Dimethyl terephthalate

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Published study, conducted for the National Toxicology Program

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

publication

Title:

Evaluation of a Three-Exposure Mouse Bone Marrow Micronucleus Protocol: Results with 49 Chemicals

Author:

Shelby MD, Erexson GL, Hook GJ & Tice RR

Year:

1993

Bibliographic source:

Environmental and Molecular Mutagenesis, 21, 160-179 (1993)

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: NTP protocol

GLP compliance:

no

Remarks:

: published literature study

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

Dimethyl terephthalate

EC Number:

204-411-8

EC Name:

Dimethyl terephthalate

Cas Number:

120-61-6

Molecular formula:

C10H10O4

IUPAC Name:

dimethyl terephthalate

Details on test material:

The test chemical was received from the NTP chemical repository (Radian Corporation, Austin).

Test animals

Species:

mouse

Strain:

B6C3F1

Sex:

male

Details on test animals or test system and environmental conditions:

Male B6C3F1 mice obtained from the National Toxicology Program production facility at Taconic Farms of a common age between 9 and 14 weeks and weighing between 25 and 33 g were used (within a 2 g range of the mean)

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

Each chemical was prepared in the appopriate solvent (PBS for water soluble chemicals, corn oil for water insoluble chemicals). All test chemicals were administered within 30 min of preparation.

Details on exposure:

The test substance was administered by intraperitoneal injection at a volume of 0.4 ml per mouse. Three consecutive daily injections were carried out per mouse.

Duration of treatment / exposure:

The test chemical was administered by IP injection on three consecutive days.

Frequency of treatment:

The test chemical was administered by IP injection on three consecutive days.

Post exposure period:

The animals were monitored twice daily and 24 hours after the third treatment (48 h in preliminary experiments).

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 438, 875 and 1750 mg/kg bw
Basis:
other: actual administered dose

No. of animals per sex per dose:

In the preliminary dose determination studies, 5 mice per group were used.
Groups of 5 to 6 male mice were used per dose in the micronucleus (MN) initial test.

Control animals:

yes, concurrent vehicle

Positive control(s):

DMBA in corn oil was used as the positive control

Examinations

Tissues and cell types examined:

Bone marrow

Details of tissue and slide preparation:

24 h after the third treatment, surviving mice were euthanised by CO2 asphyxiation.
Bone marrow smears (two slides mouse) were prepared, fixed in absolute methanol and stained with acridine orange.

Evaluation criteria:

Bone marrow smears from each animal were evaluated at 1000x magnification using epi-illuminated fluorescence microscopy (450-490 nm excitation, 520 nm emission) for determination of the percentage of PCE among 200 erythrocytes.

Statistics:

The data were analysed using the Micronucleus Assay Data Management and Statistical software package. To determine whether a specific tretament resulted in a significant increase in MN-PCE, the number of MN-PCE were pooled within each dose group and analysed by a one tailed trend test.

Results and discussion

Test results

Sex:

male

Genotoxicity:

negative

Toxicity:

no effects

Vehicle controls validity:

valid

Negative controls validity:

not examined

Positive controls validity:

valid

Additional information on results:

The initial result was negative to 1750 mg/kg bw and was therefore the test was not repeated. There were no mortalities at any dose.

Any other information on results incl. tables

The result of this study contrasts with the positive findinings reported by Goncharova et al (1988), in which dimethyl terephthalate was reported to induce micronuclei in the bone marrow cells of male mice following single intraperitoneal injections of doses ranging from 0.2 to 1.0 mmol/kg (approximately 33 to 166 mg/kg bw). It is notable that DMSO was used as the solvent in that study, which may have contributed to the difference in results between these two studies.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative
DMT did not induce micronuclei in the bone marrow of male mice following three intraperitoneal injections up to a dose of 1750 mg/kg bw.

Executive summary:

Dimethyl terephthalate was tested in the mouse bone marrow micronucleus assay, for the US National Toxicology Program. The test substance was administered in three daily exposures by intraperitoneal injection, at doses of 0, 438, 875 and 1750 mg/kg bw. Bone marrow samples were obtained 24 h following the final exposure. DMT did not induce micronuclei in the bone marrow of male mice following three intraperitoneal injections at up to and including a dose of 1750 mg/kg. Administration of DMT did not result in any mortality.