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Background: 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., Objective: We investigated whether maternal and paternal preconception and maternal pregnancy urinary concentrations of parabens were associated with child behavior., Methods: 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 log e -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)., Results: 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 β $\beta \;$ = 1.7; 95% confidence interval: 0.6, 2.8, methyl paraben β $\beta \;$ = 2.2; 95% confidence interval: 0.5, 3.9) and higher Behavioral Symptom Index T-scores (propyl paraben β $\beta \;$ = 1.4; 95% confidence interval: 0.3, 2.5, methyl paraben β $\beta \;$ = 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 ( β $\beta \;$ = 1.0; 95% confidence interval: 0.04, 1.9) and maternal preconception ( β $\beta \;$ = 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., Conclusion: In this cohort, paternal preconception urinary concentrations of propyl and methyl paraben were associated with worse parent-reported child behaviors., (© 2023 The Authors. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology.)

Introduction: Exposure to endocrine disrupting chemicals (EDCs) can result in alterations of natural hormones in the body. The aim of this review article is to highlight the knowledge about EDCs and obesity., Methods: A scoping review of the electronic literature was performed using PubMed platform for studies on EDCs and obesity published between the years 2013-2023. A total of 10 systematic reviews and meta-analysis studies met our inclusion criteria on more prominent EDCs focusing mainly on bisphenols, including parabens, triclosan, and phthalates, and their association with obesity., Design: Scoping review., Results: EDCs, mostly bisphenols and phthalates, are related to health effects, while there is less information on the impact of parabens and triclosan. A series of negative physiological effects involving obesogenic, diabetogenic, carcinogenic, and inflammatory mechanisms as well as epigenetic and microbiota modulations was related to a prolonged EDCs exposure. A more profound research of particular pollutants is required to illuminate the accelerating effects of particular EDCs, mixtures or their metabolites on the mechanism of the development of obesity., Conclusion: Considering the characteristics of EDCs and the heterogeneity of studies, it is necessary to design specific studies of effect tracking and, in particular, education about daily preventive exposure to EDCs for the preservation of long-term public health., (© 2024. The Author(s).)

Preterm birth in humans (PTB), defined as birth prior to 37 weeks of gestation, is one of the most important causes of neonatal morbidity and mortality and is associated with adverse health outcomes later in life. Attributed to many different etiological factors, estimated 15.1 million or 11.1% of births each year are preterm, which is more than 1 per 10 livebirths globally. Environmental pollution is a well-established risk factor that could influence the pathogenesis of PTB. Increasing evidence has shown an association between maternal exposure to endocrine disrupting chemicals (EDCs) and PTB. This scoping review aims to summarize current research on the association between EDC exposure and PTB in humans. Database PubMed was used to identify articles discussing the effect of selected EDCs, namely bisphenol A, bisphenol S, bisphenol F, parabens, and triclosan, found in plastics, cosmetics and other personal care products, on PTB occurrence. Regardless of some inconsistences in the findings across studies, the reviewed studies suggest a potential association between involuntary exposure to reviewed EDCs and the risk of PTB. However, further studies are needed to delineate exact correlations and mechanisms through which EDC exposure causes PTB so that efficient preventative measures could be implemented. Until then, health care providers should inform women about possible EDC exposure thus empowering them to make healthy choices and at the same time decrease the EDC negative effects., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: From menarche until menopause, the average menstruator will use over 11 000 tampons or sanitary pads. Vaginal and vulvar tissue is highly permeable, and chemicals are absorbed without undergoing first-pass metabolism., Objectives: To conduct a review of the literature to determine exposure to environmental chemicals in menstrual products., Search Strategy: This review identified 15 papers over the past 10 years., Selection Criteria: Papers that measured chemicals in menstrual products and that measured human biomarkers of chemical exposure were included. Papers had to also be available in English., Data Collection and Analysis: Reviewers assessed the articles and data provided. Multiple chemical groups were found., Main Results: Phthalates, volatile organic compounds, parabens, environmental phenols, fragrance chemicals, dioxins and dioxin-like compounds were detected in menstrual products. Research gaps were identified, including the lack of studies on newer products such as menstrual underwear and cups/discs. In addition to measuring chemicals in these products, future research should focus on clarifying the exposure per menstrual cycle to these chemicals to understand how menorrhagia and cycle length influence exposure from menstrual products., Conclusion: Menstrual products contained measurable levels of a range of endocrine disrupting chemicals including phthalates, phenols and parabens. This reflects a potentially important route of exposure to chemicals that can impact women's reproductive health., (© 2023 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Background: Our study aimed to investigate the impact of urinary concentrations of personal care products (PCPs)-related phenols (PNs) and parabens (PBs), including Triclosan (TCS), Bisphenol A (BPA), Benzophenone-3 (BP-3), Butylparaben (BPB), Ethylparaben (EPB), Methylparaben (MPB), and Propylparaben (PPB), on urinary incontinence (UI) occurrence., Method: We conducted a cross-sectional analysis using data from the National Health and Nutrition Examination Survey (NHANES) spanning the years 2007 to 2016. Regression analysis was employed to investigate the relationship between exposure to PCPs-related substances, various levels of exposure, and UI within both the general population and the female demographic. Additionally, the Bayesian Kernel Machine Regression (BKMR) model was used to assess the effects of mixtures on UI., Results: Our analysis comprised 7,690 participants who self-reported their diagnosis. Among them, 12.80% experienced stress urinary incontinence (SUI), 11.80% reported urge urinary incontinence (UUI), and 10.22% exhibited mixed urinary incontinence (MUI). In our fully adjusted multivariable models, BP-3 exposure exhibited a positive association with SUI (OR 1.07, 95% CI 1.02-1.14, p = 0.045). BPA exposure correlated with an increased risk of UUI (OR 1.21, 95% CI 1.01-1.44, p = 0.046) and MUI (OR 1.26, 95% CI 1.02-1.54, p = 0.029). TCS exposure displayed a negative correlation with the incidence of MUI (OR 0.87, 95% CI 0.79-0.97, p = 0.009). No significant links were observed between parabens and urinary incontinence. Notably, among the female population, our investigation revealed that BPA exposure heightened the risk of MUI (OR 1.28, 95% CI 1.01-1.63, p = 0.043). Participants in the highest tertile of BP-3 exposure demonstrated elevated likelihoods of SUI and MUI compared to those in the lowest tertile. In the BKMR analysis, negative trends were observed between the mixture and the risks of UUI and MUI when the mixture ranged from the 25th to the 40th and 35th to the 40th percentiles or above, respectively. Additionally, a positive trend was identified between the mixture and MUI when it was in the 40th to 55th percentile., Conclusion: In conclusion, our findings suggest that exposure to BPA, TCS, and BP-3 may contribute to the development of urinary incontinence., (© 2024. The Author(s).)

