Subchronic oral toxicity of succinate tartrates in rats

A subchronic oral toxicity study was carried out in rats. Groups of ten male and ten female Fischer 344 rats were administered succinate tartrates (ST) at concentrations of 0 (control), 0.01, 0.05, 0.1 and 0.5%, w/w, active ingredient in the drinking-water for 91 days. No mortality was caused by the treatment and no toxicological signs were observed. No treatment-related effects were noted in wk 13 body weights, body-weight gains or food consumption. Urinary haematological and clinical chemistry parameters showed no treatment-related effects, with the exception of a significant decrease in serum magnesium levels in all ST-treated females, but not including the 0.1% dose group. At necropsy, no treatment-related changes in absolute or relative organ weights were noted with the exception of the adrenals. A significant increase in absolute and relative adrenal weights was observed in females administered 0.1% and 0.5% ST; however, the overall analysis of variance was significant only for the relative adrenal weights. In addition, no treatment-related gross or microscopic tissue changes were observed in any organs or tissues including the adrenals. In the absence of histological changes, the adrenal weight changes were not considered biologically significant. The no-observed-adverse-effect level for this study was thus 0.5% ST.