[2-(2-methoxymethylethoxy)methylethoxy]propanol

Carcinogenicity

Description of key information

No specific studies for tripropylene glycol methyl ether are available. Two inhalation studies with propylene glycol methyl ether in rats and mice are available for read-across to tripropylene glycol methyl ether. Both studies are reliable without restrictions as they were conducted under GLP and according to OECD guideline 453.

Key value for chemical safety assessment

Carcinogenicity: via inhalation route

Endpoint conclusion

Dose descriptor:

NOAEC

25 312.88 mg/m³

Justification for classification or non-classification

No carcinogenic effect as evidenced by any increase in tumor incidence occurred from exposure to propylene glycol methyl ether at any concentration in either species.

Additional information

Repeated exposure to tripropylene glycol methyl ether resulted in toxicity only at high exposure levels and usually consisted of increased organ weights without accompanying histopathology. In vitro genotoxicty studies are negative, indicating that tripropylene glycol methyl ether is not genotoxic. No carcinogenicity studies are available for tripropylene glycol methyl ether. The sole propylene glycol ether that has been subjected to chronic toxicity/carcinogenicity testing is propylene glycol methyl ether. The glycol ethers propylene glycol methyl ether (PGME), dipropylene glycol methyl ether (DPGME) and tripropylene glycol methyl ether (TPGME) are closely related in molecular structure and physicochemical properties and thus, the potential for toxicological effects. They are liquids with similar boiling points, moderate volatility, and high water solubility. Increasing boiling point and vapor pressure are consistent with increasing molecular weight. Metabolism of propylene glycol methyl ethers takes place predominantly in the liver where mixed function oxidase cleaves the ether linkage, yielding propylene glycol and an alcohol. These two byproducts may be consumed in intermediary metabolism to CO2 and water, with the latter ultimately being excreted in expired air. Alternatively, the parent ether (or intermediate metabolite) may be conjugated in the liver with glucuronide, sulfate, or glutathione for ultimate excretion, predominantly in the urine. As a class, the propylene glycol methyl ethers are rapidly absorbed and distributed throughout the body when introduced by inhalation or oral exposure. Metabolism studies (by oral exposure) conducted with PGME and DPM support this conclusion. A higher proportion of PGME was eliminated via the lungs as opposed to the urine than the larger molecular weight DPGME. The ether bond may be broken via O-dealkylation by mixed function oxidase to yield mono-, di-, or tripropylene glycol (depending on the parent compound). The (mono-, di-, or tri-) propylene glycol released may then undergo further metabolism to yield CO2. Alternatively, propylene glycol methyl ethers or their partially metabolized by-products may be conjugated with glucuronide or sulfate and excreted via the kidneys into the urine. No differences in gene mutation potential have been observed between other glycol ethers families (e.g. mono- and di-propylene glycol n-propyl ethers and mono-, di- and tri-propylene glycol n-butyl ethers) and similar effects were observed in the repeated dose toxicity studies. The results of propylene glycol ethers were consistently negative in gene mutation studies. Thus, the propylene glycol methyl ether study is used as a surrogate for tripropylene glycol methyl ether. Propylene glycol methyl ether, tested by inhalation in rats and mice at concentrations up to 3,000 ppm, caused very little chronic toxicity and caused no cancer. Further justification for the use of read across is contained in the category document attached at section 13.