UNASSIGNED: Parabens, which are chemicals used as preservatives in cosmetic and pharmaceutical products, have been reported to be associated with low sperm quality in animal and human models. Despite the high exposure of men to paraben-containing products in Nigeria, there are no known studies that investigate the association of parabens with sperm quality in the country.
UNASSIGNED: To determine the association of urinary levels of metabolites of parabens with sperm count and quality.
UNASSIGNED: A multicenter case-control study among fertile and infertile men in five hospitals in southern Nigeria. A total of 136 men diagnosed with male infertility (cases) were compared with 154 controls with normal fertility. Urinary levels of parabens (ethyl-paraben, methylparaben, propylparaben, and butylparaben) were measured using liquid chromatography mass spectrometry, while semen analysis and hormone assays were carried out using World Health Organization standards and radioimmunoassay, respectively. Data were analyzed with non-parametric statistics and non-parametric linear regression.
UNASSIGNED: The results showed high levels of parabens in both cases and controls. However, there was no statistically significant difference in urinary levels of ethyl-paraben, methylparaben, propylparaben, and butylparaben between cases and controls. In contrast, propylparaben had a decreasing association with total motility in both groups, but the effect was only statistically significant in the case of male infertility. The results of the regression analysis showed that a unit increase in propylparaben significantly decreased total motility in the cases (infertile men). Similarly, a unit increase in propylparaben decreased morphology significantly in the unadjusted model for infertile men. Only serum testosterone showed an insignificant correlation with urinary parabens.
UNASSIGNED: We conclude that urinary parabens are associated with features of poor sperm quality - motility, morphology, and volume. Measures to reduce exposure of men to agents containing parabens in Nigeria may reduce the prevalence of male infertility in the country.

Parabens have emerged as the primary preservative of choice in numerous consumer goods, prompting growing apprehension regarding their potential for human exposure. The study employed the optimized QuEChERs sample extraction method and the UHPLC-Q-Orbitrap HRMS system to generate the initial contamination profiles of seven parabens and their four metabolites in a total of 114 fish samples found along the coastline of Vietnam. The findings of the study indicated that methylparaben was the predominant substance detected, exhibiting the highest concentration in the largehead hairtail (Trichiurus lepturus) species at 32.8 ng g-1 dry weight (dw). Additionally, the metabolites with the highest detectable concentrations in the largehead hairtail were found to be 4-HB and 3,4-DHB, with levels of 8822.0 ng g-1 dw and 3490.8 ng g-1 dw, respectively. Besides, the study reveals notable variations in paraben concentrations across three distinct regions in Vietnam, namely the Central, North, and South (Mann-Whitney U test, p < 0.05). The trophic magnification factors (TMF) for methylparaben, ethylparaben, ethyl protocatechuate, and 4-hydroxybenzoic acid exhibited values exceeding 1, indicating substantial biomagnification of these substances within the marine food web of Vietnam. Additionally, noteworthy positive associations have been observed between methylparaben and ethylparaben, as well as their respective metabolites. Based on the findings of the study, it can be concluded that there is no direct impact of seafood consumption on human health in Vietnam.

Consumer exposure to cosmetic ingredients is estimated in a tiered manner. Simple Tier1 deterministic aggregate exposure modelling generates a worst case estimate of exposure. Tier1 assumes that a consumer uses all cosmetic products concomitantly daily, at maximum frequency, and products always contain the ingredient at the maximum allowed % w/w concentration. Refining exposure assessment from worst case to more realistic estimates uses evidence from surveys of actual use levels of ingredients and Tier2 probabilistic models, where distributions of consumer use data can be applied. In Tier2+ modelling, occurrence data provides evidence of products on the market actually containing the ingredient. Three case studies are presented using this tiered approach to illustrate progressive refinement. The scale of refinements from Tier1 to Tier2+ modelling for the ingredients, propyl paraben, benzoic acid and DMDM hydantoin were: 0.492 to 0.026; 1.93 to 0.042 and 1.61 to 0.027 mg/kg/day exposure dose. For propyl paraben, moving from Tier1 to Tier2+ represents a refinement from 49-fold to 3-fold overestimate of exposure when compared to a maximum estimate of 0.01 mg/kg/day exposure seen in human studies. Such refinements from worst case to realistic levels of exposure estimation can be critical in the demonstration of consumer safety.