Importance: Postpartum depression (PPD) affects up to 20% of childbearing individuals, and a significant limitation in reducing its morbidity is the difficulty in modifying established risk factors. Exposure to synthetic environmental chemicals found in plastics and personal care products, such as phenols, phthalates, and parabens, are potentially modifiable and plausibly linked to PPD and have yet to be explored., Objective: To evaluate associations of prenatal exposure to phenols, phthalates, parabens, and triclocarban with PPD symptoms., Design, Setting, and Participants: This was a prospective cohort study from 5 US sites, conducted from 2006 to 2020, and included pooled data from 5 US birth cohorts from the National Institutes of Health Environmental Influences on Child Health Outcomes (ECHO) consortium. Participants were pregnant individuals with data on urinary chemical concentrations (phenols, phthalate metabolites, parabens, or triclocarban) from at least 1 time point in pregnancy and self-reported postnatal depression screening assessment collected between 2 weeks and 12 months after delivery. Data were analyzed from February to May 2022., Exposures: Phenols (bisphenols and triclosan), phthalate metabolites, parabens, and triclocarban measured in prenatal urine samples., Main Outcomes and Measures: Depression symptom scores were assessed using the Edinburgh Postnatal Depression Scale (EPDS) or the Center for Epidemiologic Studies Depression Scale (CES-D), harmonized to the Patient-Reported Measurement Information System (PROMIS) Depression scale. Measures of dichotomous PPD were created using both sensitive (EPDS scores ≥10 and CES-D scores ≥16) and specific (EPDS scores ≥13 and CES-D scores ≥20) definitions., Results: Among the 2174 pregnant individuals eligible for analysis, nearly all (>99%) had detectable levels of several phthalate metabolites and parabens. PPD was assessed a mean (SD) of 3 (2.5) months after delivery, with 349 individuals (16.1%) and 170 individuals (7.8%) screening positive for PPD using the sensitive and specific definitions, respectively. Linear regression results of continuous PROMIS depression T scores showed no statistically significant associations with any chemical exposures. Models examining LMW and HMW phthalates and di (2-ethylhexyl) phthalate had estimates in the positive direction whereas all others were negative. A 1-unit increase in log-transformed LMW phthalates was associated with a 0.26-unit increase in the PROMIS depression T score (95% CI, -0.01 to 0.53; P = .06). This corresponded to an odds ratio (OR) of 1.08 (95% CI, 0.98-1.19) when modeling PPD as a dichotomous outcome and using the sensitive PPD definition. HMW phthalates were associated with increased odds of PPD (OR, 1.11; 95% CI, 1.00-1.23 and OR, 1.10; 95% CI, 0.96-1.27) for the sensitive and specific PPD definitions, respectively. Sensitivity analyses produced stronger results., Conclusions and Relevance: Phthalates, ubiquitous chemicals in the environment, may be associated with PPD and could serve as important modifiable targets for preventive interventions. Future studies are needed to confirm these observations.

Increasing evidence has been published over recent years on the implication of endocrine-disrupting chemicals (EDCs), including parabens and benzophenones in the pathogenesis and pathophysiology of endometriosis. However, to the best of our knowledge, no study has been published on the ways in which exposure to EDCs might affect cell-signaling pathways related to endometriosis. We aimed to describe the endometriotic tissue expression profile of a panel of 23 genes related to crucial cell-signaling pathways for the development and progression of endometriosis (cell adhesion, invasion/migration, inflammation, angiogenesis, and cell proliferation/hormone stimulation) and explore its relationship with the exposure of patients to parabens (PBs) and benzophenones (BPs). This cross-sectional study included a subsample of 33 women with endometriosis from the EndEA study, measuring their endometriotic tissue expressions of 23 genes, while urinary concentrations of methyl-, ethyl-, propyl-, butyl-paraben, benzophenone-1, benzophenone-3, and 4-hydroxybenzophenone were determined in 22 women. Spearman's correlations test and linear and logistic regression analyses were performed. The expression of 52.2% of studied genes was observed in >75% of endometriotic tissue samples and the expression of 17.4% (n = 4) of them in 50-75%. Exposure to certain PB and BP congeners was positively associated with the expression of key genes for the development and proliferation of endometriosis. Genes related to the development and progression of endometriosis were expressed in most endometriotic tissue samples studied, suggesting that exposure of women to PBs and BPs may be associated with the altered expression profile of genes related to cellular pathways involved in the development of endometriosis.

Background: Concerns have been raised whether exposure to endocrine-disrupting chemicals (EDCs) can alter reproductive functions and play a role in the aetiology of infertility in women. With increasing evidence of adverse effects, information on factors associated with exposure is necessary to form firm recommendations aiming at reducing exposure., Objective: Our aim was to identify associations between lifestyle factors including the home environment, use of personal care products (PCP), and dietary habits and concentrations of EDCs in ovarian follicular fluid., Methods: April-June 2016, 185 women undergoing ovum pick-up for in vitro fertilisation in Sweden were recruited. Correlation analyses were performed between self-reported lifestyle factors and concentration of EDCs analysed in follicular fluid. Habits related to cleaning, PCPs, and diet were assessed together with concentration of six per- and polyfluoroalkyl substances (PFASs) [PFHxS, PFOA, PFOS, PFNA, PFDA and PFUnDA], methyl paraben and eight phthalate metabolites [MECPP, MEHPP, MEOHP, MEHP, cxMinCH, cxMiNP, ohMiNP, MEP, MOHiBP]. Spearman's partial correlations were adjusted for age, parity and BMI., Results: Significant associations were discovered between multiple lifestyle factors and concentrations of EDCs in ovarian follicular fluid. After correcting p values for multiple testing, frequent use of perfume was associated with MEP (correlation ρ = 0.41 (confidence interval 0.21-0.47), p < 0.001); hens' egg consumption was positively associated with PFOS (ρ = 0.30 (0.15-0.43), p = 0.007) and PFUnDA (ρ = 0.27 (0.12-0.40), p = 0.036). White fish consumption was positively associated with PFUnDA (ρ = 0.34 (0.20-0.47), p < 0.001) and PFDA (ρ = 0.27 (0.13-0.41), p = 0.028). More correlations were discovered when considering the raw uncorrected p values. Altogether, our results suggest that multiple lifestyle variables affect chemical contamination of follicular fluid., Impact Statement: This study shows how lifestyle factors correlate with the level of contamination in the ovary by both persistent and semi-persistent chemicals in women of reproductive age. Subsequently, these data can be used to form recommendations regarding lifestyle to mitigate possible negative health outcomes and fertility problems associated with chemical exposure, and to inform chemical policy decision making. Our study can also help form the basis for the design of larger observational and intervention studies to examine possible effects of lifestyle changes on exposure levels, and to unravel the complex interactions between biological factors, lifestyle and chemical exposures in more detail., (© 2023. The Author(s).)

Background: Neurobehavioural 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., Objective: To determine whether urinary concentrations of parabens and bisphenols are associated with attention and concentration in adolescents, in general and sex-specific., Methods: We 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., Results: 101 (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., Conclusion: In 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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Patients with chronic wounds have an increased risk of developing allergic contact dermatitis (ACD). Reports of ACD to wound care products are not uncommon. To minimize contact sensitization in patients with chronic wounds, allergenic ingredients should be avoided when possible. Objective: With more than 5000 wound care products available in the United States, it is essential to understand which products can be chosen to minimize allergen exposures. Methods: Ingredients in wound care products in 5 wound care clinics across 2 institutions were cross-referenced with the American Contact Dermatitis Society core allergen series 2020. Results: Of the 267 wound care products included, 97 (36.3%) contained at least one allergen, including 31 dressings/wraps (22.3%), 25 medications (69.4%), 12 cleaning supplies (36.3%), 16 tapes/glues (80%), 2 instruments (14.3%), 8 emollients and vehicles (61.5%), 1 ostomy product (11.1%), and 2 odor-eliminating products (66.7%). Thirty-four different allergens were identified across all products. The most common allergens present in the included items were acrylates and propylene glycol, followed by parabens, cetyl stearyl alcohol, tocopherol, fragrance, and phenoxyethanol. Conclusions: Many wound care products contain at least one contact allergen, highlighting the importance of clinician education on ACD in the context of wound care product selection.

