Quantitative assessment of tolerance development to diisopropylfluorophosphate

Rats were treated with diisopropylfluorophosphate (DFP) acutely or daily for 14 days. The quantitative assessment of tolerance development after a challenge dose of DFP, 2 mg/kg, was studied. The subacutely-treated rats developed tolerance to DFP-induced tremors. However, the severity of tremors in DFP-tolerant animals was not significantly different from that of the controls after the challenge dose of DFP was administered. Hind-limb abduction was significantly lower in the subacutely-treated group than in the acutely-treated group. The recovery of body weights in subacutely-treated rats (3.5%/day) was significantly higher than that in acutely-treated rats (2.0%/day). The consummatory behaviors (food and water consumption) recovered faster in subacutely-treated rats than in the acutely-treated group. Body temperatures were decreased to the same extent in both groups, but the subacutely-treated group recovered faster. The total mortality was significantly lower in subacutely-treated rats (10%) than in acutely-treated rats (35%). The results further substantiate the finding that tolerance develops to various DFP-induced signs of toxicity.