Butylparaben Research Articles

The administration of methyl and butyl parabens interferes with the enzymatic antioxidant system and induces genotoxicity in rat testis: possible relation to male infertility

Parabens are esters of p-hydroxybenzoic acid, used for decades as a preservative in many products, including agrochemicals, pharmaceuticals, foods and cosmetics. Concerns regarding parabens toxicity include adverse effects on endocrine activity, carcinogenesis, infertility, spermatogenesis, and adipogenesis. The present study aimed to investigate the in vivo administration of methyl and butylparaben at concentrations of 100 and 200 mg/kg body weight, by subcutaneous injection, in variable murinometric measurements, antioxidant systems and genotoxicity. The administration of parabens did not affect the consumption of water and food. However, there was a decrease in the weight of the testes and the seminal vesicle (p < 0.05). The administration of parabens caused an increase in superoxide dismutase for methylparaben (200 mg/kg) and both concentrations of butylparaben (p < 0.05). Catalase showed increased activity in all groups treated with parabens. In contrast, glutathione reductase and glutathione S-transferase suffered a decrease in the groups treated with both parabens. These results show that parabens, especially butyl, can affect the rat testis enzymatic antioxidant system, decreasing the cellular antioxidant capacity, which was confirmed by the decrease in the glutathione reducing power, expressed by the reduced glutathione/oxidized glutathione ratio. Therefore, an increase in lipid peroxidation was observed, which was significant in the case of butyl. Genetic Damage Indicator values show that butylparaben treatments displayed significantly higher values than the control. This study shows for the first time that parabens can induce genotoxicity in the rat male reproductive organ.

Impact of parabens on drinking water bacteria and their biofilms: The role of exposure time and substrate materials

Parabens have been detected in drinking water (DW) worldwide, however, their impact on DW microbial communities remains to be explored. Microorganisms can easily adapt to environmental changes. Therefore, their exposure to contaminants of emerging concern, particularly parabens, in DW distribution systems (DWDS) may affect the microbiological quality and safety of the DW reaching the consumers tap. This work provides a pioneer evaluation of the effects of methylparaben (MP), propylparaben (PP), butylparaben (BP), and their combination (MIX), in bacterial biofilms formed on different surfaces, representative of DWDS materials - high-density polyethylene (HDPE), polypropylene (PPL) and polyvinyl chloride (PVC). Acinetobacter calcoaceticus and Stenotrophomonas maltophilia, isolated from DW, were used to form single and dual-species biofilms on the surface materials selected. The exposure to MP for 7 days caused the most significant effects on biofilms, by increasing their cellular culturability, density, and thickness up to 233%, 150%, and 224%, respectively, in comparison to non-exposed biofilms. Overall, more pronounced alterations were detected for single biofilms than for dual-species biofilms when HDPE and PPL, demonstrating that the surface material used affected the action of parabens on biofilms. Swimming motility and the production of virulence factors (protease and gelatinase) by S. maltophilia were increased up to 141%, 41%, and 73%, respectively, when exposed to MP for 7 days. The overall results highlight the potential of parabens to interfere with DW bacteria in planktonic state and biofilms, and compromise the DW microbiological quality and safety.

Paraben exposure and couple fecundity: a preconception cohort study.

