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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2002-03-29 to 2002-05-13
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002
Report date:
2002

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
no
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay

Test material

Constituent 1
Chemical structure
Reference substance name:
2-butyloctanoic acid
EC Number:
248-570-1
EC Name:
2-butyloctanoic acid
Cas Number:
27610-92-0
Molecular formula:
C12H24O2
IUPAC Name:
2-butyloctanoic acid
Test material form:
liquid
Details on test material:
- Name of test material: 2-butyl octanoic acid
- Molecular formula: C12H24O2
- Molecular weight: 200.32 g/mole
- Smiles notation: O=C(O)C(CCCCCC)CCCC

Method

Details on test system and experimental conditions:
SYSTEM OF TESTING
- Species/cell type: Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102
- Deficiencies/Proficiencies: histidine auxotroph
- Metabolic activation system: rat liver S9 of Phenobarbital/beta-Naphthoflavone induced male Sprague-Dawley rats
ADMINISTRATION:
- Dosing:
experiment I:
313, 625, 1250, 2500 and 5000 µg/plate (TA 1535, TA 98 and TA 1537 only with metabolic activation)78.1, 156, 313, 625, 1250, 2500 µg/plate (TA 102, TA 100 and TA1537 only without metabolic activation)
experiment II:
156, 313, 625, 1250, 2500 and 5000 µg/plate (TA 1535 and TA 1537 only with metabolic activation)
78.1, 156, 313, 625, 1250, 2500 µg/plate (TA 100 and TA1537 only without metabolic activation)
313, 625, 1250, 2500 and 5000 µg/plate (TA 98)
78.1, 156, 313, 625, 1250 µg/plate (TA 102)
experiment III:
9.77, 19.5, 39.1, 78.1, 156 µg/plate (TA 1535, TA 100 and TA 1537 only with metabolic activation)
4.88, 9.77, 19.5, 39.1, 78.1 µg/plate (Ta 102 and TA 1537 only without metabolic activation)
19.5, 39.1, 78.1, 156, 313 µg/plate (TA 98)
- Number of replicates: 3
- Application:
Experiment I (plate-incorporation method): Bacteria cultures, test item, S9 mix or phosphate buffer were added to the molten overlay agar and vortexed. The mixture was poured onto the surface of a medium agar plate and allowed to solidify prior to incubation. Plates were incubated upside down for approx. 72 hours at 37° C.
Experiment II and III (pre-incubation method): Bacteria cultures, test item, S9 mix or phosphate buffer were mixed and placed at 37° C for 30 minutes. Afterwards overlay agar was added and the mixture was vortexed and poured onto the surface of a medium agar plate and allowed to solidify. Plates were incubated upside down for approx. 72 hours at 37° C.
- Positive control: without metabolic activation: Sodium azide (1 µg/plate with TA 1535 and TA 100), 9-aminoacridine (50 µg/plate with TA 1537), 2-nitrofluorene (2 µl/plate with TA 98), cumene hydroperoxide (100 µg/plate with TA 102); with metabolic activation: with metabolic activation: 2-aminoanthacene (1 µg/plate with TA 1535, Ta 1537, TA 98 and TA 100; 10 µg/plate with TA 102)
- Negative control: solvent control (DMSO) and untreated control
- Pre-incubation time: 30 minutes (only in experiment II and III)
DESCRIPTION OF FOLLOW UP REPEAT STUDY: see above
Evaluation criteria:
The test item is considered as a mutagen if at least a two-fold increases in mean revertant numbers are observed at two consecutive dose-levels or at the highest practicable dose level only. In addition there must be evidence of a dose-response relationship showing increasing numbers of mutant colonies with increasing dose-levels.

Results and discussion

Test resultsopen allclose all
Key result
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
toxicity was observed at higher dose-levels with all tester strains, both in the absence and presence of S9 metabolic activation, with the exception of TA98
Vehicle controls validity:
valid
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 102
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
toxicity was observed at higher dose-levels, both in the absence and presence of S9 metabolic activation
Vehicle controls validity:
valid
Positive controls validity:
valid

Applicant's summary and conclusion

Conclusions:
Interpretation of results:
negative

The test item ISOCARB 12 does not induce reverse mutation in Salmonella typhimurium under the reported experimental conditions.