IDENTIFICATION AND USE: Brometalin is a solid. It is a rodenticide, effective against rodents resistant to anticoagulant rodenticides. HUMAN STUDIES: Mild gastrointestinal upset is possible. CNS target symptoms: include hyperexcitability, altered mental status, ataxia, tremor, seizures, coma, cerebral edema, increased intracranial pressure and paralysis. A delusional 21-year-old male presented to a hospital with altered mental status the day after ingesting a bromethalin-based rodenticide. He died 7 days after his self-reported exposure. His clinicopathologic course was characterized by altered mental status, obtundation, increased cerebrospinal fluid pressure, cerebral edema, death, and diffuse histologic vacuolization of the white matter in the central nervous system seen on microscopic examination at autopsy. The presence of a demethylated form of bromethalin in the patient's liver and brain was confirmed by gas chromatography with mass spectrometry. There were 129 calls related to human bromethalin exposures. The age range of cases was 7 months-90 years old, with the majority of exposures (89 cases; 70.6%), occurring in children younger than 5 years of age (median age of 2 years). Most exposures occurred in the pediatric population as a result of exploratory oral exposure. One hundred and thirteen patients (89.7%) had no effects post exposure, while 10 patients (7.9%) had a minor outcome. Adverse effects were minor, self-limited, and mostly gastrointestinal upset. ANIMAL STUDIES: Rats received daily gavage doses of 0, 5, 25, or 125 ug/kg/day of bromethalin technical for 13 weeks. The NOEL in rats was 25 ug/kg/day. The LOEL in rats was 125 ug/kg/day, based on spongy degeneration (leukoencephalomyelopathy) observed in most of the central white fiber tracts of the brain, cerebellum, pons, brain stem, and thoracic spinal cord of both sexes and optic nerves of males. Dogs given a single oral dose of bromethalin at 6.25 mg/kg developed a toxic syndrome characterized by hyperexcitability, tremors, seizures, depression, and death within 15-63 hours after bromethalin administration. Gross lesions included mild cerebral edema (2/5) and mild pulmonary congestion (2/5). Histologic lesions included diffuse white matter spongiosis (5/5), mild microgliosis (3/5), optic nerve vacuolization (3/5), mild thickening of Bowman's capsule (2/5), and occasional splenic megakaryocytes (2/5). Electroencephalogram (EEG) recordings were obtained before and during the clinical syndrome induced by a bromethalin rodenticide given to dogs. Nine dogs given 6.25 mg bromethalin/kg po developed clinical signs and EEG abnormalities 15-58 hr postdosing. Predominant abnormal EEG changes included spike and spike-and-wave EEG patterns (66%), high voltage slow wave (HVSA, 50-150 microV, 1-6 Hz) activity (44%) photoconvulsive or photoparoxysmal irritative responses (44%), and marked voltage depression (dominant activity <10 microV) in all leads (33%). Male and female dogs were orally dosed by gavage for 90 days at levels of 0, 5, 25, 125, or 200 ug/kg/day with bromethalin technical. The NOEL in dogs was 25 ug/kg/day. The LOEL in dogs was 125 ug/kg/day based on spongy degeneration observed in nervous tissue components in both sexes of dogs. At the high dose, 3 male dogs displayed the following neurotoxic signs before death or being sacrificed moribund: salivation and hypoactivity, followed by trembling, myoclonia, hyperesthesia, groaning, and decubitus. Bromethalin did not produce acute delayed neurotoxicity in the hen. Cats typically develop paralytic syndrome irrespective of dose of bromethalin. In rats, there were no compound-related external, visceral or skeletal effects in bromethalin-treated fetuses in comparison to controls on either a litter or fetal basis. Definitive post mortem confirmation of intoxication by the neurotoxic rodenticide bromethalin can be challenging. Brain lesions are not specific and detection of bromethalin and its metabolites are unpredictable due to rapid photodegradation and inconsistent behavior in tissues. ECOTOXICITY STUDIES: In cases of wildlife species with unknown deaths or inconsistent clinical signs with normal or minimal histological findings, bromethalin toxicosis should be considered as a differential. Adipose tissue is the tissue of choice and can be easily harvested from a live or deceased animal to help confirm or rule out bromethalin exposure or intoxication.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
副作用
神经毒素 - 其他中枢神经系统神经毒素
Neurotoxin - Other CNS neurotoxin
来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases
毒理性
毒性数据
大鼠LC50 = 24毫克/立方米/小时
LC50 (rat) = 24 mg/m3/1h
来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases
A metabolism study was conducted in Fischer 344 rats following oral admin of (14)C-bromethalin at 1 mg/kg. Blood samples were taken from the orbital sinus at 0.25, 0.5, 1, 2, 4, and 24 hours, and at 2, 3, 4, 6, 8, 11, 14, 17, and 21 days after dosing. Based on radiolabeled material, the plasma half-life was 134 hours (5.6 days). The half-life of the distributive phase suggested distribution in total body water.