Is pre-conception exposure to parabens associated with fecundity in couples of childbearing age? Paraben exposure in female partners was associated with reduced couple fecundity and anti-Müllerian hormone (AMH) might be one of the possible mediators. The reproductive toxicity of parabens, a class of widely used preservatives, has been suggested but evidence regarding their effects on couple fecundity is scarce. In this couple-based prospective cohort study, a total of 884 pre-conception couples who participated in the Shanghai Birth Cohort between 2013 and 2015 were included. Concentrations of six parabens were measured in urine samples collected from couples. Malondialdehyde, C-reactive protein, and AMH were assessed in female partners. The outcomes included couple fecundability (time-to-pregnancy, TTP) and infertility (TTP > 12 menstrual cycles). Partner-specific and couple-based models were applied to estimate the associations. The joint effect of paraben mixture on couple fecundity was estimated by quantile-based g-computation (q-gcomp). Mediation analysis was used to assess the mediating roles of oxidative stress, inflammation and ovarian reserve. A total of 525 couples (59.4%) conceived spontaneously. In the partner-specific model, propyl paraben (PrP), butyl paraben (BuP), and heptyl paraben (HeP) in female partners were associated with reduced fecundability (fecundability odds ratio (95% CI): 0.96 (0.94-0.98) for PrP; 0.90 (0.87-0.94) for BuP; 0.42 (0.28-0.65) for HeP) and increased risk of infertility (rate ratio (95% CI): 1.06 (1.03-1.10) for PrP; 1.14 (1.08-1.21) for BuP; 1.89 (1.26-2.83) for HeP). Similar associations were observed in the couple-based model. AMH played a significant mediation role in the association (average causal mediation effect (95% CI): 0.001 (0.0001-0.003)). Paraben exposure in male partners was not associated with couple fecundity. The joint effect of paraben mixture on couple fecundity was non-significant. Self-reported pregnancy and single urine sample may lead to misclassification. The mediation analysis is limited in that levels of sex hormones were not measured. The inclusion of women with irregular menstrual cycles might affect the results. It is possible that the observed association was due to reverse causation. This is the first study to assess the effects of paraben exposure on couple fecundity in Asians. Given the widespread exposure to parabens in couples of childbearing age, the present findings may have important public health implications. This study was supported in part by the National Natural Science Foundation of China (41991314), the Shanghai Science and Technology Development Foundation (22YF1426700), the Science and Technology Commission of Shanghai Municipality (21410713500), and the Shanghai Municipal Health Commission (2020CXJQ01). All authors declare no conflict of interest. N/A.

Urinary concentration of selected nonpersistent endocrine disrupting chemicals—reproductive outcomes among women from a fertility clinic

Parabens and benzophenones are compounds widely used in cosmetics and personal care products. Although human exposure is widespread there is a limited number of epidemiological studies assessing the relationship between exposure to these chemicals and female reproductive health. The aim of the study is to explore the relationship between paraben and benzophenone concentrations and reproductive outcomes among women attending a fertility center. This prospective cohort included 450 women undergoing in vitro treatment (IVF) at fertility clinic in Poland. The validated gas chromatography ion-tap mass spectrometry to assess concentrations of parabens in urine (methyl (MP), ethyl (EP), propyl (PP), butyl paraben (BP)) and benzophenone-3 (BP-3) was used. To explore the relationship between concentrations of examined chemicals and reproductive outcomes (methaphase II (MII) oocyte yield, total oocyte yield, implantation rate, fertilization rate, clinical pregnancy, live births), multivariable generalized linear mixed model was used for the analysis. Increased exposure to butyl paraben was associated with a significant decrease in MII oocyte count (p = 0.007) when exposure to BP was treated as the continuous variable. Additionally, the exposure to BP in the highest quartile of exposure also decreases MII oocyte count (p = 0.02) compared to the lowest quartile. Urinary concentrations of BP were not related to total oocyte count, fertilization and implantation rate, clinical pregnancy, and live birth when the exposure variable was continuous variable or in the quartiles of exposure. Exposure to MP, EP, PP, the sum of examined parabens, and benzophenone-3 were not related to any of the examined reproductive outcomes. Exposure to butyl paraben was associated with a decrease in MII oocyte count among women attending fertility clinic rinsing concerns that exposure may have a potential adverse impact on embryological outcomes. The results emphasize the importance to reduce chemicals in the environment in order to minimize exposure. As this is the first study showing such an association, further research is needed to confirm these novel results in other populations.Graphical

Butylparaben Exposure Induced Darker Skin Pigmentation in Nile Tilapia (Oreochromis niloticus)

