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Salmonella-Escherichia coli/mammalian-microsome bacterial mutagenicity assay:

Dipropylene glycol n-propyl ether (Dowanol DPnP) was evaluated in the Salmonella-Escherichia coli/mammalian-microsome bacterial mutagenicity assay using a pre-incubation modification of the standard method with a confirmatory assay. The test was conducted in the presence and absence of an externally supplied metabolic activation system (S-9) using Salmonella typhimurium tester strainsTA98, TA100, TA1535, and TA1537 and Escherichia coli tester strain WP2uvrA. The concentrations of the test material in the presence and absence of S9 mix ranged from 100 to 5000 pg per plate. The results were confirmed in an independent repeat assay. The results indicate that Dowanol DPnP did not cause a positive increase in the number of revertants per plate of any of the tester strains in this bacterial mutagenicity test under the experimental conditions used.

In vitro chromosomal aberration assay utilizing rat lymphocytes:

Dipropylene glycol n-propyl ether (DPnP) was evaluated in anin vitrochromosomal aberration assay utilizing rat lymphocytes. Approximately 48 hr after the initiation of whole blood cultures, cells in the absence and presence of S-9 activation were treated for 4 hr with targeted concentrations of 0 (negative control) to 1760 μg DPnP per ml of culture medium and the cultures were harvested 20 hours later (Assay A1). Based upon the mitotic indices, cultures treated with targeted concentrations of 0, 440, 880 and 1760 μg/ml in the absence and presence of S-9 activation were selected for determining the incidence of chromosomal aberrations. There were no significant increases in the frequencies of cells with aberrations in this assay. In a confirmatory assay (Assay B1), cultures were treated as above except that the cultures were treated continuously for 24 hr until the time of their harvest in the absence of S-9. Based upon the mitotic indices, the incidence of chromosomal abnormalities was determined from cultures treated with 0, 440, 880 and 1760 μg/ml in the absence and presence of S-9. In Assay B1, statistical analyses of the data did not identify a significant difference between the negative control and any of the treated cultures with or without S-9 activation. Cultures treated with the positive control chemicals (i.e., mitomycin C without S-9 and cyclophosphamide with S-9) had significantly higher incidences of abnormal cells in all assays. Hence, DPnP was considered to be negative in thein vitrochromosomal aberration assay utilizing rat lymphocytes.

Gene mutation in mammalian cells was evaluated using Chinese Hamster ovary (CHO) cells:

The genotoxic potential of the test article dipropylene glycol n-propyl ether to induce gene mutation in mammalian cells was evaluated using Chinese Hamster ovary (CHO) cells.

 

The study consisted of a preliminary toxicity test, an initial gene mutation assay and a confirmatory gene mutation assay. Each of these mutation assays comprised of two independent experiments, one each in the presence and absence of metabolic activation system (S-9 fraction prepared from Aroclor 1254 induced rat liver).

 

Dipropylene glycol n-propyl ether formed a solution in sterile water (SW) at 88.2 mg/mL and was found to be stable in water at concentrations of 500 and 88100 μg/mL for 24 hours at room temperature.

In a preliminary cytotoxicity test, dipropylene glycol n-propyl ether did not cause a significant cell growth inhibition as evaluated by Relative Cloning Efficiency (RCE) up to the highest tested concentration of 1762 μg/mL (equivalent to 10 mM) in the presence as well as in the absence of metabolic activation. The test article did not precipitate in the treatment medium, and did not cause any appreciable change in the pH and osmolarity of the test solution at 1762 μg/mL at the end of the 4-hour exposure to treatment either in the presence or in the absence of metabolic activation.

 

In the initial gene mutation assay, CHO cells were exposed to the test article in duplicate at concentrations of 18, 56, 176, 558, and 1762 μg/mL of the medium for 4 hours in the presence and absence of metabolic activation. In the confirmatory gene mutation assay, CHO cells were exposed to the test article in duplicate at concentrations of 22, 65, 196, 587, and 1762 μg/mL of the medium for 4 hours in the presence and absence of metabolic activation. In a similar way, a concurrent solvent control and appropriate positive controls i.e., 3-methylcholanthrene in the presence of metabolic activation and ethyl methanesulphonate in the absence of metabolic activation were also tested in duplicate.

 

There was no evidence of induction of gene mutations in any of the test material treated cultures either in the presence or absence of metabolic activation. In each of these experiments, the respective positive controls produced a statistically significant increase in the frequencies of mutants, under identical conditions and concurrent solvent control cultures values were within laboratory historical controls.

 

The results of the forward gene mutation assay at thehprtlocus with dipropylene glycol n-propyl ether indicate that under the conditions of this study, the test article was non-mutagenic when evaluated in the presence or absence of an externally supplied metabolic activation (S9) system


Short description of key information:
Salmonella-Escherichia coli/mammalian-microsome bacterial mutagenicity assay, in vitro chromosomal aberration assay utilizing rat lymphocytes and gene mutation in mammalian cells was evaluated using Chinese Hamster ovary (CHO) cells.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the results of the study and Guidance to Regulation (EC) No. 1272/2008 on Classification, Labelling and Packaging of substances and mixtures, dipropylene glycol n-propyl ether will not be classified for genetic toxicity.