Butyl 2,3-epoxypropyl ether

Endpoint summary

Description of key information

The undiluted substance caused slight to severe irritation to the skin of rabbits.

The substance was considered to be irritant to the eyes of rabbits.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Principles of method if other than guideline:

To evaluate the primary irritation potential of the test materials, 0.5 mL of the undiluted test material was applied to the shaved backs of 6 New Zealand White rabbits. Exposure duration was 24 hours.

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Type of coverage:

occlusive

Preparation of test site:

other: One abraded and one intact site was used on each animal.

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.5 mL

Duration of treatment / exposure:

24 hours

Observation period:

72 hours

Number of animals:

6

Details on study design:

The backs of the rabbits were shaved from shoulder to flank on the day preceding application. The treated areas were covered with Elastoplast coverlets and the rabbits were wrapped in elastic bandages. After exposure the skin sites were uncovered and scored for irritation; the patches were then replaces for an additional 20 hours. Readings were made again at 24 and 72 hours. The scoring method of Draize was followed.

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: 24/72 h

Score:

1

Max. score:

4

Remarks on result:

other: intact skin

Irritation parameter:

edema score

Basis:

animal: #2, #3, #4, #5, #6

Time point:

other: 24/72 h

Score:

2

Max. score:

4

Remarks on result:

other: intact skin

Irritation parameter:

erythema score

Basis:

animal: #1, #4

Time point:

other: 24/72 h

Score:

1.5

Max. score:

4

Remarks on result:

other: intact skin

Irritation parameter:

erythema score

Basis:

animal: #2, #5, #6

Time point:

other: 24/72 h

Score:

2

Max. score:

4

Remarks on result:

other: intact skin

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: 24/72 h

Score:

2.5

Max. score:

4

Remarks on result:

other: intact skin

Irritant / corrosive response data:

At 4 hours: There was negative to moderate irritation on intact skin and moderate to severe irritation on abraded skin, with no eschar present.
At 24 hours, there was moderate irritation on intact skin and severe irritation on abraded skin, with beginning eschar barely discernible in 2/6 rabbits.
At 72 hours, there was slight to severe irritation on intact skin and severe irritation on abraded skin, with eschar present in 5 animals.
The primary irritation score was 4.3 which classifies the substance as severely irritating. Escharotic for abraded skin.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Principles of method if other than guideline:

To evaluate the primary irritation potential of the test materials, 0.5 mL of the undiluted test material was applied to the intact, as well as scarified, skin area on each of 3 albino rabbits.

GLP compliance:

no

Specific details on test material used for the study:

Name as sited in report: Butyl glycidyl ether (BGE)

Species:

rabbit

Strain:

other: California Albino or New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: the Casa Ladrillo Rabbitry, California or the Simonsen Laboratories
- Weight at study initiation: 2 to 3 kg
- Housing: Single housing
- Diet: Standard rabbit pellets

Type of coverage:

other: The rabbits were wrapped in towels

Preparation of test site:

clipped

Remarks:

two areas being scarified and two left intact.

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

0.5 mL at each area

Duration of treatment / exposure:

24 hours

Observation period:

72 hours

Number of animals:

3

Details on study design:

The backs and flanks of rabbits were clipped 24 hours prior to use. The shoulders and hips were used as test sites. Scarification was accomplished by making 4 intersecting epidermal scratches, each about 2 cm long with a scalpel blade. A patch consisted of 3 layers of gauze was secured over each area with adhesive tape. The test material was introduced under the gauze. The animals were wrapped in towels and immobilized for 24 hours. After this exposure period were examined an irritation scored noted. A second reading was made at 72 hours.
Irritation was scored according to the method of Draize (1955).

