Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: well-documented publication, which meets basic scientific principles
Reason / purpose:
reference to same study
Qualifier:
no guideline followed
Principles of method if other than guideline:
The test material was applied on the clipped backs of Albino rabbits and held in contact under semiocclusive conditions during 24 hours. The readings were made directly and after 48 hours after the pathch removal.
GLP compliance:
no
Species:
rabbit
Strain:
other: Albino
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2.0 - 3.2 kg
Type of coverage:
semiocclusive
Preparation of test site:
other: clipped over the back and flanks, and four areas of the back designated for the test, two intact and two scarified with wire mesh
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
no details given
Duration of treatment / exposure:
24 hours
Observation period:
72 hours
Number of animals:
no data
Details on study design:
Albino rabbits were clipped over the back and flanks, and four areas of the back designated for the test, two intact and two scarified with wire mesh. The animals were immobilized in a multiple rabbit holder (Laug, 1944), and patches of gauze were secured over the areas with adhesive tape. The compounds were introduced under the patches, and the entire trunk of the rabbits enveloped in rubber dam. After 24 hours the rabbits were released, the resins removed, and a first reading made. After 72 hours a second reading was made.
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24 and 72 h
Score:
5
Reversibility:
no data
Remarks on result:
other: moderately irritating
Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
This well-documented publication gives a detailed information about the experiments conducted and meets basic scientific principles. Therefore it is considered to be of the high quality (reliability Klimisch 2). The validity criteria of the test system are fulfilled. EPON 562 was moderately irritating, with a score of five.
Executive summary:

The skin irritation potential of Polyglycidyl Ether of Substituted Glycerin (EPON 562) was investigated by Hine et al.(1958). The test material was administered semiocclusively to rabbits (male Albino). The rabbits were clipped over the back and flanks, and four areas of the back designated for the test, two intact and two scarified with wire mesh. The animals were immobilized in a multiple rabbit holder, and patches of gauze were secured over the areas with adhesive tape. The compound was introduced under the patches, and the entire trunk of the rabbits enveloped in rubber dam. After 24 hours the rabbits were released, the resin removed, and a first reading made. After 72 hours a second reading was made. EPON 562 was moderately irritating, with a score of 5.

 

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: well-documented publication, which meets basic scientific principles
Reason / purpose:
reference to same study
Qualifier:
no guideline followed
Principles of method if other than guideline:
The irritating effect of the test material was tested on normal rabbit eyes by dropping 0.1 mL of a 20% suspension in propylene glycol on the center of the cornea. Readings were made at 1, 24 and 48 hours, with the cornea unstained and then stained with a 2% solution of fluorescein sodium. Injury was scored according to the method of Draize.
GLP compliance:
not specified
Species:
rabbit
Strain:
other: Albino
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2.0 - 3.2 kg
Vehicle:
other: propylene glycol
Controls:
other: yes the other eye served as control
Amount / concentration applied:
0.1 mL
Duration of treatment / exposure:
not specified
Observation period (in vivo):
48 hours
Number of animals or in vitro replicates:
no details given
Details on study design:
Dropping 0.1 mL of a 20 % suspension in propylene glycol on the centre of the cornea

SCORING SYSTEM: according to Draize

TOOL USED TO ASSESS SCORE: fluorescein
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 1, 24 and 48 hours
Score:
82
Max. score:
120
Reversibility:
not specified
Remarks on result:
other: severely irritating
Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
This well-documented publication gives a detailed information about the experiments conducted and meets basic scientific principles. Therefore it is considered to be of the high quality (reliability Klimisch 2). The validity criteria of the test system are fulfilled. EPON 562 was severely irritating to rabbit eyes (score 82 of 120).
Executive summary:

