Toxicokinetics under extracorporeal clearance and temporal dissociation of hepatotoxicity and coagulopathy in ACDMB poisoning: Two index cases

Background: 2-Amino-5-chloro-N,3-dimethylbenzamide (ACDMB), a synthetic intermediate for the insecticide chlorantraniliprole, causes extremely rare occupational poisoning (six cases worldwide) with unknown human toxicokinetics. We report two consecutive index cases from the same manufacturing facility.Case presentationCase A (22-year-old male) and Case B (37-year-old male) developed fulminant hepatitis following brief accidental occupational exposure. Both received plasma exchange and continuous venovenous hemofiltration; Case A additionally received hemoperfusion. Both achieved full recovery and were discharged on Day 28 (Case A) and Day 14 (Case B), respectively. Results: Serial serum monitoring in Case B revealed mono-exponential elimination (apparent half-life 18.4 h, 95% CI 15.3-22.1). Both patients exhibited temporal dissociation: peak hepatotoxicity occurred at 54-65 h, whereas critical coagulopathy (Coagulation Reserve Index [CRI] <5) developed later at 123-127 h when > 95% of toxin had been cleared. At comparable CRI nadirs, hemoperfusion in Case A resulted in immediate circuit clotting and prolonged DIC reversal (48 h), whereas cryoprecipitate support in Case B achieved rapid recovery (8.3 h) without adsorptive therapy. Conclusion: These observations provide the first human ACDMB toxicokinetic profile under extracorporeal clearance and generate the hypothesis that CRI < 5 may identify high-risk periods for hemoperfusion, though prospective validation is required.