Acute, distribution, and subchronic toxicological studies of succinate tartrates

The estimated single-dose oral toxicity (50% lethality) of succinate tartrates (ST) was 2-3 g/kg in rats. ST produced minimal to moderate dermal irritation but no evidence of systemic toxicity in a standard acute percutaneous toxicity test in rabbits. ST was not an eye irritant in a standard rabbit low-volume eye irritation test. ST was not genotoxic in a series of six genotoxicity tests. A 14-day oral gavage study in rats at a dose range of 0.05-1.0 g ST/kg/day produced only gastric irritation. The no-observed-effect level (NOEL) for gastric irritation was 0.1 g/kg for males and 0.05 g/kg for females. A 28-day percutaneous toxicity study in rabbits produced minimal to moderate dermal irritation and no adverse systemic effects at a high dose of 450 mg ST/kg/day. Single-dose absorption, distribution, and elimination (ADE) studies in male rats showed that 10-15% of an oral dose and 1-3% of a dermal dose were absorbed. Approximately 98% of the orally administered ST was eliminated as 14C in urine, feces, or expired CO2 after 72 hr. Approximately 80% of the dermally absorbed 14C dose was eliminated in urine, feces, or expired CO2 after 72 hr. In conclusion, no adverse effects were noted in acute toxicity, genotoxicity, or subchronic toxicity studies conducted with ST.