Butylparaben (BuP), as an emerging contaminant with endocrine-disrupting effects, may exert effects on skin pigmentation in fish by interfering with the neuroendocrine system. Therefore, models of BuP exposure in Nile tilapia (Oreochromis niloticus) were established by adding different doses of BuP (0, 5, 50, 500, and 5000 ng/L) for 56 days. The obtained results showed that BuP exposure induced darker skin pigmentation, manifested as increased melanin content of skin, while genes related to melanin synthesis, including α-MSH and Asip2, significantly changed. In addition, BuP exposure reduced dopamine and γ-aminobutyric acid content in the brain, which is related to the synthesis of α-MSH. Furthermore, the release of neurotransmitters from the brain is affected by light. Thus, the relative gene expression levels in the phototransduction pathway were evaluated to explore the molecular mechanism of BuP-induced darker skin pigmentation, and the obtained results showed that Arr3a and Arr3b expression was significantly upregulated, whereas Opsin expression was significantly downregulated in a BuP dose-dependent manner, indicating that BuP inhibited phototransduction from the retina to the brain. Importantly, correlation analysis results showed that all melanin indexes were significantly positively correlated with Arr3b expression and negatively correlated with Opsin expression. This study indicated that BuP induced darker skin pigmentation in Nile tilapia via the neuroendocrine circuit, which reveals the underlying molecular mechanism for the effects of contaminants in aquatic environments on skin pigmentation in fish.

Studying paraben-induced estrogen receptor- and steroid hormone-related endocrine disruption effects via multi-level approaches

Increasing concerns have been raised on the health risks of parabens in the regard of their widespread applications and potential endocrine disrupting activities. In this study, four typical parabens, including methyl paraben (MeP), ethyl paraben (EtP), propyl paraben (PrP), and butyl paraben (BuP) were systematically investigated for their estrogen receptor- and steroid hormone-related endocrine disruptions using multi-level approaches. Paraben exposure promoted the proliferation of MCF-7 cells, increased the luciferase activity in MVLN cells, and induced the vitellogenin (vtg) expression in zebrafish larvae, showing the typical estrogenic effects. The in vitro protein assays further revealed that PrP and BuP could bind with two isoforms of estrogen receptors (ERs). The estrogenic activities of parabens were predicted to be positively correlated with their chemical structure complexity by using molecular docking analysis. Furthermore, the synthesis and secretion of estradiol (E2) and testosterone (T) were significantly disturbed in H295R cells and zebrafish larvae, which could be regulated by paraben-induced transcriptional disturbance in both in vitro steroidogenesis and in vivo hypothalamic-pituitary-gonadal (HPG) axis. Parabens could disturb the endocrine system by activating the ERs and disrupting the steroid hormone synthesis and secretion, suggesting their potential deleterious risks to the environment and human health.

Evaluation of Parabens and Bisphenol A Concentration Levels in Wild Bat Guano Samples.

Parabens and bisphenol A are synthetic compounds found in many everyday objects, including bottles, food containers, personal care products, cosmetics and medicines. These substances may penetrate the environment and living organisms, on which they have a negative impact. Till now, numerous studies have described parabens and BPA in humans, but knowledge about terrestrial wild mammals' exposure to these compounds is very limited. Therefore, during this study, the most common concentration levels of BPA and parabens were selected (such as methyl paraben-MeP, ethyl paraben-EtP, propyl paraben-PrP and butyl paraben-BuP) and analyzed in guano samples collected in summer (nursery) colonies of greater mouse-eared bats (Myotis myotis) using liquid chromatography with the tandem mass spectrometry (LC-MS-MS) method. MeP has been found in all guano samples and its median concentration levels amounted to 39.6 ng/g. Other parabens were present in smaller number of samples (from 5% for BuP to 62.5% for EtP) and in lower concentrations. Median concentration levels of these substances achieved 0.95 ng/g, 1.45 ng/g and 15.56 ng/g for EtP, PrP and BuP, respectively. BPA concentration levels did not exceed the method quantification limit (5 ng/g dw) in any sample. The present study has shown that wild bats are exposed to parabens and BPA, and guano samples are a suitable matrix for studies on wild animal exposure to these substances.