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 24/72 h

Score:

1.5

Max. score:

4

Reversibility:

fully reversible within: 72 h

Remarks on result:

other: intact skin

Irritation parameter:

erythema score

Basis:

animal: #2 and #3

Time point:

other: 24/72 h

Score:

0.5

Max. score:

4

Reversibility:

fully reversible within: 72 h

Remarks on result:

other: intact skin

Irritation parameter:

edema score

Basis:

animal: all

Time point:

other: 24/72 h

Score:

0

Max. score:

4

Remarks on result:

other: intact skin

Irritant / corrosive response data:

The combined average for all treated areas of both endpoints and for both readings was 2.8. This was considered moderate.

Reference 3

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Principles of method if other than guideline:

To evaluate the primary irritation potential of the test materials, 0.5 mL of the undiluted test material was applied under a one inch-square surgical 1 gauze patch, two layers thick, to an intact skin area and an abraded skin area on each of 6 albino rabbits.

GLP compliance:

no

Specific details on test material used for the study:

Name as cited in report: 37-149 Butyl Glycidal Ether

Species:

rabbit

Strain:

other: Albino, not further specified.

Type of coverage:

occlusive

Preparation of test site:

other: One abraded and one intact site was used on each animal.

Controls:

not required

Amount / concentration applied:

0.5 mL

Duration of treatment / exposure:

24 hours

Observation period:

72 hours

Number of animals:

6

Details on study design:

The undiluted test material was applied under a one inch-square surgical 1 gauze patch, two layers thick, to an intact skin area and an abraded skin area on each of 6 albino rabbits. The application sites were prepared by clipping the hair from the saddle area of the rabbits. The abraded areas were prepared by making minor epidermal incisions with a hypodermic needle. The abrasions were sufficiently deep to penetrate the epidermis but not to induce bleeding. Each patch was held in place with 2 strips of one-inch adhesive tape. After application of the patches, the trunk of each rabbit was wrapped with rubber dental damming which was secured with staples. An outer layer of gauze and tape was placed around the trunk of the animals. The animals were restrained in Newmann restraining harnesses for 24 hours.
At the end of the 24-hour exposure period, the patches were removed and any residual sample was gently sponged from the skin with a moistened towel. The reactions were scored immediately after removal of the patches (24-hour reading), and again 2 days later (72-hour reading).

Irritation parameter:

erythema score

Basis:

animal: all

Time point:

other: 24/72 h

Score:

4

Max. score:

4

Remarks on result:

other: intact skin

Irritation parameter:

edema score

Basis:

animal: #1, #2, #3, #4, #5

Time point:

other: 24/72 h

Score:

3.5

Max. score:

4

Remarks on result:

other: intact skin

Irritation parameter:

edema score

Basis:

animal #6

Time point:

other: 24/72 h

Score:

4

Max. score:

4

Remarks on result:

other: intact skin

Irritant / corrosive response data:

Irritating effects produced by patch application of the test substance included diffuse blanching and necrosis with severe peripheral erythema at 5 intact and 4 abraded sites and spotted to complete blanching with slight or severe erythema at one intact and 2 abraded sites at the 24- hour reading. At the 72-hour reading irritation effects noted were diffuse or complete coriaceousness at 5 intact and four abraded, sites and spotted to complete blanching with slight or severe erythema at 1 intact and 2 abraded sites. Moderate to severe edema at all intact and abraded sites was noted at both the 24 and 72-hour readings. The Primary Irritation Index was found to be 7.67.

Reference 4

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Principles of method if other than guideline:

Undiluted test material (0.5 mL) was applied to abraded and intact skin of rabbits for 24 hrs.

GLP compliance:

no

Specific details on test material used for the study:

Name as cited in report: Butyl glycidyl ether

Species:

rabbit

Strain:

other: Albino, not further specified

Type of coverage:

occlusive

Preparation of test site:

other: one abraded and one intact site was used on each animal

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

0.5 mL

Duration of treatment / exposure:

24 hours

Observation period:

72 hours

Number of animals:

3

Details on study design:

Gauze pads 1 inch square containing 0.5 ml of the undiluted material were affixed to the skin of the rabbits with thin pieces of tape. The sites were clipped free of hair; one abraded and one intact site was used on each animal. The trunks of the animals were wrapped with impervious plastic sheeting and the animals were immobilized for the total exposure time of 24 hours. Each site was evaluated at the 24-hour and 72-hour point using the Draize scoring system for edema (swelling) and erythema (redness). The scores from a pair of sites (24 and 72 hours, -intact and abraded) were averaged for edema and erythema, and then these two averaged scores were added to give the Primary Irritation Index.

