Serum synthetic phenolic antioxidants, transformation products, and thyroid homeostasis in adults from eastern China: Association and benchmark dose assessment.

Novel transformation products of synthetic antioxidants in serum samples from general population.

As extensively used additives in food industries, synthetic antioxidants (SAOs) and their transformation products (TPs) always expose to humans through multiple pathways. Here, we established a suspected screening strategy based on segmental scanning and detected 33 SAOs and 21 TPs in serum samples, which included 9 newly-found TPs from the hydroxylation, sulfation or acetylation of SAOs. The concentration of SAOs, including synthetic phenolic antioxidants (SPAs) and amino antioxidants (SAAs), was 22.9-398 ng/mL. Higher levels of SPAs than SAAs aligned with their more common application in direct-consumption foods. Moreover, several TPs were present at higher concentrations than their parent compounds, which exhibited high accumulation potentials. Specially, concentrations of oxidative TPs of BHT and hydroxylated TPs of BHA were 6.50 and 91.9 times of their parent compounds, respectively. These results improve our understanding on the internal exposure of human to SAO and their TPs, providing critical data for their comprehensive evaluation.

Metabolomics insights into the association between organochlorine pesticides, synthetic pyrethroids exposure and thyroid cancer risk.

BACKGROUND The association between organochlorine pesticides (OCPs)/synthetic pyrethroids (SPs) and thyroid cancer (TC) remains poorly understood, with metabolic mechanisms unexplored. METHODS We conducted a 1:1 age- and sex-matched case-control study (n = 668). Serum levels of 27 target analytes (19 OCPs and 8 SPs) were quantified; subsequent analyses were restricted to 13 compounds (10 OCPs and 3 SPs) with detection frequencies ≥85%. Eight machine learning (ML) algorithms with Shapley Additive Explanations (SHAP) were used to identify key pollutants in the 334 case-control pairs. Untargeted metabolomics was performed in a subset of 50 age- and sex-matched case-control pairs. Mixture effects were assessed by Bayesian kernel machine regression (BKMR) and weighted quantile sum (WQS) regression. Furthermore, the Latent Unknown Clustering Integrating Multi-Omics Data (LUCID) model was employed to integrate exposure and metabolic data, enabling the identification of TC patient subgroups and the exploration of underlying metabolic mechanisms. RESULTS Participants (mean age 45.2 years, 82.3% female) had serum OCPs at 0.007-0.333 ng/mL and SPs at 0.046-0.095 ng/mL. ML algorithms identified fenpropathrin, β-BHC, cyhalothrin, α-BHC, and p,p'-DDD as the top five contributors to TC. Elevated OCPs/SPs exposure was significantly associated with increased TC risk (WQS: adjusted OR = 1.45, 95%CI = 1.34-2.24, P = 0.019; LUCID: OR = 9.33). Fenpropathrin was the primary contributor (BKMR posterior inclusion probability = 1.00; WQS weight = 67.6%). A total of 45 significant differential metabolites (DMs) were identified (VIP ≥1, P < 0.05, and qualitative level 1). LUCID revealed a distinct TC cluster characterized by upregulated S-sulfo-L-cysteine/adenosine and downregulated 2-hydroxycaprylic acid. CONCLUSION OCPs/SPs mixtures, driven by fenpropathrin, disrupt amino acid/nucleotide metabolism while suppressing organic acid metabolism, representing a potential TC-associated metabolic signature.

Associations between Heavy Metals and Metalloids and Hepatic Fibrosis Risk in Chinese Adults: A Potential Modifying Effect of Thyroid Hormones.

Organophosphate Flame Retardants Exposure Disrupts Serum Lipid Metabolism and Induces Hepatotoxicity: Evidence from the Population and Mouse Model.

TDCIPP exposure induced hepatotoxicity in mice, and may induce hepatic lipid toxicity in mice, indicating that the non-cancer risk of BDCIPP should be of concern.

Source-specific health risks and potential source-oriented biological effects of synthetic phenolic antioxidants in Mactra veneriformis from typical bays of the Bohai Sea and the Yellow Sea, China.