AN In-silico MOLECULAR DOCKING STUDY ON THE INTERACTION OF DIFFERENT PARABEN ESTERS (METHYL-, ETHYL-, PROPYL- AND BUTYL-PARABEN) WITH HUMAN THYROID HORMONE RECEPTOR α1 (THRα1) AND β1 (THRβ1)

Thyroid hormones (THs) activate transcription of a large number of genes via binding with nuclear thyroid hormone receptors (THRs) that are either attached to the DNA genetic strands or located in proximity to them. However, the ever-increasing human anthropogenic activities have introduced numerous harmful chemicals in the environment, many of which share high degree of structural resemblance with the THs i.e., triiodothyronine (T3) and thyroxine (T4) and thus can interfere with the normal downstream receptor signalling. The present study used bioinformatics to perform a molecular docking analysis (Autodock 4.2.6) where different paraben esters (PBs) i.e., methyl- (MP), ethyl- (EP), propyl- (PP) and butyl- paraben (BP) were examined for their possible interaction with two human THR isoforms viz., THRα1 and THRβ1. Perceiving the free binding energies (ΔG) of different PB-THRs complexes, it has become evident that BP has the strongest binding interaction with both THRα1 (PDB Id- 1NAV) and THRβ1 (PDB Id- 1NAX) i.e., -6.51 and -6.14 kcal/mol respectively and also has highest number of amino acids interactions in the active sites, followed by PP, EP and MP. The co-crystal ligand exhibited binding energies of -10.43 and -10.52 kcal/mol for THRα1 and THRβ1 respectively. Therefore, the study firmly demonstrates that thyroid hormone receptor interaction of the selected PB esters rise with increase in length/complexity of the alkyl side chain. Given that all the investigated PB esters are capable binders of both the THRs, unremitting use of these chemical preservatives certainly could amend the receptor mediated signalling of THs.

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

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

New insights on the binding of butyl-paraben to trypsin: experimental and computational approaches

Butyl-paraben (BP) is one of the most widely used preservatives in numerous foodstuffs, skin care products, and a variety of drugs, and trypsin is the main digestive enzyme, the research on the binding between the two is essential for human health. In the present paper, the effect of BP on trypsin has been explored using experimental and computational techniques to evaluate BP toxicity at the protein level. The obtained results from molecular docking and kinetic assay revealed BP was embedded in the hydrophobic cavity-S1 binding pocket of the enzyme to inhibit its activity by a competitive model. Intrinsic fluorescence of trypsin after interaction with BP revealed the static mode of quenching. FRET indicated that the distance of the enzyme to BP is 1.89 nm with high energy efficiency. Thermodynamic results proved that BP spontaneously bound to trypsin in an enthalpy-driven manner, the van der Waals interactions and H-bonds serving as the predominant forces in binding processes. CD spectroscopy and molecular dynamics (MD) simulation revealed that the trypsin structure transformed from the β-Sheet structure to the unordered Coil structure upon interacting with BP. Resonance light scattering (RLS), synchronous fluorescence, and three-dimensional (3 D) spectroscopies further supported the alteration in the conformation of trypsin. Differential scanning calorimetry (DSC) showed that trypsin was somewhat destabilized in the presence of BP. Accordingly, all of the experimental data were confirmed by MD simulation. Communicated by Ramaswamy H. Sarma

ZnHCF@PB nanoparticles with reduced bandgap as a promising photocatalyst for the degradation of conventional and emerging water contaminants

