[(butoxymethylethoxy)methylethoxy]propan-1-ol

Endpoint summary

Description of key information

Short description of key information on bioaccumulation potential result: 
No ADME studies are available for tripropylene glycol n-butyl ether (TPnB) as such. Therefore, the toxicokinetics assessment is based on the available data for structurally related propylene glycol ethers (PGEs) such as propylene glycol methyl ether (PM), dipropylene glycol methyl ether DPM, tripropylene glycol methyl ether (TPM), propylene glycol n-butyl ether (PnB) and dipropylene glycol n-butyl ether (DPnB).

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

No ADME studies are available for tripropylene glycol n-butyl ether (TPnB) as such. Therefore, the toxicokinetics assessment is based on the available data for structurally related propylene glycol ethers (PGEs) such as propylene glycol methyl ether (PM), dipropylene glycol methyl ether DPM, tripropylene glycol methyl ether (TPM), propylene glycol n-butyl ether (PnB) and dipropylene glycol n-butyl ether (DPnB). As a class, the propylene glycol ethers are rapidly absorbed and distributed throughout the body when introduced by inhalation or oral exposure. Metabolism studies (by oral exposure) conducted with several PGEs support this conclusion. While not tested directly, absorption by inhalation exposure also would be expected to be rapid for vapors of PGEs and for aerosols that are in the respirable range. However, due to the low vapor pressure of TPnB no inhalation exposure is expected for this substance. 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 was based on DPM data (see read-across justification document) and set at 20%, a conservative assumption for TPnB.

Dermal absorption is expected to be somewhat slower for but, once absorbed, subsequent distribution also should be rapid. When a single dose of DPnB was administered orally to rats, most of the dose was eliminated within 48 hours indicating rapid excretion. Similar rapid absorption, distribution, and elimination occurred within 48 hours for TPM. Most excretion for PGEs is via the urine and expired air. A small portion is excreted in the feces. In analogy to PnB and DPnB the metabolism of TPnB is expected to take place predominantly in the liver where mixed function oxidase cleaves the ether linkage, yielding propylene glycol and an alcohol. These two products may be further metabolised to CO2 and water, with the latter ultimately being excreted in expired air. Alternatively, TPnB (or intermediate metabolites) may be conjugated in the liver with glucuronide, sulfate, or glutathione for ultimate excretion, predominantly in the urine. TPnB is expected to be rapidly absorbed and distributed throughout the body when introduced by oral exposure. Dermal absorption is expected to be somewhat slower but subsequent distribution will be rapid.

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. Metabolism studies (by oral exposure) conducted with several PGEs support this conclusion. While not tested directly, absorption by inhalation exposure also would be expected to be rapid for vapors of PGEs and for aerosols that are in the respirable range. However, due to the low vapor pressure of TPnB no inhalation exposure is expected for this substance. Dermal absorption is expected to be somewhat slower but, once absorbed, subsequent distribution also should be rapid. When a single dose of DPnB was administered orally to rats, most of the dose was eliminated within 48 hours indicating rapid excretion. Similar rapid absorption, distribution, and elimination occurred within 48 hours for TPM. Most excretion for PGEs is via the urine and expired air. A small portion is excreted in the feces. In analogy to PnB and DPnB the metabolism of TPnB is expected to take place predominantly in the liver where mixed function oxidase cleaves the ether linkage, yielding propylene glycol and an alcohol. These two products may be further metabolised to CO2 and water, with the latter ultimately being excreted in expired air. Alternatively, TPnB (or intermediate metabolites) may be conjugated in the liver with glucuronide, sulfate, or glutathione for ultimate excretion, predominantly in the urine. TPnB is expected to be rapidly absorbed and distributed throughout the body when introduced by oral exposure. Dermal absorption is expected to be somewhat slower but subsequent distribution will be rapid.