The scoring system for Degree of Irritation is described by Draize and is based on the Primary Irritation Index (PII) as follows:
PII:
2 = mild degree of irritation
2-5 = moderate degree of irritation
5-6 = moderate to severe degree of irritation
6-8 = severe degree of irritation
If the skin condition is necrotic it cannot be scored by this system since it would be more severe than a PII of 8.

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 24 h / 72 h

Score:

8

Max. score:

8

Remarks on result:

other: chemical burn

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Principles of method if other than guideline:

To test the eye irritating potential of the test substance two tests were performed by instilling 0.1 mL of undiluted test material into rabbit eyes without a rinse. Scoring of effects was according to the method of Draize.

GLP compliance:

no

Specific details on test material used for the study:

Name as cited in report: Butyl glycidyl ether

Species:

rabbit

Strain:

New Zealand White

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.1 mL

Duration of treatment / exposure:

Eyes were not washed out.

Observation period (in vivo):

Until no gross evidence of irritation to the ocular tissue was observed.

Number of animals or in vitro replicates:

3

Details on study design:

Scoring was by the Draize method with a maximum score of 110 based on up to 80 points for irritation to the cornea, 10 for the iris, and 20 for the conjunctiva. The “maximum average score” is obtained by averaging the score of each rabbit at the time of maximum irritation. The descriptive rating is based on a combination of the Draize score and corneal involvement (i.e., degree and duration) as described by J.C. Calandra, Interpretation of Eye Irritation tests”, J. Soc. Cosmet. Chem., 13, 281-289, 1962.

Irritation parameter:

other: Draize score (max. ave. score)

Basis:

mean

Time point:

other: time of maximum irritation

Score:

23.2

Max. score:

110

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: Degree of Irritaion: moderate

Irritation parameter:

other: Draize score (max. ave. score)

Basis:

mean

Time point:

other: time of maximum irritation

Score:

41.3

Max. score:

110

Reversibility:

not reversible

Remarks:

for 1/3 animals

Remarks on result:

other: Degree of Irritation: moderate to severe

Irritant / corrosive response data:

In the first test, the effects observed in the eye of one animal were fully reversed within three days and of the other two animals in seven days.
In the second test, the effects observed in the eye of 2 animals were fully reversed within 4 days. The third animal showed severe ocular damage. This was not cleared after 3 days and judged to be irreversible damage.

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Principles of method if other than guideline:

To test the eye irritating potential of the test substance rabbit eyes were instilled with 0.1 mL of undiluted test material without a rinse. Scoring of effects was according to the method of Draize.

GLP compliance:

no

Specific details on test material used for the study:

Name as cited in report: Butyl glycidyl ether (BGE)

Species:

rabbit

Strain:

other: California Albino or New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: the Casa Ladrillo Rabbitry, California or the Simonsen Laboratories
- Weight at study initiation: 2 to 3 kg
- Housing: Single housing
- Diet: Standard rabbit pellets

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.1 mL

Observation period (in vivo):

48 hours

Details on study design:

Normal rabbit eyes were preselected on the basis of absence of grossly visible staining by a 5 % solution fluorescein sodium, flushed with distilled water 20 seconds after instillation. After a 2-hour interval, to allow the eyes to return to normal, the test material was instilled into one eye. The test material was dropped on the centre of the cornea while the lids were retracted; about one minute later the lids were released.
Readings were according to Draize at 1, 24, and 48 hours.

