Comparative investigation of behavioral, neurotoxicological, and immunotoxicological indices in detection of subacute combined exposure with methyl parathion and propoxur in rats

Abstract

The effects of 6 weeks of oral exposure to propoxur (PR; at doses of 0.851 and 8.51 mg/kg body wt.), methylparathion (MP; at doses of 0.218 and 0.872 mg/kg body wt.), and their combinations were investigated in male Wistar rats. Measurement endpoints of the investigation were certain general toxicological parameters (body weight gain, organ weights), plaque-forming cell (PFC) count from the spleen, open field (OF) behavior, auditory startle response (ASR), prepulse inhibition (PPI), rotarod performance, somatosensory and auditory cortical evoked potentials, and peripheral nerve conduction velocity. The treated rats did not show any sign of acute intoxication during the 6 weeks of exposure. The higher dose of PR, but not of MP, significantly decreased the relative liver weight. Both agents produced a significant dose-dependent increase of OF activity, with larger expression after 2 weeks than after 6 weeks. The number of ASR responses and the ASR amplitude increased. The amplitude after PPI was increased by MP but only minimally altered by PR and the combinations. There was a small, but with high-dose PR significant, increase in the latency of the somatosensory evoked potentials. Neither of the two substances alone had any effect on the PFC response. The effect of the combination of high-dose PR and low-dose MP was significantly different from that of high-dose PR alone on the liver weight, on the ASR amplitude, and on the PFC/10 6 cell and PFC/spleen counts. With high-dose MP and low-dose PR, no such interaction was observed. According to the results, the noneffective dose of MP can influence the toxicity of the effective dose of PR in a combined exposure situation.