Reaction mass of 1-(2,3-epoxypropoxy)-2,2-bis ((2,3-epoxypropoxy)methyl) butane and 1-(2,3-epoxypropoxy)-2-((2,3-epoxypropoxy)methyl)-2-hydroxymethyl butane

Endpoint summary

Description of key information

In vivo studies demonstrate the test substance to be corrosive to skin and eyes.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

study report dated 12 Nov 1976 (no additional details)

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

EPA OTS 798.4470 (Acute Dermal Irritation)

GLP compliance:

no

Remarks:

prior to GLP

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Healthy New Zealand White rabbits (Porton strain) aged ·13 - 17 weeks with average body weights of 3.04 kg. (males) and 2.46 kg (females), bred on the premises and maintained under a semi-barrier system. Six rabbits (3 of each sex) were acclimatized in the test area for one week prior to the start of the trial. The rabbits were caged singly in an experimental room maintained at a temperature of 20degrees C (+/-1°) and a relative humidity of 50-70%. Animals were exposed to artificial light for 10 hours daily from 08.00 - 18.00 hours. A commercial irradiated diet (Styles-Oxoid) was fed ad lib. Sterile filtered water was available at all times.

Type of coverage:

occlusive

Preparation of test site:

other: shaved with one area intact and one area abraded

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.5 ml

Duration of treatment / exposure:

24 hours

Observation period:

14 days

Number of animals:

6

Details on study design:

Twenty-four hours prior to the dermal application, the backs of the rabhits were shaved over an area consisting of at least 10% of the total body surface. Two test sites lateral to the mid line "of the back were used on each rabbit. lmmediately before the application of the test compound, the right hand site was abraded with the point of a sterile hypodermic needle. The abrasions were sufficiently deep to penetrate the stratum corneum but not to damage the dermis. The left hand site remained intact.
0.5ml of the test compound was applied to each test site on a 2.5cm square gauze pad. These were covered with aluminium foil secured with adhesive tape. The test sites were then covered by a 6 inch wide self adhesive bandage in order to retain the test substance in close contace with the skin.
After 24 hours the dressing was removed and· the intact and abraded application sites were assessed for oedema and erythema. A further assessment was made at 72 hours and for any further period considered necessary up to 14 .

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 24-72 hrs

Score:

7.17

Max. score:

8

Reversibility:

not fully reversible within: 14 days

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not specified

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not specified

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

3.5

Max. score:

4

Reversibility:

not specified

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

not specified

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not specified

Irritant / corrosive response data:

24 hours: Well defined erythema was present on 2/6 intact sites and all the remaining sites were showing evidence of necrosis. Moderate to severe oedema was also seen on all sites.
72 hours: Eschar formation involving dermal layers was ssen on 4/6 intact and 6/6 abraded sites. The remaining 2 intact sites were showing slight to well defined erythema. Slight to severe oedema was present on all sites.
6 days: Eschar formation was seen on 4/6 intact and 6/6 abraded sites with the remaining 2 intact sites showing well defined-erythema. Slight ·to moderate oedema was also present on all sites. 3 rabbits were sacrificed at this time.
10 days: The 3 remaining rabbits showed eschar formation and very slight to slight oedema on all sites.
14 days: (Termination of study) Eschar formation was still present on all sites and very slight to slight oedema on 2/3 intact and 3/3 abraded sites.
"If sufficient time had been allowed to elapse all sites would have eventually healed with some residual scarring.

Generally, there was very little difference seen in the reactions between intact and abraded sites.
The primary irritation score was 7.2.

Interpretation of results:

corrosive

Remarks:

Migrated information Criteria used for interpretation of results: OECD GHS

Conclusions:

The test material is corrosive to skin in the albino rabbit.

