Simultaneous geno- and immunotoxicological investigations for early detection of organophosphate toxicity in rats

Detectability of toxic effects by repeated doses of dimethoate (DM) and met hylparathion (MPT) were investigated by geno- and immunotoxicological metho ds in male Wistar rats following a 28-day oral exposure, In the dose range of 28.2, 14.1, and 7.04, and 7.04 mg/kg/day DM, the two higher doses decrea sed the body weight gain, The top dose increased the weight of liver, kidne ys, and testicles; the white blood cell count; and the cell content of the femoral bone marrow. From immune function parameters measured [IgM-plaque f orming cells (PFC) assay, delayed-type hypersensitivity (DTH) reaction] onl y the maximum of the DTH reaction decreased at the top dose. Of the MPT dos es (0.872, 0.436, and 0.218 mg/kg/day) the two higher ones increased the li ver weight, and a dose-dependent increase was found in the MCV value. No ev aluable changes in the examined immune function parameters were observed. B oth substances increased the number of numerical but not the structural chr omosome aberretions at lower dose levels (the two larger doses of DM, and a ll the three doses of MPT) than those ones which caused changes in the exam ined immune function parameters. According to these results, the genotoxico logical approach seems to be more sensitive for detection of repeated-dose oral toxicity of the investigated two organophosphates than the immunotoxic ological one. (C) 2000 Academic Press.