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Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information
GLP and non-GLP studies equivalent to OECD guidelines 471, 473 and 482 are available for propylene glycol methyl ether acetate. A gene mutation study in mammalian cells (OECD guideline 476) is available for propylene glycol methyl ether, which is used as read-across to propylene glycol methyl ether acetate. In addition a GLP study equivalent to OECD guideline 481 is available for propylen glycol methyl ether acetate. All studies were considered to be valid.
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:
1983
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study, similar to OECD guideline No. 471.
Qualifier:
equivalent or similar to guideline
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 strains TA98, TA100, TA1535, TA1537, TA1538
Metabolic activation:
with and without
Metabolic activation system:
Rat liver homogenate (S9)
Test concentrations with justification for top dose:
50, 10, 1, 0.1 mg/plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: DMSO
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: N-ethyl-N-nitro-N-nitrosoguanidine ( TA 100 & TA 1535 -S9), nitrofluorene ( TA98 & TA 1538 -S9), quinacrine mustard.2HCl ( TA 1537 -S9) 2-anthramine ( TA 100 & TA 1535 +S9), 2-acetylaminofluorene ( TA98 & TA 1538 +S9), 8-aminoquinoline (TA 1537
Remarks:
N-ethyl-N-nitro-N-nitrosoguanidine ( TA 100 & TA 1535 -S9), nitrofluorene ( TA98 & TA 1538 -S9), quinacrine mustard.2HCl ( TA 1537 -S9) 2-anthramine ( TA 100 & TA 1535 +S9), 2-acetylaminofluorene ( TA98 & TA 1538 +S9), 8-aminoquinoline (TA 1537
Details on test system and experimental conditions:
METHOD OF APPLICATION: in medium; preincubation
DURATION
- Preincubation period:30 min
- Incubation period: 48 hours

NUMBER OF REPLICATIONS:
3 replicates per dose

DETERMINATION OF CYTOTOXICITY
- Method: bacterial background lawn evaluation
- cytotoxcity was evident at 50mg test chemical per plate in all strains of bacteria, both with and without metabolic activation system


Evaluation criteria:
Concentrations of the test chemical which are overtly toxic are easily visualized as showing no bacterial growth on the plate (i.e. absence of background lawn). Lower levels of toxicity may be seen as a thin or sparse bacterial lawn, a reduction in the number of revertants, or the appearance of microcolonies (overgrown background lawn). Positive and negative controls were run concurrently with the test chemical, and appropriate responses for these controls are prerequesites for evaluating the response of the bacteria to the test chemical.

A test chemical is considered a bacterial mutagen if both the mean number of revertant colonies observed is at least three times higher than the mea
Species / strain:
other: Salmonella typhimurium strains TA98, TA100, TA1535, TA1537, TA1538
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
other: cytotoxcity was evident at 50mg test chemical per plate in all strains of bacteria, both with and without metabolic activation system
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
cytotoxcity was evident at 50mg test chemical per plate in all strains of bacteria, both with and without metabolic activation system.
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

See the attached word document for tables and figures:

Conclusions:
Interpretation of results (migrated information):
negative

Propylene glycol methyl ether acetate (DOWANOL PMA) did not cause mutations in the Ames Salmonela reverse mutation assay both with or without S-9 metabolic activation. Hence, the test material was classified as negative in the Ames test under the experimental conditions used.
Executive summary:

Propylene glycol methyl ether acetate was evaluated in the Salmonella/mammalian-microsome bacterial mutagenicity assay (Ames test) using a preincubation assay. The test was conducted using Salmonella typhimurium bacterial tester strains TA98, TA100, TA1535, TA 1537 and TA1538 at 4 doses in triplicate. The test agent was assayed 50, 10, 1, 0.1 mg/plate in all the tester strains both in the presence and absence of external metabolic activation system.

All solvent (negative) control plates and positive control plates gave frequencies of induced revertants within expected ranges. Cytotoxcity was evident at 50mg test chemical per plate in all strains of bacteria, both with and without metabolic activation system.

The test material did not induce a mutagenic response in any of the tester strains in the assays as judged by the frequencies of histidine-independent (his+) revertants. Hence, the test material was classified as negative in the Ames test under the experimental conditions used.

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

Additional information

Additional information from genetic toxicity in vitro:

The studies selected as key studies are considered to be valid as they are reliable, either without restrictions (Klimisch rating 1) or with some restrictions (Klimisch rating 2). The results of the studies indicate that propylene glycol methyl ether acetate is not mutagenic, with and without an exogenous metabolic activation, in bacteria and Saccharomyces cerevisae. No increase in chromosomal aberrations was observed in vitro with and without metabolic activation. Propylene glycol methyl ether acetate did not induce UDS in rat hepatocytes.

There is no gene mutation study in mammalian cells available for PGMA. However, PGME and PGMEA 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. No apparent differences in toxicological profile have been observed because of the rapid and extensive hydrolysis of propylene glycol methyl ether acetate (PGMA) to propylene glycol methyl ether (PGME). Metabolites and disposition profiles of PGMA are approximately identical to the results obtained with PGME. Therefore, it is justified to use the gene mutation study conducted with PGME for read-across purposes to fill the data gap for PGMA.


Justification for selection of genetic toxicity endpoint
The study methodology followed was equivalent or similar to OECD TG 471

Justification for classification or non-classification

Propylene glycol methyl ether acetate was not mutagenic, with and without an exogenous metabolic activation, in bacteria and Saccharomyces cerevisae. No increase in chromosomal aberrations was observed in vitro with and without metabolic activation. Propylene glycol methyl ether acetate did not induce UDS in rat hepatocytes. Therefore, no classification is needed for genotoxicity.

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