Generation and distribution of cyanide in rats and humans following sodium cyanoborohydride exposure.

Sodium cyanoborohydride (NaBH₃CN) is a commonly used reducing agent. However, its metabolism and mechanism of toxicity are still unclear. In this study, we first demonstrated that NaBH₃CN underwent rapid hydrolysis in aqueous solution and produced hydrocyanic acid. Cyanide was detected in the gastric contents of rats following oral administration of NaBH₃CN, and cyanide poisoning symptoms such as tachypnea, limb convulsions, and opisthotonos were observed. Combined with a gas chromatography-mass spectrometry (GC-MS) method and rat poisoning models, we systematically investigated the metabolism and distribution of cyanide generated from NaBH₃CN and validated the findings through a human poisoning case. In vitro experiments demonstrated that NaBH₃CN hydrolyzed to produce hydrogen cyanide in acidic, neutral, and alkaline aqueous solutions, as well as in simulated gastric fluid. Animal experiments revealed that NaBH₃CN can metabolize to release cyanide in vivo, with a dose-dependent distribution profile. The cyanide concentration in the blood and tissues peaked at 20 min after exposure and then rapidly decreased within 2 h. Under various exposure doses, peak blood cyanide concentrations (9.57 ± 1.01-47.57 ± 3.35 μg/mL) consistently exceeded tissue concentrations by 2- to 6-fold. Finally, we reported a clinical poisoning case involving an adolescent male with depression, who experienced generalized convulsions after oral intake of sodium cyanoborohydride. Laboratory tests confirmed the presence of cyanide in both blood and urine specimens. In addition, the blood cyanide concentrations decreased from 2.43 ± 0.05 to 0.45 ± 0.03 μg/mL, while urine levels decreased from 1.26 ± 0.04 to 0.22 ± 0.03 μg/mL within 24 h after antidote administration. In conclusion, our research demonstrated for the first time that oral exposure to NaBH₃CN leads to generation of cyanide in the stomach and resulted in symptoms consistent with cyanide poisoning. The distribution profile of cyanide after oral NaBH₃CN exposure in rats suggested that blood samples were optimal for identifying acute NaBH₃CN poisoning, with liver tissue as an alternative. More importantly, our findings provided an experimental basis for identifying NaBH₃CN poisoning and were validated through a clinical poisoning case.