Purpose of Review: Exposure to endocrine disrupting chemicals through personal care products (PCPs) is widespread and may disrupt hormone-sensitive endpoints, such as timing of puberty. Given the well-documented (and ongoing) decline in age at menarche in many populations, we conducted a systematic review of the epidemiological literature on exposure to chemicals commonly found in PCPs (including certain phthalates, phenols, and parabens) in relation to girls' pubertal development., Recent Findings: The preponderance of research on this topic has examined phthalate exposures with the strongest evidence indicating that prenatal monoethyl phthalate (MEP) concentrations may be associated with slightly earlier timing of puberty, including age at menarche. Findings examining peri-pubertal phthalate exposures and pubertal outcomes were less consistent as were studies of prenatal and peri-pubertal phenol exposures. Very few studies had examined parabens in relation to girls' pubertal development. Common study limitations included potential exposure misclassification related to use of spot samples and/or mistimed biomarker assessment with respect to the outcomes. The role of body size as a mediator in these relationships remains unresolved. Overall, evidence of associations between chemical exposures in PCPs and girls' pubertal development was conflicting. When associations were observed, effect sizes were small. Nevertheless, given the many environmental, social, and behavioral factors in the modern environment that may act synergistically to accelerate timing of puberty, even marginal changes may be cause for concern, with implications for cancer risk, mental health, and cardiometabolic disease in later life., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Product disclaimers listed on personal care products face limited regulation. These disclaimers may be helpful or may mislead the public., Objective: Review the evidence supporting the potential harms of 3 compounds commonly addressed by product disclaimers: parabens, aluminum, and sulfates., Methods: Reported cases of adverse events to these compounds were identified. Trends in allergic contact dermatitis reactions to chemicals used in place of these compounds were also identified., Results: There is limited evidence that parabens and aluminum pose a threat to human health; there is even less evidence that topical sulfate-containing products pose a danger to consumers. In the setting of paraben avoidance, there has been a steady increase in cases of allergic contact dermatitis to preservatives that are more allergenic, specifically the isothiazolinones., Limitations: Assessment of the toxicology of these compounds is ongoing and may change with new data., Conclusion: There is limited evidence that parabens, aluminum, and sulfates used in personal care products pose a health risk. There is evidence that avoidance of parabens has resulted in an epidemic of allergic contact dermatitis to isothiazolonine preservatives., Competing Interests: Conflicts of interest None disclosed., (Copyright © 2021 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Parabens are antimicrobial agents prevalently found in daily-use products that can interfere with the endocrine and reproductive systems. In this study, we examined the cross-sectional associations of parabens with hot flashes, hormone concentrations, and ovarian volume in a subsample of 101 nonsmoking, non-Hispanic 45- to 54-year-old women from the Midlife Women's Health Study. Materials and Methods: Women self-reported their hot flash history and underwent a transvaginal ultrasound to measure ovarian volume. Participants provided blood for quantification of serum hormones (by enzyme-linked immunosorbent assay or radioimmunoassay) and urine samples for measurements of urinary paraben biomarker levels (by high-performance liquid chromatography negative-ion electrospray ionization-tandem mass spectrometry). Linear or logistic regression models evaluated associations of specific gravity-adjusted paraben biomarker concentrations with hot flashes, hormone concentrations, and ovarian volume. Results: We observed marginal associations of propylparaben, methylparaben, and ∑parabens biomarkers (molar sum of four parabens) with hot flashes and follicle-stimulating hormone (FSH) concentrations, and of these paraben biomarkers and ethylparaben with ovarian volume. For example, women tended to have 32% (95% confidence intervals [CI]: 0.9 to 1.81), 40% (95% CI: 1.0 to 1.95), and 40% (95% CI: 0.98 to 2.01) higher odds of having recent, monthly, and mild hot flashes, respectively, for every two-fold increase in ∑parabens. Similarly, women tended to have 14.54% (95% CI: -0.10 to 31.32) higher FSH concentrations, but 5.67% (95% CI: -12.54 to 1.75) reduced ovarian volume for every two-fold increase in ∑parabens Conclusions: Overall, our preliminary findings suggest that urinary paraben biomarkers may be associated with menopause-related outcomes in midlife women. Additional studies in larger and diverse populations are needed to expand on these findings.

Background: Pregnant women are simultaneously exposed to several non-persistent endocrine-disrupting chemicals, which may influence the risk of childhood obesity and cardiovascular diseases later in life. Previous prospective studies have mostly examined single-chemical effects, with inconsistent findings. We assessed the association between prenatal exposure to phthalates and phenols, individually and as a mixture, and body mass index (BMI) and blood pressure (BP) in preadolescents., Methods: We used data from the Spanish INMA birth cohort study (n = 1,015), where the 1st and 3rd- trimester maternal urinary concentrations of eight phthalate metabolites and six phenols were quantified. At 11 years of age, we calculated BMI z-scores and measured systolic and diastolic BP. We estimated individual chemical effects with linear mixed models and joint effects of the chemical mixture with hierarchical Bayesian kernel machine regression (BKMR). Analyses were stratified by sex and by puberty status., Results: In single-exposure models, benzophenone-3 (BP3) was nonmonotonically associated with higher BMI z-score (e.g. Quartile (Q) 3: β = 0.23 [95% CI = 0.03, 0.44] vs Q1) and higher diastolic BP (Q2: β = 1.27 [0.00, 2.53] mmHg vs Q1). Methyl paraben (MEPA) was associated with lower systolic BP (Q4: β = -1.67 [-3.31, -0.04] mmHg vs Q1). No consistent associations were observed for the other compounds. Results from the BKMR confirmed the single-exposure results and showed similar patterns of associations, with BP3 having the highest importance in the mixture models, especially among preadolescents who reached puberty status. No overall mixture effect was found, except for a tendency of higher BMI z-score and lower systolic BP in girls., Conclusions: Prenatal exposure to UV-filter BP3 may be associated with higher BMI and diastolic BP during preadolescence, but there is little evidence for an overall phthalate and phenol mixture effect., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The widespread use of skin sensitizing preservatives is well-known. Contact allergy to preservatives is often caused by their presence in cosmetic products. Preservative use in non-cosmetic products is less well-known. We have reviewed European Union (EU) legislations on classification and labelling, biocides and cosmetics, concerning conditions for use of the most used sensitizing preservatives (including formaldehyde-releasing substances, isothiazolinones and parabens). We have analysed temporal trends in their use in non-cosmetic products (tonnes, number of products, concentrations), based on annual reports to the Swedish Products Register 1995-2018; and we discuss implications for stakeholders. Major changes over time are that the use of most of the preservatives has increased by tonnes and/or by number of products, and that several use concentrations have declined following harmonized classification as a skin sensitizer with low concentration limits for this classification. We conclude that the massive increase in use of preservatives is alarming, and that urgent action is needed for protection of health. Their use in non-cosmetic products is broad, increasing and often undisclosed. In the EU, legislations concerning chemicals can provide relevant restrictions to reduce their use and associated health risks, monitored by efficient surveillance. Prevention would be benefited by better coordination between legislations., (© 2022 The Authors. Contact Dermatitis published by John Wiley & Sons Ltd.)

Cosmetics, cosmeceuticals, and variable healthcare products used parabens, among other excipients, for their preservative and antimicrobial activities. Paraben derivatives exhibit distinguished physiochemical properties that enable them to be compatible with the formulation of cosmetic agents in different dosage forms. In addition to their potency and efficacy, parabens are economically efficient as they have low-manufacturing costs. Despite the desirable characteristics, the safety of parabens use is controversial after detecting these chemicals in various biological tissues after repetitive and long-term use of formulations containing them. The use of parabens drew public health attention after scientific reports linked skin exposure to parabens with health issues, in particular, breast cancer. In response, worldwide authorities set regulations for the allowance concentrations of paraben to be used in variable cosmetic products., (© 2022 Wiley Periodicals LLC.)

Parabens (PBs) are a group of substances commonly used in industry. They also pollute the environment, penetrate into living organisms and adversely affect various internal organs. During this study, the degree of exposure of people living in Olsztyn, a city in north eastern Poland, to selected parabens most often used in industry was studied. The chemicals under investigation included: methyl paraben-MePB, ethyl paraben-EtPB, propyl paraben-PrPB, benzyl paraben BePB and butyl paraben -BuPB. To this aim, hair samples collected from the scalps of 30 volunteers were analyzed using a liquid chromatography-mass spectrometry technique. All PBs studied were present in a high percentage of analyzed samples (from 76.7% in the case of BePB to 100% in the case of MePB and PrPB). The mean concentration levels were 4425.3 pg/mg for MeBP, 704.0 pg/mg for EtPB, 825.7 pg/mg for PrPB, 135.2 pg/mg for BePB and 154.5 pg/mg for BuPB. Significant differences in PB concentration levels between particular persons were visible. On the other hand, gender, age and artificial hair coloring did not cause statistically significant differences in PB levels. Obtained results have clearly indicated that people living in north eastern Poland are exposed to various PBs, and therefore these substances may affect their health status. However, the evaluation of PBs influence on human health requires further research., (© 2021. The Author(s).)

