Butyric anhydride

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptabel restrictions (only 4 strains of S. thyphimurium tested)

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

: only 4strains of S. thyphimurium tested

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Butyric acid

EC Number:

203-532-3

EC Name:

Butyric acid

Cas Number:

107-92-6

Molecular formula:

C4H8O2

IUPAC Name:

butanoic acid

Details on test material:

- Name of test material (as cited in study report): butyric acid
- no further information on test substance reported

Method

Target gene:

his

Species / strain

Species / strain / cell type:

S. typhimurium, other: TA97, TA 98, TA 100, TA1535

Metabolic activation:

with and without

Metabolic activation system:

S9 mix from livers of induced male Sprague Dawley rats and induced male Syrian hamsters (10% and 30% each)

Test concentrations with justification for top dose:

0, 100, 333, 1000, 3333, 10000 µg/plate, for TA 100 in addition 5000, 6667, and 7500 µg/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: water

Controls

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: without metabolic activation: 9-aminoacridine (TA97), sodium azide (TA 100, TA 1535), 2-nitrofluorene (TA 98); with metabolic activation: 2-aminoanthracene

Details on test system and experimental conditions:

METHOD OF APPLICATION: preincubation

DURATION
- Preincubation period: 20 min at 37°C
- Exposure duration: 2 days
- Expression time (cells in growth medium): 2 days at 37°C

DETERMINATION OF CYTOTOXICITY
- Method: no data

Evaluation criteria:

Number of mutant colonies of positive controls must be significantly increased over the spontaneous control numbers for the test to be considered valid.
Numbers of mutant colonies of test plates have to be significantly increased over the mutant colony numbers of negative control plates.

Statistics:

Mean and standard error of the mean of replicate plates were calculated

Results and discussion

Test results

Species / strain:

S. typhimurium, other: TA97, TA 98, TA 100, TA1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

observed at concentrations above 5000 µg/plate in some strains

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

Tables presenting the revertant counts for all tests are appended under attached background material.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative with and without metabolic activation

Butyric acid was not mutagenic in Salmonella typhimurium strains TA 97, TA 98, TA100 and TA1535 with and without metabolic activation.
According to OECD 471 butyric acid is not mutagenic to Salmonella typhimurium.

Executive summary:

In a reverse gene mutation assay in bacteria, strains of S. typhimurium (TA 97, TA 98, TA 100, and TA 1535) were exposed to butyric acid at concentrations of 0, 100, 333, 1000, 3333, and 10000 µg/plate in the presence and absence of mammalian metabolic activation (S9 mix from induced rabbit and rat liver) with 20 min preincubation before plating.

  

Butyric acid was tested up to the limit concentration of 10000 µg/plate. With the highest concentration cytotoxicity was observed. The positive controls induced the appropriate responses in the corresponding strains. Butyric acid did not increase the number of revertants in any of the test strains. There was no evidence of induced mutant colonies over background (NTP, 1991).

  

This study is classified as acceptable. It was performed according to OECD test guideline 471 with minor restrictions (only 4 strains of S. thyphimurium tested).