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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Link to relevant study record(s)

Description of key information

TTEG is expected to be completely absorbed by oral route and mainly excreted unchanged in urine. Dermal absorption is also rapid. Metabolism is limited, as TTEG is expected to be found mainly unchanged in urine, with some monocarboxylic acid arising by metabolic oxidation of the terminal hydroxyl group as well as glucuronide conjugation of the parent glycol. Overall, TTEG has no bioaccumulation potential.

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

The metabolism data is based on lower ethylene glycol analogues and in vitro DEG, TEG, TTEG and pentaEG studies with alcohol dehydrogenase. Their potential for metabolic oxidation decreases with increasing number of ethylene glycol units per molecule as seen experimentally from in vitro derived Vmax and Km kinetic values. Tetraethylene glycol has similar MWs and physicochemical properties to other higher ethylene glycol analogues. However, the use of ethylene glycols with lower chain lengths such as triethylene glycol is considered as worst-case scenario as metabolism decreases with increasing number of ethylene glycol units per molecule. Therefore, this represents a conservative approach to deriving absorption rate values. For more detailed discussion on the metabolism of higher ethylene glycol source analogues, refer to the read-across justification document.

Absorption:

Triethylene glycol (TEG), as well as lower ethylene glycol substances, are completely and rapidly absorbed via oral route in animals. Therefore, it is expected that tetraethylene glycol (TTEG) will also be completely absorbed from gastrointestinal tract due to ethylene glycols' complete solubility in water and low molecular weights. Likewise, the absorption estimate via inhalation route will be assumed as 100 percent. Dermal bioavailability of TTEG is based on diethylene glycol (DEG) data and 20% absorption rate assumed for TTEG. As 13-week dermal data is available for TTEG with NOEL of 3360 mg/kg/day, there is no systemic and local toxicity observed via the dermal route. For dermally applied DEG, 47.2, 32.6, 29.2 and 16.8% remained after 15 minutes, 64 minutes, 8 hours and 24 hours, respectively. After 15 minutes of dermal contact with DEG, a radioactive peak appeared at ~ 112 microns into the layer of the skin indicating rapid absorption via dermal route. After 8h and 24h contact, 11.9% and 32.2% radioactivity was detected in the rat urine.

Distribution and Bioaccumulation Potential:

Since ethylene glycol substances are completely soluble in water, they are expected to be well distributed throughout the aqueous tissues of the body and have no or low concentrations in adipose tissue. Therefore, ethylene glycol analogues and TTEG are considered to have no bioaccumulation potential.

Metabolism:

The main pathway for metabolism of the ethylene glycol analogues is oxidation via alcohol dehydrogenases and aldehyde dehydrogenases however, the majority of ethylene glycol analogues will be either unchanged or conjugated with glucuronide. 

In vitro, ethylene glycols are substrates for alcohol dehydrogenase. Vmax and Km for metabolism of the ethylene glycols consistently decreases with the increased number of glycol units from tri- to pentaethylene glycol.

In both the rat and the rabbit, TEG showed a high degree of urinary excretion of unchanged compound, in addition to monocarboxylic acid arising by metabolic oxidation of the terminal hydroxyl group on the parent glycol as well as glucuronide conjugation.  The oxidation product is a monocarboxylic acid that arises by metabolic oxidation of the terminal hydroxyl group of the parent glycol in both rats and rabbits. The low order of excretion of radioactivity by way of respiratory carbon dioxide demonstrated that the cleavage of carbon bonds of the administered TEG occurred to only a limited extent. Respiratory carbon dioxide in the rat constituted only 1% of the radioactive dose and most of this activity appeared during the first 12-hour period after administration. The evidence suggests that metabolic cleavage of the ether linkages and formation of ethylene glycol wound not be important events in the metabolism of TTEG.

Excretion:

The excretion of ethylene glycols is rapid with the urine being the major excretory route in the rat and rabbit. Animal studies indicate a high degree of urinary excretion of unchanged TEG in addition to the excretion of oxidized glycol acid metabolite. >85% of the orally administered TEG to rats was recovered within 24 hours. 86.1 - 94.0% of the administered dose was recovered within 5 days in the urine. Approximately 95% of the recovered radioactivity, or 90% of the C14 dose, appeared in the urine with lesser amount in the feces. The total elimination of radioactivity (in urine, feces, and expired air) during the 5-day period following a single oral dose in rat was 91-98%. For dermally applied DEG, in contact with the rat skin for 8 and 24 hours,12 and 32.2% of the radioactivity was identified in the urine, respectively.