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Registration Dossier
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EC number: 939-579-8 | CAS number: -
Endpoint summary
Administrative data
Key value for chemical safety assessment
Additional information
In a GLP-compliant reverse gene mutation assay in bacteria performed according to the OECD Guideline 471, Chimexane HB induced an increased number of revertants in two strains of Salmonella typhimurium (TA 1535 and TA 98) only in the presence of metabolic activation. In the TA 1535 strain it induced a 3.3 to 4.2 -fold increase of the number of revertants at 150 and 300 µg/plate, respectively; and a 2.1 to 2.4 -fold increase at 300 µg/plate in the TA 98 strain. Chimexane HB was not mutagenic in S. typhimurium TA 1537, TA 100 and TA 102 with and without metabolic activation.
In a GLP-compliant in vitro mammalian cell gene mutation test performed according to OECD Guideline 476, a 3 h exposure of Chimexane HB diluted in purified water with and without metabolic activation did not induce any mutation in the hprt locus of mouse lymphoma L5178Y tk+/- cells.
In the two experiments performed, when tested up to toxic concentrations (yielding 12 -18% relative survival without metabolic activation and 5 -12% relative survival with metabolic activation), no statistically significant increases in mutant frequency were observed following treatment with Chimexane HB at any concentration tested.
In a GLP-compliant in vitro chromosome aberration test performed according to OECD Guideline 473 in cultured human lymphocytes, Chimexane HB induced a statistically significant increase in the number of cells with structural and numerical chromosome aberrations at 312.5 μg/mL, a moderately cytotoxic concentration (37.5% mitotic index relative to the control), with metabolic activation. These effects at this particular concentration were only observed in the assay performed with 10 % S9-mix, but not in the one performed with 5% S9 -mix. In the experiments without metabolic activation, it did not induce any biologically relevant and statistically significant increase in the number of cells with structural and numerical chromosome aberrations at any of the concentrations, when compared with the vehicle control values.
In a GLP-compliant in vivo bone marrow micronucleus assay performed according to OECD Guideline 474, Chimexane HB did not induce any increase in the number of micronucleated polychromatic erythrocytes in the bone marrow of Sprague-Dawley rats dosed up to 2000 mg/kg bw/day for two consecutive days, for which plasma levels reached values demonstrating systemic exposure of the treated animals.
Short description of key information:
Chimexane HB was found to be mutagenic in two strains of S. typhimurium (TA 1535 and TA98) in the presence of metabolic activation only. It was not mutagenic in mammalian cells (i.e, it did not induce mutations at the hprt locus of L5178Y mouse lymphoma cell).
Chimexane HB was clastogenic in the presence of metabolic activation (10% S9 but not with 5% S9) at a moderately cytotoxic concentration in cultured human peripheric blood lymphocytes. It did not induce any increase in the number of micronucleated polychromatic erythrocytes in the bone marrow of rats dosed up to 2000 mg/kw bw.
Endpoint Conclusion: No adverse effect observed (negative)
Justification for classification or non-classification
As Chimexane HB was positive in an in vitro mutation assay in bacteria in only two strains in the presence of metabolic activation, and was negative in an in vitro mammalian cell gene mutation test with and without metabolic activation, it must not be classified as mutagenic according to Annex VI to the Directive 67/548/EEC and to the CLP Regulation (EC) N°1272/2008.
As Chimexane HB was clastogenic in an in vitro chromosome aberration test at only one moderately cytotoxic concentration in the presence of a high concentration of metabolic activation, but was negative in an in vivo bone marrow micronucleus assay in which systemic exposure of the treated animals was demonstrated, Chimexane must not be classified as clastogenic according to Annex VI to the Directive 67/548/EEC and to the CLP Regulation (EC) N°1272/2008.
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