Studies on low dose sub-acute administration of soman, sarin and tabun in the rat.

The effects of low-dose administration of the organophosphate cholinesterase inhibitors, soman, sarin and tabun, on growth rates over 85 days were studied in rats. Acetylcholinesterase (AChE) activity was determined in the striatum and the remainder of the brain 24 hrs following the last exposure to these agents. Further, the cumulative mortality of daily administration of several doses of soman, sarin and tabun for 25 days was studied. The animals treated with 25 micrograms/kg of soman or sarin for 85 days demonstrated reduced growth rates which returned to control levels after 30 days. The animals which received 50 micrograms/kg of sarin also grew at reduced rates which returned to control levels after 35 days, while the tabun-treated (100 micrograms/kg) animals required 38 days to return to control growth rates. The striatal AChE activity of the soman-treated group was reduced to 36% of control while the AChE activities of the high-dose sarin-treated group were reduced to 66% of control. The striatal AChE activity of the tabun-treated group was only 13% of control. It is suggested that growth rates may be used to monitor the development of tolerance to low-dose administration of organophosphate cholinesterase inhibitors.