2-(2-hexyloxyethoxy)ethanol

Endpoint summary

Description of key information

Glycol ethers are believed to be rapidly absorbed following oral administration or inhalation and to distibute within the body. Uptake via the dermal route occurs, but to a significantly lesser amount compared to the outher exposure routes. No substantial accumulation in tissue has been observed for glycol ethers in general. Fast metabolism by aldehyde and alcohol dehydrogenase is a common mechnism shared by all glycol ethers. Thus, it can be expected that the major metabolite of the test substance is 2 -(2 -hexylyethoxy)acetic acid, which is excreted via urine.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

100

Absorption rate - dermal (%):

50

Absorption rate - inhalation (%):

100

Additional information

Absorption

There is no specific information available on DEGHE regarding absorption. Based on the low molecular weight (< 200 g/mol), high water solubility, and low partition coefficient (below 2), high oral absorption is expected. Exposure via inhalation is considered less relevant due to the low vapour pressure of 0.2 Pa. But, if exposure occurs, uptake will likely be high due to the same physico-chemical properties as described above. Since the substance is probably already completely absorbed orally, no higher absorption after inhalation can occur. Consequently, absorption rates are 100% after oral and inhalation exposure.

After dermal exposure, data are available for the two read across substances EGHE and DEGBE. After cutaneous dosing of EGHE to rats and rabbits, EGHE penetrates the skin rapidly and is widely distributed. The cutaneous bioavailability after exposure to 25mg/kg was greater than 75% in rats and greater than 65% in rabbits(DOW, 1989). Compared to EGHE, DEGBE has a lower Log Pow (1 vs 1.97) and higher water solubility, which likely makes this substance too hydrophilic for efficient dermal uptake. In an in vivo study in rat using DEGBE between 44 and 72% of the applied dose of 200mg/kg was absorbed under occlusive conditions. The absorption rates were between 0.73 and 1.46mg/cm²/hr(Boatman, et al., 1993). In vitro, a comparable value of 0.51mg/cm²/hr was obtained (Barber, et al., 1992). Human skin seems to be less permeable. In the same study, a value of 0.29mg/cm²/hr was obtained for human skin, about half that of rat skin. Anotherin vitro study determined the permeability co-efficient through human skin only to be in the range 35μg/cm2/hr(Dugard, et al., 1984). A more recent study measured the permeability of neat DEGBE to be603±81ug/cm2/hr(Korinth, et al., 2012).

For DEGHE, Dermwin calculates a Kp value of 0.00181cm/hr, which corresponds to 30µg/cm²/hr. This is in the range of the values obtained for DEGBE. Taking this value into account as well as the reduced permeability of human compared to rat skin, dermal absorption for DEGHE will not exceed 50% compared to oral absorption.

Distribution

It seems reasonable to conclude based on the similar physicochemical characteristics of DEGHE (completely water soluble and highly hydrophilic) that once absorbed, the substance will be rapidly dispersed around the body. This is confirmed by data on EGHE, where comparable amounts were detected in all organs after dermal exposure (DOW, 1989). Additionally, no accumulation was detected with either EGHE or DEGBE, but instead the substances were rapidly excreted via urine.

Metabolism

Data from DEGBE from a dermal exposure study in rats shows that butoxyethoxyacetic acid is the primary metabolite, with some minor amounts of conjugates also produced (Boatman, et al., 1993). Recovered radioactivity was primarily in the urine and cage wash samples. This particular study did detect trace amounts of butoxyacetic acid, but not sufficient to be quantifiable and certainly not at toxicologically significant levels. An oral exposure study in rats using the acetate ether of DEGBE (which is rapidly metabolised back to DEGBE in vivo) showed a similar profile of major metabolites but also indicated that oxidation of the butyl chain can occur to produce a dihydroxide metabolite that is detected in urine(Deisinger, et al., 1989). This difference may be attributable to the different routes of exposure. This study also reported trace levels of butoxyethanol as a metabolite but the authors stated that this could not be quantified and could not rule out that its presence was be due to contamination.

The same structural groups with the same neighbouring environments are present with DEGHE as for DEGBE. It seems reasonable to expect similar metabolites produced from the same metabolic processes, since the only differences between the two substances is the longer alkyl chain as a result of the different alcohol used (hexanol instead of butanol). Based on the data for DEGBE, the following metabolites would be expected in the approximate proportions shown:

DEGHE metabolite	Approximate percentage
2-(2-(hexyloxy)ethoxy)acetic acid	60 - 80 %
Diethylene glycol	5 – 15%
2-(hexyloxy)ethanol (EGHE)	negligible
2-(2-,3- or 4- hydroxyhexyloxyethoxy)ethanol	app. 12%
DEGHE conjugates (glucuronide principally)	5 - 15%

 

Excretion

DEGBE, or rather is metabolites, are primarily excreted in urine (60-80%)(Boatman, et al., 1993). A small fraction leaves the body via the faeces or is exhaled as CO₂. 97% of the dermally absorbed material was eliminated within 24 hours in rats. EGHE is also quickly metabolised in rats and rabbits and mainly, i.e., 65 – 80%, excreted in urine(DOW, 1989). Half-lives for the rat vary between app. 16h after i.v. and 29h after dermal exposure. In the rabbit, the half-lives were between 25 and 39h after i.v. and dermal exposure, with generally lower values obtained after dermal uptake. As already described above, both substances are mainly metabolised via ADH, while a minor fraction might also be conjugated to glutathione. Similar elimination times and primary excretion via urine are also expected for DEGHE.