(2-methoxymethylethoxy)propanol

Endpoint summary

Description of key information

Short description of key information on bioaccumulation potential result: 
An in vivo study on the metabolism and disposition of dipropylene glycol methyl ether (DPGME) in male rats and a limited in vivo metabolism study in female rats and rabbits are available for dipropylene glycol methyl ether. Both studies were conducted under GLP.
Short description of key information on absorption rate: 
Dipropylene Glycol Methyl Ether (DPGME), 100% pure, liquid was evaluated for in vitro dermal absorption rate testing following OECD guideline 428 and European Commission and OECD guidance document on Skin Absorption.  The study was conducted according to GLP.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

100

Absorption rate - dermal (%):

20

Absorption rate - inhalation (%):

100

Additional information

Both oral and inhalation absorption rates were set at 100%. For detailed information, refer to read-across justification document for P-series glycol ethers. Dermal absorption rate for DPGME based on data was set at 20%.

After oral dosing expired air, excreta and tissues were analysed for 14C activity and metabolites in urine were isolated and identified. Approximately 60% of the 14C DPGME was excreted in urine, while 27% was eliminated as 14CO2 within 48 hours after an oral dose of 14C DPGME. Less than 3% of the dose was recovered in feces, indicating that the test material was effectively absorbed. DPGME was not completely hydrolysed to propylene glycol methyl ether (PGME) and a higher percentage of the radiolabeled DPGME was eliminated in the urine after dosing with DPGME than occurred with PGME or propylene glycol methyl ether acetate (PGMEA). DPGME, PGME, dipropylene glycol, propylene glycol as well as sulfate and glucuronide conjugates of DPGME were identifed in urine of animals. Therefore, DPGME is apparently metabolized via the same routes to the same general types of metabolites as those for PGME.

The short-term dermal absorption rates at 10 and 60 minutes have been determined for dipropylene glycol methyl ether (DPGME) using human abdominal skin from cadavers mounted in an in vitro static diffusion cell model. The 10-minute absorption rate was calculated to be 658.6 μg/cm2/h. The 60-minute absorption rate was calculated to be 228.5 μg/cm2/h.

Discussion on bioaccumulation potential result:

Male Fischer 344 rats were given a single oral dose of 14C dipropylene glycol methyl ether (DPGME). After dosing expired air, excreta and tissues were analysed for 14C activity and metabolites in urine were isolated and identified. Approximately 60% of the 14C DPGME was excreted in urine, while 27% was eliminated as 14CO2 within 48 hours after an oral dose of 14C DPGME. Less than 3% of the dose was recovered in feces, indicating that the test material was effectively absorbed. DPGME was not completely hydrolysed to propylene glycol methyl ether (PGME) and a higher percentage of the radiolabeled DPGME was eliminated in the urine after dosing with DPGME than occurred with PGME or propylene glycol methyl ether acetate (PGMEA). DPGME, PGME, dipropylene glycol, propylene glycol as well as sulfate and glucuronide conjugates of DPGME were identifed in urine of animals. Therefore, DPGME is apparently metabolized via the same routes to the same general types of metabolites as those for PGME. The metabolic conversion of dipropylene glycol methyl ether (DPM) to 2 -methoxypropionic acid (MPA) was examined in three female CD rats and three female New Zealand White rabbits. MPA was found as a measurable metabolite from both species, at both dose levels and from both lots of the test material. The relative formation of MPA was highest in the rat, comprising 5.8 -12.2% of the administered dose. In contrast, substantially lower levels of MPA were found in the urine of the rabbit (1.5-2.4% of administered dose). The rate of MPA formation appears to be dose proportional in the rabbit, and more than dose proportional in the rat. Excretion of MPA was substantially slower in the rabbit than the rat, with calculated half-lives of 17.4-20.9 hours and 7.5-8.1 hours, respectively.

Discussion on absorption rate:

The short-term absorption rates at 10 and 60 minutes have been determined for dipropylene glycol methyl ether (DPGME) using human abdominal skin from cadavers mounted in an in vitro static diffusion cell model. The 10-minute absorption rate was calculated to be 658.6 μg/cm2/h. The 60-minute absorption rate was calculated to be 228.5 μg/cm2/h.