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Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Genotoxicity studies of isobutanol were used as read-across for isobutyl-R-lactate. Isobutanol was tested negative in three in vitro tests similar to OECD 471, OECD 476 and OECD 487. Moreover, lactic acid, as the second primary metabolite of isobutyl-R-lactate, was also tested negative in three GLP studies according to OECD guidelines 471, 473 and 476. These findings are supported by the negative results for the lactate esters ethyl-L-lactate and 2-ethylhexyl-L-lactate in bacterial reverse mutation tests as mentioned in the review article of Clary et al. (1998).

Link to relevant study records
in vitro gene mutation study in mammalian cells
Type of genotoxicity: gene mutation
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Publication, results are based on the read-across partner 2-Methyl-1-propanol (isobutanol).
equivalent or similar to guideline
OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
no positive control in the experiment with metabolic activation reported
GLP compliance:
Type of assay:
mammalian cell gene mutation assay
Target gene:
Species / strain / cell type:
Chinese hamster lung fibroblasts (V79)
Details on mammalian cell type (if applicable):
- Type and identity of media:
without metabolic activation: MEM Eagle medium with 10% fetal calf serum, 2mM L-glutamine, 100 IU/mL penicillin and streptomycin
with metabolic activation: above mentioned medium plus 3% S9-mix
Additional strain / cell type characteristics:
not applicable
Metabolic activation:
with and without
Metabolic activation system:
S9 mix
Test concentrations with justification for top dose:
only the highest non-toxic concentration tested is reported: 107 mM
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: medium
Untreated negative controls:
Negative solvent / vehicle controls:
True negative controls:
Positive controls:
Positive control substance:
final concentration: 0.5 mM
Details on test system and experimental conditions:
in medium

- Preincubation period: 24h
- Exposure duration: 2h
- Expression time (cells in growth medium): 7 days
- Selection time (if incubation with a selection agent): 7 days
- Fixation time (start of exposure up to fixation or harvest of cells): 14 days

SELECTION AGENT (mutation assays): 6-thioguanine (10 µg/mL)

- Method: cloning efficiency
Evaluation criteria:
The test compound was classified as a mutagen when it was able to enhance in a concentration-depended manner the spontaneous HPRT frequency by a factor of three or more.
Species / strain:
Chinese hamster lung fibroblasts (V79)
Metabolic activation:
with and without
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
not applicable
Untreated negative controls validity:
Positive controls validity:
Remarks on result:
other: all strains/cell types tested
Migrated from field 'Test system'.

Table 1: Mutant frequency for HPRT gene in V79 cells

Substance Highest non toxic concentration tested (mM) Mutant frequency (x 106)
without S9 with S9
Negative Control 0 0 - 2.8 0 - 3.1
MMS (Positive control) 0.5 92 -
2-Methyl-1-propanol 107 0 1.3
Interpretation of results (migrated information):
negative with metabolic activation
negative without metabolic activation

In conclusion, in the described in vitro cell gene mutagenicity test under the experimental conditions reported, the test item 2-Methyl-1-propanol is considered to be non-mutagenic in the HPRT locus using V79 cells of the Chinese Hamster.
Executive summary:

In a mammalian cell HPRT gene mutation assay similar to OECD guideline 476, V79 cells cultured in vitro were exposed to 2-Methyl-1-propanol in medium. The highest non toxic concentration reported and tested was 107 mM in the presence and absence of mammalian metabolic activation. No increase in mutant frequency was observed after treatment with 2-Methyl-1-propanol in comparison to the untreated control. The positive control did induce the appropriate response. 2-Methyl-1-propanol (isobutanol) is used as read-across partner to isobutyl-R-lactate.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vitro

Due to the rapid, enzymatically catalysed, hydrolysis of isobutyl-R-lactate into isobutanol and lactic acid, the toxicology of isobutyl-R-lactate can be understood in terms of the toxicology of isobutanol and lactic acid. Lactic acid is an ubiquitous and integral element of mammalian metabolism and therefore of minor toxicological relevance in comparison to isobutanol which is, as an alcohol, more important for the toxicological assessment. As no data was available for isobutyl-R-lactate, genotoxicity studies on isobutanol and lactic acid were used for read-across. Both read-across partners were tested as not genotoxic. Isobutanol was tested negative in three in vitro tests similar to OECD 471, OECD 476 and OECD 487. Moreover, lactic acid showed no genotoxic effects in three GLP studies according to OECD 471, OECD 473 and OECD 476. These findings were supported by the negative results for the two lactate esters ethyl-L-lactate and 2-ethylhexyl-L-lactate in bacterial reverse mutation tests as mentioned in the review article of Clary et al. (1998).

Based on the available data on the read-across partners, isobutyl-R-lactate is considered to be non-genotoxic.

Justification for selection of genetic toxicity endpoint

In vitro cell gene mutation assay (HPRT), conducted similar to OECD guideline 476 on the primary metabolite isobutanol. Isobutyl-R-lactate undergoes a rapid enzymatically catalysed hydrolysis resulting in isobutanol and lactic acid. Thus, lactic acid and isobutanol are suitable read-across partners.

Justification for classification or non-classification

Genotoxicity of the read-across partners were assessed in a standard in vitro testing battery. The substances showed no genotoxic effects in the specific tests. Therefore, based on the available data no classification of isobutyl-R-lactate is warranted.