Bromethalin-based rodenticides: Mode of action, toxicity, clinical effects, and treatment efficacy in rats, dogs, and cats

The purpose of these studies was to define the toxicity of bromethalin-based rodenticides, develop treatments, and determine new modes of action of bromethalin. Bromethalin-based rodenticides are highly neurotoxic to cats (bait LD$\sb{50}$ 0.54 mg bromethalin/kg) and dogs (bait LD$\sb{50}$ 3.56 mg bromethalin/kg). Bromethalin poisoning in the dog and cat produced a dose dependent delayed toxic syndrome. Sublethal doses of bromethalin to dogs and cats resulted in delayed CNS depression, hindlimb ataxia, paresis, and paralysis. Higher doses given to dogs resulted in rapid severe muscle tremors and generalized seizures. Bromethalin toxicosis was also associated with increased cerebrospinal fluid pressure and cerebral edema. Bromethalin toxicosis produces acute and chronic EEG changes. Predominant abnormal EEG changes included: spike and spike-and-wave EEG patterns; high voltage slow wave activity; photoconvulsive or photoparoxysmal irritative responses, and marked voltage depression. Histologic lesions included diffuse white matter spongiosis, mild microgliosis, and optic nerve vacuolization. Ultramicroscopic examination of brainstem revealed occasional swollen axons, intramyelenic vacuolization, and myelin splitting at the intraperiod line. Bromethalin was detected in kidney, liver, fat, and brain tissues using gas chromatography with electron capture detection. Bromethalin caused increased feline hepatic cytochrome P-450 and cytochrome b$\sb5$ concentrations and decreased microsomal aminopyrine N-demethylase and 4-nitrophenetole-O-deethylase activities.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Veterinary Biosciences

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2011

Author dc:creator

• Dorman, David Christopher

Contributors dc:contributor

• Buck, William B.

• Health Sciences, Pharmacology
• Biology, Veterinary Science

Statement dc:rights

• Copyright 1990 Dorman, David Christopher

Language dc:language

eng

Identifier

AAI9026170
(UMI)AAI9026170

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/22060