Oxydipropanol

Endpoint summary

Additional information

Dipropylene glycol was tested for genetic toxicity in a number of in vitro and in vivo assays. Two GLP-compliant studies on gene mutation in bacteria were available for assessment. One of them (LPT Laboratory of Pharmacology and Toxicology, 1992) was performed in accordance with OECD Guideline 471 (Bacterial Reverse Mutation Assay); however, the highest tested concentration of 100 µl/plate, used in this study, was much lower than the limit concentration of 5000 µl/plate recommended by the guideline and no cytotoxicity was observed at this dose level. Therefore the other, more recent study (National Toxicology Program, 2004), using sufficiently high test substance concentrations, was chosen as a key study. Mutagenicity of dipropylene glycol was studied in S. typhimurium strains TA97, TA98, TA100, TA1535, TA1537, with and without metabolic activation, at concentration levels 0, 100, 333, 1000, 3333 and 10000 µg/plate. No cytotoxicity was observed at the highest dose tested and no increase in mutation frequency was found, indicating that the substance is not mutagenic in Ames test.

The ability of dipropylene glycol to induce gene mutations in mammalian cells was evaluated in a GLP-compliant mouse lymphoma assay (SITEK Research Laboratories, 1988). No increase in the mutation frequency was evidenced both with and without metabolic activation, when the substance was tested at concentration levels of 50, 100, 300, 500, 750, 1000, 2500 and 5000 µg/ml. No evidence of cytotoxicity was evidenced up to the highest dose level, which corresponds to the limit dose level suggested by modern guidelines.

No in vitro cytogenicity studies were available for assessment; however, in accordance with Column 2 of REACH Annex VIII, they are not necessary, as a reliable in vivo micronucleus test is available.

Cytogenicity of dipropylene glycol in vivo was evaluated in a mouse bone marrow micronucleus assay, performed in accordance with OECD Guideline 478 (Dow Chemical Company, 1999). Mice (6 males/dose) were administered single doses of 0, 500, 1000 and 2000 mg/kg bw dipropylene glycol by oral gavage for two consecutive days. All treated animals were sacrificed at 24 hours after the last administered dose for the collection of bone marrow sample. No clinical signs were observed in the study and no statistically significant differences were observed between the frequencies of micronucleated polychromatic erythrocytes (MN-PCE), % polychromatic erythrocytes (% PCE), and body weight in mice treated with the vehicle (negative control) and the test material.

Short description of key information:
Dipropylene glycol did not induce increased mutation frequency in Salmonella typhimurium strains TA98, TA98, TA100, TA1535 and TA1537, with and without metabolic activation, at concentrations up to 10000 µg/plate, and in mouse lymphoma cells, with and without metabolic acitvation, at concentration levels up to 5000 µg/ml. It was also negative in the in vivo mouse bone marrow micronucleus assay, performed in accordance with OECD Guideline 478 at dose levels up to 2000 mg/kg bw. Based on the results, dipropylene glycol is considered to be non genotoxic.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the negative results of two gene mutation studies in bacteria, negative result in an in vitro mouse lymphoma assay and the in vivo micronucleus assay in mice, classification of dipropylene glycol for genotoxicity is not warranted in accordance with Directive 67/548/EEC and EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.