Toxicity and mechanism of action of bromethalin: a new single-feeding rodenticide

Journal Article · Tue Nov 01 04:00:00 EST 1988 · Fundam. Appl. Toxicol.; (United States)

DOI:https://doi.org/10.1016/0272-0590(88)90129-7· OSTI ID:6323476

van Lier, R B; Cherry, L D

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.

• Research Organization: Lilly Research Laboratories, Greenfield, IN (USA)
• OSTI ID: 6323476
• Journal Information: Fundam. Appl. Toxicol.; (United States), Journal Name: Fundam. Appl. Toxicol.; (United States) Vol. 11:4; ISSN FAATD
• Country of Publication: United States
• Language: English

Related Subjects

3-METHYLCHOLANTHRENE
560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANESTHETICS
ANIMALS
ANTICONVULSANTS
AROMATICS
AZINES
BARBITURATES
BIOLOGICAL VARIABILITY
BODY
BRAIN
CATS
CELL CONSTITUENTS
CENTRAL NERVOUS SYSTEM
CENTRAL NERVOUS SYSTEM DEPRESSANTS
CHROMATOGRAPHY
DOGS
DRUGS
GENETIC VARIABILITY
GUINEA PIGS
HETEROCYCLIC COMPOUNDS
HYDROCARBONS
HYPNOTICS AND SEDATIVES
MAMMALS
MASS SPECTRA
METABOLISM
MICE
MITOCHONDRIA
NERVOUS SYSTEM
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANOIDS
ORGANS
PESTICIDES
PHENOBARBITAL
POLYCYCLIC AROMATIC HYDROCARBONS
PYRIMIDINES
RABBITS
RATS
RODENTS
SEPARATION PROCESSES
SPECTRA
SPINAL CORD
TOXICITY
VERTEBRATES