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Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information
Several GLP-studies according to or equivalent to OECD guidelines 471, 473, 481 and 482 are available for dipropylene glycol methyl ether. In addition, studies according to OECD guideline 476 (gene mutation in mammalian cells) are available for the structural analogues propylene glycol methyl ether and tripropylene glycol methyl ether which are used for read-across.
Link to relevant study records
Reference
Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study, similar to Japan Guidelines (Kanpogyo 700, Yakuhatsu 1039, Kikyoku 1014, Kanpoan 298, Eisie 127, Kikyoku 2)
Qualifier:
according to
Guideline:
JAPAN: Guidelines for Screening Mutagenicity Testing Of Chemicals
Version / remarks:
Kanpogyo 700, Yakuhatsu 1039, Kikyoku 1014, Kanpoan 298, Eisie 127, Kikyoku 2
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay
Species / strain / cell type:
other: Salmonella typhimurium TA98, TA100,TA1535, TA1537; Escherichia coli WP2uvrA
Metabolic activation:
with and without
Metabolic activation system:
rat liver homogenate (S9)
Test concentrations with justification for top dose:
313, 625, 1250, 5000 ug/plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: distilled water
positive controls were dissolved in DMSO
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
Positive controls:
yes
Positive control substance:
other: AF-2, sodium azide, 9-aminoacrydine, 2-aminothracene
Details on test system and experimental conditions:
Test Type: Ames test
METHOD OF APPLICATION: pre incorporation

DURATION
- Preincubation period: 20 min
- incubation duration: 48 hrs



NUMBER OF REPLICATIONS: 3 for test substance and 2 for the controls


Evaluation criteria:
There are several criteria for determining a positive result, such as a concentration-related
increase over the range tested and/or a reproducible increase at one or more concentrations in the
number of revertant colonies per plate in at least one strain with or without metabolic activation
system.
Biological relevance of the results should be considered first. Statistical methods may
be used as an aid in evaluating the test results.
However, statistical significance should not be
the only determining factor for a positive response.
. A test substance for which the results do not meet the above criteria is considered nonmutagenic in this test.
Although most experiments will give clearly positive or negative results, in rare cases the data set will preclude making a definite judgement about the activity of the test substance.
Results may remain equivocal or questionable regardless of the number of times the experiment is repeated.
Positive results from the bacterial reverse mutation test indicate that a substance induces
point mutations by base substitutions or frameshifts in the genome of either Salmonella typhimurium
and/or Escherichia coli. Negative results indicate that under the test conditions, the test substance is
not mutagenic in the tested species.
Species / strain:
other: Salmonella typhimurium TA98, TA100,TA1535, TA1537; Escherichia coli WP2uvrA
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.
See the attached word doc:
Conclusions:
Interpretation of results (migrated information):
negative

Dipropylene glycol methyl ether showed no evidence of mutagenic activity under the conditions of this assay.
Executive summary:

Test substance, dipropylene glycol methyl ether (DPM) was tested for mutagenic potential using histidine dependent auxotrophic mutants of Salmonella typhimurium, strains TA 98, TA100, TA1535 and TA1537, and a tryptophan dependent mutant of Escherichia coli, strain WP2uvrA in two independent mutation tests in the presence (with metabolic activity) and absence (without metabolic activity) of liver preparations (S9-mix) by preincubation method.

                      

DPM dissolved in the distilled water for injection (Japan Pharmacopoeia) up to 5000 μg/plate were tested, and 6 dose levels were separated by 4 of common ratio in the preliminary study. Based on the dose rangefinding study, in the definitive study, 5000 μg/plate was a highest dose level and then 5 dose levels were selected by 2 common ratio as set those in the preliminary test.

No evidence of mutagenic activity to show the increases in the reverse mutation colonies exceeding 2 folds of those of negative control value was seen at any dose level of DPM in either mutation test.

The values calculated for the concurrent negative and positive controls of each strain were within the range of the background data.

It can be concluded that DPM shows no evidence of mutagenic activity in this bacterial system.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vitro:

All in vitro genoxicity studies conducted with dipropylene glycol methyl ether are of high quality and reliable without restrictions. The results of all studies were consistent. Dipropylene glycol methyl ether did not induce gene mutations in bacterial cells and in yeast. No increase in chromosomal aberrations and UDS was observed with this test material.

No gene mutation study in mammalian cells is available for dipropylene glycol methyl ether (DPGME). Therefore, studies on propylene glycol methyl ether (PGME) and tripropylene glycol methyl ether (TPGME) are used as surrogates for DPGME. The glycol ethers PGME, DPGME and TPGME are closely related in molecular structure and physicochemical properties and thus, the potential for toxicological effects. They are liquids with similar boiling points, moderate volatility, and high water solubility. Increasing boiling point and vapor pressure are consistent with increasing molecular weight. No differences in gene mutation potential have been observed between other glycol ethers families (e.g. mono- and di-propylene glycol n-propyl ethers and mono-, di- and tri-propylene glycol n-butyl ethers). The results of propylene glycol ethers were consistently negative in gene mutation studies. Therefore, it is justified to use the gene mutation studies conducted with PGME and TPGME for read-across purposes to fill the data gap for DPGME. Negative results were obtained in the gene mutation studies in mammalian cells conducted with PGME and TPGME.

No in vivo studies are available.


Justification for selection of genetic toxicity endpoint
Study conducted according to guidelines and Principles of GLP

Justification for classification or non-classification

Dipropylene glycol methyl ether was not mutagenic in bacteria (Salmonella typhimuriumTA 1535, TA 1537, TA 1538, TA 98, and TA 100) and in yeast, and no cytogenetic effect were observed in mammalian cells. The data available indicates that dipropylene glycol methyl ether is not genotoxic.