Dear Editor: The European Baseline Series (EBS) of contact allergens is used throughout Europe as a screening test to diagnose contact allergy as a proxy for allergy contact dermatitis and other hypersensitivity skin diseases (1). Parabens are alkyl esters of p-hydroxybenzoic acid with antimicrobial effects used as preservatives in cosmetics, foods, and drugs that have been included in the so called "baseline series" (2) for more than 40 years. Parabens, which are considered allergologically safe biocides and are classified as safe by the US Food and Drug Administration (FDA) and the Scientific Committee on Consumer Safety (SCCS) in Europe (2-4), are frequently present in cosmetics (5). Despite extensive and progressively expanding use worldwide, studies confirm that parabens are seldom responsible for allergic contact dermatitis to cosmetics, and the frequency of sensitivity to parabens has been low and stable for many decades (2). The frequency of positive reactions to paraben mix is less than 0.5% in most clinical series, although it seems that when it occurs it is often of high clinical relevance (6). Nevertheless, several authors have stated that these patients rarely or never have to avoid foods or cosmetics that contain parabens to control their dermatitis (2). Paraben allergy most frequently occurs in patients with long-lasting stasis dermatitis or disruption of skin integrity, with high use of topical drugs, and in those who do not get better under normal treatment and/or skin care (5). The EBS has been periodically adapted by the European Environmental and Contact Dermatitis Research Group (EECDRG) and the European Society of Contact Dermatitis (ESCD), according to frequency studies, but ensuring that tested haptens remain relevant (1). Bruze et al. recommend that haptens should be considered for inclusion in a baseline series when the contact allergy prevalence is 0.5-1.0% or above (7). So, why not exclude paraben mix from the EBS? We analysed all the EBS tests performed at our institution in the last 21 years (2000-2020) to evaluate the frequency of positive reactions to paraben mix 16% pet (Chemotechnique diagnostics, Vellinge Sweden). In total, 5885 patients were patch tested (MOAHLFA index - Table 1), of whom 29 (10 men and 19 women) patients presented with a positive reaction (1+ or more according to ESCD guidelines) to paraben mix (0.49%), with positivity rates varying between 1.79% and 0.0% and progressively falling for the past 20 years (Figure 1). Present or past clinical relevance was found in 19/29 (65.5%) patients (6 men and 13 women), and was related to the use of topical drugs in 16 patients (55.2%) and cosmetics in three patients (10.3%). Paraben reactions occurred mostly in patients with history of leg ulcer, leg dermatitis, and/or chronic venous insufficiency, which is in agreement with the overrepresentation of the group of patients with leg dermatitis compared with the whole population tested (Table 1). The proportion of patients with positive reactions to paraben mix was significantly higher in patients with leg dermatitis compared with patients without leg dermatitis (P<0.05), as well in patients aged >40 (P<0.05), in whom these leg comorbidities are more frequent. Additionally, the higher number of reactions frequently coincided with the highest number of patients with leg dermatitis patch tested in the same year (Figure 1). Cosmetics were considered the causative factor in only three patients, which explains the identical percentage of facial and atopic dermatitis in the paraben mix positive group and the total population tested. As expected, both hand and occupational dermatitis were underrepresented in the group of positive reactions to parabens. In 34.5% of the patients, positive tests were considered not relevant or of unknown relevance. Therefore, in total only 0.32% of all paraben mix reactions were clinically relevant. Patch test reactivity to paraben mix of 0.49% supports the ongoing discussion that parabens should not continue in the baseline series, a position that is further strengthened by the fact that only 0.32% represent relevant reactions (8). As the most relevant sensitizations are related to topical medications and, less frequently, from cosmetics, paraben mix should be part of the topical drugs and cosmetic series.

Parabens, including the most common methylparaben (MeP), are popular preservatives, which possess estrogenic activity. The aims of this study were to assess the impact of MeP on estrogen receptors (ERs) and/or NF-κB-dependent generation of IL-8 and production of nitric oxide (NO), and also to verify the hypothesis about the crosstalk of ERs with NF-κB in xenoestrogen-exposed neutrophils. Human neutrophils were incubated for 20-h with MeP (0.06 μM) and/or ER antagonist (1 μM) and/or NF-κB inhibitor (100 μM). After the isolation of cell lysates and cytoplasmic and nuclear fraction, the expression of ERα, ERβ, p-IKKα/β, p65 NF-κB, and inducible nitric oxide synthase (iNOS) was measured by Western blot analysis, The concentration of NO was evaluated by Griess reaction, and that of IL-8 was measured by ELISA. The results showed that MeP modulated the expression of ERα, but not ERβ. Exposure to paraben activated iKKα/β-dependent NF-κB pathway, but translocation of p65 NF-κB into the cell nucleus was inhibited by ERs. MeP also decreased the iNOS-dependent production of NO, but did not influence the secretion of IL-8 by neutrophils. The study indicates that MeP may affect the functioning of human neutrophils by modulating intracellular signal transduction pathways, including ERs and NF-κB pathway., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Parabens are used as antimicrobial preservatives in personal care products. Few studies have dealt with adverse health outcomes, transplacental transfer, and obesogenic effects of prenatal exposure to parabens. We examined the association between placental paraben levels and cord blood metabolic biomarkers, considering modulating effects of maternal pre-pregnancy BMI and underlying epigenetic mechanisms, and investigated longitudinal effects of in utero paraben exposure on early childhood trajectories of BMI z-scores., Methods: Placental concentrations of four parabens [methyl (MeP), ethyl (EtP), propyl (PrP), and butyl (BuP)] were measured by ultra-performance liquid chromatography/tandem mass spectrometry in 229 placentas of the ENVIRONAGE birth cohort. The association with cord blood metabolic biomarkers [glucose, insulin, γ-glutamyltransferase (GGT), high-density and low-density lipoprotein (HDL and LDL)] was analyzed in multiple regression models with two different sets of, a priori selected potential confounders, additionally stratified for different maternal BMI groups and assessed by causal mediation analysis. The association between placental paraben concentration and differential DNA methylation of CpGs annotated to GGT and longitudinal measurements of BMI z-scores were investigated with adjusted linear mixed models., Results: The geometric means of placental MeP, EtP, PrP, and BuP levels above the limit of detection (LOD) were 4.42, 1.32, 1.51, and 0.35 ng/g respectively, with only EtP showing sufficient (88%) measurements above LOD for further analyses. An interquartile ratio (IQR) increase in placental EtP was associated with an increase of 12.61 % (95% CI: 1.80 24.57) in the geometric mean of cord GGT activity, and with a decrease of -3.64 % (95% CI: -6.80 to -0.39) in the geometric mean of cord glucose. Placental EtP levels were significantly associated with hypermethylation of cg08612779 annotated to GGT7 after correcting for multiple testing (ß = 0.0017, p = 0.049). An interquartile ratio (IQR) increment in placental EtP was associated with a decrease in longitudinal BMI z-score of 0.27 points (95% CI: -0.46 to -0.088)., Conclusion: Prenatal EtP exposure may affect early childhood BMI. The association of placental EtP with cord blood GGT and glucose levels provides a starting point for further research on mechanisms of paraben-related metabolic processes in utero., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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.

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., (© 2021 John Wiley & Sons, Ltd.)

In cosmetic products, the ingredient propylparaben (CAS No 94-13-3, EC No 202-307-7) with the chemical names Propyl 4-hydroxybenzoate and 4-Hydroxybenzoic acid propyl ester is currently regulated as a preservative in a concentration up to 0.14% (as acid) (Annex V/12a). In addition, a safe concentration was established for mixtures of parabens, where the sum of the individual concentrations should not exceed 0.8% (as acid). However, in such mixtures the sum of the individual concentrations of butyl- and propylparaben and their salts should not exceed 0.14%. Propylparaben was subject to different safety evaluations in 2005 (SCCP/0874/05), 2006 (SCCP/1017/06), 2008 (SCCP/1183/08), 2010 (SCCS/1348/10), 2011 (SCCS/1446/11), and in 2013 (SCCS/1514/13). On the basis of the safety assessment of propylparaben, and considering the concerns related to potential endocrine disrupting properties, the SCCS has concluded that propylparaben is safe when used as a preservative in cosmetic products up to a maximum concentration of 0.14%. The available data on propylparaben provide some indications for potential endocrine effects. However, the current level of evidence is not sufficient to regard it as an endocrine disrupting substance, or to derive a toxicological point of departure based on endocrine disrupting properties for use in human health risk assessment. The SCCS mandate does not address environmental aspects. Therefore, this assessment did not cover the safety of propylparaben for the environment. Link to the Opinion (SCCS/1623/20): https://ec.europa.eu/health/sites/default/files/scientific&#95;committees/consumer&#95;safety/docs/sccs&#95;o&#95;243.pdf., (Copyright © 2021. Published by Elsevier Inc.)

