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EC number: 203-550-1 | CAS number: 108-10-1
- Life Cycle description
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- Endpoint summary
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- Ecotoxicological Summary
- Aquatic toxicity
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- Short-term toxicity to fish
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- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
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- Endocrine disrupter testing in aquatic vertebrates – in vivo
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- Toxicological Summary
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- Acute Toxicity
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- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
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- Specific investigations
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- Additional toxicological data

Endpoint summary
Administrative data
Key value for chemical safety assessment
Additional information
In vitro assay
In the key bacterial reverse mutation assay (equivalent to OECD guideline 471), MIBK was tested in a GLP study at doses of 0, 0.04, 0.1, 0.4, 1.0, or 4.0 µL/plate in Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537, and TA 1538 both in the presence and absence of exogenous metabolic activation (Aroclor 1254-induced rat liver S9) (Haworth, 1984; O'Donoghue et al., 1988). The experiment was conducted in triplicate; however, an independent repeat experiment was not performed. Dimethyl sulfoxide (DMSO) was used as the vehicle and positive controls were included in all incubations. No cytotoxicity was observed and no increase in the reverse mutation rate was observed at any MIBK concentration either in the presence or absence of metabolic activation. Incubation with positive control substances in the presence or absence of metabolic activation resulted in anticipated increases in reverse mutation rates.
In a supportive non-GLP bacterial reverse mutation assay (equivalent to OECD guideline 471), MIBK was tested at doses of 0, 31.25, 62.5, 125, 250, 500, 1,000, 2,000, or 4,000µg/plate in S. typhimurium strains TA 98, TA 100, TA 1535, TA 1537, and TA 1538 and in Escherichia coli strains WP2 and WP2 uvr A both in the presence and absence of exogenous metabolic activation (Aroclor 1254-induced rat liver S9) (Thorpe, 1982; Brooks et al., 1988). Incubations at each concentration were done in triplicate and an independent repeat experiment was performed. DMSO was used as the vehicle and positive controls were included in all incubations. No cytotoxicity and no increase in the reverse mutation rate were observed at any MIBK concentration in any of the tester strains either in the presence or absence of metabolic activation. Incubation with positive control substances either in the presence or absence of metabolic activation did not always result in anticipated increases in the reverse mutation rate. This study is therefore considered reliable with restrictions.
In a non-GLP mammalian chromosome aberration test (equivalent to OECD guideline 473), MIBK was tested at doses of 0, 250, 500, or 1000 µg/mL in rat liver (RL4) cells in the absence of exogenous metabolic activation (Thorpe, 1982; Brooks et al., 1988). Incubations at each concentration were done in triplicate; however, an independent repeat experiment was not performed. 7,12-Dimethylbenzanthracene was used as the positive control compound; however, the use of a vehicle control was not reported. No cytotoxicity was observed and no chromosome damage was noted at any MIBK concentration. Incubations with the positive control compound resulted in anticipated increases in chromatid damage.
In a GLP mammalian gene mutation assay (equivalent toOECD guideline 476), MIBK was tested at doses of 0, 0.6, 1.4, 2.1, 2.9, or 3.7 µL/mL in the absence of exogenous metabolic activation (Aroclor 1254-induced rat liver S9) and at doses of 0, 1.4, 1.9, 2.5, 3.0, or 3.4 µL/mL in the presence of exogenous metabolic activation in mouse lymphoma L5178Y cells (Rogers-Back, 1984; O'Donoghue et al., 1988). The experiment was conducted in duplicate; however, an independent repeat experiment was not performed. DMSO was used as the vehicle and ethylmethanesulfonate and 7,12-dimethylbenzanthracene were used as the positive control compounds in the absence and presence of metabolic activation, respectively. No cytotoxicity and no increase in the mutant frequency were observed at any MIBK concentration in the presence of metabolic activation. Cytotoxicity and equivocal genotoxicity (defined as a two-fold increase in the mutation frequency over solvent control levels at one or more dose levels but the absence of a dose-response) were noted at 3.7 µL/mL (the highest concentration tested) in the absence of metabolic activation. Incubation with positive control substances in the presence or absence of metabolic activation resulted in anticipated increases in the mutation frequencies.
