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Additional information

Sufficient data are available to judge that Cyclohexane, oxidized, aquous extract (COP Acid) is not mutagenic in bacterial or mammalian cell test systems. In two GLP OECD 471 in vitro gene mutation assays (ames test), COP Acid was not mutagenic with or without metabolic activation (BASF, 1998). In addition, COP Acid was not mutagenic in a GLP OECD 474 in vivo mammalian micronucleus study (BASF, 2007). Futhermore, it can be presumed that COP Acid would be negative in mammalian cell gene mutation studies as determined by read-across to adipic acid, a primary component of COP Acid and representative of the other components as well.

Read Across (Adipic Acid):

In vitro:

Hazards identified by OECD/ICCA high production volume chemicals program in 2004:

"Adipic acid was neither mutagenic nor cytotoxic in studies similar to OECD TG 471 in bacteria such as Salmonella typhimurium strains TA98, TA100, TA1535, TA1537 and TA1538 or Escherichia coli WP2 up to concentrations of 10 mg/plate with or without metabolic activator S9. Negative and positive controls were functional in all experiments (Mortelmans and Griffin 1982; Prival et al. 1991 ; Shimizu et al. 1985).

Adipic acid was negative in a yeast gene mutation assay using Saccharomyces cerevisiae D3 as a reporter strain in the absence of S9-mix and adipic acid concentrations up to 200 mg/l. Cytotoxicity was not mentioned. The positive and negative controls were functional (Litton Bionetics, Inc. 1974).

Adipic acid was also inactive in a cytogenetic assay using human embryonic lung fibroblast cells (WI-38) and compound concentrations up to 200 mg/l. Cytotoxicity was observed at 400 mg/l. No metabolic activation system was used in these experiments and the positive and negative controls were functional (Litton Bionetics, Inc. 1974)."

Updated relevant information:

Adipic acid was investigated in an OECD TG 476 study in Chinese hamster V79 cells in the absence and in the presence of metabolic activator (S9) up to concentrations of 10 mM. No precipitation of the test item was noted in any experiment; no biological relevant growth inhibition was observed with and without metabolic activation. In both experiments no biologically relevant increase of mutants was found after treatment with the test item. DMBA and EMS were used as positive controls and showed distinct and biologically relevant effects in mutation frequencies. In conclusion, adipic acid is considered to be non-mutagenic in the HPRT locus using V79 cells (BSI Bioservice, 2009).

In vivo: Hazards identified by OECD/ICCA high production volume chemicals program in 2004: "Adipic acid was investigated in a host mediated assay with Salmonella typhimurium TA-1530 and G-46 or Saccharomyces cerevisiae D3 as indicator strains. In an acute and subacute study groups of 10 male mice were dosed with 3.75, 37.5 and 375 mg/kg bw/day for one and 5 days, respectively. Adipic acid produced no significant increase in mutation frequencies in any experiment, except when using Saccharomyces cerevisiae D3 in the acute study. In this case an increased frequency of mutations as well as dose response was observed. In further experiments in the same study animals were dosed with 5000 mg/kg bw once and with 2500 mg/kg bw/day for 5 days, respectively. In these studies the results were negative for all three indicator strains TA-1530, G-46 and Saccharomyces cerevisiae D3 in both, the acute and subacute, experiments. The positive control groups, employed only during the acute studies, were functional (Litton Bionetics, Inc. 1974). Adipic acid was not mutagenic in in vivo cytogenetic studies where groups of five rats were dosed with adipic acid doses up to 5000 mg/kg bw (acute studies) and with doses up to 2500 mg/kg bw/day (five-days subacute studies). 200 to 500 metaphase chromosomes per dose were scored for chromatid gaps and breaks, chromosome gaps and breaks, reunions, cells with greater than ten aberrations, polyploidy, pulverization, and other chromosomal aberrations. The mitotic indices for all dose groups were considered to be within the normal limits of the controls and there was no evidence of chromosomal damage. The positive control groups, performed only during the acute studies, were functional (Litton Bionetics, Inc. 1974). Adipic acid was administered to groups of 10 male rats in a dominant lethal assay. Each treated male rat was mated with two virgin female rats each week for seven (subacute study) or eight (acute study) weeks. Two weeks after mating, female rats were sacrificed and the fertility index, preimplantation loss and lethal effects on the embryos were determined and compared with those same parameters calculated from control animals. In an acute study (3.75, 37.5 and 375 mg/kg bw) a decrease in average implantations at week 1 and 4, and corpora lutea at week 4 and 7 were seen only in the intermediate dose level. Increase in preimplantation losses were shown at week 1 for both the low and intermediate dose groups with no changes at any other week and parameter. In a five days subacute study with the same doses significant differences between the negative control and experimental groups were shown in a few instances, but no clear indications of change were seen. In a second test (acute single dose of 5000 mg/kg bw and subacute five doses of 2500 mg/kg bw/day) the values from those animals dosed with adipic acid did not significantly vary from those obtained from the negative control. Positive control groups, performed during the acute studies, gave the expected results. In summary, adipic acid does not induce dominant lethal mutations in doses up to 5000 mg/kg bw (Litton Bionetics, Inc. 1974)."

Updated relevant information:

None

Short description of key information:

Cyclohexane, oxidized, aquous extract (COP Acid) and its primary component, adipic acid, have been tested in different in vitro and in vivo tests and revealed no mutagenic or clastogenic activity.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Cyclohexane, oxidized, aquous extract (COP Acid) does not warrant classification as a mutagen based on negative results observed in all in vitro and in vivo gene mutation and micronucleus assays.