Background: Parabens, widely used as preservatives in cosmetics, foods, and other consumer products, are suspected of contributing to allergy susceptibility. The detection of parabens in the placenta or amniotic fluid raised concerns about potential health consequences for the child. Recently, an increased asthma risk following prenatal exposure has been reported. Here, we investigated whether prenatal paraben exposure can influence the risk for atopic dermatitis (AD)., Methods: 261 mother-child pairs of the German mother-child study LINA were included in this analysis. Eight paraben species were quantified in maternal urine obtained at gestational week 34. According to the parental report of physician-diagnosed AD from age 1 to 8 years, disease onset, and persistence, childhood AD was classified into four different phenotypes., Results: 4.6% (n = 12) and 12.3% (n = 32) of the children were classified as having very early-onset AD (until age two) either with or without remission, 11.9% (n = 31) as early-onset (after age two), and 3.1% (n = 8) as childhood-onset AD (after age six). Exposure to ethylparaben and n-butylparaben was associated with an increased risk to develop very early-onset AD without remission (EtP: adj.OR/95% CI:1.44/1.04-2.00,nBuP:adj.OR/95% CI:1.95/1.22-3.12). The effects of both parabens were predominant in children without a history of maternal AD and independent of children's sex., Conclusion: Prenatal EtP or nBuP exposure may increase children's susceptibility for persistent AD with disease onset at very early age. This association was particularly pronounced in children without a history of maternal AD, indicating that children without a genetic predisposition are more susceptible to paraben exposure., (© 2021 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Parabens are alkyl esters of p-hydroxybenzoic acid which are extensively used in cosmetics, pharmaceuticals and foodstuffs due to their antimicrobial properties. The most commonly used parabens are methyl-(MeP), ethyl-(EtP), propyl-(PrP) and butyl-(BuP) paraben. Most human exposure to parabens is achieved through the consumption of food or pharmaceutical products and the use of personal care products. However, studies on dietary parabens exposure and the associated factors are very scarce. The main aim of the present study was to explore factors associated with dietary exposure to parabens in Spanish adolescents according to gender. Dietary data and anthropometric measures were collected from 585 adolescents (53.4% boys) aged 12-16 years. Parabens exposure through diet was assessed using a food frequency questionnaire with food products providing more than 95% of energy and macronutrient intake being included in analysis. Stepwise regression was used to identify the foods that most contributed to parabens intake. Logistic regression was used to evaluate factors predicting higher dietary exposure to parabens. The main contributors to dietary MeP, EtP, PrP and BuP exposure in adolescent boys were eggs (41.9%), canned tuna (46.4%), bakery and baked goods products (57.3%) and pineapple (61.1%). In adolescent girls, the main contributors were apples and pears (35.3%), canned tuna (42.1%), bakery and baked goods products (55.1%) and olives (62.1%). Overweight/obese girls were more likely to belong to the highest tertile of overall parabens intake (odds ratio [OR]: 3.32; 95% confidence interval [95% CI]: 1.21-9.15) and MeP (OR: 3.05; 95% CI: 1.14-8.12) than those with a body mass index lower than 25 kg/m 2 . These findings suggest a positive association between dietary exposure to parabens and overweight/obesity in adolescent girls., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To explore windows of vulnerability to prenatal urinary phenol concentrations and preterm birth., Design: Prospective cohort., Setting: A large fertility center in Boston, Massachusetts., Patient(s): A total of 386 mothers who sought fertility treatment and gave birth to a singleton between 2005 and 2018., Intervention(s): None., Main Outcome Measure(s): Singleton live birth with gestational age <37 completed weeks., Result(s): Compared with women with non-preterm births, urinary bisphenol A (BPA) concentrations were higher across gestation among women with preterm births, particularly during mid-to-late pregnancy and among those with female infants. Second trimester BPA concentrations were associated with preterm birth (Risk Ratio [RR] 1.24; 95%CI: 0.92, 1.69), which was primarily driven by female (RR 1.40; 95%CI: 1.04, 1.89) and not male (RR 0.85; 95%CI 0.50, 1.46) infants. First trimester paraben concentrations were also associated with preterm birth (RR 1.17; 95%CI: 0.94, 1.46) and similarly the association was only observed for female (RR 1.46; 95% CI: 1.10, 1.94) and not male infants (RR 0.94; 95%CIC: 0.72, 1.23). First trimester urinary bisphenol S concentrations showed a suggested risk of preterm birth (RR 1.25; 95%CI: 0.82, 1.89), although the small case numbers precluded sex-specific examination., Conclusion(s): We found preliminary evidence of associations between mid-to-late pregnancy BPA and early pregnancy paraben concentrations with preterm birth among those with female infants only. Preterm birth risk may be compound, sex, and window specific. Given the limited sample size of this cohort, results should be confirmed in larger studies, including fertile populations., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Parabens are widely applied as preservatives in cosmetics, drugs and food. Previous studies suggested that parabens could exhibit potential risks to human health. However, data on human exposure levels and health effects of parabens remain limited, especially in the potential effects on DNA oxidative stress. This study aimed to investigate urinary levels of parabens in adults from South China and explore the relationships between urinary parabens and DNA oxidative stress. Five short chain parabens, including methyl paraben (MeP), ethyl paraben (EtP), n-propyl paraben (PrP), butyl paraben (BuP) and benzyl paraben (BzP), were determined in urine from 319 adults in Shenzhen, China. MeP, EtP and PrP were frequently detected in urine samples (detection frequencies >66.5%), suggesting broad exposure in South China adults. Median concentrations of MeP, EtP, PrP, BuP and BzP were 5.78, 0.39, 0.35, 0.01 and 0.02 μg/L, respectively. A significantly positive correlation was observed between the urinary concentrations of MeP and PrP (p < 0.01), suggesting similar sources for these two chemicals. In addition, participants with alcohol consumption exhibited significantly lower paraben concentrations in urine than those without alcohol drinking (p < 0.05). Significant association was observed between urinary concentrations of parabens and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels (p < 0.01), while no significant dose-response relationship was found (p > 0.05). A potential risk from PrP exposure was found in South China adults., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Parabens are added to personal care products as antimicrobial preservatives. They have been suggested to have endocrine disrupting abilities. Prenatal exposure to parabens has been associated with reproductive endpoints including reduced male anogenital distance (AGD, distance from anus to genitals), which is sensitive to prenatal anti-androgenic exposure., Objectives: To study the associations between maternal paraben concentrations in second trimester urine and AGD and reproductive hormone concentrations at 3 months of age in offspring., Methods: Pregnant women from Odense, Denmark were included in early pregnancy from 2010 to 12, and their children are being followed up. Fasting spot urine samples from 536 pregnant women were analyzed for methylparaben (MeP), ethyl-paraben (EtP), iso-propylparaben (i-PrP), n-propylparaben (n-PrP), n-butylparaben (n-BuP) and benzylparaben (BzP) by liquid chromatography tandem mass spectrometry and thereafter osmolarity adjusted. Three months after expected date of birth, AGD was measured in 452 children, and serum concentrations of follicle stimulating hormone (FSH), luteinizing (LH), testosterone, dehydroepiandrosterone-sulphate (DHEAS), androstenedione and 17-hydroxyprogesterone (17-OHP) were measured in 198 children. Maternal paraben exposure was categorized into tertiles or below and above level of detection, and sex-stratified multiple linear regression analyses were performed with AGD or reproductive hormones as outcomes., Results: Most pregnant women had low concentrations of parabens in urine, but 10% exceeded the threshold for adverse estrogenic effects. Higher maternal paraben exposure was associated with shorter AGD in male offspring and longer AGD in girls, although only significant for MeP in boys. In addition, FSH, LH, DHEAS, 17-OHP concentrations were lower in girls with high prenatal paraben exposure, whereas no consistent pattern was found in boys., Discussion: The endocrine disrupting abilities of parabens may affect humans at vulnerable time periods during development, which may have long term impact on reproductive function. This is the first study to find these associations in girls and our findings need confirmation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Antimicrobial and/or preservative ingredients incorporated in wound care products are subjected to certain safety restrictions. However, several of those agents, and paraben preservatives in particular, have been criticised. Conflicting reports on the potential of parabens to induce allergic contact dermatitis, and their assumed oestrogen-like activity, raised public health concerns about their overall safety. Here, we seek to provide a balanced perspective on the most significant purported adverse health effects, and thereby allay the many misconceptions regarding the safety of parabens. Extensive and long-term monitoring of paraben allergy frequencies illustrate that allergic reactions are quite uncommon, especially when compared with other antimicrobial and preservative agents. The estrogenic potential of parabens was illustrated to be far less potent than that of natural oestrogen receptor ligands, and the etiological significance of their presence in human tissue has not been established. The general consensus based on investigations by both the scientific community and regulatory agencies indicates that, with current safety regulations regarding their use in place, this effective and well-documented group of preservatives should not warrant drastic measures to replace them. As such, despite the ongoing concern, it is indicated that, when used at typical concentrations, parabens are unlikely to affect human health., (© 2020 The Authors. International Wound Journal published by Medicalhelplines.com Inc (3M) and John Wiley & Sons Ltd.)

