Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Oral: LD50 = 3930 mg/kg bw
Inhalation: LC0 = ca. 1 mg/L
Dermal: LD50 = > 2000 mg/kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Principles of method if other than guideline:
Single oral administration by stomach tube in male rats.
GLP compliance:
no
Test type:
standard acute method
Species:
rat
Strain:
other: albino Wistar
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 90 - 120 g
- Diet: Purina chows, supplemented by fresh vegetables
- Water: ad libitum
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: maximal concentration 500 mg/mL

MAXIMUM DOSE VOLUME APPLIED: Individual dose levels were not reported for any of the substances tested including the test substance considered herein. According to the authors, the highest dose level which could safely be hold at one time by the animal was just over 10% of the animal’s bodyweight, corresponding to approx. 50 g/kg bw, when a substance was administered as a 50% solution. This is equivalent to a dose volume of 100 mL/kg bw.
Furthermore, it was reported that in most cases 10 animals were dosed to determine the toxicity of a particular dosage and enough dosages were given to include those at which no mortality occurred and those at which all tested animals died.
The test substance was administered as a 50% solution and based on the information above and the resulting LD50 value, it appears unlikely that the test substance could have been administered at a dose volume > 100 mL/kg bw.
It is therefore assumed that the maximum dose volume applied was 100 mL/kg bw corresponding to a maximum dose level of 50000 mg/kg bw.
Doses:
Not specified (presumably up to 50000 mg/kg bw)
No. of animals per sex per dose:
ca. 10
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
Statistics:
The data were calculated by the method of probits, described by Bliss C.I. (1935. The calculation of the dosage-mortality curve. Ann. Appl. Biol. 22:134-167).
Sex:
male
Dose descriptor:
LD50
Effect level:
11 000 mg/kg bw
Based on:
test mat.
95% CL:
10 400 - 11 590
Remarks on result:
other: slope: 21.21
Mortality:
Mortality data were summarised for all substances tested. Therefore, no substance specific data were reported.
According to the authors, most deaths occurred within the first 48 h post-dose, but all deaths within 14 days post-administration were taken into account for calculation of LD50 values. In particular for ethers, death was delayed about a week.
Clinical signs:
other: The test substance was tested along with other glycol ethers. For this group, narcosis was observed but in most cases only at the LD50 or above.
Gross pathology:
Gross pathology findings were summarised for all substances tested. According to the authors, all doses caused some degree of irritation of the digestive tract. The primary target organ was the kidney; blood in urine and free blood beneath the capsule were seen at the highest dosages. The liver was less affected, but orange or reddish bile was often observed.
Interpretation of results:
GHS criteria not met
Conclusions:
CLP: not classified
DSD: not classified
Executive summary:

Median lethal dose (LD50) following administration of a single oral dose to the rat was in excess of 2000 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises adequate, reliable (Klimisch score 2) and consistent studies, and is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Principles of method if other than guideline:
8 h exposure to saturated vapour at room temperature to rats
GLP compliance:
no
Test type:
standard acute method
Species:
rat
Strain:
not specified
Sex:
not specified
Route of administration:
inhalation: vapour
Type of inhalation exposure:
not specified
Vehicle:
not specified
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
8 h
Concentrations:
saturated vapour (ca. 1 mg/L)
No. of animals per sex per dose:
no data
Control animals:
not specified
Details on study design:
- Necropsy of survivors performed: yes, 2 rats were killed for examination two weeks after exposure.
- Other examinations performed: heart, liver, kidney, spleen and lung were observed.
Sex:
not specified
Dose descriptor:
LC0
Effect level:
ca. 1 mg/L air
Based on:
test mat.
Exp. duration:
8 h
Remarks on result:
other: saturated vapour concentration based on molecular weight = 176.21 g/mol and vapour pressure = 13.19 Pa at 20°C
Mortality:
None of the test animals died.
Gross pathology:
The tissues from the two rats were completely normal.
Interpretation of results:
GHS criteria not met
Conclusions:
CLP: not classified
DSD: not classified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises adequate, reliable (Klimisch score 2) and consistent studies, and is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Principles of method if other than guideline:
Single dermal application of the test substance to guinea pigs.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
guinea pig
Strain:
not specified
Sex:
male/female
Type of coverage:
not specified
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Type of wrap if used: cotton poultice
Doses:
5, 10, 15, 20 and 30 mL/kg
No. of animals per sex per dose:
10 (each in total for 5 and 30 mL/kg)
4 (in total for 20 mL/kg)
8 (in total for 15 mL/kg)
12 (in total for 10 mL/kg)
Control animals:
not required
Sex:
male/female
Dose descriptor:
LD50
Effect level:
>= 30 000 mg/kg bw
Based on:
test mat.
Interpretation of results:
GHS criteria not met
Conclusions:
CLP: not classified
DSD: not classified
Executive summary:

