Disposition of β-N-methylamino-L-alanine (L-BMAA), a neurotoxin, in rodents following a single or repeated oral exposure

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β-N-methylamino-L-alanine (L-BMAA) is produced by cyanobacteria (blue-green algae). Human exposure to L-BMAA occurs via consumption of L-BMAA-contaminated water and food. It is speculated that exposure to L-BMAA, and subsequent brain accumulation, may contribute to an increased incidence of neurodegenerative diseases indicating the need to evaluate risk of L-BMAA exposure to humans. As an initial step in this process, we have evaluated disposition following a single or repeated gavage administration of 1, 10 or 100 mg/kg [14C]L-BMAA in rats and mice.L-BMAA was well absorbed following a single gavage administration with minimal dose, species, or sex-related effect. In both species, the main excretion route was as exhaled CO2 (46–61%) with 7–13% and 1.4–8% of the administered dose excreted in the urine and feces, respectively. L-BMAA was distributed to all tissues examined; the total radioactivity in tissues increased with the dose and was significant in both species (8–20%). In male rats, L-BMAA was slowly eliminated from blood and tissues (half-lives ≥ 48 h). Following 1, 5 and 10 days of dosing in male rats, levels in tissues increased with the number of doses demonstrating potential for accumulation of BMAA-derived equivalents. There was no greater affinity for accumulation in the brain compared to other organs and tissues. Following repeated exposure in rats, amino acid mass shifts associated with L-BMAA were detected in brain peptides. However, the low frequency of occurrence suggests that the substitution of an amino acid with L-BMAA is not significant relative to substitutions and/or modifications by other L-BMAA-derived equivalents.HighlightsL-BMAA may contribute to incidences of neurodegenerative diseases in humans.We studied the disposition and brain accumulation of [14C] L-BMAA in rodents.L-BMAA was absorbed and distributed to tissues following oral administration.Following repeated exposure, BMAA was accumulated in tissues including brain.Frequency of amino acid substitution with L-BMAA was low in brain proteins.

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