O,O,S-Trimethyl phosphorothioate effects on immunocompetence

O,O,S-Trimethyl phosphorothioate (OOS), a contaminant of technical formulations of some organophosphorus pesticides, was found to be immunotoxic at subtoxic doses in female C57Bl/6 mice. Mice treated orally with acute doses of 10 mg/kg OOS show no overt toxic signs such as weight loss or malaise. In addition, the levels of serum cholinesterase was not decreased. Histopathologic investigation demonstrated no alterations in liver, lung, kidney, heart, skin, brain, spleen, or gut. The LD₅₀ for delayed toxicity was approximately 35 mg/kg. Despite the lack of general toxic changes at doses of 5-10 mg/kg OOS, specific immunotoxic changes were found. The humoral or cell-mediated immune response of splenocytes from mice treated with 10 mg/kg OOS to in vivo immunization was diminished with respect to control animals. Responses were measured in ex vivo assays. Cytotoxic T-lymphocyte (CTL) responses were assessed by alloimmunization with the tumor P815 followed by a ⁵¹Cr release assay done ex vivo with splenic lymphocytes. Humoral responses were assessed by immunization with sheep red blood cells followed by a Jerne plaque assay to determine anti-sheep red blood cell antibody. Both cellular and humoral responses could be stimulated in vitro using cells from OOS-pretreated, primed animals, thus indicating that no permanent cellular elterations had occurred.