Tributyl O-acetylcitrate

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Study period:

21.01.2001-26.02.2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 472 (Genetic Toxicology: Escherichia coli, Reverse Mutation Assay)

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Details on test material:

Purity: 98.8%

Method

Target gene:

his-operon

Species / strain

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2

Metabolic activation:

with and without

Metabolic activation system:

Phenobarbital and 5,6-benzoflavone induced rat liver S9

Test concentrations with justification for top dose:

-S9: 0, 156.3, 312.5, 625, 1250, 2500, 5000 µg/plate (five strains)
+S9: 0, 156.3, 312.5, 625, 1250, 2500, 5000 µ/g/plate (five strains)

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: Choice based on information from sponsor

Controls

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: -S9 mix: 2-(2-furyl)-3-(5-nitro-2-furyl) acrylamide (TAlOO, TA98, WP2uvrA), sodium azide (TA1535) and 9-aminoacridine(TA1537) +S9 mix: 2-arninoanthracene (five strains).

Details on test system and experimental conditions:

Test Design:
Procedure
(1) Plate incorporation test with and without S9 using five strains
(2) Pre-incubation test with and without S9 using five strains
Number of replicates: 2
Plates/dose: 3

Rationale for test conditions:

A confirmation test was carried out in pre-incubation method as negative mutagenic effect (-) was noted in plate incorporation test.

Evaluation criteria:

The test substance was judged positive ( +) when the number of revertant colonies in the test substance treated plates increased dose dependently and became two-fold or more compared to that of the negative control and this effect was reasonably reproducible or significant reproducible increase was noted at one or more concentrations at least in one strain with or without metabolic activation system and negative (-) when any of the above criteria were not fulfilled.

Statistics:

No statistical method was followed.

Results and discussion

Test results

Key result

Species / strain:

bacteria, other: Salmonella typhimurium TAlOO, TA1535, TA98, TA1537 Escherichia coli Wp2uvrA

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Applicant's summary and conclusion

Conclusions:

ATBC has been tested according OECD TG 471 and 472 in compliance with GLP. Under conditions of the test, no mutagenic effect was observed for ATBC tested up to cytotoxic concentration in any of the test strains (S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2) without and with metabolic activation. ATBC is non-mutagenic in test strains used.