Effects of organochlorine pesticides (OCPs) on adolescent body composition: Integrating epidemiology and bioinformatics

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.

Combined Effects of Metals and PFAS Exposure on Prevalent Diabetes

Limiting to directly measured exposures, incorporating the full NHANES design in the primary regression, and triangulating across complementary mixture frameworks provide a more rigorous platform than prior single-pollutant or design-naive approaches.

Prenatal Exposure to Organophosphate Esters and Infantile Neurobehavior: Integrating the Gut Microbiome and Metabolome.

Prenatal TBEP exposure was associated with greater behavioral problems in early childhood, and Alter neonatal gut microbiota and related metabolic pathways may partly underlie this association.

[Study of associations between childhood phthalate exposure and physical growth].

Exploring the connection between organophosphate flame retardants and Hyperlipidemia: an integrated analysis using NHANES (2011–2018), network toxicology, and mendelian randomization

Organophosphorus flame retardants (OPFRs) are ubiquitous contaminants associated with metabolic disorders. This study examined the association between human exposure to OPFRs and hyperlipidemia and explored potential underlying biological mechanisms. Using data from 3,228 adults from the NHANES cycles of 2011–2018, we analyzed associations using weighted multiple logistic regression, restricted cubic spline analysis, and weighted quantile sum regression. Results showed a robust positive association between urinary OPFRs metabolite levels and hyperlipidemia (OR = 1.33, 95% CI: 1.15–1.55, P < 0.01). Cumulative exposure to OPFRs mixtures was also significantly associated with hyperlipidemia (OR = 1.27, 95% CI: 1.09–1.47, P = 0.002). Subsequent network toxicology and Mendelian randomization analyses suggested that OPFRs may be associated with hyperlipidemia by potentially regulating key targets (e.g. TP53, STAT3, AKT1) and activating specific pathways, including those involved in cancer and the PI3K-Akt signaling cascade. This study supports an association between OPFRs exposure and hyperlipidemia and suggests a potential multi-target, multi-pathway regulatory mechanism.

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

Although toxicological studies suggest that synthetic phenolic antioxidants and their transformation products (SPAs/TPs) may disrupt thyroid function, epidemiological evidence and exposure safety thresholds remain limited. This study included 810 adults from Jiangsu Province, China, and measured serum concentrations of 12 SPAs, 3 TPs, and 7 thyroid function indicators (TFIs). Multiple linear regression (MLR) and restricted cubic spline (RCS) analyses were used to evaluate associations between individual SPAs/TPs and TFIs, whereas quantile g-computation (qgcomp) and Bayesian kernel machine regression (BKMR) were applied to assess the joint effects of mixed exposure. In addition, the Benchmark Dose Software (BMDS) was used to estimate the benchmark dose (BMD) and its lower confidence limit (BMDL) for serum SPAs/TPs, and to derive the corresponding reference doses (RfDs). The results showed widespread exposure to multiple SPAs/TPs among the study participants. Both individual and mixed exposure to SPAs/TPs were significantly associated with increased levels of free thyroxine (FT4) and total triiodothyronine (T3), as well as decreased levels of thyroid-stimulating hormone (TSH) and the T4/T3 ratio. Among the detected compounds, BHT-COOH (3,5-di-tert-butyl-4-hydroxybenzoic acid) and AO245 (triethylene glycol bis(3-tert-butyl-4-hydroxy-5-methylphenyl)propionate) were the primary contributors to elevated FT4 and T3 levels. Under a benchmark response (BMR) of 5%, the estimated RfDs were 0.018 mg/kg/day for BHT-COOH and 0.181 mg/kg/day for AO245, and potential health risks may exist (HQc > 1). This study is the first to evaluate the effects of exposure to SPAs/TPs on thyroid homeostasis, providing a scientific basis for the formulation and improvement of targeted regulatory policies.