Acute, Distribution, and Subchronic Toxicological Studies of Succinate Tartrates123.

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 C in urine, feces, or expired CO after 72 hr. Approximately 80% of the dermally absorbed C dose was eliminated in urine, feces, or expired CO after 72 hr. In conclusion, no adverse effects were noted in acute toxicity, genotoxicity, or subchronic toxicity studies conducted with ST. [ABSTRACT FROM PUBLISHER]