The photocatalytic degradation of conventional and emerging pollutants (i.e., methyl, ethyl, and butyl parabens) was investigated under light irradiation with 315–1050 nm wavelength using core–shell zinc doped hexacyanoferrate@Prussian blue nanoparticles. Different synthesis parameters including precursors loading, drying temperature and different metal ions precursors were studied. The ten different composite systems obtained, were investigated for the photodegradation of methylene blue in deionized water. The optimal performance photocatalyst (20 mg/L) photodegrade 94% of 10 ppm methylene blue within 24 min. The optimized sample was further used for the photodegradation of methylene blue in municipal wastewater matrix; it completely degraded the methylene blue after 51 min. Finally, the developed nanoparticles were investigated for the photodegradation of parabens. The chemical oxygen demand showed 30% of parabens was degraded in the municipal wastewater matrix. The results of this research show that ZnHCF@PB nanoparticles could be used for the effective photocatalytic remediation of conventional and emerging pollutants, i.e., parabens. Statement of environmental implicationThrough this study, it is anticipated that ZnO-derived ZnHCF@PB NPs can achieve a bandgap of 1.11 eV, which is much lower than that of ZnO NPs (3.15 eV). Interestingly, ZnHCF@PB NPs were efficiently used for the degradation of conventional (i.e., dyes) and emerging contaminants (i.e., parabens) in deionized water and municipal wastewater matrices to mimic industrial wastewater.

Investigation of the applicability of fatty acid-based deep eutectic solvent based air assisted liquid liquid microextraction for the rapid determination and extraction of butylparaben in cosmetic products

In this research paper, fatty acid-based deep eutectic solvents (FA-DESs) were prepared and investigated for the extraction of butylparaben (BP) from cosmetic products by air assisted liquid liquid microextraction (AA-DLLME). The amounts of BP were determined by UV/Vis spectrophotometry. By combining single factor optimization and Box-Behnken design based multivariate approach, key extraction parameters affecting the FA-DES AA-LLME procedure were systematically optimized. Under the optimized conditions, wide working range (5–800 μg L−1) was obtained with a good r2:0.9972 and high enrichment factor (205). For three replications run of 10 μg L−1 (low), 300 μg L−1 (medium) and 600 μg L−1 (high) of BP, the percent extraction recovery and relative standard deviation were in the range of 92 ± 4%-98 ± 2% and 1.8–2.6%, respectively. The limit of detection and the limit of quantification were 1.5 μg L−1 and 5 μg L−1, respectively. The study of the matrix effect showed that the proposed method has high selectivity for measuring BP in the selected samples. Therefore, it has great potential in sample pre-treatment and quantification of trace BP in cosmetic products.

RF22 | PMON05 Parabens Promote Pro-Tumorigenic Effects in Luminal Breast Cancer Cell Lines With Diverse Genetic Ancestry

