The toxicity and mechanism of action of bromethalin: a new single-feeding rodenticide.
Bromethalin is a new rodenticide for the control of commensal rodents. Doses in excess of the LD50 (2 mg/kg in rats) will cause death within 8-12 hr and it is preceded by one to three episodes of clonic convulsions with death usually due to respiratory arrest. Multiple low doses or sublethal intoxication yields hind leg weakness and loss of tactile sensation in rodents. Histopathology of the brain and spinal cord of these animals revealed a spongy degeneration of the white matter which was shown upon ultramicroscopic examination to be intramyelenic edema. No inflammation or cellular destruction of neuronal tissue was noted. LD50 values ranged from 1.8 mg/kg in the cat to approximately 13 mg/kg in rabbits. The only apparent nonsusceptible species was the guinea pig which could tolerate doses in excess of 1000 mg/kg without effect. Identification of the desmethyl metabolite was demonstrated in the blood and liver of treated animals by comparison of chromatographic retention times to that of a reference standard, but direct mass spectral identification was unsuccessful in part due to the low dose which could be administered. Therefore, the metabolism of bromethalin was studied by indirect means. Animals were pretreated with three inducers of microsomal drug metabolism: phenobarbital, 3-methylcholanthrene (3MC), and Aroclor 1254 (Aroclor) and one inhibitor, SKF-525A. Pretreated mice or rats were given an LD50 dose of bromethalin or the desmethyl analog and the percentage of surviving animals was determined.(ABSTRACT TRUNCATED AT 250 WORDS)
van Lier
R B
RB
Toxicology Division, Lilly Research Laboratories, Greenfield, Indiana 46140.
Cherry
L D
LD
D000814:Aniline Compounds / Q000633:toxicity*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002250:Carbon Radioisotopes; D002415:Cats; D015170:Cerebrospinal Fluid Pressure / Q000187:drug effects; D004285:Dogs; D005260:Female; D006168:Guinea Pigs; D007928:Lethal Dose 50; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D011916:Rats, Inbred F344; D012378:Rodenticides / Q000633:toxicity*; D013116:Spinal Cord / Q000378:metabolism
D000814:Aniline Compounds; D002250:Carbon Radioisotopes; D012378:Rodenticides; C040307:bromethalin