Terephthaloyl dichloride

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

The test substance was concluded to be negative in Salmonella typhimurium strains TA98, TA100, TA1535, and TA1537. No indications of mutagenicity were observed at any dose level in any tester strain when tested up to 10000 μg/plate in the absence or presence of S9. The assay was conducted prior to the 1997 adaptation of the current OECD 471, and did not include an E.coli WP2 or S. typhimurium TA102 tester strain. These strains are known to specifically detect certain oxidising mutagens, cross-linking agents and hydrazines that other Salmonella tester strains may not be sensitive to. However, based on the physico-chemical characteristics of the test substance, the inclusion of a fifth tester strain would not have changed the clearly negative outcome of the Ames assay. In addition, there was no indication of in vitro or in vivo mutagenicity for any other genetic toxicology endpoint.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1979

Report date:

1979

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

Tested up to 10000 µg/plate with and without S9 metabolic activation in 4 Salmonella strains.

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Terephthalic acid

EC Number:

202-830-0

EC Name:

Terephthalic acid

Cas Number:

100-21-0

Molecular formula:

C8H6O4

IUPAC Name:

Terephthalic acid

Details on test material:

- Purity: 99.99%

Method

Species / strain

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Metabolic activation:

with and without

Metabolic activation system:

Aroclor 1254-induced rat liver homogenate (S9)

Test concentrations with justification for top dose:

0, 500, 1000, 2500, 5000, 10000 µg/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: Not reported

Controls

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: N-methyl-N'-nitro-N-nitrosoguanidine (TA1535 -S9 and TA100 -S9); 9-aminoacridine (TA1537 -S9); 2-nitrofluorene (TA98 -S9); 2-aminoanthracene (all strains +S9)

Details on test system and experimental conditions:

METHOD OF APPLICATION: Treatment without activation was conducted by adding 0.1 mL of overnight culture containing the test sample and 1e8 bacteria to top agar supplemented with L-histidine, NaCl, and biotin. The components were mixed and poured onto a plate containing Davis minimal agar. Treatments with activation were conducted as those without activation except that S9 mix was added to the bacteria/top agar mixture before it was poured onto a Davis minimal agar plate. The plates were incubated at approximately 37°C for approximately 48 hours.

DURATION
- Exposure duration: 48 hours

NUMBER OF REPLICATIONS: 2 trials for all strains, except TA1537 which had 3 trials when tested with activation

DETERMINATION OF CYTOTOXICITY
- Method: Cytotoxicity of the test sample in the presence and absence of an activation system, as measured in strain TA1535, was the same as the method of application for mutagenesis except that 10e3 rather than 10e8 bacteria were used per plate and a non-limiting concentration of histidine was present.

Evaluation criteria:

A chemical is classified as nonmutagenic if the reversion frequency is less than two times the spontaneous frequency, and if less than 0.02 revertants/nmole are observed.

Statistics:

Data from replicate plates within a single experiments are averaged. The highest average number of revertants that is obtained is expressed as a multiple of the control value for the sensitive strain(s). When a test sample is active, the average numbers of revertants observed before activity plateaus or decreases at the various concentrations tested are submitted to linear regression analysis. The slope of the line thus obtained is used to determine the number of revertants/nmole or µg of test sample.

Results and discussion

Test results

Species / strain:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Remarks:

The hint of activity observed in strain TA1537 in Trial 2 in the presence of activation was not observed in other trials.

Cytotoxicity / choice of top concentrations:

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

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Applicant's summary and conclusion

Conclusions:

The test substance was not mutagenic in an Ames assay with Salmonella typhimurium strains TA 1535, TA 1537, TA 98 and TA 100, in the presence and absence of an exogenous activation system.

Executive summary:

The test substance was evaluated for mutagenicity in Salmonella typhimurium strains TA100, TA1535, TA98, and TA100 with and without an exogenous metabolic activation system (S9). The maximum concentration tested was 10000 µg/plate. The hint of activity observed in strain TA1537 in Trial 2 in the presence of activation was not observed in other trials. In this study, the test substance was negative.