title: Evaluation of protective efficacy of CC-2 formulation against topical lethal dose of T-2 toxin in mice.
abstract: T-2 toxin is the type-A trichothecene and a common contaminant of food and cereals, produced by Fusarium species. T-2 toxin easily penetrates skin due to its lipophilic nature and causes skin irritation and blisters in humans. Physical protection of the skin and airway is the only proven effective method of protection. To date, no chemical antidotes are available to prevent T-2 induced lethality. In the present study, we evaluated the protective efficacy of 20% N,N'-dichloro-bis(2,4,6-trichlorophenyl) urea (CC-2) formulation against lethal topical exposure dose of T-2 toxin in mice. None of the animals exposed to only T-2 toxin at lethal dose of 2 and 4 LD50 (11.8 and 23.76 mg/kg body weight) survived beyond 36 and 16 h, respectively. CC-2 application at 5 and 15 min post-exposure protected mice 100% from lethality at 2 LD50. Survival rate was 100% and 50% at 4LD50 dose if CC-2 was applied dermally within 5 and 15 min post-exposure. Recovery profile of surviving animals after 2LD50 T-2 toxin exposure at 1, 3, 7, and 14 days was assessed in terms of hepatic GSH, lipid peroxidation, serum ALP, ALT and AST. Hepatic lipid peroxidation significantly increased in all groups exposed to T-2 toxin by 3 day but normalized by day 7. A delayed GSH depletion was noted in surviving animals on day 7 but recovered by day 14. ALT and AST levels were elevated in all CC-2 protected mice on day 1 and normalized by day 3. ALP level decreased till day 7 in all protected groups. The biochemical variables recovered to control values by 14th day. GC-MS analysis after in vitro interaction of CC-2 formulation with T-2 toxin had shown that nearly 86% of T-2 toxin is decontaminated in 5 min but 8-10% of T-2 toxin was still present even after 60 min of interaction. Results of our study suggest that CC-2 may be an effective dermal decontaminant against lethal topical exposure of T-2 toxin.
authors.affiliation: Division of Pharmacology & Toxicology, Defence Research and Development Establishment, Jhansi Road, Gwalior 474002, India.
authors.forename: Mona
authors.initials: M
authors.lastname: Agrawal
authors.forename: Deepak
authors.initials: D
authors.lastname: Pardasani
authors.forename: P V
authors.initials: PV
authors.lastname: Lakshmana Rao
mesh_terms: D000287:Administration, Topical; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002722:Chlorobenzenes / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D005978:Glutathione / Q000378:metabolism; D007928:Lethal Dose 50; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D010671:Phenylurea Compounds / Q000494:pharmacology*; D011041:Poisoning / Q000517:prevention & control*; D013534:Survival; D013605:T-2 Toxin / Q000008:administration & dosage / Q000506:poisoning*
chemical_list: D002722:Chlorobenzenes; C466760:N,N'-dichlorobis(2,4,6-trichlorophenyl)urea; D010671:Phenylurea Compounds; D005978:Glutathione; D013605:T-2 Toxin