Abstract In the United States, Black women are 39% more likely to die from breast cancer compared to White women (AACR Cancer Disparities Progress Report 2020). Furthermore, Black women are at a higher risk of developing breast cancer under the age of 40 than any other racial or ethnic group. While the underlying cause of these disparities is multifactorial, exposure to endocrine disrupting chemicals (EDCs) in hair and personal care products has been associated with increased risk of breast cancer. Parabens are known EDCs that are commonly used as preservatives in hair and other personal care products. The Environmental Working Group scores methylparaben (MP), propylparaben (PP), and butylparaben (BP) moderate (MP) to high (BP and PP) on a hazardous scale of chemicals found in personal care products. Furthermore, these parabens are restricted in personal care products with set maximum concentration standards in Japan, the European Union, and Southeast Asia. Studies have shown that parabens impact breast cancer cell proliferation, death, migration/invasion, and metabolism, as well as gene expression in vitro. However, these studies were conducted using cell lines of European ancestry; to date, no studies have utilized breast cancer cell lines of West African ancestry to examine effects of parabens. We hypothesize that, like what has been shown for breast cancer cell lines with European ancestry, parabens will promote pro-tumorigenic effects in breast cancer cell lines with West African ancestry. To test this hypothesis, we treated MCF-7 (European ancestry) and HCC1500 (West African ancestry) luminal breast cancer cell lines with biologically relevant doses of either MP, PP, or BP. We also co-treated with the estrogen receptor (ER) antagonist ICI 182,780 to determine whether observed effects are mediated by ER. We found BP increases HCC1500 cell viability, but not MCF-7 cell viability. This effect was not blocked by co-treatment with ICI 182,780. We also observed that BP and PP, but not MP, increased expression of estrogen-regulated genes in both MCF-7 and HCC1500. The increase in gene expression was reduced with co-treatment of ICI 182,780 in both cell lines, suggesting that these effects are ER-mediated. Preliminary studies suggest that parabens promote migration of both cell lines, with a potentially greater effect on HCC1500 cells. Taken together, these data demonstrate that parabens, particularly BP and PP, promote pro-tumorigenic effects in diverse luminal breast cancer cell lines. These findings have future translational relevance as we are part of a community-led initiative called Bench to Community. Bench to Community brings together basic researchers in endocrinology and social-behavioral scientists, community stakeholders including breast cancer survivors to develop interventions to reduce adverse exposures to EDCs in hair and other personal care products in Black women. Presentation: Sunday, June 12, 2022 12:42 p.m. - 12:47 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Fabrication of Ternary Nanoparticles for Catalytic Ozonation to Treat Parabens: Mechanisms, Efficiency, and Effects on Ceratophyllum demersum L. and Eker Leiomyoma Tumor-3 Cells.

The use of parabens in personal care products can result in their leakage into water bodies, especially in public swimming pools with insufficient water treatment. We found that ferrite-based nanomaterials could catalytically enhance ozone efficiency through the production of reactive oxygen species. Our objective was to develop a catalytic ozonation system using ternary nanocomposites that could minimize the ozone supply while ensuring the treated water was acceptable for disposal into the environment. A ternary CuFe2O4/CuO/Fe2O3 nanocomposite (CF) delivered excellent degradation performance in catalytic ozonation systems for butylparaben (BP). By calcining with melamine, we obtained the CF/g-C3N4 (CFM) nanocomposite, which had excellent magnetic separation properties with slightly lower degradation efficiency than CF, due to possible self-agglomeration that reduced its electron capture ability. The presence of other constituent ions in synthetic wastewater and actual discharge water resulted in varying degradation rates due to the formation of secondary active radicals. 1O2 and •O2− were the main dominant reactive species for BP degradation, which originated from the O3 adsorption that occurs on the CF≡Cu(I)–OH and CF≡Fe(III)–OH surface, and from the reaction with •OH from indirect ozonation. Up to 50% of O3-treated water resulted in >80% ELT3 cell viability, the presence of well-adhered cells, and no effect on the young tip of Ceratophyllum demersum L. Overall, our results demonstrated that both materials could be potential catalysts for ozonation because of their excellent degrading performance and, consequently, their non-toxic by-products.

Human serum paraben levels and their associations with rheumatoid arthritis: a case-control study from Hangzhou, China.

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.

Reproductive toxicity of maternal exposure to di(2-ethylhexyl)phthalate and butyl paraben (alone or in association) on both male and female Wistar offspring.