The eye irritation potential of EPON 562 was investigated by Hine et al.(Hine, 1958). The irritating effect was tested on normal rabbit (male Albino) eyes by dropping 0.1 mL of a 20% suspension in propylene glycol on the center of the cornea. Readings were made at 1, 24, and 48 hours, with the corneas unstained and then stained with a 2% solution of fluorescein sodium. Injury was scored according to the method of Draize. EPON 562 was severely irritating to rabbit eyes (score 82 of maximum 120).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Skin irritation

Data on 1,2,3 - propanetriol, glycidyl ethers (GE-100)

The Handbook of Filler, Extenders, and Diluents also gives some information about the skin irritating potential of 1,2,3 -propanetriol, glycidyl ethers (Ash, 2-nd Edition, 2007). There is stated that the substance is strongly irritating to eyes and skin, with possible risks of irreversible effects. No further details are given. However, the acute dermal toxicity study conducted with 1,2,3 - propanetriol glycidyl ethers indicate that no cutaneous reactions were observed in treated animals after 24 -h dermal exposure (Manciaux, 1998, see section 5.2.1.3 of the CSR or section 7.2.3.of IUCLID file).

Data on read across substances:

Data on Polyglycidyl Ether of Substituted Glycerin (EPON 562)

The skin irritation potential of polyglycidyl ether of substituted glycerine (EPON 562) was investigated by Hine et al. (1958). The test material was administered semiocclusively to rabbits (male Albino). The rabbits were clipped over the back and flanks, and four areas of the back designated for the test, two intact and two scarified with wire mesh. The animals were immobilized in a multiple rabbit holder, and patches of gauze were secured over the areas with adhesive tape. The compound was introduced under the patches, and the entire trunk of the rabbits enveloped in rubber dam. After 24 hours the rabbits were released, the resin removed, and a first reading made. After 72 hours a second reading was made. EPON 562 was moderately irritating, with a score of 5.

The "Patty´s Industial Hygiene and Toxicology" also contains information about Polyglycidyl ether of substituted glycerine (Hine et al., 1981). It is mentioned, that a score of 0 was obtained by the Draize test for a single application. The compound is classified as non-irritating by this method.

Data on glycidol, allyl glycidyl-, n-butyl glycidyl-, isopropyl-, phenyl glycidyl ethers and diglycidyl ether

The skin irritation of glycidol and five related ethers - allyl glycidyl ether, n-butyl glycidyl ether, diglycidyl ether, isopropyl glycidyl ether and phenyl glycidyl ether - was evaluated experimentally in California Albino or New Zealand White rabbits (Hine et al., 1956). The back and flanks of rabbits (2 to 3 kg) were clipped 24 hours prior to use. The shoulders and hips were used as test sites, two areas on each animal being scarified and two intact. A patch consisting of three layers of gauze was secured over each area with adhesive tape and 0.5 mL of the undiluted compound was introduced under the gauze. The rabbits were wrapped in towels and immobilised for 24 hours, after which the areas were examined and irritation scores noted.The skin reactions were evaluated according to the method of Draize.A second reading was made at 72 hours. The average of all readings was used as the basis for grading the compound. BGE and PGE were mildly irritating and DGE would be considered severe (score 7.5 out of 8). The other glycidyl ethers were moderate irritating. The maximum injury score for erythema was obtained in some rabbits with all compounds except PGE, however. The personal experience of laboratory personnel working with theses compounds confirmed the observation that DGE was by far the most irritating of the compounds in skin contact. The skin irritation values were given for glycidol (mean average score: 4.5, moderate), for allyl glycidyl ether (mean average score 4, moderate ), for n-butyl glycidyl ether (mean average score 2.8, mild), for diglycidyl ether (mean average score 7.5, severe), for isopropyl glycidyl ether (mean average score 4.3, moderate) and for phenylglycidyl ether (mean average score 0.7, mild).