Executive summary:

Healthy New Zealand White rabbits (Porton strain) were tested for skin irritation with the test material. Reactions of 4+ (according to Draize scoring) for erythema and oedema was seem on abraded and intact sites on all animals at 72 hours and was still seen at 14 days on 3/6 animals. The test material is considered corrosive to skin in the albino rabbit.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

study report 12 Nov. 1976 (no additional details)

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

other: "Hazardous Substances Regulations" under the U.S.A. rederel Hazardous Substances Labelling Act Sect. 191.12 (February 1965)

Deviations:

yes

Remarks:

slight modification (no additional details)

GLP compliance:

no

Remarks:

prior to GLP

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Healthy New Zealand White rabbits (Porton strain) aged 13 - 17 weeks with average body weights of 3.04 kgs. (male) and 2.46 kgs. (female), bred on the premises and maintained under a semi-barrier system. Six rabbits (3 male and 3 female) were acclimatised in the test area for one week prior to the start of the trial.
The rabbits were caged singly in an experimental room maintained at a temperature of 20°C. (+/-1°) and a relative humidity of 50-70%. Animals were exposed to artificial light for 10 hours daily from 08:00 - 18.00 hours. A commercial irradiated diet (Styles-Oxoid) was fed ad lib. Sterile filtered water was available at all times.

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.1 ml

Duration of treatment / exposure:

After 30 seconds the compound was, as far as possible, flushed out of the eyes of three of the rabbits. The eyes of other three rabbits remained unwashed.

Observation period (in vivo):

10 days

Number of animals or in vitro replicates:

6

Details on study design:

The eyes of the experimental animals were examined and found normal prior to the test.
0.1ml of the test compound were instilled into the conjunctival sac of the left eye. The eyelids were then held closed for 1 second. The right eye served as a control. After 30 seconds the compound was, as far as possible, flushed out of the eyes of three of the rabbits with approximately 200 ml. of warm water.
The rabbits were examined 1, 24, 48 and 72 hours after application of the test compound and for any further period that was considered necessary. The ocular reactions were scored by the method described in "Appraisal of the Safety of Chemicals in rood Drugs and Cosmetics" page 51, published by the Association of rood and Drug Officials of the U.S.A. Corneal damage was assessed after staining with fluorescein.

Irritation parameter:

chemosis score

Basis:

animal #6

Time point:

72 h

Score:

0

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: eye washed

Irritation parameter:

chemosis score

Basis:

animal #5

Time point:

72 h

Score:

0

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: eye washed

Irritation parameter:

chemosis score

Basis:

animal #4

Time point:

72 h

Score:

2

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

72 h

Score:

0

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: eye washed

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

72 h

Score:

2

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

72 h

Score:

2

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

chemosis score

Basis:

animal #6

Time point:

48 h

Score:

1

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

chemosis score

Basis:

animal #5

Time point:

48 h

Score:

1

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

chemosis score

Basis:

animal #4

Time point:

48 h

Score:

2

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

48 h

Score:

0

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: eye washed

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

48 h

Score:

2

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

48 h

Score:

2

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

chemosis score

Basis:

animal #6

Time point:

24 h

Score:

1

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

chemosis score

Basis:

animal #5

Time point:

24 h

Score:

1

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

chemosis score

Basis:

animal #4

Time point:

24 h

Score:

3

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24 h

Score:

1

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24 h

Score:

2

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24 h

Score:

2

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24 h

Score:

40

Max. score:

80

Reversibility:

not reversible

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24 h

Score:

15

Max. score:

80

Reversibility:

not reversible

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24 h

Score:

15

Max. score:

80

Reversibility:

not reversible

Irritation parameter:

cornea opacity score

Basis:

animal #4

Time point:

24 h

Score:

40

Max. score:

80

Reversibility:

not reversible

Irritation parameter:

cornea opacity score

Basis:

animal #5

Time point:

24 h

Score:

30

Max. score:

80

Reversibility:

not reversible

Irritation parameter:

cornea opacity score

Basis:

animal #6

Time point:

24 h

Score:

5

Max. score:

80

Reversibility:

not reversible

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

48 h

Score:

40

Max. score:

80

Reversibility:

not reversible

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

48 h

Score:

30

Max. score:

80

Reversibility:

not reversible

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

48 h

Score:

5

Max. score:

80

Reversibility:

not reversible

Irritation parameter:

cornea opacity score

Basis:

animal #4

Time point:

48 h

Score:

40

Max. score:

80

Reversibility:

not reversible

Irritation parameter:

cornea opacity score

Basis:

animal #5

Time point:

48 h

Score:

15

Max. score:

80

Reversibility:

not reversible

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

72 h

Score:

40

Max. score:

80

Reversibility:

not reversible

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

72 h

Score:

30

Max. score:

80

Reversibility:

not reversible

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

72 h

Score:

5

Max. score:

80

Reversibility:

not reversible

Irritation parameter:

cornea opacity score

Basis:

animal #4

Time point:

72 h

Score:

40

Max. score:

80

Reversibility:

not reversible

Irritation parameter:

cornea opacity score

Basis:

animal #5

Time point:

72 h

Score:

10

Max. score:

80

Reversibility:

not reversible

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24 h

Score:

5

Max. score:

20

Reversibility:

not reversible

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24 h

Score:

5

Max. score:

20

Reversibility:

not reversible

Irritation parameter:

iris score

Basis:

animal #1

Time point:

48 h

Score:

5

Max. score:

20

Reversibility:

not reversible

Irritation parameter:

iris score

Basis:

animal #2

Time point:

48 h

Score:

5

Max. score:

20

Reversibility:

not reversible

Irritation parameter:

iris score

Basis:

animal #1

Time point:

72 h

Score:

5

Max. score:

20

Reversibility:

not reversible

Irritation parameter:

iris score

Basis:

animal #2

Time point:

72 h

Score:

5

Max. score:

20

Reversibility:

not reversible

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24 h

Score:

61

Max. score:

110

Reversibility:

not reversible

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24 h

Score:

32

Max. score:

110

Reversibility:

not reversible

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24 h

Score:

26

Max. score:

110

Reversibility:

not reversible

Irritation parameter:

conjunctivae score

Basis:

animal #4

Time point:

24 h

Score:

63

Max. score:

110

Reversibility:

not reversible

Irritation parameter:

conjunctivae score

Basis:

animal #5

Time point:

24 h

Score:

47

Max. score:

110

Reversibility:

not reversible

Irritation parameter:

conjunctivae score

Basis:

animal #6

Time point:

24 h

Score:

13

Max. score:

110

Reversibility:

not reversible

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

48 h

Score:

61

Max. score:

110

Reversibility:

not reversible

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

48 h

Score:

49

Max. score:

110

Reversibility:

not reversible

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

48 h

Score:

7

Max. score:

110

Reversibility:

not reversible

Irritation parameter:

conjunctivae score

Basis:

animal #4

Time point:

48 h

Score:

61

Max. score:

110

Reversibility:

not reversible

Irritation parameter:

conjunctivae score

Basis:

animal #5

Time point:

48 h

Score:

30

Max. score:

110

Reversibility:

not reversible

Irritation parameter:

conjunctivae score

Basis:

animal #6

Time point:

48 h

Score:

4

Max. score:

110

Reversibility:

not reversible

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

72 h

Score:

59

Max. score:

110

Reversibility:

not reversible

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

72 h

Score:

47

Max. score:

110

Reversibility:

not reversible

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

72 h

Score:

7

Max. score:

110

Reversibility:

not reversible

Irritation parameter:

conjunctivae score

Basis:

animal #4

Time point:

72 h

Score:

61

Max. score:

110

Reversibility:

not reversible

Irritation parameter:

conjunctivae score

Basis:

animal #5

Time point:

72 h

Score:

14

Max. score:

110

Reversibility:

not reversible

Irritation parameter:

conjunctivae score

Basis:

animal #6

Time point:

72 h

Score:

2

Max. score:

110

Reversibility:

not reversible

Irritant / corrosive response data:

The 3 rabbits with unwashed eyes were killed after 6 days because of the severity of the reactions.

