Investigating the biphasic impacts of dodecamethylcyclohexasiloxane on Caenorhabditis elegans: From reproductive and mitochondrial dysfunctions to biochemical and molecular responses

Dodecamethylcyclohexasiloxane (D6), an organosilicon compound, is an emerging environmental pollutant commonly found in personal care products, healthcare formulations, industrial processes, consumer goods, and surface coatings. Despite its widespread use, the toxicological effects of D6 are not well understood. In current study, Caenorhabditis elegans was used as a model organism to investigate the multifaceted impacts of D6 toxicity. We examined physiological changes, biochemical disruptions, molecular responses in gene expression, reproductive impairments, and mitochondrial dysfunction across different concentrations of D6 (0.05-1.00 mg/L). We firstly observed a biphasic dose-response relationship: low concentrations of D6 slightly enhanced growth and stimulated physiological responses, while higher concentrations significantly reduced growth and lifespan, indicating toxicity of D6. At elevated concentrations, D6 induced oxidative stress and cellular damage, reduced food intake, and lowered glucose, pyruvate and adenosine triphosphate (ATP) levels, suggesting mitochondrial dysfunction. Additionally, changes in the activity of antioxidant enzymes, such as hexokinase (HK), adenosine triphosphatase (ATPase), peroxidase (POD), catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px), were observed, indicating a counter-adaptive response to oxidative stress. RNA interference of genes like mtl-1, sod-3, and daf-2 made C. elegans more susceptible to D6 toxicity, while vit-2 and gpx-3 exhibited resistance. The study also highlights the role of germ cell apoptosis in the adverse effects of D6. Overall, our findings provide novel insights into the toxicological mechanisms of D6 and highlight its potential environmental risks, and these findings suggest that excessive use of D6 could have harmful ecological consequences, underscoring the need for further investigation into its ecotoxicity.