Open research questions in Effects and risks of endocrine disrupting chemicals

What the literature leaves open

• The paper addresses the need for a robust and reliable methodology for metabolomic analysis. The study overcomes the challenge of analyzing complex biological samples using advanced statistical and computational methods.

  Integrated metabolomic and histopathological analysis of renal alterations in mice following chronic bisphenol A (BPA) exposure · 2026 · DOI

• The present findings provide exploratory evidence for a potential association between prenatal and lactation BPA exposure, pro-inflammatory signaling, and altered social behavior and also underscore the need for additional studies on the effects of low-dose prenatal BPA exposure.

  Prenatal and Lactation Exposure to Bisphenol A (BPA) at the Global Mean Daily Intake Level Leads to Sex-Dependent Changes in Microglial State, Gene Expression, and Behavioral Patterns in Newborn and Juvenile Wistar Rat Offspring · 2026 · DOI

• Because the neonatal brain is in a highly dynamic state of development, it remains unclear whether the observed alterations in microglial morphology, estrogen receptor expression, and neural progenitor differentiation represent permanent structural deficits or transient developmental delays.

  Prenatal and Lactation Exposure to Bisphenol A (BPA) at the Global Mean Daily Intake Level Leads to Sex-Dependent Changes in Microglial State, Gene Expression, and Behavioral Patterns in Newborn and Juvenile Wistar Rat Offspring · 2026 · DOI

• As a substitute for phthalates, ASE has been widely used in PVC product such as medical tubing; however, it remains unclear whether ASE exerts adverse cardiovascular effects and which nuclear receptor(s) may be activated by ASE to mediate its cellular signaling.

  A Universal Plasticizer Alkylsulfonic Phenyl Ester Activates Pregnane X Receptor to Increase Intestinal Cholesterol Uptake · 2026 · DOI

• While DEHP neurotoxicity has been extensively studied in the context of transgenerational and developmental exposure, or behavioral deficits in adult males, the potential impact on the adult female brain has remained largely underexplored.

  Integrated Profiling of DEHP-Induced Hippocampal Neurotoxicity in Adult Female Rats Based on Transcriptomic and Neurobiological Analyses · 2026 · DOI

• There is limited information available on how maternal metabolic and physiological state, such as higher BMI, may complicate interactions, toxicokinetics, bioaccumulation, metabolism, and the body’s response to multiple parallel environmental chemical exposures.

  Early Pregnancy Targeted Exposome: Biological Response and Maternal BMI · 2026 · DOI

• That these pathways operate simultaneously in exposed individuals, and interact with independent psychological vulnerabilities, warrants serious attention from both researchers and regulators. At the molecular level, the mechanisms by which these compounds may precipitate mood disorder are multiple and partially overlapping.

  Phthalates and Bisphenols as Endocrine-Disrupting Chemicals: Possible Determinants of Mood Disorders · 2026 · DOI

• In conclusion, our findings show that BPS exposure induces a marked morphology-based phenotypic shift in healthy arterial endothelial cells, supporting its biological activity as an environmental endocrine-disrupting pollutant. Therefore, the links between BPS-induced morphological remodeling, endothelial dysfunction, ER stress, mitochondrial activity, and inflammatory signaling remain to be experimentally validated.

  Differential impact of bisphenol S on human arterial endothelial cells from healthy and type-2 diabetic donors: a high-content imaging study · 2026 · DOI

• Further research is required, particularly prospective studies with careful exposure assessment and adequate UV adjustment. For most chemicals reviewed, direct evidence that endocrine disruption specifically mediates skin carcinogenesis is lacking; an association with carcinogenicity and an association with endocrine disruption does not necessarily imply that one causes the other.

  Is Exposure to Certain Endocrine-Disrupting Chemicals Associated with Increased Skin Cancer Risk? · 2026 · DOI

• Follow-up assessments should cover birth outcomes, growth, neurodevelopment, endocrine and reproductive function, and immune-related biomarkers such as IL-6, TNF-α, and complement should also include these assessments C3. Where feasible, validated measures of immune function and indicators of placental function.

