Bis(2-(2-methoxyethoxy)ethyl) ether

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1984

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

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:

1984

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

The target chemical belongs to the homologues series of glymes, where there is an incrementa increase in the number of CH2CH2O (glycol) units. It can be assumed that target and other glyme members (mono., di. and triglyme) share the same toxic mode of action.

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, only 2 animals per dose tested, limitations in study reporting

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
-Strain: COBS/Wistar rats
- Age at study initiation: no data
- Weight at study initiation: 225-306 g (male animals)
- Animalsa caged singly

Type of coverage:

other: non-occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: shaved, ca. 20 - 25% of the body surface on the backs and the flanks of the animals

Duration of exposure:

no data

Doses:

1.7 g/kg body weight
3.5 g/kg body weight
6.9 g/kg body weight

No. of animals per sex per dose:

2 males

Control animals:

no

Details on study design:

The tests used a non-occluded technique.
Volumes of the compound (0.1 ml to 2.0 ml maximum) were applied to shaved areas (approximately 20-25% of the body surface) on the backs and the flanks of the animals. "Toby" collars prevented grooming and the contaminated areas were not covered.
Animals were caged singely under normal conditions.

Statistics:

not required

Preliminary study:

no preliminary study performed

Sex:

male

Dose descriptor:

LD50

Effect level:

> 6 900 mg/kg bw

Mortality:

No mortality

Clinical signs:

other: no effects observed

Gross pathology:

no data

Other findings:

No further findings

Analog Approach Justification:

The analogue approach using glymes as source chemical is justified:

a.   The target chemical belongs to the homologues series of glymes, where there is an incremental increase in the number of CH2CH2O units. Therefore, it can be assumed that target and other glyme members (mono-, di-, and triglyme) share the same toxic mode action.

b.   The findings in repeated dose toxicity studies are comparable for target and source chemicals: the target is the male reproductive organ. Further, findings in thymus and altered hematological values are indicative of altered blood system.

c.    The findings in reproductive performance are comparable: No live pubs and/or reduced number of pubs were the common finding.

d.   The findings in developmental toxicity studies are comparable: the most notable findings were paw skeletal malformations. These findings were observed also at dose levels not associated with apparent maternal toxicity.

Interpretation of results:

GHS criteria not met

Conclusions:

No classification is warranted for tetraglyme based on the read-across approach using triglyme as read-across supporting substance. The median lethal dose (LD50) of triglyme for the dermal route of application is greater 6900 mg/kg body weight in male rats.

Executive summary:

The acute dermal toxicity of tetraglyme was assessed based on the read-across appoach using triglyme as read-across supporting substance.

Three groups of male wistar rats (2 animals per group) were exposed to triglyme on the shaved areas on the backs and flanks of the animals. The median lethal dose (LD50) of triglyme for the dermal route of application is greater 6900 mg/kg body weight in male rats.

No classification is warranted for tetraethylene glycol dimethyl ether based on the analogue approach.

Data source

Reference

Reference Type:

publication

Title:

Dermal toxicity of (...) triethylene glycol dimethyl ether

Author:

Clark, B. , Furlong, J., Ladner, A., Slovnak, A.

Year:

1984

Bibliographic source:

IRCD Med. Sci. 12, 296-297, 1984.

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, only 2 animals per dose tested, limitations in study reporting

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

1,2-bis(2-methoxyethoxy)ethane

EC Number:

203-977-3

EC Name:

1,2-bis(2-methoxyethoxy)ethane

Cas Number:

112-49-2

Molecular formula:

C8H18O4

IUPAC Name:

2,5,8,11-tetraoxadodecane

Constituent 2

Reference substance name:

Triethylene glycol dimethyl ether

IUPAC Name:

Triethylene glycol dimethyl ether

Constituent 3

Reference substance name:

Triglyme

IUPAC Name:

Triglyme

Details on test material:

- Name of test material (as cited in publication): Triglyme
- Analytical purity: not stated
- physical state: clear colourless liquid
- MW 178.23
- LogPow - 0.52
- Vapour pressure (20°C) 2.7 Pa
- Water solubility miscible

Test animals

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
-Strain: COBS/Wistar rats
- Age at study initiation: no data
- Weight at study initiation: 225-306 g (male animals)
- Animalsa caged singly

Administration / exposure

Type of coverage:

other: non-occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: shaved, ca. 20 - 25% of the body surface on the backs and the flanks of the animals

Duration of exposure:

no data

Doses:

1.7 g/kg body weight
3.5 g/kg body weight
6.9 g/kg body weight

No. of animals per sex per dose:

2 males

Control animals:

no

Details on study design:

The tests used a non-occluded technique.
Volumes of the compound (0.1 ml to 2.0 ml maximum) were applied to shaved areas (approximately 20-25% of the body surface) on the backs and the flanks of the animals. "Toby" collars prevented grooming and the contaminated areas were not covered.
Animals were caged singely under normal conditions.

Statistics:

not required

Results and discussion

Preliminary study:

no preliminary study performed

Effect levels

Sex:

male

Dose descriptor:

LD50

Effect level:

> 6 900 mg/kg bw

Mortality:

No mortality

Clinical signs:

other: no effects observed

Gross pathology:

no data

Other findings:

No further findings

Any other information on results incl. tables

Analog Approach Justification:

The analogue approach using glymes as source chemical is justified:

a.   The target chemical belongs to the homologues series of glymes, where there is an incremental increase in the number of CH2CH2O units. Therefore, it can be assumed that target and other glyme members (mono-, di-, and triglyme) share the same toxic mode action.

b.   The findings in repeated dose toxicity studies are comparable for target and source chemicals: the target is the male reproductive organ. Further, findings in thymus and altered hematological values are indicative of altered blood system.

c.    The findings in reproductive performance are comparable: No live pubs and/or reduced number of pubs were the common finding.

d.   The findings in developmental toxicity studies are comparable: the most notable findings were paw skeletal malformations. These findings were observed also at dose levels not associated with apparent maternal toxicity.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 > 6900 mg/kg is obtained for acute dermal toxicity for triglyme.

Executive summary:

Three groups of male wistar rats (2 animals per group) were exposed to triglyme on the shaved areas on the backs and flanks of the animals. The median lethal dose (LD50) of triglyme for the dermal route of application is greater 6900 mg/kg body weight in male rats.