Acute toxicity and sex-dependent lethality of isotonitazene in fischer 344 rats

was 0.08 mg/kg (95% CI 0.02996-0.182 mg/kg) in males and 0.25 mg/kg (95% CI 0.04841-0.768 mg/kg) in females, indicating greater male sensitivity. Rapid respiratory depression and neuromuscular rigidity occurred within minutes of dosing and preceded lethality. The narrow separation between survival and death demonstrates a steep dose-response relationship and limited safety margin. These findings provide quantitative data for toxicological risk assessment of nitazene opioids and underscore the importance of sex as a biological variable in opioid toxicity studies.