Hydroxylated metabolites in the living body are considered as a potential biomarker of exposure to emerging contaminations (ECs) and breast cancer, but their formation mechanism has not received enough attention. Besides, the adverse impacts of metabolites during the metabolic transformation of ECs largely remain unknown. In this study, we employed a density functional calculation combing with in-vitro incubation of human liver microsomes to explore the bio-transformation of preservative methylparaben (MPB) in human bodies. Our results showed that hydroxylated metabolites of MPB (OH-MPB) were observed experimentally, while a formation mechanism was revealed at the molecular level. That is, hydroxylated metabolite was exclusively formed via the hydrogen abstraction from the phenolic hydroxyl group of MPB followed by the OH-rebound pathway, rather than the direct hydroxylation on the benzene ring. The increasing of hydroxyl groups on ECs could improve the metabolisms. This was confirmed in the metabolism of ECs without hydroxyl group and with multiple-hydroxyl groups, respectively. Furthermore, toxicity assessments show that compared to parent MPB, the hydroxylated metabolites have increased negative impacts on the gastrointestinal system and liver. A semiquinone product exhibits potential damage in the cardiovascular system and epoxides are toxic to the blood and gastrointestinal system. The findings deepen our insight into the biotransformation of parabens in human health, especially by providing health warnings about the potential impacts caused by semiquinone and epoxides.

Parabens are widely used in consumer products resulting in frequent exposure to humans. To date, little is known about the association between human paraben exposure and rheumatoid arthritis (RA). In this study, a case-control study (n = 290) was conducted in Hangzhou, China, aiming to quantify the concentrations of methyl paraben (MeP), ethyl paraben (EtP), propyl paraben (PrP), and butyl paraben (BuP) in serum samples and to determine their associations with RA risks. MeP (mean 4.7 ng/mL, range <0.05-20 ng/mL) was the predominant paraben in human serum, followed by PrP (1.9 ng/mL, <0.12-24 ng/mL), EtP (1.4 ng/mL, <0.09-10 ng/mL), and BuP (1.09 ng/mL, <0.10-10 ng/mL). With 1-unit increase of MeP concentrations in human serum, the levels of rheumatoid factors, anticyclic citrullinated peptide antibody, and immunoglobulin G will increase by 0.19 unit (95% confidence intervals [CI]: 0.12-0.46), 0.30 unit (95% CI: 0.26-0.58), and 0.24 unit (95% CI: 0.21-0.30) in the adjusted model, respectively. One-unit increase of MeP and PrP concentrations in human serum was associated with an increase of 0.15 (95% CI: 0.037-0.28) and 0.20 (95% CI: 0.10-0.32) in the C-reactive protein concentrations. In addition, an association between serum MeP levels and the incidence of RA (odds ratios (OR)crude = 1.33, CI: 1.11-1.62, p = 0.03; ORadjusted = 1.86, CI: 1.32-2.63, p = 0.02) was positive and significant. Based on the measurements of serum paraben concentrations, this work supports the evidence for the significant associations among paraben exposure, change of specific immune marker, and RA risks.