Remarks on result:

other: see "Irritant/corrosive response data"

Irritant / corrosive response data:

At 1 hour after instillation the Primary irritation index (PII) was determined to be 9, 7, 7 for animal #1, #2, and #3 respectively.
At 24 hours after instillation the Primary irritation index (PII) was determined to be 7, 2, 2 for animal #1, #2, and #3 respectively.
At 48 hours after instillation the Primary irritation index (PII) was determined to be 2, 0, 2 for animal #1, #2, and #3 respectively.

Reference 3

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Principles of method if other than guideline:

The test material was instilled into one eye of each of six New Zealand White rabbits. Readings according to the method of Draize were made at 24, 48 and 72 hours.

GLP compliance:

no

Specific details on test material used for the study:

Substance identified as N butyl glycidal ether, CWLR-434-201

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Age at study initiation: 4 months
- Weight at study initiation: 2.5 - 3 kg
- Acclimation period: at least one week

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.1 mL

Observation period (in vivo):

72 h

Number of animals or in vitro replicates:

6

Details on study design:

One-tenth mL of the test material was instilled into the conjunctival sac of one eye of each of six New Zealand White rabbits. The eye was held closed for a few seconds and the animal was returned to its cage. Readings according to the method of Draize werre made at 24, 48 and 72 hours.

Irritation parameter:

cornea opacity score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

cornea opacity score

Basis:

animal: #1, #5

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Irritation parameter:

iris score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

animal: #1, #2, #5, #6

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Basis:

animal #4

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Basis:

animal: #1, #2, #5

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Basis:

animal: #3, #6

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Irritation parameter:

chemosis score

Basis:

animal #4

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Irritation parameter:

chemosis score

Basis:

animal: #1, #2, #5

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Irritation parameter:

chemosis score

Basis:

animal: #3, #6

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Irritant / corrosive response data:

The material produced conjunctival irritation in all six rabbits and iritis and corneal effects in five. The corneal opacity was reversible in three to seven days. The average scores for 24, 48, and 72 hours were 28.8, 13.0, and 7.3 respectively.

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation:

Three sufficiently documented tests exist. These were used in a weight-of-evidence approach.

In each case the undiluted test material was applied to the intact and abraded skin of the rabbits with an exposure duration of 24 hours under occlusive conditions. The results are as follows:

In the first study, the undiluted test material was applied to the shaved backs of 6 New Zealand White rabbits (US EPA, 1982). Exposure duration was 24 hours under occlusive conditions with an observation period of 72 hours. One abraded and one intact site was used on each animal. For assessment purposes only the results for the intact skin are relevant. At 4 hours there was negative to moderate irritation visible. At 24 hours there was slight irritation present (erythema and oedema scores between 1 and 2). At 72 hours, there was slight to moderate irritation on intact skin. The oedema score at 72 hours was between 1 and 2 and for erythema between 1.5 and 2.5.

In the second study (US EPA, 1975), the test substance was applied to the skin of 6 albino rabbits (not further specified). Irritating effects produced by patch application of the test substance included diffuse blanching and necrosis with severe peripheral erythema in 5 animals and spotted to complete blanching with slight or severe erythema in one animal at the 24- hour reading. At the 72-hour reading irritative effects noted with diffuse or complete coriaceousness in 5 animals and spotted to complete blanching with slight or severe erythema in 1 animal. Moderate to severe oedema at all intact sites was noted at both the 24 and 72-hour readings (scores 3 to 4).

In the third study (US EPA, 1956): The erythema score for one animal was 3 and for the two other animals 1 which was fully reversible within 72 hours (intact skin). No oedema was observed at any of the intact sites.

In a very briefly reported fourth study (US EPA, 1973) only the primary dermal irritation index (PII) for abraded and intact skin were reported. A PII of 8 (8 is maximum score) was reported.