Synthetic phenolic antioxidants (SPAs) are emerging additive-derived contaminants widely detected in marine ecosystems, yet their source-specific health risks and potential source-oriented biological effects remain unclear. This study quantified 10 SPAs in Mactra veneriformis collected from the Bohai Sea and the Yellow Sea in May and August 2025 and integrated bioaccumulation, multi-pathway biomarker responses, and receptor modeling to establish a source-specific risk assessment framework. Total SPA concentrations ranged from 5802.21 to 14396.50 ng/g d.w. in May and increased to 13129.13 to 23676.85 ng/g d.w. in August. Biomarker analyses partly reflected coordinated activation of detoxification and antioxidant systems, accompanied by oxidative damage, neurotoxicity, and immunomodulation. Although most individual hazard quotients were below 1, assessment results support prioritizing AO1010 as a potential risk compound. Positive matrix factorization tentatively interpreted four sources: plastics (F1), rubber (F2), personal care products (F3), and petroleum/lubricants (F4). By coupling partial least squares regression with PMF, source-specific health risks (PMF-HQ) and potential source-oriented biological effects (PMF-IBR) were quantified alongside. By integrating the results of PMF-IBR and PMF-HQ, we ranked risk contributions as F2 > F1 ≈ F4 > F3, indicating that rubber-related inputs exert disproportionately high toxicological pressure. This study establishes a source-specific risk control priority framework for emerging contaminants in coastal ecosystems.

Conditional neuroprotection: Blood selenium attenuates the cognitive toxicity of DEHP metabolites in older adults.

BACKGROUND Phthalates, particularly di(2-ethylhexyl) phthalate (DEHP), are ubiquitous environmental contaminants with well-documented neurotoxic potential. Selenium, an essential antioxidant trace element, may mitigate oxidative stress-induced neuronal damage. However, whether selenium modifies the cognitive effects of phthalate exposure remains unclear in human populations. METHODS We analyzed cross-sectional data from adults aged ≥60 years in the National Health and Nutrition Examination Survey (NHANES) 2011-2014. Urinary phthalate metabolites and blood metals (lead, cadmium, mercury, manganese) were quantified. Survey-weighted linear regression with interaction terms tested whether blood selenium modified the associations between these exposures and global cognitive Z-scores. Effect modification was further evaluated using restricted cubic splines, simple slope analysis, and joint Wald tests. Oxidative stress biomarkers (alkaline phosphatase, total bilirubin, serum iron) were assessed as potential mediators. To contextualize the main NHANES findings, we performed two supplementary analyses: (i) bidirectional two-sample Mendelian randomization (MR) to test whether selenium has an independent causal effect on Alzheimer's disease (AD), and (ii) an exploratory ecological analysis using Global Burden of Disease (GBD) 2021 data to illustrate the risk of ecological fallacy when environmental co-exposures are unaccounted for. These ancillary analyses do not constitute formal triangulation, as they address selenium's main effects rather than its interaction with phthalates. RESULTS Among 573 participants (mean age 69.5 years, 52.2% female), blood selenium significantly modified the associations of four DEHP metabolites with cognitive function, with the strongest interaction observed for MEHP (β = 0.00103, 95% CI: 0.00081-0.00124, P < 0.001). In individuals with low selenium, higher MEHP was associated with lower cognitive scores; this association was reversed in those with high selenium. In contrast, no significant interactions were found for any heavy metal (all P > 0.05). Joint Wald tests confirmed effect modification for phthalates (F = 13.34, P = 0.003) but not for metals (F = 1.03, P = 0.43). Oxidative stress biomarkers did not mediate the observed interactions. Bidirectional MR found no causal effect of selenium on AD (IVW β = -0.008, P = 0.87), ruling out reverse causation as an explanation. An exploratory ecological analysis using GBD data found a counterintuitive inverse association between dietary selenium inadequacy and dementia burden (β = -0.325, P = 0.037). This paradoxical pattern remained consistent in sensitivity analyses and likely reflects ecological confounding. It underscores that population-level nutrient-disease links can be strongly distorted by differences in diagnostic practices and unmeasured co-exposures, such as phthalates. CONCLUSIONS Selenium reduces the cognitive harm of DEHP metabolites in older adults, with clearer and more consistent evidence for phthalates than for heavy metals. Null MR results rule out an independent causal effect of selenium on Alzheimer's disease, reinforcing that selenium's role is conditional rather than universal. A paradoxical ecological pattern, presented as a cautionary example, highlights the risk of ecological fallacy when co-exposures are unaccounted for. Together, these findings suggest that selenium's neuroprotection is context-dependent-it appears to act mainly under specific toxicant exposure rather than offering universal benefits. These findings caution against indiscriminate selenium supplementation and suggest that further longitudinal studies are needed before targeted interventions can be recommended.