水素吸入の生体内遺伝毒性評価：ラットを用いたICHガイドライン準拠試験
This study evaluated the genotoxic potential of inhaled molecular hydrogen in male Wistar rats exposed to a 3.1% H2 gas mixture for 72 hours, following ICH S2(R1) guidelines. Three experimental groups were established: a negative control, a positive control administered methyl methanesulfonate, and an H2-exposed group. Alkaline comet assays, formamidopyrimidine DNA glycosylase (Fpg)-modified comet assays, and bone marrow micronucleus assays were conducted. Across all assessed tissues—blood, liver, lungs, and bronchoalveolar lavage fluid—no elevation in comet-tail DNA intensity or hedgehog frequency was detected. Additionally, no increase in Fpg-sensitive oxidative DNA lesions in lung tissue, no induction of micronuclei, and no alteration in the immature-to-total erythrocyte ratio were observed. The complete ICH S2(R1) test battery confirmed an absence of in vivo genotoxicity under these conditions.
Exposure to 3.1% H2 gas for 72 hours did not elevate markers of oxidative DNA damage, chromosomal aberration, or micronucleus formation in multiple tissues, indicating no genotoxic mechanism was activated.
For inhalation applications of molecular hydrogen, the lower flammability limit (LFL) deserves careful handling. The classical 4% figure applies to closed-system mixtures; the practical inhalation-environment threshold is 10%. Even pure-hydrogen output (the UFL 75% paradox) passes through the flammable range at the air–gas boundary. High-concentration (66% / 100%) inhalers are documented in the Japanese Consumer Affairs Agency accident-information database and are not recommended.
See also:
https://h2-papers.org/en/papers/38432775