Propane-1,2-diol, propoxylated

Endpoint summary

Additional information

No data on genetic toxicity of ‘propane-1,2-diol, propoxylated’ are available. However, Article 13 of the REACH legislation states that, in case no appropriate animal studies are available for assessment, information should be generated whenever possible by means other than vertebrate animal tests, i. e. applying alternative methods such as in vitro tests, QSARs, grouping and read-across.

Reliable data on genetic toxicity are available on structural analogues of ‘propane-1,2-diol, propoxylated’, mono-, di- and tripropylene glycol. All three substances are also the constituents of ‘propane-1,2-diol, propoxylated’ (a multi-constituent substance), usually present in the commercial product at following concentrations: 0 -2% monopropylene glycol, 0 -50% dipropylene glycol and 10 -80% tripropylene glycol. Therefore it is considered acceptable to derive the data on genetic toxicity of ‘propane-1,2-diol, propoxylated’ by read-across from its constituents.

Genetic toxicity of monopropylene glycol has been studied in a number of in vitro and in vivo assays. Ishidate et al., 1994 reported the results of the Ames test with Salmonella typhimurium strains TA 92, TA 94, TA 98, TA 100, TA 1535, TA 1537 at concentration levels up to 10 mg/plate in the presence of metabolic activation system. No increase in the number of revertants was observed at any dose levels. Also negative results were reported by Pfeiffer et al., 1980, who reported the results of the Ames test with S. typhimurium strains TA 1535, TA 1537, TA 98 and TA 100 at concentration range between 5 and 300 μmol/plate (380-228270 μg/plate) without metabolic activation. Monopropylene glycol also did not induce the increase in chromosome aberration frequency in human lymphocytes at dose levels up to 3810 μg/ml, both in the presence and absence of metabolic activation system (Huntingdon Research Center Ltd., 1990).

Also results of several in vivo studies addressing chromosome aberrations were reported. The study of Litton Bionetics, Inc., 1974, reported the results of a micronucleous test with rats and a dominant lethal assay with rats treated with monopropylene glycol. In the first experiment, groups of 5 male rats were administered by gastric intubation either a single dose of monopropylene glycol at dose levels of 30, 2500 and 5000 mg/kg bw (acute study), or 5 times the same doses 24 hours apart (subacute study). In the acute study animals were killed 6, 24 and 48 hours post-administration, in the subacute study 6 hours after the last dose. In the second study, male rats were administered the test substance at the same dose levels by oral gavage either once (acute study), or for 5 days (1 dose/day, subacute study). Following the treatment, the males were sequentially mated to 2 females per week for 8 weeks (7 weeks in subacute study). Females were killed at 14 days after separating from the male, and at necropsy the uterus was examined for early deaths, late fetal deaths and total implantations. In both cases no evidence of genotoxic effect was observed. Also negative results were reported in the mouse micronucleus test by Hayashi et al., 1988, who administered monopropylene glycol by single intraperitoneal injection at dose levels of 0, 2500, 5000, 10000 and 15000 mg/kg bw to groups of 6 male mice. Animals were killed 18 hr post-administration and femoral bone marrow cells were scored for the number of micronucleated polychromatic erythrocytes. Three of six mice from the top dose group died during the course of the study. There was no statistically significant increase or trend in mononucleated polychromatic erythrocytes numbers. The percentage of polychromated erythrocytes in the top dose group appeared decreased relative to controls (31% versus 54%) suggesting that the test substance had reached the bone marrow.  

Also dipropylene glycol was tested for genetic toxicity in a number of in vitro and in vivo assays. Mutagenicity of dipropylene glycol in bacteria 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 (National Toxicology Program, 2004a). 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.

Cytogenicity of dipropylene glycol in vivo was evaluated in a mouse bone marrow micronucleus assay, performed in accordance with OECD Guideline 478 (The 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.

For tripropylene glycol, only in vitro studies were available. One gene mutation study in bacteria, conducted in accordance with Japanese Guidelines for Screening Mutagenicity Testing of Chemicals and with GLP, was conducted by the Ministry of Health and Welfare of Japan (MHW, 1993c). Although the study has been requested, only its abstract in English could be recovered. Nevertheless, as the study was conducted within the HPV/SIDS framework and considered to be reliable by OECD (1994), it is considered to be acceptable for assessment. Mutagenicity of tripropylene glycol was studied in S. typhimurium strains TA 1535, TA 1537, TA 98 and TA 100 and E. coli WP2 uvr A strain, with and without metabolic activation, at concentration levels 0, 312.5, 625, 1250, 2500 and 5000 μg/plate, using water as a vehicle. No cytotoxicity was observed at the highest dose tested (which corresponds to the limit dose established by OECD guideline 471) and no increase in mutation frequency was found, indicating that the substance is not mutagenic in the Ames test.

Another study of the Ministry of Health and Welfare of Japan (MHW, 1993c), of which also only the abstract in English could be recovered, studied the ability of tripropylene glycol to induce chromosome aberrationsin vitro, using Chinese hamster lung (CHL/IU) cells, with and without metabolic activation. The testing concentrations were 0, 0.48, 0.95 and 1.90 mg/mL in the long-term treatment; in the short term treatment, the concentration was set to 3.5 mg/mL because it was equivalent to ca. 10 mM as required in test guidelines. No structural or numeric chromosomal aberrations were observed up to a maximum concentration of 3.5 mg/mL under conditions of both continuous treatment and short-term treatment with or without an exogeneous metabolic activation system.

In summary, there is conclusive evidence that lower homologues and constituents of ‘propane-1,2-diol, propoxylated’, mono-, di- and tripropylene glycol, are not genotoxic in vivo and in vitro. Based on these results, it is concluded that ‘propane-1,2-diol, propoxylated’ is also not genotoxic.

Short description of key information:
The following information is taken into account for any hazard / risk assessment:
No data on genotoxicity of ‘propane-1,2-diol, propoxylated’ are available. Experimental data is available as follows:
• Bacterial gene mutation (Ames): monopropylene glycol, dipropylene glycol, tripropylene glycol.
• Chromosome aberration in vitro: monopropylene glycol, tripropylene glycol.
• Mammalian cell gene mutation in vitro: dipropylene glycol.
• Chromosome aberration in vivo: monopropylene glycol (Dominant lethal assay, chromosome aberration, micronucleus), dipropylene glycol (micronucleus.)
All results in all assays are consistently negative. The higher molecular weight members of the homologous series are metabolised via the lower molecular weight members of the series for which experimental data exists. It can be concluded with confidence that there are no metabolites of pentapropylene glycol, tetrapropylene glycol and tripropylene glycol that exhibit genotoxicity. In addition, the higher molecular weight members contain exactly the same functional groups as dipropylene glycol and tripropylene glycol, which show no evidence of genotoxic properties.. Based on this, it is concluded that ‘propane-1,2-diol, propoxylated’ is not genotoxic.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

None of the components of ‘propane-1,2-diol, propoxylated’ for which data is available show any evidence of skin genotoxicity . Data on the components can be considered representative of the substance itself, which would lead to the conclusion that the multi-constituent substance ‘propane-1,2-diol, propoxylated’ does not need to be classified for genotoxicity in accordance with EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.