 

For assessment purposes it should be noted that, according to OECD guideline 404, a maximum exposure duration of 4 hours in recommended under semi-occlusive conditions. Since all identified studies herein were performed with a 24 hour exposure duration under occlusive conditions these represent a strong overestimation of effects caused by the test substance.

 

Eye irritation/corrosion:

Three sufficiently documented tests exist. These were used in a weight-of-evidence approach.

To test the eye irritating potential of the test substance two tests were performed two groups of three New Zealand White rabbits each by instilling 0.1 mL of the undiluted test material into one eye without a rinse (US EPA, 1973). Scoring of effects was according to the method of Draize. Observation took place until no gross evidence of irritation to the ocular tissue was observed. In the first test, the ocular effects were scored as moderate (mean score of 23.2) and were fully reversed in one animal within three days and in the other two animals within seven days. In the second test, the ocular effects were scored as moderate to severe (mean score of 41.3); the effects were fully reversed within 4 days. However, the third animal showed severe ocular damage which was not cleared after 3 days and judged to be irreversible.

In another study (US EPA, undated), 0.1 mL of the test substance was instilled into one eye of New Zealand White rabbits. Scoring of effects was according to the method of Draize and observations were made at 24, 48 and 72 hours. The material produced conjunctival irritation in all six rabbits and iritis and corneal effects in five.The average (24, 48, 72 hours) scores per animal for corneal opacity were determined to be 0.0, 0.33, 0.67, 0.67, 1.0 and 1.33. The average (24, 48, 72 hours) scores per animal for iritis were determined to be 0.0, 0.33, 0.33, 0.33, 0.33 and 1.0. The average (24, 48, 72 hours) scores per animal for conjunctival redness were determined to be 1.0, 1.33, 1.33, 1.33, 1.67 and 1.67. The average (24, 48, 72 hours) scores per animal for chemosis were determined to be 1.0, 1.33, 1.33, 1.33, 2.0 and 2.0.The corneal opacity was reversible in three to seven days. Based on these results the substancewas not considered to be irritating to the eyes. In another study (US EPA, 1956) the compound was instilled into one eye of a rabbit in the amount of 0.1 mL undiluted, leaving the other for a control. The substance was dropped in the centre of the cornea while the lids were retracted, about 1 minute later the lids were released. Readings were made at 1, 24, and 48 hours, according to the method of Draize. At 1 hour after instillation the Primary irritation index (PII) was determined to be 9, 7, 7 for animal #1, #2, and #3 respectively.

At 24 hours after instillation the Primary irritation index (PII) was determined to be 7, 2, 2 for animal #1, #2, and #3 respectively. At 48 hours after instillation the Primary irritation index (PII) was determined to be 2, 0, 2 for animal #1, #2, and #3 respectively. The substance was considered to be mildly irritating.

 

The current OECD test guideline 405 indicates that the test substance should be placed in the conjunctival sac of one eye after gently pulling the lowed lid away from the eyeball. The lids are then gently held together for about one second in order to prevent loss of the material. The current guideline therefore indicates that an animal can start blinking and thus clearing its eye almost immediately, whereas in the 1956 study this would be only after one minute. Even with this longer duration, the effects observed were considered to be only mild. In the other studies, however no information was given about the time eyelids were retracted or gently hold together, which could perhaps explain why there was one outlier our out of 15 rabbits. Based on the mild to moderate eye irritation in the other 14 rabbits, it conservatively proposed that the test substance should be considered to be irritating to the eyes.

Justification for classification or non-classification

Based on weight-of-evidence of the three sufficiently reported studies, the results observed in the skin irritation tests (24 hour exposure under occlusive conditions) showing slight to severe skin effects, the test substance has to be classified as Skin Irrit Cat 2, H315: Causes skin irritation, in accordance with EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

 

Based on weight-of-evidence of the three sufficiently reported studies, showing that the substance should be considered irritating to the eyes, the test substance has to be classified as Eye Irrit. 2, H318: Causes serious eye irritation, in accordance with EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.