Eye irritation

Data on 1,2,3 - propanetriol, glycidyl ethers (GE-100)

The Handbook of Filler, Extenders, and Diluents also gives some information about the skin irritating potential of 1,2,3 -propanetriol, glycidyl ethers (Ash, 2-nd Edition, 2007). There is stated that the substance is strongly irritating to eyes and skin, with possible risks of irreversible effects. No further details are given.

Data on read across substances

Data on Polyglycidyl Ether of Substituted Glycerin (EPON 562)

The eye irritation potential of polyglycidyl ether of substituted glycerine (EPON 562) was investigated by Hine et al.(1958). The irritating effect was tested on rabbit (male Albino) eyes by dropping 0.1 mL of a 20% suspension in propylene glycol on the centre of the cornea. Readings were made at 1, 24, and 48 hours, with the corneas unstained and then stained with a 2% solution of fluorescein sodium. Injury was scored according to the method of Draize. EPON 562 was severely irritating to rabbit eyes (score 82 of maximum 120).

The "Patty´s Industrial Hygiene and Toxicology" also contains information about the eye irritating properties of 1,2,3 -propanetriol, glycidyl ethers (Hine et al., 1981). It is mentioned, that the substance, when administered to the eyes in a Draize test, a score of 82 was obtained.

Data on glycidol, allyl glycidyl-, n-butyl glycidyl-, isopropyl-, phenyl glycidyl ethers and diglycidyl ether

The eye irritation of glycidol and five related ethers - allyl glycidyl ether, n-butyl glycidyl ether, diglycidyl ether, isopropyl glycidyl ether and phenyl glycidyl ether - was evaluated experimentally in California Albino or New Zealand White rabbits (Hine, 1956). Normal rabbit eyes were preselected on the basis of absence of grossly visible staining by a 5% aqueous solution for fluorescein sodium, flushed with distilled water 20 seconds after instillation. After a two-hour interval, to allow the eyes to return to normal, 0.1 mL of an undiluted compound was instilled into one eye, leaving the other for a control. The liquids were dropped on the centre of the cornea, while the lids were retracted; about one minute later the lids were released. Readings were made at 1, 24, and 48 hours an then averaged as a basis for grading the compound.There was a marked difference in the eye-irritating properties of BGE and PGE in comparison with the other ethers and glycidol. These two compounds were only mildly irritating, while severe irritation was caused in individual rabbits by all four of the other compounds, and three of them - glycidol, DGE and AGE - had average scores, indicating them to be severe irritants. However, despite the severity of primary injury, no blindness or permanent defects in the cornea, lens, or iris resulted from the applications.The compounds are very irritating to the eyes, and proper precautions should be instituted to prevent droplet contact. The eye irritation values were given for glycidol (mean average score: 68, severe), for allyl glycidyl ether (mean average score 72, severe ), for n-butyl glycidyl ether (mean average score 4, mild), for diglycidyl ether (mean average score 74, severe), for isopropyl glycidyl ether (mean average score 40, moderate) and for phenylglycidyl ether (mean average score 8, mild).

 


Justification for selection of skin irritation / corrosion endpoint:
The study result originates from a well documented publication which meets basic scientific principles.

Justification for selection of eye irritation endpoint:
The study result originates from a well documented publication which meets basic scientific principles

Effects on skin irritation/corrosion: irritating

Effects on eye irritation: irritating

Justification for classification or non-classification

Skin irritation:

The body of evidence points to an irritating potential of 1,2,3 - propanetriol glycidyl ethers.

According to the European regulation (EC) No. 1272/2008, the test material does meet the criteria for classification and will require labelling as irritating to the skin (Warning, Category 2, H315: causes skin irritation). However, the substance did not produce cutaneous reactions in rats exposed during 24 hour in the acute dermal toxicity study (Manciaux, 1998). It is very likely that the substance induces only minimal dermal irritation.

Eye irritation:

According to the European regulation (EC) No. 1272/2008, the test material does meet the criteria for classification and will require labelling as irritating to eyes (Warning, Category 2, H319 : causes serious eye irritation).