Parabens and phthalates are commonly found as contaminants in human fluids and are able to provoke reproductive toxicity, being considered endocrine disruptors. To evaluate the effects of phthalate and paraben, alone or in combination, on reproductive development of the offspring, female pregnant Wistar rats were allocated in six experimental groups: Three control groups (gavage [CG], subcutaneous [CS], and gavage + subcutaneous) received corn oil as vehicle, and the remaining groups were exposed to di(2-ethylhexyl)phthalate (DEHP) (500 mg/kg, gavage), butyl paraben (BP) (100 mg/kg, subcutaneously), or MIX (DEHP + BP), from Gestational Day 12 until Postnatal Day (PND) 21. The following parameters were assessed on the offspring: anogenital distance and weight at PND 1, nipple counting at PND 13, puberty onset, estrous cycle, weights of reproductive and detoxifying organs, histological evaluation of reproductive organs, and sperm evaluations (counts, morphology, and motility). Female pups from MIX group presented reduced body weight at PND 1, lower AGD, and decreased endometrium thickness. Male animals showed decreased body weight at PND 1 and lower number of Sertoli cells on DEHP and MIX groups, MIX group revealed increase of abnormal seminiferous tubules, DEHP animals presented delayed preputial separation and higher percentage of immotile sperms, and BP males presented diminished number of Leydig cells. In conclusion, the male offspring was more susceptible to DEHP toxicity; even when mixed to paraben, the main negative effects observed seem to be due to antiandrogenic phthalate action. On the other hand, DEHP seems to be necessary to improve the effects of BP on reducing estrogen-dependent and increasing androgen-dependent events.

Chronic exposure to butyl-paraben causes photosensitivity disruption and memory impairment in adult zebrafish

Limited studies on neurotoxicity following chronic exposure to butyl‑paraben (BuP) have been conducted. In this study, neurobehavior in zebrafish adults was assessed using the novel tank test, photomotor response test, and T-maze test after exposure to BuP for 28 days at concentrations of 0, 0.01, 0.1, and 1.0 mg/L. To comprehensively understand the underlying molecular perturbations in the brain, alterations in transcripts, neurotransmitters, and neurosteroids were measured. We found that BuP penetrated the blood-brain barrier and impaired neurobehavior in photosensitivity at 1.0 mg/L and in memory at 0.1 and 1.0 mg/L. RNA-seq analysis showed that phototransduction, tight junctions, and neuroactive ligand receptor activity were significantly affected, which explains the observed abnormal neurobehaviors. Neurosteroid analysis revealed that BuP increased cortisol levels in a concentration-dependent manner and specifically reduced allopregnanolone levels at all tested concentrations, suggesting that cortisol and allopregnanolone are significant neurosteroid markers associated with photosensitivity and memory deficits. Collectively, we demonstrated that BuP can cross the blood-brain and modulate the levels of transcripts, associated with phototransduction and circadian rhythm, and neurosteroidal cortisol and allopregnanolone, resulting in abnormal neurobehavioral responses to light stimulation and learning and memory.

Association between phenols and thyroid hormones: The role of iodothyronine deiodinase genes

Previous literature on prenatal phenol exposure and thyroid hormone (TH) alteration is conflicting, and the possible mechanisms of action involved remain unclear. We aimed to examine the association between prenatal phenol exposure and levels of maternal and neonatal THs, as well as the possible role of iodothyronine deiodinase (DIO) gene polymorphisms in this relation.We studied 387 Spanish mother–neonate pairs with measurements of maternal phenols, total triiodothyronine (TT3) and free thyroxine (FT4), maternal and neonatal thyroid-stimulating hormone (TSH), and maternal genotypes for single nucleotide polymorphisms in the DIO1(rs2235544) and DIO2(rs12885300) genes. We implemented multivariate linear and weighted quantile sum (WQS) regressions to examine the association between phenols and THs (including sex-stratified models for neonatal TSH) and investigated effect modification of genotypes in the maternal phenol-TH associations.In single exposure models, we found negative associations between maternal triclosan (TCS) and neonatal TSH (% change [95%CI]: −2.95 [-5.70, -0.11], per twofold phenol increase) – stronger for girls – and less clearly for maternal ethylparaben (EPB) and TSH (−2.27 [-4.55, 0.07]). In phenol mixture models, we found no association with THs. In the genetic interaction models, we found some evidence of effect modification of DIO gene polymorphisms with stronger negative associations between methylparaben (MPB), propylparaben (PPB), butylparaben (BPB) and TT3 as well as bisphenol A (BPA) and FT4 for DIO1(rs2235544)-CC. Stronger inverse associations for genotypes DIO2(rs12885300)-CC and DIO2(rs12885300)-CT and positive ones for DIO2(rs12885300)-TT were also reported for BPA and FT4.In conclusion, we found some evidence of an association between phenols and TSH during pregnancy and at birth in single exposure models, the latter being stronger for girls. Since no association was observed between maternal levels of phenols and TT3 or FT4, the possible role of the genetic background in these associations warrants further investigation.