Background: Phenols and parabens (P&Ps) are commonly found in skin care products. However, P&Ps' role in pruritus and eczema has not been studied., Objective: The aim of the study was to investigate the association between P&Ps, and pruritus and eczema., Methods: This is a cross-sectional population-based study of 2202 participants. We examined the association between urinary phenols (triclosan, bisphenol A, benzophenone-3) and parabens (methyl and propyl parabens) and itchy rash/eczema using the 2005-2006 National Health and Nutrition Examination Survey database. Phenols and parabens were divided into quartiles (Qs) with the first Q as the reference. We calculated odds ratios and 95% confidence intervals, adjusting for multiple variables., Results: Urinary triclosan was inversely associated with itchy rash (P trend = 0.048). In a subpopulation analysis by race/ethnicity, urinary methyl paraben was positively associated with itchy rash in African Americans (fourth Q vs first Q: odds ratio, 12.60; 95% confidence interval, 1.03-154.06; P trend = 0.02). Triclosan was inversely associated with eczema in whites (P trend = 0.04)., Conclusions: Methyl paraben exposure may increase the risk of itchy rash in African Americans, whereas triclosan may decrease the risk of itchy rash and eczema. The potential effect of triclosan and methyl paraben in pruritus and eczema warrants further study., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2019 American Contact Dermatitis Society. All Rights Reserved.)

Effects of paraben toxicity, i.e., endocrine-disruption properties, are in the focus of researchers for decades, but still - they are a hot subject of debate. Parabens are aliphatic esters of p-hydroxybenzoic acid, which are widely used as antimicrobial agents for the preservation of cosmetics, pharmaceuticals and foods. Mostly used parabens are methyl-, ethyl-, propyl- and butylparaben. Although the toxicity of parabens is reported in animals and in in vitro studies, it cannot be taken for granted when discussing hazards for human health due to an unrealistic exposure -safety profile. Many studies have demonstrated that parabens are non-teratogenic, non-mutagenic, non-carcinogenic and the real evidence for their toxicity in humans has not been established. For now, methyl-, ethyl- and propylparaben are considered safe for use in cosmetics and pharmaceuticals within the recommended range of doses. Regarding alternatives for parabens, a variety of approaches have been proposed, but every substitute would need to be tested rigorously for toxicity and safety.

Background: Evidence suggests exposure to endocrine-disrupting chemicals (EDCs) can influence Metabolic Syndrome (MetS) risk in adults, but it is unclear if EDCs impact women during midlife. We examined if EDCs measured in adult women were predictive of MetS and its components 9 years later. Methods: We measured urinary phthalate metabolites, phenols, and parabens collected in 2008 among 73 females from the ELEMENT study. MetS and its components (Abdominal Obesity, Hypertriglyceridemia, Cholesterolemia, Hypertension, and Hyperglycemia) were assessed in 2017. We regressed log-transformed EDC concentrations on MetS and MetS components using logistic regression, adjusting for age and physical activity. Results: At follow-up, the mean (SD) age was 46.6 (6.3) years; the prevalence of MetS was 34.3%. Sum of dibutyl phthalate metabolites (ΣDBP), monobenzyl phthalate (MBzP), and monoethyl phthalate (MEP) were associated with an increased odds of hypertriglyceridemia. 2,5-dichlorophenol (2,5 DCP) and 2,4-dichlorophenol (2,4 DCP) were associated with increased odds of hypertriglyceridemia. The odds of hypertension were 4.18 (95% CI: 0.98, 17.7, p < 0.10) and 3.77 (95% CI: 0.76, 18.62, p < 0.10) times higher for every IQR increase in MCOP and propyl paraben, respectively. The odds of hyperglycemia were 0.46 (95% CI: 0.18, 1.17 p < 0.10) times lower for every IQR increase in the sum of di-2-ethylhexyl phthalate metabolites (ΣDEHP), and the odds of abdominal obesity were 0.70 (95% CI: 0.40, 1.21, p < 0.10) lower for every IQR increase in the concentration of triclosan. Conclusion: We found EDCs measured in 2008 were marginally predictive of hypertriglyceridemia and hypertension 9 years later. Results suggest that lower exposure to certain toxicants was related to lower markers of metabolic risk among midlife women., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zamora, Jansen, Tamayo-Ortiz, Goodrich, Sánchez, Watkins, Tamayo-Orozco, Téllez-Rojo, Mercado-García, Baylin, Meeker and Peterson.)

Propyl-paraben exposure is associated with aeroallergen sensitization, but its association with atopic dermatitis (AD) is inconclusive. No studies have been conducted on the metabolomic pathways underlying these associations. We investigated the associations between propyl-paraben exposure and aeroallergen sensitization, AD, and Eczema Area and Severity Index (EASI) score and identified the underlying pathways using untargeted metabolomics analysis. We enrolled 455 children in a general population study. Skin prick tests were performed with the assessment of EASI score. Urinary propyl-, butyl-, ethyl-, and methyl-paraben levels were measured. Untargeted metabolomics analysis was performed on the first and fifth urine propyl-paraben quintile groups. The highest urine propyl-paraben quintile group was associated with aeroallergen sensitization, but not with AD. Glycine, threonine, serine, ornithine, isoleucine, arabinofuranose, D-lyxofuranose, citrate, and picolinic acid levels were higher, whereas palmitic acid and 2-palmitoylglycerol levels were lower in the highest quintile propyl-paraben group, than in the lowest quintile group. The propyl-paraben-induced metabolic perturbations were associated with serine and glycine metabolisms, branched-chain amino acid metabolism, and ammonia recycling. Propyl-paraben exposure was associated with aeroallergen sensitization and EASI score, partially via metabolomic changes related with oxidative stress, mTOR, peroxisome proliferator-activated receptors pathway, aryl hydrocarbon receptor signaling pathways, and tricarboxylic acid cycle.

Exposures to phthalates, parabens, and other phenols are often correlated due to their ubiquitous use in personal care products and plastics. Examining these compounds as a complex mixture may clarify inconsistent relationships between individual chemicals and childhood adiposity. Using data from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study, a longitudinal cohort of children in Salinas Valley, California ( n = 309), we examined biomarkers of 11 phthalate metabolites and 9 phenols, including several parabens and bisphenol A, measured in maternal urine at two time points during pregnancy. We measured child height and weight at age five to calculate the body mass index (BMI) z -scores and overweight/obesity status. The association between prenatal urinary concentrations of biomarkers with the childhood BMI z -score and overweight/obesity status was analyzed using single-pollutant models and two mixture methods: Bayesian hierarchical modeling (BMH) and Bayesian kernel machine regression (BKMR). Urinary concentrations of monoethyl phthalate, monocarboxy-isononly phthalate (metabolites of diethyl phthalate and di-isodecyl phthalate, respectively), and propylparaben were consistently associated with an increased BMI z -score and overweight/obesity status across all modeling approaches. Higher prenatal exposures to the cumulative biomarker mixture also trended with greater childhood adiposity. These results, robust across two methods that control for co-pollutant confounding, suggest that prenatal exposure to certain phthalates and parabens may increase the risk for obesity in early childhood.

