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Hydrogen inhalation: in vivo rat genotoxicity tests.

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

animal study inhalation null 3.1%

Abstract

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.

Mechanism

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.

Bibliographic

Authors
Salomez-Ihl C, Tanguy S, Alcaraz JP, Davin C, Pascal-Moussellard V, Jabeur M, et al.
Journal
Mutat Res Genet Toxicol Environ Mutagen
Year
2024
PMID
38432775
DOI
10.1016/j.mrgentox.2024.503736

Tags

Delivery:inhalation delivery (196) Mechanism:hydroxyl radical scavenging (352) oxidative stress (899) reactive oxygen species (774) Safety:lower flammability limit (15)

Delivery context

In air, molecular hydrogen is reported to be combustible across approximately **4% (LFL, lower flammability limit) to 75% (UFL, upper flammability limit)**. Among high-concentration hydrogen inhalers, 66% output sits inside this range, and even pure-hydrogen (100%) output forms a 4–75% concentration-gradient layer at the device–air boundary (the UFL 75% paradox). Engineering principle would therefore call for operation below LFL (the classical 4%); that figure, however, was measured under closed, pre-mixed, static conditions. For the open, dynamic inhalation environment, the empirical value reported in the literature is **10%**, which is the figure referenced in practice as the operating ceiling. The 66% / 100% output devices are recorded in the Japanese Consumer Affairs Agency accident-information database, and from these considerations are not recommended.

→ Evidence by delivery route

Safety notes

In air, molecular hydrogen is reported to be combustible across approximately **4% (LFL, lower flammability limit) to 75% (UFL, upper flammability limit)**. Among high-concentration hydrogen inhalers, 66% output sits inside this range, and even pure-hydrogen (100%) output forms a 4–75% concentration-gradient layer at the device–air boundary (the UFL 75% paradox). Engineering principle would therefore call for operation below LFL (the classical 4%); that figure, however, was measured under closed, pre-mixed, static conditions. For the open, dynamic inhalation environment, the empirical value reported in the literature is **10%**, which is the figure referenced in practice as the operating ceiling. The 66% / 100% output devices are recorded in the Japanese Consumer Affairs Agency accident-information database, and from these considerations are not recommended.

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