Comparative cytotoxicity induced by parabens and their halogenated byproducts in human and fish cell lines

Parabens are a group of para-hydroxybenzoic acid (p-HBA) esters widely used in pharmaceutical industries. Their safety is well documented in mammalian models, but little is known about their toxicity in non-mammal species. In addition, chlorinated and brominated parabens resulting from wastewater treatment have been identified in effluents. In the present study, we explored the cytotoxic effects (EC50) of five parabens: methylparaben (MP), ethylparaben (EP), propylparaben (PP), butylparaben (BuP), and benzylparaben (BeP); the primary metabolite, 4-hydroxybenzoic acid (4-HBA), and three of the wastewater chlorinated/brominated byproducts on fish and human cell lines. In general, higher cytotoxicity was observed with increased paraben chain length. The tested compounds induced toxicity in the order of 4-HBA < MP < EP < PP < BuP < BeP. The halogenated byproducts led to higher toxicity with the addition of second chlorine. The longer chain-parabens (BuP and BeP) caused a concentration-dependent decrease in cell viability in fish cell lines. Intriguingly, the main paraben metabolite, 4-HBA, proved to be more toxic to fish hepatocytes than human hepatocytes by 100-fold. Our study demonstrated that the cytotoxicity of some of these compounds appears to be tissue-dependent. These observations provide valuable information for early cellular responses in human and non-mammalian models upon exposure to paraben congeners.

Perfluoroalkyl and polyfluoroalkyl substances, bisphenol and paraben compounds in dust collected from residential homes in Klang Valley, Malaysia

Endocrine disrupting chemicals (EDCs) are a growing global concern due to their widespread use and potential harm to human and animal health. Several EDCs have been linked to cancer, obesity, and diabetes in children and adults. EDCs come from manufacturers or everyday products like cookware, textile, cosmetic, furniture, and plastic. Some EDCs are volatile and may be inhaled by the inhabitants where indoor exposure to EDCs is considered worse than outdoor exposure due to the limited and confined area allowing dermal contact and ingestion of EDCs. During the COVID-19 pandemic in 2020–2021, all Malaysians were confined to their homes, prompting the goal of this study to investigate EDCs in household dust collected from Klang Valley homes. A total of 57 dust samples were collected, filtered, and extracted using methanol. EDCs including perfluoroalkyl and polyfluoroalkyl substances (PFAS), bisphenol and parabens were identified and quantified in dust samples by liquid chromatography mass tandem spectrometry (LCMS/MS). The presence of perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), butylparaben (BuP), methylparaben (MeP), ethylparaben (EtP), and propylparaben (PrP) was detected in 50–100% of dust samples, with range of concentration of 0.31–3693.96 ng/g, indicating that these compounds are common in indoor dust. Methylparaben was the most prevalent EDC in collected dust samples with mean concentration at 148. 18 ng/g, accounting for 54% of the concentration distribution, followed by BuP and PFOA. There were regional differences in EDC profiles, with higher PFAS and paraben levels in urban areas such as Putrajaya, Kuala Lumpur, and Petaling. The estimated daily intake (EDI) of EDCs from indoor dust ingestion varied by age, with infants having a significantly higher EDI (p < .01) than children and adults. Despite safe for consumption (Hazard Quotient, HQ < 1), these findings provide a baseline for assessing PFAS, bisphenol, and paraben in indoor dust from Malaysian homes.