  From environmental occurrence to human exposure: multisystem toxicity, immune-relevant mechanisms, and gaps in health-risk assessment of liquid crystal monomers · 2026 · DOI

• The data reviewed in this article underscore the potential of EDCs to pose a risk against ruminant fertility and have a negative impact on reproductive physiology, advocating for further investigation. Despite the extensive research over the past 15 years, the data, particularly those concerning PFAS, are still limited.

  Reproductive Effects of Endocrine Disruptors in Domestic Ruminants: Integrating In Vitro and In Vivo Evidence · 2025 · DOI

• Although current risk-assessment methodologies rely on strong scientific principles, continuous refinement is needed. Emerging priorities include evaluating cumulative chemical effects, protecting vulnerable populations, and understanding climate- and environment-driven changes in contamination patterns.

  Health Risk Assessment of Dietary Chemical Exposures: A Comprehensive Review · 2025 · DOI

• The immunomodulatory effects of BPA and its analogs involve a complex interplay of pro-inflammatory and immunosuppressive mechanisms that are not fully understood. Currently, limited data on these analogs are available in the literature.

  Disrupting Defenses: Effects of Bisphenol A and Its Analogs on Human Antibody Production In Vitro · 2025 · DOI

• Inconsistent evidence for critical windows; highlighted need for standardized methodologies.

  Thematic Review of Endocrine Disruptors and Their Role in Shaping Pubertal Timing · 2025 · DOI

• To mitigate this, clinicians should consider rinsing/soaking new clear retainers before delivery. Additionally, selecting products that are BPA-free (and have data to back it up) is wise. If a particular thermoplastic has known higher leach rates, alternatives should be used, particularly for young patients or those desiring pregnancy, etc., as a precautionary measure, particularly in susceptible populations.

  Cytotoxicity and Endocrine Disruption in Materials Used for Removable Orthodontic Retainers: A Comprehensive Review · 2025 · DOI

• While conventional polymers like PET, PE, and PP remain focal points due to their ubiquity, emerging materials such as bioplastics, recycled polymers, and composite systems introduce new dimensions of uncertainty, particularly regarding novel migrants and legacy contaminants.

  Recent Trends and Challenges on the Non-Targeted Analysis and Risk Assessment of Migrant Non-Intentionally Added Substances from Plastic Food Contact Materials · 2025 · DOI

• Although BPS exerts endocrine-disrupting effects, the mechanisms underlying the metabolic disturbances triggered by BPS in hepatocytes remain unclear.

  Bisphenol S Induces Lipid Metabolism Disorders in HepG2 and SK-Hep-1 Cells via Oxidative Stress · 2025 · DOI

• Although oxidative stress and endoplasmic reticulum stress have been consistently identified as key mechanisms, further research is required to elucidate other molecular pathways and the relevance of animal findings to humans.

  Nephrotoxicity of Phthalates: A Review Based on Epidemiological and Toxicological Evidence · 2025 · DOI

• The review concluded that there was insufficient evidence for the association of prenatal exposure to phthalates and allergic diseases; however, it did not include any studies from Latin America.

  Associations Between Prenatal Phthalate Exposure and Atopic Symptoms in Childhood: Effect Modification by Child Sex · 2025 · DOI

• Although the involved mechanism remains uncertain, phthalates have been shown to either trigger or inhibit receptor activity, inducing both positive or negative responses on androgen and estrogenic receptors.

  Evidence About the Possible Role of Phthalates and Bisphenol A in Recurrent Pregnancy Loss and Endocrine Dysfunctions: A Case–Control Study · 2025 · DOI

• Decrease in brain expression of Homer2 in male and Homer1a in female mice may be an important mechanism through which DEHP acts and should be investigated further in human birth cohort studies.

  475. DOES PRENATAL EXPOSURE TO LOW-DOSE DI-2-ETHYLHEXYL PHTHALATE IMPAIR NEURODEVELOPMENT IN A VAL66MET BDNF MOUSE MODEL? · 2025 · DOI

• From 2010 to 2025, mixture risk assessment for food xenobiotics has transitioned from a largely theoretical concern into a structured, operational domain within foodsafety regulation. Three pillars underpin this maturation.

  Risk Assessment of Chemical Mixtures in Foods: A Comprehensive Methodological and Regulatory Review · 2026 · DOI

• The future of food toxicology should not be framed as a choice between traditional risk assessment and precision toxicology. The two approaches serve different but complementary purposes. Population-based thresholds remain essential for public health protection, whereas exposomics and precision toxicology can reveal exposure patterns, mechanisms, and susceptible populations that conventional approaches may overlook.

