Subchronic Exposure of Tri‐Ortho‐Cresyl Phosphate Reduces T‐Cell Population in Mice

Tri‐ortho‐cresyl phosphate (TOCP) is a widely used organophosphorus compound in industry and agriculture, but its immunotoxicity has not been thoroughly investigated. Therefore, this study aimed to assess the immunotoxicity of TOCP in mice by examining changes in immune cell populations and histopathological alterations in the spleen. Male ICR mice were administered TOCP via daily oral gavage at doses of 200 and 400 mg/kg body weight (BW)/d for 28 days to evaluate its effects on immune cell populations in blood and spleen. TOCP treatment at 400 mg/kg BW/d reduced white blood cell counts by 18% and decreased lymphocyte counts by 10.5% compared to the control group. Specifically, CD3+CD4+ T cell counts in blood decreased by 17.4%. In the spleen, TOCP exposure reduced the proportion of T cells by 13.3%. TOCP also disrupted the structural integrity of the splenic white pulp. In vitro the TOCP metabolite cresyl saligenic phosphate (CBDP) inhibited splenic lymphocyte proliferation, selectively increasing T cell proportions by 21.25% and inhibiting B cell proportions by 13.18%, different from in vivo findings. This suggests that the reduction of T cells observed in vivo may not be solely due to direct cytotoxic effects of TOCP on T cells. These observed changes in immune cell counts and spleen histology indicate that TOCP has a systemic immunotoxicity in vivo, which could lead to compromised immune surveillance and defense function.