Conjunctiva. A slight to moderate reaction was seen in all treated eyes one hour after the application of the compound. This was still present at 24 hours. Small areas of necrosis were seen in 2/3 unwashed eyes from 24 hours onwards and in the third unwashed eye at 6 days. Because
of the severity of the reactions these rabbits were killed at this time. Washed eyes had returned to normal by 6 days {one eye) and 10 days (2 eyes).

Cornea. Slight opacity with damage to the surface epithelium was seen in all treated eyes at one hour. By 24 hours, the unwashed eyes were showing small areas of ulceration, whereas the reactions in washed eyes were similar to those at one hour. Slight pannus was present in the 3 unwashed eyes at 6 days. The washed eyes had returned to normal by 48 hours (one eye) and 6 days (2 eyes).

Iris: Increased folding was seen in 3/3 unwashed and 2/3 washed eyes at 24 hours. The washed eyes had returned to normal by 48 hours (one eye) and 72 hours (one eye). The unwashed eyes were still showing a reaction at 6 days.

Washed eyes showed a much less severe reaction than unwashed eyes.

Interpretation of results:

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

Remarks:

Migrated information

Conclusions:

The test material is a corrosive eye irritant in the albino rabbit on clinical assessment.

Executive summary:

The irritative effects of the test material was assessed in six New Zealand White rabbits exposed to 0.1ml of the test compound instilled into the conjunctival sac of the left eye. The eyelids were then held closed for 1 second. The right eye served as a control. In three animals, after 30 seconds, the compound was flushed out of the eyes with approximately 200 ml. of warm water. The rabbits were examined 1, 24, 48 and 72 hours and day 6 and 10 after application of the test compound. The ocular reactions were scored by the method described in "Appraisal of the Safety of Chemicals in rood Drugs and Cosmetics" page 51, published by the Association of rood and Drug Officials of the U.S.A. Corneal damage was assessed after staining with fluorescein.

Small areas of necrosis were seen in 2/3 unwashed eyes from 24 hours onwards and in the third unwashed eye at 6 days. The washed eyes had returned to normal by 48 hours (one eye) and 6 days (2 eyes).

The test material is a corrosive eye irritant in the albino rabbit based on clinical assessment.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Additional information

In-vivo skin irritation/corrosion test

Healthy New Zealand White rabbits (Porton strain) were tested for skin irritation with the test substance. Reactions of 4 + (according to Draize scoring) for erythema and oedema was seem on abraded and intact sites on all animals at 72 hours and was still seen at 14 days on 3/6 animals. The test substance is considered corrosive to skin in the albino rabbit.

 

In-vivo eye irritation test

The irrtative effects of the test substance were assessed in six New Zealand White rabbits exposed to 0.1ml of the test compound instilled into the conjunctival sac of the left eye. The eyelids were then held closed for 1 second. The right eye served as a control. In three animals, after 30 seconds, the compound was flushed out of the eyes with approximately 200 ml. of warm water. The rabbits were examined 1, 24, 48 and 72 hours and day 6 and 10 after application of the test compound. The ocular reactions were scored by the method described in "Appraisal of the Safety of Chemicals in rood Drugs and Cosmetics" page 51, published by the Association of rood and Drug Officials of the U.S.A. Corneal damage was assessed after staining with fluorescein.

Small areas of necrosis were seen in 2/3 unwashed eyes from 24 hours onwards and in the third unwashed eye at 6 days. The washed eyes had returned to normal by 48 hours (one eye) and 6 days (2 eyes).

 

The test substance is corrosive to the eye in the albino rabbit based on clinical assessment.

Effects on skin irritation/corrosion: corrosive

Effects on eye irritation: corrosive

Justification for classification or non-classification

For classification purposes in accordance with UN-GHS the test substance is classified for Skin Corrosion, Category 1C and Category 1 for Eye damage.