1-methoxypropan-2-ol

Endpoint summary

Description of key information

Short description of key information on bioaccumulation potential result: 
Several in vitro and in vivo toxicokinetics studies are available for propylene glycol methyl ether.
Short description of key information on absorption rate: 
An in vitro dermal absorption using human skin s available for propylene glycol methyl ether.

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

Propylene glycol methyl ether is readily absorbed via oral and inhalation route. An absorption percentage of 100 % can be taken into account for these routes. Human data have shown that dermal absorption of vapour via the skin is limited. When exposed whole-body (normal clothing), vapour provided contribution of approximately 4-8 % to the total body burden. An in vitro absorption rate of 1.17 mg/cm²/h was estimated for pure propylene glycol methyl ether on human skin. If the dermal absorption of liquid propylene glycol methyl ether is compared to other glycol ethers, the available data shows that propylene glycol methyl ether is less absorbed than ethylene glycol butyl ether (it is estimated that propylene glycol methyl ether is twice less absorbed that ethylene glycol butyl ether). According to this data, a dermal absorption factor of 30 % for liquid propylene glycol methyl ether should be considered as a worst case value for the risk assessment.

According to the PBPK model, vapour of propylene glycol methyl ether absorbed through the skin in humans contributed to about 5 to 10 % to the total body burden of propylene glycol methyl ether. Also according to this model, maximum concentration in blood are about 2.5 fold more higher in rats than in humans after a 6h inhalation exposure at the same level (for exposure levels above 100 ppm). For exposure concentrations below 100 ppm, the rat and human blood levels of propylene glycol methyl ether are similar which leads to the use of a factor of 1 instead of 0.4 in this range of concentrations. Main target organs were liver, thymus and spleen (concentration > blood levels after oral dosing). Little amount of the parent molecule or metabolites were found in fat or testes. According to the data available, propylene glycol methyl ether does not seem to accumulate in the body.

The main metabolic pathway is O-demethylation leading to propylene glycol formation. This mechanism is easily saturable. Other paths are glucurono- and sulfo-conjugation. Propylene glycol is excreted via urine or enter metabolic pathways to produce CO₂. 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:

According to the PBPK model, vapour of propylene glycol methyl ether absorbed through the skin in humans contributed to about 5 to 10 % to the total body burden of propylene glycol methyl ether. Also according to this model, maximum concentration in blood are about 2.5 fold more higher in rats than in humans after a 6h inhalation exposure at the same level (for exposure levels above 100 ppm). For exposure concentrations below 100 ppm, the rat and human blood levels of propylene glycol methyl ether are similar which leads to the use of a factor of 1 instead of 0.4 in this range of concentrations. Main target organs were liver, thymus and spleen (concentration > blood levels after oral dosing). Little amount of the parent molecule or metabolites were found in fat or testes. According to the data available, propylene glycol methyl ether does not seem to accumulate in the body.

The main metabolic pathway is O-demethylation leading to propylene glycol formation. This mechanism is easily saturable. Other paths are glucurono- and sulfo-conjugation. Propylene glycol is excreted via urine or enter metabolic pathways to produce CO₂. At high dose, saturationof 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 absorption rate:

Propylene glycol methyl ether is readily absorbed via oral and inhalation route. An absorption percentage of 100 % can be taken into account for these routes. Human data have shown that dermal absorption of vapour via the skin is limited. When exposed whole-body (normal clothing), vapour provided contribution of approximately 4-8 % to the total body burden. An in vitro absorption rate of 1.17 mg/cm²/h was estimated for pure propylene glycol methyl ether on human skin. If the dermal absorption of liquid propylene glycol methyl ether is compared to other glycol ethers, the available data shows that propylene glycol methyl ether is less absorbed than ethylene glycol butyl ether (it is estimated that propylene glycol methyl ether is twice less absorbed that ethylene glycol butyl ether). According to this data, a dermal absorption factor of 30 % for liquid propylene glycol methyl ether should be considered as a worst case value for the risk assessment. For detailed information on rates also refer to read-across justification document for P-series glycol ethers.