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GLP-compliant bacterial gene mutation (Ames, using 5 S.typhimur and 1 E.coli strain) and in vitro mammalian gene mutation (mouse lymphoma L5178Y) test in the absence and presence of S9 were conducted. Results from both tests confirmed carbon monoxide was negative when tested up to 100%(v/v) (Ames) or 70% (v/v) (maximum practicable concentration in the mouse lymphoma assay).

A rat repeat dose inhalation (28 day) GLP-compliant study was conducted in which the bone marrow was harvested and collected at the end of the study to address the micronucleus endpoint. It should be noted that due to continual bone marrow turn over, bone marrow analysis was restricted to a 48 hour exposure (dosing on days 27 and 28, with necropsy on day 29), rather than a true dosing regimen over a period of 1 to 28 days (if the true effects of exposure to CO were to be examined following a 28 day exposure, concurrent peripheral blood micronucleus analysis (pre dose, day 4 and day 29) should have been undertaken to assess potential accumulation and toxicity). However, the micronucleus endpoint has been adequately addressed using this protocol design.

Under REACH, the integrated testing strategy for mutagenicity states that if no data from an in vitro cytogenetic study is available, the study does will not need to be conducted if adequate data from an in vivo cytogenetic study is available. The negative results obtained for the bacterial gene mutation test, in vitro mammalian gene mutation test and in vivo rat micronucleus study confirm that no further testing is required and carbon monoxide is concluded to be devoid of genotoxic potential.

Short description of key information:

Bacterial reverse gene mutation test - May, K (2004) VAB009

In vitro mammalian gene mutation test - Soanes, E (2004) VAB010

In vivo rat micronucleus test - Mason, C (2004) VAB008

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

There was no evidence of genotoxicity in studies with carbon monoxide; therefore carbon monoxide has not been classified as genotoxic.