Prior studies have identified the associations between environmental phenol and paraben exposures and increased risk of gestational diabetes mellitus (GDM), but no study addressed these exposures as mixtures. As methods have emerged to better assess exposures to multiple chemicals, our study aimed to apply Bayesian kernel machine regression (BKMR) to evaluate the association between phenol and paraben mixtures and GDM. This study included 64 GDM cases and 237 obstetric patient controls from the University of Oklahoma Medical Center. Mid-pregnancy spot urine samples were collected to quantify concentrations of bisphenol A (BPA), benzophenone-3, triclosan, 2,4-dichlorophenol, 2,5-dichlorophenol, butylparaben, methylparaben, and propylparaben. Multivariable logistic regression was used to evaluate the associations between individual chemical biomarkers and GDM while controlling for confounding. We used probit implementation of BKMR with hierarchical variable selection to estimate the mean difference in GDM probability for each component of the phenol and paraben mixtures while controlling for the correlation among the chemical biomarkers. When analyzing individual chemicals using logistic regression, benzophenone-3 was positively associated with GDM [adjusted odds ratio (aOR) per interquartile range (IQR) = 1.54, 95% confidence interval (CI) 1.15, 2.08], while BPA was negatively associated with GDM (aOR 0.61, 95% CI 0.37, 0.99). In probit-BKMR analysis, an increase in z-score transformed log urinary concentrations of benzophenone-3 from the 10th to 90th percentile was associated with an increase in the estimated difference in the probability of GDM (0.67, 95% Credible Interval 0.04, 1.30), holding other chemicals fixed at their medians. No associations were identified between other chemical biomarkers and GDM in the BKMR analyses. We observed that the association of BPA and GDM was attenuated when accounting for correlated phenols and parabens, suggesting the importance of addressing chemical mixtures in perinatal environmental exposure studies. Additional prospective investigations will increase the understanding of the relationship between benzophenone-3 exposure and GDM development.

Parabens are esters of para-hydroxybenzoic acid that have been used as preservatives in many types of products for decades including agrochemicals, pharmaceuticals, food and cosmetics. This illustrative case study with propylparaben (PP) demonstrates a 10-step read-across (RAX) framework in practice. It aims at establishing a proof-of-concept for the value added by new approach methodologies (NAMs) in read-across (RAX) for use in a next-generation risk assessment (NGRA) in order to assess consumer safety after exposure to PP-containing cosmetics. In addition to structural and physico-chemical properties, in silico information, toxicogenomics, in vitro toxicodynamic, toxicokinetic data from PBK models, and bioactivity data are used to provide evidence of the chemical and biological similarity of PP and analogues and to establish potency trends for observed effects in vitro. The chemical category under consideration is short (C1-C4) linear chain n-alkyl parabens: methylparaben, ethylparaben, propylparaben and butylparaben. The goal of this case study is to illustrate how a practical framework for RAX can be used to fill a hypothetical data gap for reproductive toxicity of the target chemical PP.

The widespread use of methylparaben as a preservative has caused increased exposure to natural aquatic systems in recent decades. However, current studies have suggested that exposure to this compound can result in endocrine disrupting effects, raising much concern regarding its environmental impact. In contast, methylparaben has also been found to be part of the metabolome of some organisms, prompting the question as to whether this compound may be more natural than previously assumed. Through a combination of field studies investigating the natural presence of methylparaben across different taxa, and a 54-day microcosm experiment examining the bioaccumulation and movement of methylparaben across different life stages of aquatic insects (order Trichoptera), our results offer evidence suggesting the natural origin of methylparaben in aquatic and terrestrial biota. This study improves our understanding of the role and impact this compound has on biota and challenges the current paradigm that methylparaben is exclusively a harmful anthropogenic contaminant. Our findings highlight the need for further research on this topic to fully understand the origin and role of parabens in the environment which will allow for a comprehensive understanding of the extent of environmental contamination and result in a representative assessment of the environmental risk that may pose.

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Skin sensitisation is a key adverse health effect to be addressed in the safety assessment of cosmetic ingredients. Regulatory demands have urged the development of Next Generation Risk Assessment (NGRA) using New Approach Methodologies (NAM) and Defined Approaches (DA) instead of animal models. An illustrative NGRA case study shall demonstrate if the use of propyl paraben at 0.2% in a face cream was safe for consumers. A sequential stacking tier testing DA based on NAM data predicted propyl paraben to be a non-sensitiser, while some NAM input data showed positive results. To increase confidence, structurally related parabens were considered, which revealed NAM and DA hazard predictions similar to those of propyl paraben, non-sensitiser classifications in animal models and very rare cases of human skin allergy. Based on a weight of evidence it was decided that propyl paraben should be considered a non-sensitiser leading to a favourable NGRA conclusion, in line with traditional risk assessment. Examination of an ab initio NGRA based on NAM and metabolism data resulted in a more conservative weak sensitiser consideration as point of departure, which still led to a favourable conclusion.