Bis(2-methoxyethyl) ether

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1981

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study according to OECD402; no individual data reported

Justification for type of information:

Diethylene glycol dimethylether and 1,2-Diemethoxyethane which is tested for its acute inhalation toxicity, belong to the glycol ether family. These substances have been demonstrated to be very similar in structure, physical/chemical properties and the toxicological profile. Due to the fact that diethylene glycol dimethylether and 1,2-Diemethoxyethane have nearly the same chemical structure (especially with reference to the functional groups):

1. Diethylene glycol dimethyl ether: H3C-O-CH2-CH2-O-CH2-CH2-O-CH3

2. 1,2-Diemethoxyethane: H3C-O-CH2-CH2-O-CH3

the same mode of interaction with living cells and tissue is expected based in the same metabolism. Within metabolism, the active metabolite 2-methoxyethanol is formed for both substances. This metabolite is driving force behind the toxicological profile of both substances. Therefore, a read-across from diethylene glycol dimethylether to data obtained with 1,2-Diemethoxyethane is scientifically justified.

Cross-reference

Reason / purpose for cross-reference:

read-across source

Reference

Endpoint:

acute toxicity: dermal

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

1981

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study according to OECD402; no individual data reported

Justification for type of information:

Diethylene glycol dimethylether and 1,2-Diemethoxyethane which is tested for its acute inhalation toxicity, belong to the glycol ether family. These substances have been demonstrated to be very similar in structure, physical/chemical properties and the toxicological profile. Due to the fact that diethylene glycol dimethylether and 1,2-Diemethoxyethane have nearly the same chemical structure (especially with reference to the functional groups):

1. Diethylene glycol dimethyl ether: H3C-O-CH2-CH2-O-CH2-CH2-O-CH3

2. 1,2-Diemethoxyethane: H3C-O-CH2-CH2-O-CH3

the same mode of interaction with living cells and tissue is expected based in the same metabolism. Within metabolism, the active metabolite 2-methoxyethanol is formed for both substances. This metabolite is driving force behind the toxicological profile of both substances. Therefore, a read-across from diethylene glycol dimethylether to data obtained with 1,2-Diemethoxyethane is scientifically justified.

Reason / purpose for cross-reference:

assessment report

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

only one sex tested, limitations in study reporting

Principles of method if other than guideline:

acute dermal toxicity after single application

GLP compliance:

no

Remarks:

performed before GLP guidelines

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hoechst AG, Kastengrund, SPF breed
-Strain: Hoe WISKf(SPF71)
- Age at study initiation: no data
- Weight at study initiation: 170 - 176 g (female animals); (mean = 172,7 g; s = ± 2,42; n = 6)
- Diet (e.g. ad libitum): Altromin 1324 ad libitum
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Housing: single, in plastic cages, softwood pellets

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 30 cm2
- % coverage: 100
- Type of wrap if used: aluminium foil (6 x 8 cm) fixed with elastic bandage (Elastoplast, 8 cm)


REMOVAL OF TEST SUBSTANCE
- Washing. lukewarm water
- Time after start of exposure: 24 h


TEST MATERIAL
- Amount(s) applied: 500 mg/kg bw undiluted test substance was applied

Duration of exposure:

24 hours

Doses:

5000 mg/kg body weight

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical observation after application; weighing once weekly
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, mortality

Preliminary study:

no preliminary study performed

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Mortality:

No mortality

Clinical signs:

other: No clinical symptoms detectable.

Gross pathology:

No macroscopic visible changes.

Other findings:

No further findings.

Interpretation of results:

GHS criteria not met

Conclusions:

The median lethal dose (LD50) of diethylenglykol dimethylether was derived from the structural analogue supporting substance monoethylene glycol dimethyl ether to be greater 5000 mg/kg body weight in female rats.

Executive summary:

The median lethal dose (LD50) of diethylenglykol dimethylether was derived from the structural analogue supporting substance monoethylene glycol dimethyl ether to be greater 5000 mg/kg body weight in female rats. Therefore, there ist no justifaction for a classification of diethyleneglycol dimethyl ether as acute toxic.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1981

Report date:

1981

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

only one sex tested, limitations in study reporting

Principles of method if other than guideline:

acute dermal toxicity after single application

GLP compliance:

no

Remarks:

performed before GLP guidelines

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Monoethylenglykoldimethylether

IUPAC Name:

Monoethylenglykoldimethylether

Constituent 2

Reference substance name:

1,2-dimethoxyethane

EC Number:

203-794-9

EC Name:

1,2-dimethoxyethane

Cas Number:

110-71-4

Molecular formula:

C4H10O2

IUPAC Name:

1,2-dimethoxyethane

Details on test material:

- Name of test material (as cited in study report): Monoethylenglykoldimethylether
- Analytical purity: not stated
- physical state: clear colourless liquid

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hoechst AG, Kastengrund, SPF breed
-Strain: Hoe WISKf(SPF71)
- Age at study initiation: no data
- Weight at study initiation: 170 - 176 g (female animals); (mean = 172,7 g; s = ± 2,42; n = 6)
- Diet (e.g. ad libitum): Altromin 1324 ad libitum
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Housing: single, in plastic cages, softwood pellets

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 30 cm2
- % coverage: 100
- Type of wrap if used: aluminium foil (6 x 8 cm) fixed with elastic bandage (Elastoplast, 8 cm)


REMOVAL OF TEST SUBSTANCE
- Washing. lukewarm water
- Time after start of exposure: 24 h


TEST MATERIAL
- Amount(s) applied: 500 mg/kg bw undiluted test substance was applied

Duration of exposure:

24 hours

Doses:

5000 mg/kg body weight

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical observation after application; weighing once weekly
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, mortality

Results and discussion

Preliminary study:

no preliminary study performed

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Mortality:

No mortality

Clinical signs:

other: No clinical symptoms detectable.

Gross pathology:

No macroscopic visible changes.

Other findings:

No further findings.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The median lethal dose (LD50) of diethylenglykol dimethylether was derived from the structural analogue supporting substance monoethylene glycol dimethyl ether to be greater 5000 mg/kg body weight in female rats.

Executive summary:

The median lethal dose (LD50) of diethylenglykol dimethylether was derived from the structural analogue supporting substance monoethylene glycol dimethyl ether to be greater 5000 mg/kg body weight in female rats. Therefore, there ist no justifaction for a classification of diethyleneglycol dimethyl ether as acute toxic.