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In the keybacterial reverse mutation assay (equivalent toOECD guideline 471),SBA was tested in a non-GLP study at doses of 100, 500, 1,000, 5,000, or 10,000 µg/plateinSalmonella typhimuriumstrains TA 98, TA 100, TA 1535, TA 1537, and TA 1538 both in the absence and presence of exogenous metabolic activation (Aroclor 1254-induced rat liver S9) (Bichet, 1989).  The plates were incubated in duplicate and an independent repeat experiment was performed. Dimethyl sulfoxide (DMSO) was used as the vehicle and positive controls were included in all incubations. No cytotoxicity was observed and noincrease in the reverse mutation rate was noted at any SBA concentration either in the absence or presence of metabolic activation. Incubation with positive control substances in the absence or presence of metabolic activation resulted in anticipated increases inreverse mutation rates.

Negative results also were seen in a supportive GLP compliant bacterial reverse mutation assay conducted inS. typhimuriumstrains TA 98, TA 100, TA 1535, TA 1537, and TA 1538 as well asEscherichia colistrain WP2 uvr A pKM 101 both in the absence as well as the presence of exogenous metabolic activation (Aroclor 1254-induced rat liver S9) (Meyer, 1986).

In a GLP compliant mammalian chromosome aberration test (equivalent to OECD guideline 473), SBA was tested at doses of 0, 1,250, 2,500, or 5,000 µg/mL in Chinese Hamster Ovary (CHO) cells in the absence and presence of exogenous metabolic activation (Aroclor 1254-induced rat liver S9) (Meyer, 1986).  Incubations at each concentration were done in triplicate; however, an independent repeat experiment was not performed.  DMSO was used as the vehicle and ethyl methanesulphonate and cyclophosphamide were used as the positive control compounds in the absence and presence of metabolic activation, respectively. No cytotoxicity was observed and no chromosome damage was noted at any SBA concentration.  Incubations with the positive control compound resulted in anticipated increases in chromatid damage.

In a GLP compliant yeast gene mutation assay (equivalent to OECD guideline 480), SBA was tested at doses of 0, 0.01, 0.1, 0.5, 1.0, or 5.0 mg/mL inSaccharomyces cerevisiaeboth in the presence and absence of exogenous metabolic activation (Aroclor 1254-induced rat liver S9) (Meyer, 1986).  Incubations at each concentration were done in triplicate and an independent repeat experiment was performed. DMSO was used as the vehicle and 4-nitroquinoline-N-oxide and cyclophosphamide were used as the positive control compounds in the absence and presence of metabolic activation, respectively. No cytotoxicity was observed and no increase in the rate of mitotic gene conversion was noted at any SBA concentration in the absence or presence 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.

Metabolic data demonstrate that s-butanol is rapidly and extensively converted to methyl ethyl ketone via oxidation of the alcohol functional group by alcohol dehydrogenase in the liver. Thus, methyl ethyl ketone may be used as an appropriate surrogate for s-butanol and vice versa considering that exposure to either substance would essentially result in exposure to methyl ethyl ketone. In a non-GLPmammalian gene mutation assay (equivalent toOECD guideline 476), the read-across substance MEK was tested at doses of 0, 0.89, 1.2, 1.6, 2.1, 2.8, 3.8, 5.0, 6.7, 8.9, 12.0, 16, or 21 µL/mL in theabsence of exogenous metabolic activation (Aroclor-induced rat liver S9)and at doses of 0, 0.67, 0.89, 1.2, 1.6, 2.1, 2.8, 3.8, 5.0, 6.7, 8.9, 12, or 16 µL/mLin the presence of exogenous metabolic activation in mouse lymphoma L5178Y cells (Rogers-Back, 1984).  The experiment was conducted in triplicate; however, an independent repeat experiment was not performed. DMSO was used as the vehicle and ethyl methanesulfonate and 7,12-dimethylbenz[a]anthracene 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 MEK concentration in the absence or presence of metabolic activation. Incubation with positive control substances in the absence or presence of metabolic activation resulted in anticipated increases inthe mutation frequencies.

In a non-GLP micronucleus assay (equivalent to OECD guideline 474), the read-across substance MEK was administeredviaintraperitoneal (IP) injection to male and female CD-1 mice at a dose of 1.96 mL/kg body weight (Putman, 1984).  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). Test article-treated mice appeared heavily sedated immediately following dose administration; however, no animals died and no other clinical signs of toxicity were observed. No statistically significant increases in the number of micronucleated polychromatic erythrocytes were noted at any time point. The positive control compound produced anticipated increases in the number of micronucleated polychromatic erythrocytes. The use of only 1 dose level instead of the recommended 3 rendered this study reliable with restrictions.


Short description of key information:
The genetic toxicity of s-butanol (SBA) has been assessed in 4 in vitro studies, including 2 bacterial reverse mutation assays and a mammalian chromosome aberration test. Additionally, a non-GLP mammalian gene mutation assay and a non-GLP in vivo micronucleus assay have been performed with the read-across substance, methyl ethyl ketone (MEK). Negative results were reported in all the studies.

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.