Determination of acute toxic effects in mice following exposure to methyl bromide

Abstract

An inhalation system was designed and constructed for acute nose exposure of mice to methyl bromide. Animals were exposed for 1 h to concentrations ranging from 0.87 to 5.93 mg/l. Mice exposed to concentrations up to 1.72 mg/l did not exhibit any indication of developing a toxic response. Animals exposed to concentrations to 2.20 and 2.70 mg/l exhibited significantly decreased lung and liver weights when compared to controls. Animals exposed to concentrations above 3.50 mg/l exhibited kidney lesions. At concentrations of 3.82 mg/l and above, animals exhibited abnormal clinical signs, weight loss, and mortality. In addition, at 4.70 mg/l, a liver lesion was observed. At concentrations above 5.77 mg/l, pathological changes were observed in the color and a decreased motor coordination was evident. Methyl bromide exposures of up to 3.82 mg/l did not affect the ability of mice to recall a single-task passive-avoidance test. The 1-h LC50 of methyl bromide in mice via inhalation was determined to be 4.68 mg/l (approximately 1200 ppm). The dose-response curve was quite steep and the LC10 to LC90 range of mortality was contained within a doubling of concentration.

Glutathione transferase activity and formation of macromolecular adducts in two cases of acute methyl bromide poisoning.

“…Exposure to methyl bromide has induced glutathione depletion in various systems." [20][21][22] However, the significance of this finding is unclear, as shown by the conflicting results of experimental studies. On the one hand, glutathione depletion was found to increase methyl bromide toxicity in rats 21 and pretreatment of mice, rats, or rabbits with glutathione, cysteine, N-acetylcysteine, or methionine had a protective effect,2324 on the other hand, glutathione depletion before exposure inhibited toxicity of another monohalomethane, methyl chloride, in mice.25 These conflicting results may be explained by significant differences between species in the metabolism of monohalomethanes; such differences have been shown to exist-for example, glutathione transferase activity varies considerably from one species to another.…”

How unclogging a sink can be lethal: case report of an accidental methyl bromide poisoning leading to a multiple organ failure

“…Most of the authors have described a cellular toxic effect. Indeed, following a methylation reaction, the methyl bromide conjugates itself with glutathione to make methylglutathione, which is highly toxic for the respiratory chain [17-20]. A second cause often described is the modulation of the inhibitory neurotransmitter γ-aminobutyric acid receptor within the cerebellar and vestibular systems [9,16,21].…”

“…A second cause often described is the modulation of the inhibitory neurotransmitter γ-aminobutyric acid receptor within the cerebellar and vestibular systems [9,16,21]. A third hypothesis attributes toxicity to methyl bromide metabolites such as methanethiol and formaldehyde [17,19]. Another suggested mechanism is that methyl bromide rapidly inhibits creatine kinase activity in all regions of the brain and in other target organs.…”

Methyl Bromide

“…Overt toxicity (i.e., death) from acute inhalation exposures to methyl bromide has been extensively evaluated in rodents (Alexeeff and Kilgore, 1985;Irish et al, 1940;Japanese Ministry of Labour, 1992;Zwart, 1988). The majority of acute inhalation studies in mice and rats demonstrate that methyl bromide exposure-related effects and mortality are a function of both the concentration and the duration of exposure.…”

“…In a methyl bromide inhalation study in mice, Alexeeff and Kilgore (1985) followed mouse tissue bromine concentrations through 7 days postexposure. No bromide ion was detected in any tissue 1 week after exposure to concentrations up to 2.72 mg/l air.…”