Parabens, a group of endocrine-disrupting chemicals, have been associated with obesity in previous studies. However, there is a paucity of literature regarding the effects of paraben exposures on gestational weight gain (GWG), a considerable predictor of obesity risk in both mothers and offspring later in life. The aim of the present study was to evaluate the associations between urinary paraben concentrations and GWG during the three trimesters of pregnancy. We collected urine samples from 613 pregnant women during the first, second, and third trimesters of their pregnancies between 2014 and 2015 in Wuhan, China. The urine concentrations of five parabens, including methylparaben (MeP), ethylparaben (EtP), propylparaben (PrP), butylparaben, and benzylparaben, were measured. Gestational weight in each trimester and prepregnancy weight were used to calculate trimester GWG. Linear mixed models were used to evaluate the trimester-specific and overall associations between paraben exposures and GWG rate (trimester GWG divided by the gestational week of the weight measurement, kg/week). We performed stratified analysis to further explore the potential effect modification by prepregnancy BMI. In the trimester-specific association analyses, the first-trimester concentrations MeP, EtP, PrP, and ∑parabens (sum of all five parabens's molar concentrations) were associated with an increased first-trimester GWG rate, and these associations were stronger than those of the second or third trimesters. The overall association analysis showed that increased trimester GWG rates were associated with the combined effects of exposure to MeP, PrP, or ∑parabens during all three trimesters. Stratified analysis showed that higher paraben exposures were associated with higher trimester GWG rates among overweight/obese women that among normal-weight or underweight women. Our results showed that paraben exposures were positively associated with trimester GWG rate during pregnancy, especially during the first trimester. Replicated research in populations exposed to higher paraben levels is needed in the future.

Objectives: The objective of this study was to quantify parabens intake due to drug administration in neonates during hospitalization following their birth., Method: A monocentric prospective study was performed into a neonatalogy unit to collect all drug prescriptions. An exhaustive list of parabens containing medicines commercialized in France was completed from Theriaque® database. This list was combined with drug prescription to establish an exposure profile to parabens. For each paraben containing medicines, a HPLC-UV assay was performed to determine the average daily intake of paraben received by hospitalized neonates., Results: More than 300 medicines commercialized in France contain at least one paraben. A combination of methylparaben and propylparaben was found in most cases. All hospitalized neonates (n=22) were exposed at least once to methylparaben and propylparaben through medicines while 50 % were exposed to ethylparaben. The average daily intake was higher in term newborns (572,0±249,0 versus 414,6±294,1μg/kg/j for methylparaben) but frequency was higher in prematures (65,0 versus 78,6% for methylparaben) as well as cumutives doses (1421,5±758,8 versus 8618,7±7922,3). These doses are lower than toxicological reference values but these latter do not take into account endocrine disrupting effects of these compounds., Conclusions: These results highlight medicines as a high source of exposure to parabens in hospitalized neonates. It should encourage pharmaceutical companies and health professionnal to prioritize therapeutic cares without parabens., (Copyright © 2020 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.)

Endocrine Disrupting Chemicals (EDCs) have been linked to a variety of cardiometabolic diseases. Yet, few studies have investigated the exposure to EDCs and cardiometabolic health taking lifestyle into account. We aimed to assess exposure to five parabens, three bisphenols and thirteen metabolites of in total eight phthalates in a general Dutch population and to investigate their association with cardiometabolic traits. In 662 adult subjects from the population-based Lifelines cohort, 21 EDC analytes were measured in 24-hour urine collected in 2012, using LC-MS/MS. Association analyses between cardiometabolic traits and EDC concentrations were performed using multivariate linear models adjusting for age, sex, education, smoking, diabetes, physical activity and caloric intake. Quartile analyses were performed to assess linearity. Bisphenol A, four parabens and eight phthalate metabolites were detected in 84-100% of the samples. Adjusted associations for MiBP and MBzP and adiposity-related traits were robust for multiple testing (Beta's, BMI: 1.12, 2.52; waist circumference: 0.64, 1.56, respectively; FDR < 0.009). Associations for triglyceride, HDL-cholesterol, glucose and blood pressure were not. Linearity was confirmed for significant associations. Exposure to EDCs in the Dutch population is ubiquitous. We found direct associations between phthalates and adiposity-related traits. Prospective studies are needed to confirm these findings.

Parabens are widely used in personal care products due to their antimicrobial effects. Although the toxicity of parabens has been reported, little information is available on the toxicity of butylparaben (BP) on oocyte maturation. Therefore, we investigated the effects of various concentrations of BP (0 μM, 100 μM, 200 μM, 300 μM, 400 μM, and 500 μM) on the in vitro maturation of porcine oocytes. BP supplementation at a concentration greater than 300 μM significantly reduced the proportion of complete cumulus cell expansion and metaphase II oocytes compared to the control. The 300 μM BP significantly decreased fertilization, cleavage, and blastocyst formation rates with lower total cell numbers and a higher rate of apoptosis in blastocysts compared to the control. The BP-treated oocytes showed significantly higher reactive oxygen species (ROS) levels, and lower glutathione (GSH) levels than the control. BP significantly increased the aberrant mitochondrial distribution and decreased mitochondrial function compared to the control. BP-treated oocytes exhibited significantly higher percentage of γ-H2AX, annexin V-positive oocytes and expression of LC3 than the control. In conclusion, we demonstrated that BP impaired oocyte maturation and subsequent embryonic development, by inducing ROS generation and reducing GSH levels. Furthermore, BP disrupted mitochondrial function and triggered DNA damage, early apoptosis, and autophagy in oocytes.

Background and Aims: Phenols and parabens are ubiquitous and have been associated with markers of cardiovascular health. However, the literature lacks population-based studies examining the link between these endocrine disruptors and diabetes. We examined the association between paraben/phenol concentrations and diabetes among a nationally representative sample of US adults., Methods and Results: We utilized data from the 2005-2014 National Health and Nutrition Examination Surveys (N = 8498). Total urinary concentrations of BPA, triclosan, BP-3, and propyl, butyl, ethyl, and methyl parabens were measured from urine specimens collected during the examination session. Diabetes status was based on self-report of a previous diagnosis or HbA1c≥6.5%. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CI) associated with the difference in log-transformed values of the 75th and 25th percentiles for each phenol/paraben, adjusting for potential confounders. The adjusted ORs (95% CI) of diabetes comparing the 75th to 25th percentiles of each paraben/phenol were 1.09 (0.96-1.23) for BPA, 0.84 (0.72-0.98) for triclosan, 0.69 (0.61-0.79) for BP-3, 0.71 (0.61-0.83) for propyl paraben, 0.66 (0.54-0.80) for butyl paraben, 0.60 (0.51-0.71) for ethyl paraben, and 0.79 (0.68-0.91) for methyl paraben., Conclusions: Higher concentrations of triclosan, BP-3, and propyl, butyl, ethyl, and methyl parabens were associated with lower odds of diabetes. These findings warrant further investigation into the potential mechanism behind the observed associations and the temporal direction of the associations, given that we cannot rule out reverse causation. Future studies of these endocrine disruptors may improve the understanding of their relationship with diabetes., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to disclose., (Copyright © 2020 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. All rights reserved.)

