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Open research questions in Effects and risks of endocrine disrupting chemicals

63 unresolved questions extracted from the limitations and future-work sections of 424 Effects and risks of endocrine disrupting chemicals papers in our library. Each links back to the study that raised it.

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  • In addition, poten- tial non-linear exposure–response relationships at very high ambient concentrations remain insufficiently characterized. Evidence is limited in males, and heterogeneity in exposure assessment and pubertal outcome definition continues to constrain comparability across studies.

    Ambient Air Pollution, Polycyclic Aromatic Hydrocarbons, and Pubertal Development: A Critical Review of Emerging Evidence · 2026 · DOI

  • As a major replacement for traditional brominated flame retardants, TBBPA and its derivatives have left a detectable environmental footprint across multiple compartments, including water, soil, sediment, air, and biota, emerging as a global concern among emerging contaminants. This review emphasizes that the envi- ronmental challenges posed by TBBPA stem not only from the parent compound itself, but also from a com- plex pollution system comprising diverse derivatives, industrial by-products, and transformation products generated throughout its life cycle. Current studies indicate the widespread occurrence of these pollutants in various environmental media, with some compounds exhibiting greater ecotoxicity than TBBPA. Particu- larly noteworthy is the structural consistency between transformation products formed through microbial, photochemical, plant, and animal metabolic pathways and those by-products co-generated during industrial processes, revealing a notable homology. This finding not only highlights the “replication” of industrial pollu- tion signatures through environmental transformation processes, but also presents new challenges for pollu- tion source tracking and risk attribution. In terms of toxicity assessment, systematic pre- dictions based on computational toxicology models for TBBPA and 116 of its derivatives, by-products, and transformation products reveal that this group of compounds commonly exhibits prominent geno- toxicity and drug-induced liver injury risks. Over 90% of the compounds show strong genotoxicity, and more than 98% present a high potential for liver injury. Meanwhile, the predicted NOAEL values for many transformation products are lower than that of TBBPA itself, suggesting higher acute toxicity poten- tial. In addition, these substances also exhibit wide- spread endocrine-disrupting activity and carcinogenic potential, collectively forming complex combined health risks. Although significant progress has been made in understanding the environmental distribution, trans- formation pathways, and toxic effects of TBBPA- related pollutants, several key areas still demand further breakthroughs to enhance comprehensive cognition, enable more effective monitoring, and conduct rigorous risk assessment of these pollutants. First, there is an urgent need to establish a compre- hensive database characterizing TBBPA industrial by-products, systematically identifying the types, structures, formation mechanisms, and release pat- terns of unknown by-products to support pollution source tracing. Second, future research should inves- tigate the transformation pathways and ultimate fate of TBBPA and its derivatives under real environmen- tal conditions, and develop effective methods to accu- rately distinguish and quantify the respective contri- butions of industrial discharges and environmental transformation. Moreover, it is imperative to bridge the existing experimental gaps concerning the toxic effects and mechanisms of most derivatives, by-prod- ucts, and transformation products. Priority should be given to conducting health risk assessments for com- pounds that are frequently detected in the environ- ment, exhibit prolonged environmental persistence, and show high predicted toxicity. Author contribution Z. Y. and L. C. drafted the main text of the manuscript. X. W. and L. C. compiled Table 1. J. Y. and H. X. provided guidance on manuscript writing and data calcula- tion. T. Y. secured project funding and supervised manuscript revision. All authors reviewed the manuscript. Funding This work was supported by the National Natural Science Foundation of China (No. 22476104), Shandong Pro- vincial Natural Science Foundation (No. ZR2024JQ017), Natu- ral Science Foundation of Qingdao Municipality (26-1-5-smjk- 23-nsh), and Opening Project of Intelligent Policing Key Laboratory of Sichuan Province (ZNJW2024KFZD005). Vol.: (0123456789) 728 Page 24 of 29 Environ Monit Assess (2026) 198:728 Data availability No datasets were generated or analysed during the current study.