  From Food Additives and Contaminants to the Human Exposome: A Precision Toxicology Framework for Next-Generation Food Safety · 2026 · DOI

• Small sample size of 14 female mice, - Limited to a single dose of BPA, - No long-term…

  Integrated metabolomic and histopathological analysis of renal alterations in mice following chronic bisphenol A (BPA) exposure · 2026 · DOI

• Despite significant advancements in monitoring and regulatory measures, the persistence and bioaccumulation of PAEs in soil–crop systems continue to pose serious challenges to soil health, food safety, and sustainable agriculture.

  Contamination of Phthalic Acid Esters in China’s Agricultural Soils: Sources, Risk, and Control Strategies · 2025 · DOI

Most-cited papers in Effects and risks of endocrine disrupting chemicals

• Exposure of the U.S. Population to Bisphenol A and 4- tertiary -Octylphenol: 2003–2004 · Environmental Health Perspectives · 2007 · 1,563 citations
• Bisphenol S and F: A Systematic Review and Comparison of the Hormonal Activity of Bisphenol A Substitutes · Environmental Health Perspectives · 2015 · 1,415 citations
• Decrease in Anogenital Distance among Male Infants with Prenatal Phthalate Exposure · Environmental Health Perspectives · 2005 · 1,339 citations
• Association of Urinary Bisphenol A Concentration With Medical Disorders and Laboratory Abnormalities in Adults · JAMA · 2008 · 1,166 citations
• Urinary, Circulating, and Tissue Biomonitoring Studies Indicate Widespread Exposure to Bisphenol A · Environmental Health Perspectives · 2010 · 1,119 citations
• An Extensive New Literature Concerning Low-Dose Effects of Bisphenol A Shows the Need for a New Risk Assessment · Environmental Health Perspectives · 2005 · 1,000 citations
• A variety of environmentally persistent chemicals, including some phthalate plasticizers, are weakly estrogenic. · Environmental Health Perspectives · 1995 · 966 citations
• What Are the Sources of Exposure to Eight Frequently Used Phthalic Acid Esters in Europeans? · Risk Analysis · 2006 · 916 citations
• Urinary Concentrations of Bisphenol A and 4-Nonylphenol in a Human Reference Population · Environmental Health Perspectives · 2004 · 884 citations
• Urinary levels of seven phthalate metabolites in the U.S. population from the National Health and Nutrition Examination Survey (NHANES) 1999-2000. · Environmental Health Perspectives · 2003 · 877 citations

Most recent work

• Dynamic accumulation and co-occurrence of phthalates and squalene in settled dust: implications for assessing indoor phthalate homology and exposures · Environmental Science Processes & Impacts · 2026
• Low-plastic diet and urinary levels of plastic-associated phthalates and bisphenols: the randomized controlled PERTH Trial · Nature Medicine · 2026
• Risk Assessment of Chemical Mixtures in Foods: A Comprehensive Methodological and Regulatory Review · Foods · 2026
• Identification of novel polyhalogenated carbazoles in cord serum and their associations with fetal growth · Environmental Pollution · 2026
• The way forward for assessing the human health safety of cosmetics in the EU: Proceedings of Workshop 2 · Archives of Toxicology · 2026
• Extractables and Leachables in Pharmaceutical Products: Potential Adverse Effects and Toxicological Risk Assessment · Toxics · 2026
• Environmentally Relevant Doses of Bisphenol A and S Exposure In Utero Disrupt Germ Cell Programming across Generations Resolved by Single Nucleus Multiomics · Environmental Health Perspectives · 2026
• Disruptive effects of phthalates and their substitutes on adrenal steroidogenesis · Frontiers in Endocrinology · 2026
• Network toxicology and multidimensional bioinformatics analysis reveal the shared mechanism of action of bisphenol A and phthalates in glioblastoma · Ecotoxicology and Environmental Safety · 2026
• Exploring the mechanism link between endocrine disrupting chemicals and metabolic diseases: Observational and GWAS evidence · Ecotoxicology and Environmental Safety · 2026

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