Toxic Effects of High-Dose Cyanate Administration in Rodents

Cyanate inhibits hemoglobin synthesis in vitro. In vivo studies were performed to determine the effect of the drug on erythropoiesis. Adult female rats received daily intraperitoneal injections of 400 µmoles of cyanate, leading to over 3 CNO/Hb by 3 wk. Controls received sodium chloride. DPG was measured in a small number of animals and declined from 5.5 to 4.1 mmoles/liter (p < 0.02). At 4 wk, Hb, Hct, and red cell counts in cardiac blood of the treated group were all higher (p < 0.05); MCHC was normal. Mean plasma iron was 175 in treated versus 129 µg/100 ml in controls. Plasma iron turnover in mg/day increased from 0.143 to 0.260 (p < 0.01), as did erythron iron turnover, from 0.096 to 0.195 mg/day (p < 0.05). Thus the erythroid marrow of cyanate-treated animals could respond to carbamylation-induced increase in oxygen affinity, though the adequacy of the response with respect to the increase in oxygen affinity is difficult to assess. Furthermore, severe clinical toxicity was observed. Treated animals lost a mean of 62 g, compared with a gain of 25 g in controls. Twenty-five per cent died by 4 wk. The neuromuscular system appeared to be more sensitive to high-dose in vivo cyanate administration than the erythropoietic system.