The Evaluation of BMAA Inhalation as a Potential Exposure Route Using a rat Model

Chronic inhalation of aerosolized β-N-methylamino-L-alanine (BMAA) could serve as potenital route for exposure to this cyanobacterial neurotoxin implicated in the development of neurodegenerative disease. We investigated environmental aerosol BMAA loads and the fate of inhaled isotopically labeled aerosolized BMAA in adult male Sprague Dawley rats, with doses corresponding to chronic aerosolized environmental BMAA exposure of over 65 days and up to 266 years. Environmental BMAA aerosol concentrations ranged from 6-39 pg L¯¹. No clinical signs of toxicity were observed in rats exposed to aerosol containing BMAA at concentrations far exceeding the maximum recorded environmental BMAA aerosol load. Surprisingly, no labeled BMAA was observed in the brain, liver or lung tissues of exposed rats. However, a dose-dependent reduction in the Gln:Glu ratio was observed in brain and liver tissues together with an increase in 2,3 diaminopropanoic acid,¹⁵N₂, the demethylated L-BMAA-4,4,4-d₃,¹⁵N₂ product, in liver tissues. This confirmed both BMAA uptake and distribution throughout the body. The increase in 2,3 diaminopropanoic acid,¹⁵N₂ did however not account for the total loss of administered L-BMAA-4,4,4-d₃,¹⁵N₂ and thus, the absence of detectable L-BMAA-4,4,4-d₃,¹⁵N₂ in tissues and feces, together with the absence of other known BMAA catabolites, N-acetylated BMAA and methylamine, additional metabolic reactions are indicated. Significant biochemical responses to BMAA were only observed in doses corresponding to an unrealistic chronic exposure timeframe, suggesting that the inhalation of environmental levels of aerosolized BMAA might not be sufficient to elicit a biochemical response in adults.