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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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

Description of key information


Dog: 1000 mg/kg (90 day)

Rat: 250, 800 (90 day), 1340mg/kg (42 day)

Mouse: ~5000mg/kg (14 day), 1000mg/kg (28 day)

Pig: 167mg/kg (90 day)


NOEC (28 days, rats) >saturated vapour pressure. Local effects with NOEC of 0.09mg/L

DERMAL (mg/kgbw/day)

Rabbit 28 day: Systemic effects NOAEL>1000. Local effects NOAEL=300 (based on histopathology), NOEL=100 based on transient irritation.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
1 000 mg/kg bw/day

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
90 mg/m³
Study duration:

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

Oral route

In a GLP 13 -week study in male and female dogs, 2 -(2 -ethoxyethoxy)ethanol was administered at 400, 1000, or 2000mg/kg/day by oral gavage. A fourth control group was given the vehicle water. Based on the results of this study, the initial high dose of 2000mg/kg/day was not well tolerated as evidenced by clinical findings, pronounced body weight losses and decreased food consumption which resulted in mortality for 2 males and 1 female within the first 2 weeks of dose administration. The primary histologic alteration contributing to the morbidity for these dogs was severe renal tubular degeneration in the kidney. The dosage level was subsequently lowered to 1500mg/kg/day for the remaining animals. Slight, non-adverse differences from controls in hematology, serum chemistry and urine chemistry parameters were noted in the 400, 1000 and/or 2000/1500mg/kg/day groups. Higher liver weights were observed in the 1000mg/kg/day female group and the 2000/1500mg/kg/day group at the scheduled necropsy, which may be associated with the slightly elevated srum ALP levels resulting from an adpative response related to the metabolism of the test article. There were no organ-specific microscopic findings of consequence at any dosage level for the animals surviving to the scheduled necropsy, and the histologic alterations in the unscheduled death animals associated with dosage at 2000mg/kg/day were considered reversible, since there was no histologic evidence of injury in the animals continued to be dosed at 1500mg/kg/day. The 1500mg/kg/day dose was well tolerated. Based on the results of this study the NOAEL was considered to be 1000mg/kg/day (3159 -6346 ug*h/ml) for both male and female dogs.

In an old but reliable 90 -day subchronic study male and female rats were fed a diet containing 0%, 0.5% or 5% 2 -(2'-ethoxyethoxy)ethanol. Standard measurements and haematology, clinical biochemistry and urinalysis were conducted as well as necropsy, organ weight determination and histopathology. In the high dose group a decrease in body weight gain, anemia, and oxaluria were observed, as well as an increase in relative organ weight (kidneys, spleen and thyroid), hydropic degeneration of kidney and calcification of the renal cortex. No treatment related changes were seen in the low dose group which approximated an average intake of 350 mg/kg/day. In a very similar 90 -day subchronic study carried out at the same time male and female rats were fed a diet containing 0%, 0.25%, 1.0% or 5% 2 -(2'-ethoxyethoxy)ethanol. Standard body weight and food consumption measurements and haematology, blood urea and urinalysis were conducted as well as necropsy, organ weight determination and histopathology. In the high dose group a decrease in body weight gain associated with lower food intake, and renal effects in the form of increase kidney weight, raised levels of GOT, proteinuria in males, and hydropic degeneration were observed. The high dose group also presented testicular edema and fatty liver changes. No treatment related changes were seen at 0.25% and 1.0% dose groups. The authors noted the presence of low levels of ethylene glycol in the test material, to which the kidney effects could be attributed and the testicular effects need to be interpreted in context of the findings of more recent reprotoxicity studies (reported elsewhere) and the dose at which they were seen (up to 5g/kg). The NOEL in this study was established at 1.0% diet, approximately 800 mg/kg/day. This is used as the key parameter since the NOAEL from the study above is limited by the two widely spaced doses used.

In a 6 week sub-acute gavage study that broadly followed the standards for the guideline pertaining at the time, standard toxicological end points were studied for rats in doses up to 5360mg/kg of 2 -(2 -ethoxyethoxy)ethanol. A number of adverse effects were seen in the high dose group including significant mortality. The only effects seen in the mid dose group were increases and decrease in relative organ weights (liver, kidney, heart). No treatment related changes were seen in the low dose group. The NOAEL was established as 1340mg/kg/day.

