Multiple studies demonstrate mixture effects arising from the interactive toxicity of environmental chemicals in human blood, but identifying the main toxic drivers remains challenging. In a recent proof-of-principle in vitro study, we showed that personalized mixtures (PMs), reconstructed from 24 persistent organic pollutant (POPs) concentrations measured in individual blood samples from Swedish adults, induced unique interindividual effects on H295R cell viability and steroidogenesis. Here, we followed up by testing submixtures of four PMs (PM#3, PM#4, PC1-OC-Mix, and PC2-PFAS-Mix), separated by the chemical classes perfluoroalkyl substances (PFASs), organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs). Submixtures of PFAS and OCPs induced significant effects on testosterone synthesis at low (1×) and medium (10×) concentrations, consistent with effects observed in the corresponding whole PMs, and were therefore likely the primary drivers of the whole-mixture effects on testosterone. Notably, some submixtures altered estradiol and testosterone levels in ways not observed in full PMs, suggesting antagonistic interactions across chemical classes when combined. Potential antagonistic interaction in more complex mixtures, independent of concentration, was also observed within OCP submixtures, as only the less complex OCP mixtures lacking DDE or DDT induced testosterone synthesis. For additional mechanistic insight, we expanded the H295R assay to include oxidative stress analyses, which revealed no effects from the PMs. RT-qPCR analysis showed downregulation of CYP11A1 after exposure to PM#3 and PM#4 at high concentrations (100×), suggesting a feedback mechanism contributing to suppressed testosterone synthesis.

Comprehensive assessment of polybrominated diphenyl ethers: Distribution, source and ecological risk in the Bohai Bay.

Health risk assessment of emerging organic contaminants from land-applied biosolids: A comparative study between the U.S. and China.

Elucidating the role of microplastics as reservoirs of brominated flame retardants in river sediment.

Impacts of the 2024 flash flood on water quality, pathogenic bacteria and organic contaminant risks in the Albufera Natural Park (Valencia, Spain).

Release of chemical additives and potentially toxic elements from plastics under ambient outdoor environmental conditions.

Ophthalmotoxicology of polyhalogenated compounds.

Lipid oxidation and metabolism in relation to contaminants in polar bears from the Canadian high arctic and Hudson Bay.

Gestational PBDE concentrations and functional connectivity in adolescents: The HOME Study.

Efficient remediation of PBDEs in soil by combined chemical leaching and electron beam irradiation.

A novel potential toxic target of PBDEs in cetaceans: Impaired wound healing demonstrated in Indo-Pacific finless porpoise fibroblasts.

Developmental PBDE exposure persistently impairs mast cell function in vivo and drives sex-specific morphological and transcriptional changes in bone marrow-derived mast cells.

Legacy and emerging halogenated organic pollutants in Omura's whale (Balaenoptera omurai): Tissue distribution and potential health risks in a data-deficient cetacean.

Associations of endocrine disrupting chemical biomarkers and their mixture with vitamin D biomarker concentrations in childhood: The HOME Study.

BDE-47 has cytotoxicity on human sperm by inducing apoptosis, mitochondrial dysfunction, and membrane damage.

Alleviation effect of arabinogalactan on decabromodiphenyl ether (BDE-209)-stimulated intestinal epithelial barrier damage via the Nrf2/HO-1/NQO1 signaling pathway in a Caco-2 cell monolayer model.

Polybrominated diphenyl ethers have emerged as a major environmental pollutant, being used as an additive flame retardant in various kinds of products including electronic devices (computers and television sets), upholstery, carpets, plastics, textiles, and building materials. They can undergo the degradation process to form less brominated or low brominated diphenyl ethers in the environment. In the current study, genotoxic, biochemical, histopathological, and ultrastructural scanning electron microscopy (SEM) changes in liver tissue of zebrafish were studied after acute and subchronic exposure of diphenyl ether (DE). The zebrafish were exposed to 2.13 mg/L DE (¼ median lethal concentration [LC50]) and 4.25 mg/L DE (½ LC50) for the acute toxicity assessment and to 425 μg/L DE (1/20th LC50) and 850 μg/L DE (1/10th LC50) for the subchronic toxicity study. After acute and subchronic exposure of DE, % tail intensity in liver tissue was found to be significantly increased in a concentration and duration-dependent manner. The malondialdehyde content, glutathione-S-transferase, and acetylcholinesterase activity in liver tissue were found to be significantly elevated after acute and subchronic exposure of DE, whereas the activity of superoxide dismutase enzyme was found to be depleted in the liver tissue of zebrafish. The histological observations revealed various types of alterations including aggregation of hepatocytic nuclei, necrosis, vacuolization, sinusoidal dilation, disintegrated hepatocytes, and erythrocytic infiltration in liver tissue of zebrafish after DE exposure. The SEM analysis showed changes in the surface of liver tissue such as multiple pore formation, swelling in hepatocytes, necrosis, and degeneration of hepatocytes after acute and subchronic exposure of DE.

Persistent organic pollutants in hepatic and adipose tissue of Chelonia mydas stranded along the Santos Basin, Brazil.

Seasonal testicular morphometry of European brown bears in relation to pollutants.

Occurrence, fate, and integrated risk profiling of legacy and novel brominated flame retardants in the Yellow and Bohai Seas.