    A review of the environmental distribution, sources, transformation, and (eco)toxicities of tetrabromobisphenol A, its derivatives, and by-products · 2026 · DOI

  • Introduction Bisphenol S (BPS), a widely used environmental endocrine disruptor, induces multigenerational liver injury, though its underlying mechanisms remain unclear.

    Pregnancy and lactation exposure to bisphenol S induces ferroptosis via disrupted hepatic lipid metabolism in offspring mice · 2026 · DOI

  • GAS co-treatment mitigates these changes and offers neuroprotection by lowering oxidative stress and neuroin- flammation, restoring dopaminergic balance, and improving histolog- ical and ultrastructural abnormalities Further investigation is needed to clarify the exact molecular pathways and to evaluate their potential as targets for transla- tion in clinical settings.

    Protective effects of gastrodin against bisphenol A-induced dopaminergic dysregulation and cognitive impairment in rats · 2026 · DOI

  • The present research has some limitations that should be noted, despite offering significant insights into the neuroprotective effects of GAS against BPA-induced neurotoxicity in rats. In this study, we used only male Wistar rats, which may limit its translational relevance. There have been reports of sex-dependent variations in neuroinflammatory and dopaminergic dysfunctions in response to endocrine disruptors. Future studies incorporating animals of both sexes would provide a more comprehensive understanding of GAS efficacy. The PFC region was the main focus of this study. However, the hippocampus and striatum of the brain that are crucial to cognition and dopaminergic signaling were not investigated. Inclusion of these brain regions in future studies would help establish an understanding of GASmediated neuroprotection. The GAS treatment was given over a short period of time after BPA exposure. Extended treatment regimens and long-term follow-up studies would be beneficial to determine the stability and persistence of these effects, even though notable neuroprotective effects were observed during the short period of administration. Moreover, a vehicle group was not included in this study, and the study was designed to specifically assess the protective effects of GAS against BPA-induced neurotoxicity. Future studies may include a vehicle group to further strengthen the study design and provide additional baseline validation. Overall, despite these limitations, the study offers solid proof of neuroprotective potential of GAS against BPA-induced cognitive impairments and dopaminergic deficits and lays the groundwork for further research to build on these conclusions. Naunyn-Schmiedeberg's Archives of Pharmacology Fig. 11 Effects of gastrodin co-treatment on dopaminergic markers TH, DAT-1/SLC6A3, and DRD4 proteins in the PFC as studied through western blot analysis. A shows the appearance of dopaminergic proteins. Histographs B, C, and D showed the expression of TH, DAT-1/SLC6A3, and DRD4 proteins, respectively. In group II, BPAtreated rats significantly decreased TH (*P < 0.05), DAT-1/SLC6A3 (**P < 0.01), and DRD4 (**P < 0.01) expression as compared to the control group rats. GAS co-treatment group significantly restored TH (#P < 0.05), DAT-1/SLC6A3 (#P < 0.05), and DRD4 (##P < 0.01) in group III and group IV compared to the BPA-treated group rats in the PFC.

    Protective effects of gastrodin against bisphenol A-induced dopaminergic dysregulation and cognitive impairment in rats · 2026 · DOI

