Propane-1,2-diol

Carcinogenicity

Description of key information

Based on the lack of (pre-)neoplastic lesions in available long-term studies with rats and dogs, monopropylene glycol is not carcinogenic. 

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Justification for classification or non-classification

Based on the lack of increased tumor incidence, pre-neoplastic lesions or hyperplasia in available chronic toxicity studies, classification of monopropylene glycol as carcinogenic 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.

Additional information

No specific carcinogenicity studies with monopropylene glycol were available for assessment. However, two long-term studies with rats, using 2 years and 140 days exposure duration, and 104 -week study with dogs administered monopropylene glycol either in diet or in drinking water 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 propylene 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 study 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 the liquid on the dorsal skin between the flanks on a 1-inch square area which was shaved regularly. Mice were allowed to die spontaneously or killed when moribound. Complete autopsies 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 addition, two well-conducted and reported drinking water carcinogenicity studies with rats and mice are available on a structural homologue of monopropylene glycol, dipropylene glycol (National Toxicology Program, 2004b). As available toxicokinetic data indicate that monopropylene glycol is formed as a metabolite of dipropylene glycol upon its uptake by the body, it is considered acceptable to use the data on dipropylene glycol to assess the carcinogenic potential of monopropylene glycol. A full justification for read across is contained in a separate document attached to chapter 13 of the lead registrants IUCLID dossier.

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. In the mice study, no compound-related neoplasms or non-neoplastic lesions were observed; only the reduced body weights. In conclusion, no evidence of carcinogenic activity of dipropylene glycol was observed in either rats or mice in the 2 -year drinking water study. These results provide additional evidence that its metabolite monopropylene glycol is also not carcinogenic.