Median lethal dose (LD50) following dermal administration to the guinea pig was in excess of 2000 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises studies which each alone are regarded insufficient for assessment (Klimisch score 2-4). However, the information from these independent sources is consistent and provides sufficient weight of evidence for hazard assessment leading to an endpoint conclusion in accordance with Annex XI, 1.2, of Regulation (EC) No 1907/2006. Therefore, the available information as a whole is sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, of Regulation (EC) No 1907/2006.

Additional information

Acute oral toxicity

Two acute oral toxicity studies with 2-(2-ethoxyethoxy)ethyl acetate in rats and guinea pigs are available (Smyth, 1941). 2 -(2-ethoxyethoxy)ethyl acetate was administered as single oral dose by stomach tube in male rats and guinea pigs.

In rats and guinea pigs, groups of 10 animals received 2-(2-ethoxyethoxy)ethyl acetate as 50% dispersion in water. The observation period following administration was 14 days. The data were calculated by the method of probits. The precision is indicated by the range of 95% probability. The resulting LD50 value of the study in male rats was evaluated to be 11000 mg/kg bw and for guinea pigs 3930 mg/kg bw. Thus, the oral LD50 of 2-(2-ethoxyethoxy)ethyl acetate (CAS 112-15-2) is considered to be greater than 3930 mg/kg bw.

Acute inhalation toxicity

An acute inhalation toxicity study with 2-(2-ethoxyethoxy)ethyl acetate was performed in rats and guinea pigs (Smyth, 1939). Animals were exposed for 8 h to saturated vapour of the test material at room temperature. No mortality occurred and the observed tissues from two rats were normal. One guinea pig showed minor reversible changes in the kidney and another guinea pig showed slight evidence of lung irritation (no further information). Thus, the LD0 value for rats and guinea pigs was ca. 1 mg/L air.

Acute dermal toxicity

The acute dermal toxicity of 2-(2-ethoxyethoxy)ethyl acetate was evaluated by a single dermal application to guinea pigs (Smyth, 1940). Groups of 4 to 12 animals were treated with 5, 10, 15, 20 and 30 mL/kg of the undiluted test substance. The resulting LD50 value was greater than 30000 mg/kg bw.

In addition, a study report was cited in the SIDS Initial Assessment Report For SIAM 21 (OECD SIDS). 2-(1-methylethoxy)ethyl acetate was tested in rabbits and a LD50 value of 15000 mg/kg bw was evaluated.

Thus, the results of the two studies showed no effects at or exceeding the limit dose of 2000 mg/kg bw. Therefore, the dermal LD50 is considered to be greater than 2000 mg/kg bw.

Conclusion for acute toxicity

In summary, studies from 2-(2-ethoxyethoxy)ethyl acetate (CAS 112-15-2) investigating the acute oral toxicity in rats and guinea pigs resulted in oral LD50 values of 11000 and 3930 mg/kg bw, respectively, and thus greater than the limit dose value of 2000 mg/kg bw.

For acute inhalation toxicity, a study with 2-(2-ethoxyethoxy)ethyl acetate (CAS 112-15-2) in rats and guinea pigs are available. From these studies, a LC0 value of ca. 1 mg/L (saturated vapour concentration) was obtained.

Acute dermal toxicity studies conducted with 2-(2-ethoxyethoxy)ethyl acetate (CAS 112-15-2) showed no effects at or exceeding the limit dose of 2000 mg/kg bw, resulting in an dermal LD50 values of 15000-30000 mg/kg bw..

Thus, the available data indicate a very low level of acute toxicity and thus no hazard for acute oral, inhalative and dermal toxicity was identified.

Justification for classification or non-classification

The available data on acute, dermal and inhalation toxicity of 2-(2-ethoxyethoxy)ethyl acetate (CAS 112-15-2) do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and the data are therefore conclusive but not sufficient for classification.