Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
migrated 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:
other: see 'Remark'
Remarks:
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.
Cross-reference
Reason / purpose:
reference to same study

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:
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

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
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 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:
no effects observed
Body weight:
no data
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:
not classified
Remarks:
Migrated information LD50 > 6900 mg/kg Criteria used for interpretation of results: expert judgment
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.