  • This study possesses several noteworthy methodological strengths. First, the age- and sex-balanced sample allowed chemical exposure and behavioral findings to be interpreted with minimal influence from developmental confounders. Additionally, ADHD diagnoses were established in a tertia- ry-care setting, enhancing diagnostic accuracy and ensuring greater homogeneity within the clinical group; this strength- ened the reliability of the observed associations between chemical exposures and ADHD-related symptoms. The in- clusion of an extensive panel of paraben and phthalate me- tabolites provided a detailed characterization of environmen- tal exposure profiles in adolescents. The combined assessment of product-use habits and biological exposure further eluci- dated the role of personal care practices and lifestyle behav- iors in shaping exposure patterns. Moreover, evaluating ADHD symptoms through both parent- and self-report measures im- proved measurement reliability and reduced informant bias. Nonetheless, several limitations warrant consideration. The cross-sectional design precludes causal inference. Reliance on a single spot urine sample limits the ability to capture longer- term exposure dynamics for compounds with short biological half-lives and may introduce exposure misclassification. In addition, product-use behaviors were obtained through ado- lescent self-report for the 24 hours preceding urine sampling, which may be subject to recall bias or incomplete reporting. Although the short recall window and direct adolescent re- porting likely reduced classical parental recall bias, differen- tial reporting may still occur if adolescents with ADHD dif- fer from healthy peers in attention, impulsivity, or reporting accuracy. This could either inflate observed associations (if product use is overreported in the ADHD group) or attenuate true associations (if product use is underreported). The mod- erate sample size reduced statistical power, particularly for subgroup analyses. Furthermore, because participants were recruited from families presenting to a tertiary-care center— and because the ADHD group had comparatively higher so- cioeconomic status—the generalizability of the findings to broader or more socioeconomically diverse populations may be restricted. Additionally, the use of LOD/2 substitution for values below the limit of detection may introduce bias, partic- ularly for analytes with low detection frequency, where statis- tical estimates may be disproportionately influenced by im- puted values.

    Paraben and Phthalate Exposure in Adolescents With Attention-Deficit/Hyperactivity Disorder: A Case–Control Study · 2026 · DOI

  • Future studies should focus on validating these findings in larger, multi- ethnic, and prospective cohorts, while integrating direct exposure assessment and mechanistic experiments to clarify how EDC-related molecular perturbations contribute to AMI susceptibility and progression.

    Bridging environmental endocrine-disrupting chemicals and AMI: identification of MERTK as a potential diagnostic candidate for AMI via integrated bioinformatics and clinical validation · 2026 · DOI

  • EDCs is considered a potential environmental driver for the rising the incidence of cardiovascular diseases; however, molecular networks through which EDCs disrupt cardiovascular homeostasis remain to be elucidated (16, 17).

    Bridging environmental endocrine-disrupting chemicals and AMI: identification of MERTK as a potential diagnostic candidate for AMI via integrated bioinformatics and clinical validation · 2026 · DOI

  • This suggests that exposure to phthalates both prenatally and during early childhood could be hazardous to child neurodevelopment, however, large-scale prospective studies assessing phthalate exposure through multiple urine samples, and possibly investigating cocktail effects of the chemicals as well as long term follow-up are warranted.

    Prenatal and current phthalate exposure and cognitive development in 7-year-old children from the Odense child cohort · 2023 · DOI

  • However, inconsistent results suggest that the potential effects of POP exposure on the physiological parameters in birds are multifactorial, involving a multitude of biological processes, species-specific differences, gender, age and types of compounds.

    Ecotoxicology of persistent organic pollutants in birds · 2021 · DOI

  • What we know about BPA is still insufficient to enable us to protect our health against its adverse effects, and current knowledge of the influence of BPA on erythroblastic cell lines in bone marrow is rather fragmentary.

    Cytological evaluation of the influence of high and low doses of bisphenol A on an erythroblastic cell line of porcine bone marrow · 2018 · DOI

  • Because of potential adverse effects on human health, butylbenzyl phthalate [BBzP; metabolite, monobenzyl phthalate (MBzP)], di-n-butyl phthalate [DnBP; metabolite, mono-n-butyl phthalate (MnBP)], and di(2-ethylhexyl) phthalate (DEHP) are being replaced by substitutes including other phthalates; however, little is known about consequent trends in population-level exposures.

    Temporal Trends in Phthalate Exposures: Findings from the National Health and Nutrition Examination Survey, 2001–2010 · 2014 · DOI

  • BACKGROUND: Phthalates from polyvinyl chloride (PVC) plastics may have adverse effects on airways and immunologic systems, but the evidence has not been reviewed systematically.