In a GLP unscheduled DNA synthesis assay (equivalent to OECD guideline 482), MIBK was tested at doses of 0, 0.010, 0.10, 1.0, 10.0, or 100 µL/mL in primary rat liver cells (Curren, 1984; O'Donoghue et al., 1988). Incubations at each concentration were done in triplicate; however, an independent repeat experiment was not performed. DMSO was used as the vehicle and 2-acetylaminofluorene was used as the positive control compound. No cytotoxicity was noted and no increases in the average nuclear grain count were observed at any MIBK concentration. Incubation with the positive control substance resulted in an anticipated increase in the average nuclear grain count.
In a non-GLP yeast gene mutation assay (equivalent to OECD guideline 480), MIBK was tested at doses of 0, 10, 100, 500, 1,000, or 5,000 µg/mL in Saccharomyces cerevisiae both in the presence and absence of exogenous metabolic activation (Aroclor 1254-induced rat liver S9) (Thorpe, 1982; Brooks et al., 1988). Incubations at each concentration were done in quadruplicate and an independent repeat experiment was performed. 4-Nitroquinoline-N-oxide and cyclophosphamide were used as the positive control compounds in the absence and presence of metabolic activation, respectively; however, the use of a vehicle control was not reported. No cytotoxicity was observed and no increase in the rate of mitotic gene conversion was noted at any MIBK concentration in the presence or absence of metabolic activation. Incubation with the positive control substances resulted in anticipated increases in the rate of mitotic gene conversion. As the post-treatment incubation period was 3 days as opposed to the recommended 4 to 7 days, this study is considered reliable with restrictions.
In vivo assay
In a GLP micronucleus assay (equivalent to OECD guideline 474), MIBK was administered via intraperitoneal (IP) injection to male and female CD-1 mice at a dose of 0.73 mL/kg body weight (Putman, 1984; O'Donoghue et al., 1988). Corn oil was used as the vehicle and triethylenemelamine was administeredviathe IP route as the positive control compound. Mice were sacrificed at 12, 24, or 48 hours following injection of test article or control (5 mice/sex/time point). Two male mice and 4 female mice died following test article administration and animals receiving MIBK appeared heavily sedated. No other clinical signs of toxicity were observed and no statistically significant increases in the number of micronucleated polychromatic erythrocytes were noted at any time point. Injection of the positive control caused the anticipated increase in micronucleated polychromatic erythrocytes. The use of only 1 dose level instead of the recommended 3 rendered this study reliable with restrictions.
Justification for selection of genetic toxicity endpoint
A battery of genotoxicity assays yielded mostly negative responses
Short description of key information:
A battery of genotoxicity assays published in O’Donoghue et al. (1988) yielded mostly negative responses. MIBK did not induce revertant point mutations in five Salmonella tester strains (TA98, TA100, TA1535, TA1537, and TA1538), either in the presence or absence of Aroclor 1254-induced rat liver microsomal enzymatic activation. Mutant frequencies were also not affected in the L5178Y TK+/- mouse lymphoma mutagenesis assay in the presence of Aroclor-induced rat liver S-9. No dose-response relationship was observed in cultures exposed to MIBK in the absence of exogenous metabolic activation, although mutation frequency was significantly elevated in three out of six of the MIBK-treated cultures in the absence of S-9 metabolic activation. MIBK was also negative in the unscheduled DNA synthesis assay in rat primary hepatocytes and in the micronucleus cytogenetic assay in mice administered MIBK intraperitoneally at 0.73 mL/kg (the dose level selected as the LD20 on the basis of a preliminary toxicity study). The following additional set of genotoxicity assays also yielded negative results: reverse mutation assays in five strains of Salmonella typhimurium and three strains of Escherichia coli in both the presence and absence of exogenous metabolic activation and a structural chromosome damage assay in cultured rat liver cells (Brooks et al., 1988).
Endpoint Conclusion: No adverse effect observed (negative)
Justification for classification or non-classification
The substance does not meet the criteria for classification and labelling for this endpoint, as set out in Regulation (EC) NO. 1272/2008.
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