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Key value for chemical safety assessment

Additional information

In vitro data

The following text is copied from the EU risk assessment report (2003), pg. 123: "Hydrogen peroxide is a mutagen and genotoxicant in a variety of in vitro test systems (…). In bacterial tests, most gene mutation assays (in the Ames test especially the strains sensitive to oxygen radicals), and DNA damage and repair assays have yielded positive results. With mammalian cells, positive results were mostly observed in gene mutation assays, DNA damage and repair assays, UDS assays, SCE assays, and cytogenetic assays for chromosomal aberrations. The responses were often, but not invariably (Abu-Shakra and Zeiger, 1990) modified by the amount of catalase present, which varies in bacteria and mammalian cells: bacterial strains lacking catalase activity seem to be especially sensitive (Abril and Pueyo, 1990), the hydrogen peroxide resistant Chinese hamster cell line R-8 had 10-fold higher catalase activity in comparison to the parental cells (Sawada et al., 1988). Although few tests have employed metabolic activation, it can be inferred from the results that the microsomal mix (like added catalase) markedly reduced or abolished the genotoxic response indicating that S9 contains hydrogen peroxide degrading enzymes (Mehnert et al., 1984a; 1984b; Speit et al., 1982; Procter & Gamble, 1985). Apart from protecting enzymes, other recognised variables of the cells determining their sensitivity to mutation were the extent of Fenton reaction (formation of hydroxyl radical) and the cells’ repair abilities (Kruszewski and Szumiel, 1993)."

In vivo data

In vivo studies with high reliability are available: micronucleus assays in mice (Molinier 1995, Sarver 1995) or an Unscheduled DNA Synthesis (UDS) Test with mammalian liver cells in rats (Clare 1997) demonstrated that hydrogen peroxide does not have genotoxic effects in vivo when administered by intraperitoneal or intravenous injection or ad libitum via drinking water.

Short description of key information:

The following text is copied from the EU Risk Assessment Report (2003), pg. 123: "Hydrogen peroxide is a mutagen and genotoxicant in a variety of in vitro test systems (…). In bacterial tests, most gene mutation assays (in the Ames test especially the strains sensitive to oxygen radicals), and DNA damage and repair assays have yielded positive results. With mammalian cells, positive results were mostly observed in gene mutation assays, DNA damage and repair assays, UDS assays, SCE assays, and cytogenetic assays for chromosomal aberrations. The responses were often, but not invariably (Abu-Shakra and Zeiger, 1990) modified by the amount of catalase present, which varies in bacteria and mammalian cells: bacterial strains lacking catalase activity seem to be especially sensitive (Abril and Pueyo, 1990), the hydrogen peroxide resistant Chinese hamster cell line R-8 had 10-fold higher catalase activity in comparison to the parental cells (Sawada et al., 1988). Although few tests have employed metabolic activation, it can be inferred from the results that the microsomal mix (like added catalase) markedly reduced or abolished the genotoxic response indicating that S9 contains hydrogen peroxide degrading enzymes (Mehnert et al., 1984a; 1984b; Speit et al., 1982; Procter & Gamble, 1985). Apart from protecting enzymes, other recognised variables of the cells determining their sensitivity to mutation were the extent of Fenton reaction (formation of hydroxyl radical) and the cells’ repair abilities (Kruszewski and Szumiel, 1993)."

In contrast, the available in vivo studies with high reliability performing micronucleus assays in mice (Molinier 1995, Sarver 1995) or an Unscheduled DNA Synthesis (UDS) Test with Mammalian Liver Cells in rats (Clare 1997) demonstrated that hydrogen peroxide does not have genotoxic effects in vivo when administered by intraperitoneal or intravenous injection or ad libitum via drinking water.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

The following discussion of mutagenicity is copied from the EU risk assessment report for hydrogen peroxide (European Commission 2003, page 126-127):

“Hydrogen peroxide is a mutagen and genotoxicant in a variety of in vitro test systems. The responses observed were modified by the presence of degrading enzymes (catalase), the extent of formation of hydroxyl radicals by Fenton reaction, and the cells repair abilities. Regarding in vivo genotoxicity, studies employing modern methodologies have explored DNA repair in liver cells of rats administered hydrogen peroxide by intravenous infusion for 30 minutes(…) (Clare 1997), as well as micronucleus formation in mice in the context of a 2-week drinking water exposure (…) (Sarver 1995), or after a single intraperitoneal injection(…) (Molinier 1995), all with a negative outcome. Intravenous administration of hydrogen peroxide in the in vivo-in vitro unscheduled DNA synthesis study ensured that the substance had a fair chance to reach the target (liver) cells, although the duration of exposure was limited (Clare 1997). In the micronucleus study by oral drinking water exposure (…) (Sarver 1995), the systemic fate of hydrogen peroxide was uncertain, and there was no decrease in the ratio of polychromatic/normochromatic erythrocytes in the bone marrow. (…)

According to the principles followed in the EU, hydrogen peroxide is not considered for classification as a mutagen.”