Tributyl phosphate (NSC 8484, Tributyl phosphate) is a trialkyl phosphate that is often used as a solvent, plasticizer, and extractant, including in extraction processes involving transuranic elements and rare earth metals.

In GC-2 mouse spermatocyte cells, Tributyl phosphate exposure (10, 50, 200 μM for 24 h) reduced cell viability, induced apoptosis, and decreased the BCL2/BAX ratio. At 50 and 200 μM, Tributyl phosphate also triggered reactive oxygen species (ROS) accumulation and a loss of mitochondrial membrane potential, indicating oxidative stress-mediated cytotoxicity[1].

Male ICR mice orally administered TBP (50 and 100 mg/kg/day for 35 days) showed reduced sperm count and motility, testicular structural damage, and increased testicular cell apoptosis. Tributyl phosphate also caused gut microbiota dysbiosis, increased the abundance of Prevotellaceae (negatively correlated with sperm motility), and promoted Th17 cell infiltration in the small intestine along with IL-17A signaling activation in the testes, suggesting that Tributyl phosphate induces male reproductive toxicity via the gut–testis axis, oxidative stress, and inflammation[1].