Four-week-long Tabun Low-level Exposure in Rats

Prolonged administration of sublethal doses of organophosphorus cholinesterase inhibitors results in adaptation to their toxicity. In order to investigate this phenomenon, we exposed rats to 0.2, 0.3 or 0.4 LD50 of tabun sc daily during four weeks. AChE activities in erythrocytes, diaphragm and brain were inhibited dose-dependently after days 7 and 14 of the study and started to recover thereafter, except after 0.4 LD50. Tabun 0.3 LD50 decreased body weight gain, food and water consumption during the first two weeks of the study. Spontaneous locomotor activity was significantly increased in the same interval and decreased thereafter. These findings support the assumption that both the biochemical and receptor mechanisms are responsible for the occurrence of tolerance to tabun in rats. INTRODUCTION There is a plethora of the experimental and clinical studies dealing with the consequences of the poisonings with organophosphorus compounds (OPCs), including OP insecticides (OPIs) and nerve agents tabun, sarin, soman and VX. At the same time, the corresponding data on the effects of subacute low-level exposure to OPCs are rather scarce (1). The majority of the presently known publications on the subjects are four or more decades old and they are dealing with subacute poisoning with OPIs, such as parathion (2), octamethyl pyrophosphoramide (3), chlorthion, tetrapropyl dithionopyrophosphate, malathion (4), dipterex (5), systox (6) and di-syston (7). After proving that repeated administration of a meant-to-be-nerve agent diisopropylfluorophosphate (DFP) leads to development of tolerance (8), the first experimental study addressing the same issue in a similar manner, but employing real nerve agents instead of OPIs, was the one on tabun, sarin and soman subacute toxicity in rats (9). The reason for this disparity between the research in the OPI and nerve agent field was the fact that interest in the effects of OPCs after prolonged low-level exposure originated from the industrial hygiene. In fact, the stimulus for the investigations came from the notion that those individuals that are engaged in the manufacture or use of the OPIs could receive and survive repeated exposure to small doses. It was much later, when the