significant (p < 0.05), and the higher levels were found in the high-users' group. The total number of PCP applications was associated with higher urinary MP and PP. Furthermore, the urinary concentration of parabens was found to be dependent of the types of products used. Participants who reported the use of sunscreen, lotions, and deodorant had significantly higher urinary MP (76-185%) than nonusers. Bodywash users had higher levels of urinary MP and PP (112-160%). The use of mouthwash, perfume/cologne, and toothpaste also had urinary PP concentration (73-412%) higher than nonusers. The use of handwashing products remarkably increased the urinary levels of parabens (158-520%). Our findings showed that the use of certain types of PCP is an important source of paraben exposure among Iranian men. These findings can serve as a basis for more extensive studies to investigate the extent of exposure to parabens and to apply appropriate strategies for reduction of their exposure.

The sex-specific association between maternal urinary paraben levels and offspring size at birth

Parabens are a group of antimicrobial preservatives applied in an extensive range of products and are suspected to impair fetal growth because of their disrupting effect on the endocrine system. We aimed to examine maternal urinary paraben concentrations and their neonates' outcome indexes. Methylparaben (MP), ethylparaben (EP), propylparaben (PP), and butylparaben (BP) concentrations were measured in 105 maternal urine samples collected before delivery. Length, weight, and head circumference at birth were extracted from the mothers' delivery files. A multivariable linear regression analysis was performed to evaluate the association between paraben levels and neonatal anthropometric indices. The median levels of urinary parabens, especially BP, were higher than those in other countries. Prenatal urinary concentration of MP and BP showed a significantly positive association with birth weight in all neonates (β = 0.79, 95% CI: 0.16, 1.41, and β = 8.56, 95% CI: 3.95, 13.17, respectively), while these chemicals showed a significant negative association with head circumference (β = - 0.002, 95% CI: - 0.004, - 0.000, and β = - 0.016, 95% CI: - 0.030, - 0.002, respectively). A significant positive association between MP and birth length was also found (β = 0.004, 95% CI: 0.00, 0.00) in all the neonates. In sex-stratified adjusted models, MP and BP were found to be associated, respectively, with higher birth length and weight in male neonates (β = 0.008, 95% CI: - 0.001, 0.017, and β = 7.948, 95% CI: 1.045, 14.851). In girls, maternal urinary MP, PP, and BP were associated with increased birth weight (β = 0.831, 95% CI: 0.043, 1.620; β = 4.178, 95% CI: 0.877, 7.480; and β = 10.821, 95% CI: 3.545, 18.097, respectively), and MP and BP were associated with reduced head circumference at birth (β = - 0.003, 95% CI: - 0.005, - 0.001, and β = - 0.035, 95% CI: - 0.055, - 0.016). These results revealed potential impacts between neonatal growth and maternal exposure to parabens. However, these findings should be interpreted while considering the limitations of the present study.