2-(2-ethoxyethoxy)ethanol

Endpoint summary

Description of key information

ORAL LD50 values:
Rat, male: 5900-6100, 6310, 6439, 7300, 9740, 10502 (fasted), 15918 (fed) mg/kg, >5000mg/kg. 6.62mg/kg
Rat, female :4900-5600mg/kg, <5000mg/kg, 6.42mg/kg
Rat, sex not specified: 3956-4945, >5000, 5340, 5400, 5500, 6300, 6400, 6500, 7500, 8690mg/kg
Mouse, male: 6031mg/kg (fed and fasted)
Mouse, sex not specified: 6500, 7248, 7863, 12400mg/kg
Rabbit: 4450, 5600mg/kg
Guinea pig: 3000, 3800, 4970 mg/kg
INHALATION
LC50>saturated vapour pressure (0.94mg/l)
LC50>5.24mg/l (aerosol)
DERMAL (mg/kgbw)
Rabbit: male: 9143, 1176.  Female: 8476.  Sex not specified: 7714, 8500
Guinea pig: 5900

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Dose descriptor:

LD50

Value:

6 031 mg/kg bw

Acute toxicity: via dermal route

Endpoint conclusion

Dose descriptor:

LD50

Value:

9 143 mg/kg bw

Additional information

ORAL ROUTE

In a single dose acute oral toxicity study, male CD/BR rats were exposed to 2 -(2 -ethoxyethoxy)ethanol. The experiment was repeated in duplicate, once with fasted animals and once with fed animals. The LD50 values established were 10502mg/kg and 15918mg/kg in fasted and fed animals respectively.. Sub-lethal effects included labored breathing, rapid respiration, anorexia, slight to moderate weakness, tremors and prostration. In another well reported acute oral toxicity study, the LD50 of the substance in rats was reported to be approximately 6439mg/kg bw following acute oral administration, with sub-lethal effects of fur ruffling and staggering reported, both of which disappeared at the end of the observation period. In a single dose acute oral toxicity study, male Wistar albino rats were exposed to 2 -(2 -ethoxyethoxy)ethanol. The LD50 value established was 9740mg/kg. In an old acute oral toxicity study for which only basic details are reported, an LD50 of 8690mg/kg was obtained and in another pre-guideline study and LD50 of approximately 5340mg/kg bw following acute oral administration to rats is reported. Numerous other similar values have been reported and are shown in the key description field above.

In a single dose acute oral toxicity study, male CD-1 mice were exposed to 2 -(2 -ethoxyethoxy)ethanol. The experiment was repeated in duplicate, once with fasted animals and once with fed animals. The LD50 values established were 6031mg/kg for both fed and fasted mice. Sub-lethal effects included laboured breathing, rapid respiration, anorexia, slight to moderate weakness, tremors and prostration. In a single dose acute oral toxicity study, Swiss mice were exposed to 2 -(2 -ethoxyethoxy)ethanol. The LD50 established was 7863mg/kg.

In a single dose acute oral toxicity study, male and female guinea pigs were exposed to 2 -(2 -ethoxyethoxy)ethanol. The LD50 obtained was 4970mg/kg. An LD50 of 3000mg/kg after oral acute administration was reported in another study for which only limited details are available from a secondary source.

An oral LD50 of 4450mg/kg bw was reported in a study in rabbit, however the lack of experimental detail renders this result as unreliable. A secondary source reports a LD50 of 3620mg/kg bw following acute oral administration to rabbits. Another study containing sufficient details reports an LD50 of 5600mg/kg. In conclusion, much data is available on the acute oral toxicity of this substance, varying from reliable through to unreliable and including data which cannot be verified for its reliability. The key parameter chosen is the lowest value for mice. The values for rat spread over a wide range, but the value selected for the mouse is representative of the lower middle range. The rat and guinea pig are not preferred species for this end point and therefore values are not selected from this data set. LD50 values for rabbit and guinea pig fall within the range of the rat data. DERMAL ROUTE

In a single 24 hour exposure dermal toxicity study, male NZ white rabbits were exposed to 2 -(2 -ethoxyethoxy)ethanol. The LD50 value established was 9143mg/kg. Sub-lethal effects included at lower doses anorexia, slight depression, cyanosis, ataxia, soft faeces, and at higher doses salivation, nasal discharge, iritis, significant depression, llaboured breathing, and prostration.. No adverse pathology was found at doses of 5628mg/kg and below. Based on the results of this study, this substance would not be classified for acute toxicity in accordance with the current EU guidelines.  In another study rabbits were exposed to 2 -(2 -ethoxyethoxy)ethanol applied as single doses to their abdomen for two hours. The LD50 established was 8500mg/kg. Marked hydropic degradation of the renal tubular epithelium was observed in 7/16 high dose rabbits (doses were not stated). No pathological changes were detected in the liver, lungs, heart or gonads. An acute dermal toxicity study in rabbits for which results are only available from a secondary source reports a LD50 of 8476mg/kg bw in female and 11176mg/kg bw in male animals. The experimental conditions are not available. A further acute dermal toxicity study in rabbits reported an LD50 of 7714mg/kg bw although only very limited experimental details were available in what is quite an old pre-guideline study. An acute pre-guideline dermal toxicity study in guinea pigs deduced an LD50 of 5900mg/kg bw for a lower grade of 2-(2-ethoxyethoxy)ethanol and 10500mg/kg bw for glycol-free grade. These values are within the range shown in rabbits.

INHALATION

In an inhalation hazard test that followed the basic principles of a guideline acute inhalation toxicity test, male and female rats were subjected to a 'saturated' atmosphere of 2 -(2 -ethoxyethoxy)ethanol, characterised as 25mg/m3, for a period of 8 hours. No deaths were reported. On this basis, the substance was assessed to have a low hazard by the inhalation route

Justification for classification or non-classification

There are 19 oral LD50 studies in the preferred species of rat and mouse spanning the range 5900 to 15918mg/kg. The overwhelming balance of evidence indicates that this substance is of sufficient low oral toxicity that classification is not required. This conclusion is supported by the 4 additional results from a non-preferred species, which all show LD50's well above 2000mg/kg

Based on the results of this study the test substance would clearly not be classified according to the EU classification system for the dermal route.

The substance is of low volatility. A study designed to assess the hazard of the substance at saturated vapour concentrations produced no mortality in rats when subject to such conditions for 8 hours. There is therefore no data indicating classification is required by the inhalation route.