2-methoxy-1-methylethyl acetate

Endpoint summary

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

100

Absorption rate - dermal (%):

30

Absorption rate - inhalation (%):

100

Additional information

Several studies confirm that rapid and extensive hydrolysis of propylene glycol methyl ether acetate (PGMA) to propylene glycol methyl ether (PGME) occurs in vivo when PGMA is administered by the oral, inhalatory or dermal route. Since urinary metabolites and disposition profiles of PGMA were approximately identical to the results obtained with PGME, it is unlikely that there are substantial differences of the systemic toxicity between PGMA and PGME. In fact, toxicity of PGMA is almost the same of PGME. PGMA is readily absorbed via oral and inhalation route. An absortion percentage of 100 % can be taken into account for these routes of exposure. In a study comparing dermal toxicokinetics of PGME and PGMA (ACC 1999), the dermal absorption of PGMA was found to be lower than that of PGME (between 3 and 4 fold less). Dermal absorption of PGME is approximately 30%, therefore since dermal absorption of PGMA was approximately 30% of that of PGME in rats. In conclusion, PGMA is rapidly hydrolysed in vivo in PGME and acetate (blood half life of PGMA is about 2 min for a low dose of PGMA). Hydrolysis can also occur locally (i.e. in the respiratory tract).

Once hydrolysis of PGMA to PGME has occurred, the distribution, further metabolism and excretion is the same as for PGME. The acetic acid released will enter endogenous metabolic processes.

PGME is sufficiently water soluble that it can be excreted unchanged via the urine. However, it is also further metabolised and the main metabolic pathway is O-demethylation, leading to propylene glycol formation. This mechanism is easily saturable. Other pathways are glucurono- and sulfo-conjugation of PGME. Propylene glycol is excreted via urine or enters metabolic pathways to produce CO₂ which is exhaled. At high dose, saturation of the metabolic pathways led to urinary elimination of propylene glycol methyl ether as such. Parent and metabolites are rapidly eliminated.

It appears that in rats, there is a sex difference in metabolism of propylene glycol methyl ether, females eliminating faster than males.

Discussion on bioaccumulation potential result:

As a class, the propylene glycol ethers are rapidly absorbed and distributed throughout the body when introduced by inhalation or oral exposure. For detailed information, refer to read-across justification document for P-series glycol ethers. While not tested directly, absorption by inhalation exposure also would be expected to be rapid for PGEs aerosols that are in the respirable range. Dermal absorption is expected to be somewhat slower but, once absorbed, subsequent distribution also should be rapid. Most of the PGE dose would be rapidly excreted. Most excretion for PGEs is via the urine and expired air. A small portion is excreted in the feces.