Propane-1,2-diol, propoxylated

Carcinogenicity

Description of key information

No data on carcinogenicity of ‘propane-1,2-diol, propoxylated’ were available. However, it is concluded that the substance is not genotoxic, and available long-term studies on two structural homologues and constituents of ‘propane-1,2-diol, propoxylated’, mono- and dipropylene glycol, showed the absence of (pre-) neoplastic lesions. A  carcinogenicity study is available for dipropylene glycol which showed no neoplastic lesions up to the highest tested dose (rats: 2330mg/kg in females, 3040mg/kg in males; mice: 1950mg/kg females, 2390mg/kg males).  In a chronic dietary study using monopropylene glycol in rats, no neoplastic lesions were seen up to the maximum tested dose of 1700mg/kg in males and 2100mg/kg in females.  On the basis of the similar physicochemical characteristics of the first two members of the propylene glycol homologous series to the higher members (tripropylene glycol, tetrapropylene glycol and pentapropylene glycol), the similar toxicological profile for other endpoints, including genotoxicity and repeat dose toxicity findings, and the absence of any possible findings of potential concern, it can be concluded that none of the components of this multi-constituent substance will exhibit carcinogenic properties. Based on this evidence, ‘propane-1,2-diol, propoxylated’is considered to be non-carcinogenic

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 carcinogenicity. Data on the components can be considered representative of the substance itself, which would lead to the conclusion that the multi-constituent substance of ‘propane-1,2-diol, propoxylated’does not need to be classified in accordance with EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

Additional information

No data on carcinogenicity of ‘propane-1,2-diol, propoxylated’ were 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 asin vitrotests, QSARs, grouping and read-across.

Long-term studies are available for two lower homologues and constituents of ‘propane-1,2-diol, propoxylated’, mono- and dipropylene glycol. These two substances are normally present in the commercial ‘propane-1,2-diol, propoxylated’ at concentration levels of 0-2% and 0 -50%, respectively. For dipropylene glycol, an NTP 2-year drinking water study with rats and mice was available for assessment (National Toxicology Program, 2004a). In the rat study, the exposure concentrations for the 2-year drinking water study were 0, 2,500, 10,000, and 40,000 ppm, corresponding to actual average ingested doses of 115, 470 and 3040 mg/kg bw/day in males and 140, 530 and 2330 mg/kg bw/day in females. In the study with mice, the used exposure levels were 0, 10000, 20000 and 40000 ppm, corresponding to average ingested doses of 735, 1220 and 2390 mg/kg bw/day (males) and 575, 1040 and 1950 mg/kg bw/day (females). In the rat study, dipropylene glycol-related non-neoplastic lesions were found in the kidney, liver, and nose (see Section on repeated dose toxicity for more details). In the mice study, no compound-related neoplasms or non-neoplastic lesions were observed; only the reduced body weights (see Section on repeated dose toxicity for further details). In conclusion, no evidence of carcinogenic activity of dipropylene glycol was observed in either rats or mice in the 2 -year drinking water study.

Also two long-term studies with rats, using 2 years and 140 days exposure duration, and a 104 -week study with dogs with another constituent and structural homologue of ‘propane-1,2-diol, propoxylated’, monopropylene glycol, were available for assessment. Gaunt et al., 1972, administered diets containing 0, 6250, 12500, 25000 and 50000 ppm monopropylene glycol to groups 30 male and 30 female weanling rats for 2 years. No adverse effects and no histopathological changes, including (pre-) neoplastic lesions, were noted at the highest tested dose, resulting in NOAELs of 1700 mg/kg bw/day and 2100 mg/kg bw/day for male and female rats, respectively, based on the determined daily average food intake.

In the old study of Seidenfeld et al., 1932, with only limited parameters examined, groups of 5 rats were administered propylene glycol in drinking water as 0, 1, 2, 5, 10, 25 and 50% solutions for 140 days, corresponding to average daily doses of 1600, 3680, 7700, 13200, 21000 and 37000 mg/kg bw/day, respectively. Histopathological examination was performed on kidneys, hearts, spleens and livers. All animals given 25% or 50% propylene glycol in water died within the first 9 days of treatment. No adverse effects were noted in other dose groups, resulting in NOAEL of 13200 mg/kg bw/day.

In the 104-week study with dogs reported by Weil et al., 1971, groups of 5 male and 5 female beagle dogs were fed diets containing monopropylene glycol at dosage levels of 5000 and 2000 mg/kg bw for 2 years. A second series of animals was given an isocaloric amount of dextrose mixed with food (2540 and 6350 mg/kg bw/day) and served as another set of controls. Micropathology was performed at the end of the study period. Apart from a slight increase in bone marrow activity in female dogs from the high dose group, histopathological lesions occurred with comparable severity and incidence in the treated, control and equicaloric control groups. The change in bone marrow activity was considered a physiological, rather than a toxicological, response. Overall, there were no adverse, treatment-related histopathological changes linked to chronic ingestion of propylene glycol.

In a limited dermal carcinogenicity of Stenbäck et al. (1974) ), groups of 50 female Swiss mice were treated twice a week with 0.02 ml of either neat monopropylene glycol or its 50% or 10% solution in acetone, by dropping Mice were allowed to die spontaneously or killed when moribound. Complete necropsies were performed on all animals and the skin and all grossly observed tumors and other lesions were examined histopathologically. The authors concluded that no substance-caused increase in tumor evidence was evidenced in any group and monopropylene glycol is not carcinogenic by dermal route of exposure.

In summary, based on the available studies with mono- and dipropylene glycol, there is no indication that ‘propane-1,2-diol, propoxylated’ may be carcinogenic.