Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 204-411-8
CAS number: 120-61-6
Genetic toxicity in vitro
Assays for DNA damage
No evidence of DNA damage is provided by the results of
The potential of DMT to cause DNA strand breaks was
investigated in primary cultures of rat hepatocytes and in CHO cells in
the absence of exogenous metabolic activation. Concentrations of 3.75,
7.5 and 15 µmole/tube did not produce any evidence of strand breaks in
either cell type (Monarca et al, 1991). No evidence of DNA damage
(as assessed by UDS) was seen in two studies using cultured HeLa cells
(Lerda, 1996; Monarca et al, 1991).
No evidence of mutagenicity is reported in a number of
Ames tests performed with DMT.
The potential mutagenicity of DMT was investigated in Salmonella
typhimurium strains TA98, TA100, TA1535 and TA1537 using a
pre-incubation modification of the Ames test. Five concentrations of up
to 6666 ug/plate were used in the absence and presence of an exogenous
metabolic activation system (rat liver S9 fraction). Exposure to DMT did
not increase the number of revertant colonies; appropriate positive
control compounds confirmed the sensitivity of the assay (Zeiger et al,
1982). Monarca et al (1991) evaluated the mutagenic potential of
dimethyl terephthalate in a standard Ames test, with six Salmonella
typhimurium strains in the presence and absence of metabolic
activation. All the dose levels assayed (from 0.5 to 5000 µg/plate) were
negative in the Ames test, with all the strains, with or without
metabolic activation. Evidence of toxicity was observed at the highest
dose levels in TA98 (-S9) and TA1537 (+S9).
Lerda (1996) also studied dimethyl terephthalate
bacterial mutagenicity with five Salmonella typhimurium strains
by means of the Maron & Ames (1983) standard plate method. Dimethyl
terephthalate was not mutagenic in either the presence or absence of
metabolic activation, when tested up to a concentration of 5000 µg/plate.
An Ames test conducted (Anonymous, 1993d), was carried
out according to GLP and EU method B.14. The
test organisms were five Salmonella typhimurium strains (TA98,
TA100, TA1535, TA1537 and TA1538). The substance was found to be
insoluble in any of the prescribed Ames test solvents; therefore a
Spot-Test was conducted. A sterile micro-spatula was used to apply the
test substance to the top agar. There was no evidence of mutagenic
activity in any of the strains tested, with and without metabolic
Chromosomal aberration assays
No evidence of chromosomal effects is reported in a
number of studies investigating different endpoints.
Loveday et al (1990) tested dimethyl terephthalate
for its ability to induce chromosome aberrations and sister chromatid
exchanges in cultured Chinese hamster ovary (CHO) cells, with and
without exogenous metabolic activation (S9 mix). No induction of
chromosomal aberrations, sister chromatid exchanges, or cytotoxicity was
observed. The highest concentration of DMT tested in this study was 101
µg/ml. Lerda (1996) also found that dimethyl terephthalate was negative
in an in vitro mammalian cell micronucleus test with human blood
peripheral lymphocytes. There was no increase in the frequency of
micronuclei in lymphocytes treated with test substance concentrations of
0.5, 5, 50 and 500 µg/ml, compared to the solvent control.
Dimethyl terephthalate was also evaluated in a chromosome
aberration assay with human peripheral blood lymphocytes (Monarca et
al,1991). Blood was obtained from two healthy volunteers. Cells were
incubated with the test substance at concentrations of 0, 50, 100, 250
and 500 µg/ml, and mitotic activity was arrested with Colcemid. The
frequency of chromatid and chromosomal gaps (achromatic lesions) and
breaks was not significantly different from the controls. Only in the
positive control (bleomycin) were rings, dicentrics, acentric fragments
and double minutes present in addition to gaps and breaks. The mean
number of aberrations per cell was 1 for all the cell sample; it was >1
only in the positive control. It can therefore be concluded that DMT was
negative in the chromosome aberration assay in human peripheral
lymphocytes, under the conditions of this study. The same authors also
investigated micronucleus formation in human peripheral blood
lymphocytes exposed to 0, 50, 100, 250 and 500 µg/ml DMT. The difference
in frequency of micronuclei between the treated samples and controls was
not significantly different and it was concluded that DMT did not induce
micronuceli in human peripheral lymphocytes, under the conditions of
Mammalian Cell Assays
The potential mutagenicity of dimethyl terephthalate was
investigatied in a mouse lymphoma assay performed as part of the US NTP
testing propgramme (Myhr & Caspary, 1991). NTP was not mutagenic to
L5178Y cells and typically was not toxic with or without the addition of
S9 mix. No significant increases in mutant frequency were observed. Low
relative total growth values (as low as 27%) were observed randomly for
individual cultures without relationship to dose. Concentrations up to
100 µg/mL were tested with and without S9, although the solubility limit
in the culture medium was exceeded at 75 µg/mL.
Genetic toxicity in vivo
The mutagenic activity of dimethyl terephthalate was
evaluated in a micronucleus test in groups of male C57B1/6j x CBA)F1
mice (Goncharova et al, 1987). Mice were administered single
intraperitoneal injections of DMT (in DMSO) and femoral bone marrow
harvested at 24, 48 or 72 hours after administration. Positive control
animals were administered MNU. A number of deaths occurred in the
control and test groups. A clear clastogenic effect was apparent at all
concentrations of DMT studied (0.2 -1.0 mmole/kg bw), with the maximum
number of micronuclei occurred 24 h after a single intraperitoneal
injection. The reliability of the study is considererd to be severely
compromised by the incidence of mortality apparently caused by the
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.
The result is different to that reported in Goncharova et
al (1988) which found dimethyl terephthalate 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. The OECD Guideline 474 specifically states that 'the
solvent/vehicle should not produce toxic effects at the dose levels
No evidence of genetic toxicity has been reported for DMT in a
comprehensive battery of studies in vitro investigating DNA damage
(strand breakage, UDS), in numerous studies of mutation in bacterial
strains (Ames tests) and mammalian cells (mouse lymphoma assay).
Negative results were obtained in studies investigating chromosomal
effects (clastogenicity, SCE, micronucleus induction) in a number of
mammalian cell types. A negative mouse lymphoma assay is also reported. In
vivo, high quality NTP studies report negative results for the mouse
micronucleus assay and Drosophila SLRL assay. An older published mouse
micronucleus assay reports a positive result at lower dose levels than
those used in the NTP study; the reliability of this study is severely
compromised by the choice of dosing vehicle, which caused mortalities in
control and treated groups. The weight of evidence from reliable studies
therefore clearly indicates that DMT is not genotoxic.
It is concluded that DMT therefore does not require classification
according to Regulation (EC) No. 1272/2008.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
Ce site web utilise des cookies afin de vous garantir la meilleure expérience possible sur nos sites web.
Welcome to the ECHA website. This site is not fully supported in Internet Explorer 7 (and earlier versions). Please upgrade your Internet Explorer to a newer version.
Do not show this message again