In a dose range finding study for a two generation study, male and female CD-1 mice were exposed to 2 -(2'-ethoxyethoxy)ethanol at the levels of 0, 1, 2, 3, 4, or 5%w/v in drinking water for 14 days. There was one death at the highest dose and reduction of weight gain at the two highest doses. The NOAEL was established at 3% w/v of the compound in drinking water, which has been estimated to be equivalent to 5g/kg/day.

An number of other very old studies are available using rat an mice but these have significant methodological shortcomings and are therefore considered unreliable. Studies have been carried out in a number of non standard species including the pig, cat and ferret. Those in the pig cannot be rated as definitely reliable. The study in the pig is considered reliable. In this 90 -day subchronic study, male and female pigs were given an oral daily dose of 0, 167, 500, 1000 or 1500 mg/kg of 2 -(2'-ethoxyethoxy)ethanol. Standard measurements and haematology, clinical biochemistry and urinalysis were conducted as well as necropsy, organ weight determination and histopathology. There were signs toxicity and some mortality at the highest dose. Hydropic degeneration of liver and proximal tubules of the kidney was observed at 500mg/kg and above. In males, there was an increase in the relative weight of kidneys at 1000 mg/kg and anemia at 1500mg/kg. The NOAEL was established at 167mg/kg/day. As this is not a preferred species, it is not used for the key parameter. However, if allometric scaling is considered, this result is not so different to the rat derived NOAEL.

Dermal route

In a 28 -day repeat dose dermal toxicity study with male and female rabbits, 2 -(2 -ethoxyethoxy)ethanol was administered via the dermal route at 100, 300, or 1000mg/kg/day. The test substance was applied on consecutive days for six hours every day under occlusion. The control group received daily applications of distilled water at 1000mg/kg/day. Haematological, and clinical chemistry evaluations at initiation and termination, and gross necropsy and histopathology at terminal sacrifice were conducted. In addition, the dermal irritation reactions were evaluated following the Draize method. Under the conditions of this study the test substance did not induce toxicity at dose levels up to 1000mg/kg/day. However, the incidence of dermal irritation increased with increasing dose and microscopic examination revealed treatment associated change limited to the treated skin of the high dose rabbits. Therefore, under the conditions of this study, the NOAEL would be >1000mg/kg/day for systemic toxicity, and at 300mg/kg/day for local effects if based on histopathological changes or 100mg/kg/day if based on reversible irritation (erythema/odema).

Inhalation route

In a 28 -day study conducted according to guideline, male and female rats were exposed to 0.09, 0.27 or 1.1mg/l of 2 -(2'-ethoxyethoxy)ethanol in an inhalation chamber for 6 hours per day, 5 days per week. There were no changes indicative of a systemic effect at any of the doses tested. Changes indicative of mild local respiratory tract irritation were seen in rats exposed at 0.27mg/liter or 1.1mg/liter, and a slight increase in eosinophilic inclusions in the oflactory epithelium of the nasal mucosa at 1.1mg/liter. No effects indicative of mild local irritation were observed at 0.09mg/liter. In conclusion, the NOAEL for systemic effects can be established at 1.1mg/liter and for local effects at 0.09mg/liter. Bearing in mind the lack of systemic effects seen at up to the saturated vapour concentration of 0.94mg/l and the fact that only limited local effects were seen in the respiratory tract, a sub-acute study is considered sufficient for this end point and a sub-chronic study is not necessary. Any DNEL derived from this result is considered only to apply to exposure to the substance in aerosol and not vapour form for which no adverse effects are observed.

Justification for classification or non-classification

There is no evidence from oral studies that classification for repeated dose effects by the oral route is warranted.

Very mild local effects were seen following repeated daily dermal exposure in animals. In the absence of any evidence for similar effects in humans, this effect is not considered sufficient to warrant adding an EUH066 risk phrase.

A sub-acute study up to the saturated vapour pressure of the substance and using aerosol exposure above this level showed some evidence of respiratory irritation. Aerosols showed a slight increase in the levels of eosinophilic inclusions in the nasal turbinates from trace levels in controls and vapour exposures to slight in animals exposed to aerosols/mists at 1mg/l, ie above threshold for classification for repeated dose effects, even allowing for a possible extraopolation for duration. Exposure to vapour at the highest tested dose (30% of the theoretical maximum vapour pressure) showed focal necrosis in the ventral cartilage of 2/5 males but no females. Since this tissue is known to be a site of sensitivity in rat inhalation studies, the effects were only seen in males, and the differences in morphology of the rat versus the human nasal passages make it more sensitive to effects from inhalation of xenobiotics, the significance for humans is questionable. The effects are considered insufficient to warrant consideration for classification for repeated dose effects.