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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro cytogenicity / chromosome aberration study in mammalian cells
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2006 - 2007
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation

Data source

Reference
Reference Type:
other:
Title:
Unnamed
Year:
2007
Report date:
2007

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
Deviations:
not specified
GLP compliance:
not specified
Type of assay:
in vitro mammalian chromosome aberration test

Test material

Constituent 1
Chemical structure
Reference substance name:
Trimethyl benzene-1,2,4-tricarboxylate
EC Number:
219-547-3
EC Name:
Trimethyl benzene-1,2,4-tricarboxylate
Cas Number:
2459-10-1
Molecular formula:
C12H12O6
IUPAC Name:
1,2,4-trimethyl benzene-1,2,4-tricarboxylate
Test material form:
solid

Method

Species / strain
Species / strain / cell type:
Chinese hamster Ovary (CHO)
Metabolic activation:
with and without
Metabolic activation system:
Aroclor induced rat liver S9
Test concentrations with justification for top dose:
5 - 2522 micrograms/mL
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: DMSO
Controls
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no

Results and discussion

Test results
Species / strain:
Chinese hamster Ovary (CHO)
Metabolic activation:
with and without
Genotoxicity:
positive
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
valid

Any other information on results incl. tables

The highest concentrations chosen for the chromosome aberration assay were 1000 micrograms/mL for the 4 -hour exposure assay without a metabolic activation system, 2522 micrograms/mL

for the 4 hour exposure period with a metabolic activation system and 750 micrograms/mL for the 20 hour exposure period without a metabolic activation system.

A visible precipitate was observed at the beginning and end of the treatment periods at concentrations of 1000 micrograms/mL and greater.

Substantial toxicity (greater than a 50% reduction in cell growth relative to the vehicle control) was observed at the highest concentration in each test condition. The selection of doses for analysis was based on these dose concentration levels as well as precipitation. Cytogenetic evaluations were conducted at 500, 750 and 1000 microgramsg/mL for the 4 hour exposure period both with and without metabolic activation and at 100, 250 and 500 micrograms/mL for the 20 hour exposure period without metabolic activation.

The percentage of cells with structural aberrations following 4 hours exposure with metabolic activation was significantly increased above that of the vehicle control at 500, 750 and 1000 micrograms/mL. The percentage of cells with structural aberrations following 20 hours exposure without metabolic activation was also significantly increased above that of the vehicle control at 500 micrograms/mL. The observed changes were outside of the historical control range for structural aberrations, were accompanied by a concentration-related increase, and were therefore considered biologically significant. The percentage of cells with numerical aberrations following 4 hours exposure without metabolic activation showed a significant trend as compared to the vehicle control at 750 and 1000 micrograms/mL. The percentage of cells with numerical aberrations following 4 hours exposure with metabolic activation was also significantly increased above that of the vehicle control at 500, 750 and 1000 micrograms/mL. The observed changes were outside of the historical control range for numerical aberrations, and were therefore considered biologically significant.

Applicant's summary and conclusion

Conclusions:
A cytogenetic assay was positive for the induction of chromosome aberrations in Chinese hamster ovary cells.
Executive summary:

A cytogenetic assay in Chinese hamster ovary cells resulted in positive findings for the induction of chromosome aberrations.