Life-cycle exposure to environmental copper pyrithione causes multigenerational developmental and reproductive toxicity in medaka.

Copper pyrithione (CuPT), a widely used alternative to tributyltin in antifouling biocides, is recognized for its acute toxicity and potential ecological risk. However, the long-term effects of CuPT exposure on fish at environmentally relevant concentrations are virtually unknown. Using medaka (Oryzias latipes) as a model fish, multigenerational impacts on development and reproduction induced by whole-life-cycle exposure to CuPT were studied. The F0 generation was continuously exposed to 1 μg/L CuPT from fertilization to adulthood, while their F1 and F2 offspring were reared in clean water to assess multigenerational effects. Chronic F0 exposure induced a cascade of severe, persistent phenotypic defects. F0 exposure significantly reduced embryonic survival, delayed and desynchronized hatching, and induced growth retardation, pericardial edema, and skeletal deformities including scoliosis, microcephaly, and mandible bowing. Strikingly, these effects were amplified in the subsequent F1 and F2 generations. The F2 generation exhibited the highest incidence of severe morphological abnormalities such as scoliosis, microcephaly, bowed mandibles, and anal fin fusion, far exceeding those in F0 and F1 generations. Reproductive performance collapsed in F1 (77% reduction in egg production), while F2 fecundity could not be assessed due to high larval mortality. These findings establish CuPT as a potent multigenerational toxicant, albeit the underlying molecular mechanisms remain to be elucidated. This study indicates that current single-generation risk assessment paradigms substantially underestimate the long-term ecological risks of CuPT, as effects worsen even after exposure ceases.