    The Role of Exposure to Phthalates from Polyvinyl Chloride Products in the Development of Asthma and Allergies: A Systematic Review and Meta-analysis · 2008 · DOI

  • Few or no data have been reported previously for four metabolites: mono(2-ethyl-5-carboxypentyl) phthalate, tridosan, bisphenol A (BPA), and BP3; these were detected in 67-100% of samples with medians of 1.

    Pilot Study of Urinary Biomarkers of Phytoestrogens, Phthalates, and Phenols in Girls · 2006 · DOI

  • Phthalate monoesters have a biologic half-life of approximately 12 hr, and little is known about the temporal variability and daily reproducibility of urinary measures in humans.

    Reproducibility of urinary phthalate metabolites in first morning urine samples. · 2002 · DOI

  • Temporal changes in sex ratios and fertility are minimal, whereas testicular cancer is increasing in most countries; however, in Scandinavia, the difference between high (Denmark) and low (Finland) incidence areas are not well understood and are unlikely to be correlated with differences in exposure to synthetic industrial chemicals.

    Endocrine disruptors and human health--is there a problem? An update. · 2000 · DOI

  • Materials exhibiting complex or poorly characterized degradation pathways, unique non-terminal degradation products, or device configurations that substantially alter in vivo erosion behavior may warrant additional, case-specific evaluation beyond this screening-level approach.

    Compositional profiling for biodegradable medical devices: a framework for degradation-informed exposure and risk assessment · 2026 · DOI

  • Prior studies suggest that individuals may reduce their exposures by avoiding certain ingredients while shopping; however, the efficacy of this strategy has not been evaluated in Black and Hispanic/Latina women.

    Examining the Role of Self-Reported Product Selection Strategies in Shifting Chemical Exposures Among Black Women and Latinas: Lessons from the Taking Stock Study · 2025 · DOI

  • Despite the well-established links between certain plastic chemicals (bisphenols and phthalates) and adverse health effects, the composition and toxicity of real-world mixtures of plastic chemicals are not well understood.

    Plastic Food Packaging from Five Countries Contains Endocrine- and Metabolism-Disrupting Chemicals · 2024 · DOI

  • Thus far, no investigations have focused on small intestinal injury in the offspring of adult mice that were exposed to nanoplastics through the respiratory system during pregnancy.

    Ferroptosis Is Involved in Sex-Specific Small Intestinal Toxicity in the Offspring of Adult Mice Exposed to Polystyrene Nanoplastics during Pregnancy · 2023 · DOI

  • CONCLUSION: In light of the available conflicting evidence, BPA release from CAs can neither be confirmed nor denied.

    Bisphenol-A release from thermoplastic clear aligner materials: A systematic review · 2023 · DOI

  • Since studies on the reproductive consequences after the exposure to environmentally relevant doses of Benzo(a)pyrene (BaP) during critical stages of development are scarce, this study evaluated female reproductive parameters of adult rats exposed to a low dose of BaP during the juvenile phase.

    Long-term reproductive effects of benzo(a)pyrene at environmentally relevant dose on juvenile female rats · 2022 · DOI

  • Conclusions Parents’ awareness of risk to their children’s health resulting from exposure to selected chemicals that pass from plastic packaging to food is insufficient.

    Awareness of parents about risk to children’s health arising from exposure to selected chemicals passing from plastic food packaging · 2021 · DOI

  • ) shows clear causal relationships between certain environmental factors and the risk of premature birth, while for several substances the results are inconclusive.

    Pollution and the risk of premature birth – the current state of knowledge · 2021 · DOI

  • Although the transmission of AgNPs into the brain has been reported, its toxic effect on dopamine metabolism in the brain of offspring has not been studied so far.

    Silver nanoparticle exposure in pregnant rats increases gene expression of tyrosine hydroxylase and monoamine oxidase in offspring brain · 2016 · DOI

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