Background: Patch testing is the criterion standard for diagnosis of allergic contact dermatitis (ACD)., Objective: The aim of the study was to report the trends of patch testing results with the standard series at Massachusetts General Hospital from January 1, 2007, to December 31, 2016, compared with previous data from 1998 to 2006 and from 1990 to 2006 and those reported by the North American Contact Dermatitis Group., Methods: Data were collected and analyzed from retrospective chart reviews, focusing on 50 allergens in our standard series., Results: A total of 2373 patients were patch tested. One or more positive reactions were observed in 1428 patients (60.2%), and 1153 patients (48.6%) had a final primary diagnosis of ACD. Top 5 allergens were nickel (19.8%), fragrance mix I (14.6%), Myroxylon pereirae (balsam of Peru) (13.5%), neomycin (9.4%), and bacitracin (7.7%). Sensitization frequencies statistically increased over time for 3 allergens: nickel, neomycin, and propylene glycol, and decreased for 5 allergens: formaldehyde, paraben mix, thiuram mix, n-isopropyl-N-phenyl-4-phenylenediamine, and epoxy resin (P ≤ 0.001)., Conclusions: Surveillance of ACD trends is essential to detect emerging sensitizers. Patch testing is an important diagnostic tool for detection of ACD to commonly encountered and potential allergens.

Parabens, which are widely used in food, medicines and cosmetics, have a harmful effect on human health. People are most exposed to parabens transdermally by using cosmetic products containing these preservatives. The purpose of this study was to estimate the influence of parabens (methylparaben-MP and propylparaben-PP) on the metabolism of collagen in the human skin fibroblasts and above all, to assess whether rosmarinic acid (RA-50, 100, or 150 M) can protect these cells from the adverse effects of parabens (0.001% MP and 0.0003% PP, 0.003% MP and 0.001% PP, and ​​0.01% MP and 0.003% PP). The possible mechanisms of RA action were estimated as well. Parabens decreased the expression of collagen type I and III at mRNA and protein levels, while RA (depending on the concentration) provided partial or total protection against these changes. The effective protection against the adverse effects of parabens on cell viability and proliferation was also provided by RA. The beneficial impact of RA on collagen and the fibroblasts resulted from an independent action of this compound and its interaction with parabens. This study allows us to conclude that this polyphenolic compound may protect from unfavorable health outcomes caused by lifetime human exposure to parabens contained in cosmetic products., Competing Interests: The authors declare no conflicts of interest.

As a member of parabens (PBs), Isobutylparaben (IBP) has a broad-spectrum antimicrobial activity and widely used in personal care products and cosmetics. Recent studies have indicated that usage of IBP poses a potential threat to reproductive health. In this study, we aimed to reveal the effects of acute exposure to IBP on the meiotic maturation of porcine cumulus oocyte complexes. Initial study showed that 200 μM of IBP significantly reduced the rate of the first polar body extrusion with no significant effect on cumulus cell expansion; however, 400 μM of IBP could significantly affect both. Further research revealed that abnormal spindles, misalignment chromosomes, and aberrant distributed actin filaments were detected in IBP-treated oocytes, which indicates that the cytoskeleton architecture of oocyte could be the target of IBP. At the same time, ROS level and apoptosis rate of oocyte were significantly increased by IBP exposure. Moreover, the levels of H3K9me3 and H3K27me3 were significantly induced in oocytes by IBP. Collectively, these results demonstrate that acute exposure to IBP could disrupt porcine oocyte maturation through affecting cytoskeleton, oxidative stress, viability and epigenetic modification. Environ. Mol. Mutagen. 2020. © 2020 Wiley Periodicals, Inc., (© 2020 Wiley Periodicals, Inc.)

Parabens are preservatives widely used in consumer products including cosmetics and food. Whether low-dose paraben exposure may cause adverse health effects has been discussed controversially in recent years. Here we investigate the effect of prenatal paraben exposure on childhood overweight by combining epidemiological data from a mother-child cohort with experimental approaches. Mothers reporting the use of paraben-containing cosmetic products have elevated urinary paraben concentrations. For butyl paraben (BuP) a positive association is observed to overweight within the first eight years of life with a stronger trend in girls. Consistently, maternal BuP exposure of mice induces a higher food intake and weight gain in female offspring. The effect is accompanied by an epigenetic modification in the neuronal Pro-opiomelanocortin (POMC) enhancer 1 leading to a reduced hypothalamic POMC expression. Here we report that maternal paraben exposure may contribute to childhood overweight development by altered POMC-mediated neuronal appetite regulation.

Purpose of Review: We examined recent research on associations of prenatal and early-childhood exposure to the antimicrobial compounds, triclosan, and parabens, with the risk of asthma and eczema in children. We will discuss potential biological mechanisms of this association and highlight strengths and limitations of the study design and exposure assessment of current findings., Recent Findings: Results of available toxicological and epidemiologic studies indicate a potential link of triclosan and paraben exposures with asthma and eczema in children, as well as changes in microbiome diversity and immune dysfunction, which could possibly mediate an association with the health outcomes. A small number of studies suggest that triclosan and paraben exposures could be related to the risk of asthma and eczema in children. Although current findings are far from conclusive, there is emerging evidence that changes in microbiome diversity and immune function from antimicrobial exposure may mediate these relations.

Background: Contact sensitization in children is increasing. The offending allergens differ depending on patient age and sex. We aimed to determine the sensitization profiles in children (aged 6-12) and adolescents (aged 13-18), to compare these to a control group of adults (aged 60-66), and to evaluate differences in sensitization patterns between working and non-working adolescents., Patients/materials/methods: We analyzed Information Network of Departments of Dermatology (IVDK) data from 2009 to 2016 using multiple logistic regression analysis. Of the 99 082 patients documented in the IVDK database, 591 children, 2451 adolescents and 12 122 adults were included in further analysis., Results: Nickel was the most frequent contact allergen among all age-groups. Children and adolescents showed significantly lower reaction rates to fragrance mix, methyldibromo-glutaronitrile, methylisothiazolinone, and propolis than adults. Positive reactions to sorbitan sesquioleate and mercapto mix among children and to cobalt among adolescents were significantly more frequent than in adults. Working adolescents had more often positive reactions to methyl(chloro)isothiazolinone (skin lesions predominantly on hands) and paraben mix (skin lesions predominantly on feet) when compared to non-working peers. Patch-tested children were more often diagnosed with atopic dermatitis than adults (P < 0.0001)., Conclusions: Contact allergens display age-specific patterns, which should be considered in a standardized series targeting different patient populations (children and adolescents). Employed adolescents should preferably be tested with the baseline series to optimize allergen identification., (© 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Parabens are used as a preservative substance in a wide range of man-made products causing deleterious effects on aquatic organisms and therefore, the concern of their effects to aquatic organisms has been increased. In this study, acute toxicity of methylparaben (MeP), ethylparaben (EtP), and propylparaben (PrP) was assessed in the marine copepod Tigriopus japonicus. The acute toxicity assessment resulted in the median lethal concentration (LC50) values of MeP, EtP, and PrP were 29,754, 11,659, and 113 μg/L, respectively, for male and 38,183, 15,371, and 357 μg/L, respectively, for female, indicating the strongest toxicity of PrP, compared to MeP and EtP and the higher sensitivity of males compared to females. Developmental retardation and reproduction rate were also measured under chronic exposure. Furthermore, significant alteration in sex ratio was shown in PrP-exposed group, indicating PrP would have feminization effect in T. japonicus. Here we report different toxicity of three types of parabens and also shows potential estrogenic effects of PrP in T. japonicus., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Allergic contact dermatitis (ACD) is an increasing problem in children. We sought to investigate the extent of haptens or contact allergens present in baby cosmetic products. Computer programming scripts were written to web-scrape UK supermarkets and pharmacies. In total, 438 unique 'baby products' were identified, and constituent ingredient information was extracted. Data were cross-referenced against 10 standardized patch test reference series. We found that 88% of products had at least one reference contact allergen. There was a mean of 2.21 (range 1-15) reference allergens per product. The most abundant compounds were parabens, fragrances, cetyl/steryl alcohol, methylisothiazolinone, sodium lauryl sulfate and lanolin alcohol. Branded products and those marketed as 'sensitive/gentle/organic/fragrance-free' appeared to contain a greater number of reference allergens than those not marketed as such. This study highlights the increasing number of cosmetic products targeted to children in the UK, and the extent of potential allergens present in these products., (© 2018 British Association of Dermatologists.)