Dose-Dependent Hematological Effects of Sodium Cyanate (NaOCN) in Adult Wistar Rats: Gender Variability and Toxicological Thresholds via Probit and Weibull Analysis

Abstract

Sodium cyanate (NaOCN), historically used for sickle cell disease treatment, poses potential hematological risks due to environmental and occupational exposure. This study investigates the dose-dependent hematological effects of NaOCN (0, 2, 3, 4, 5, 10, 15 and 20 mg/kg bw) in adult Wistar rats (n=48, 24 males, 24 females) over 7 days, focusing on gender variability and toxicological thresholds. Blood samples were analyzed for 17 hematological parameters using a Sysmex XN-1000V analyzer. Two-way MANOVA revealed a significant NaOCN dose-sex interaction (Wilks’ Lambda=0.001, p<0.001, Partial η²=0.710), with significant effects on neutrophils, MCV, MCHC, RDW-CV, RDW-SD, and MPV (p<0.05, Partial η²=0.456–0.691). Tukey HSD tests identified the 3 mg/kg bw dose as a critical threshold, showing lower MCH, MCHC, and MPV, and higher RDW-CV compared to other doses. Females exhibited greater sensitivity (e.g., WBC EC50: 2.695 vs. male 8.680 mg/kg bw). Probit and Weibull models estimated LD50 at ~13.75 mg/kg bw (95% CI: 9.58–17.92) and LD90 at ~27.06 mg/kg bw, with females more susceptible (LD50: 12.10 mg/kg bw). Low EC50 values for HCT (0.198 mg/kg bw), MCV (0.226 mg/kg bw), and MCHC (0.192 mg/kg bw) indicate high sensitivity at low doses. These findings highlight NaOCN’s dose-dependent hematological toxicity, with significant gender differences, likely due to hormonal influence, hemoglobin carbamylation and metabolic variations. The narrow therapeutic window (100% mortality at 20 mg/kg bw) underscores the need for sex-stratified safety assessments in NaOCN applications.