7,7-dimethyl-3-oxa-6-azaoctan-1-ol

Endpoint summary

Description of key information

 Acute dermal and eye irritation / corrosion studies indicate that the substance is classified as corrosive. Acute dermal irritation : Equivalent or similar to OECD Guideline 404 (Acute Dermal Irritation / Corrosion) (Plutnick, 1985) Acute eye irritation : Equivalent or similar to OECD Guideline 405 (Acute Eye Irritation / Corrosion) (Kapp, 1982) 

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:

key study

Study period:

Dosing initiated: November 5 1985, Study termination (in vivo phase): November 8 1985

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study conducted in accordance with generally accepted scientific principles, possibly with incomplete reporting or methodological deficiencies, which do not affect the quality of the relevant results.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

not specified

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hazleton Research Products, Inc., Denver, PA
- Age at study initiation: Approximately 16 weeks
- Weight at study initiation: Males: 2.54 to 3.29 kg, Females: 2.41 to 3.41 kg
- Housing: Individual suspended stainless steel cagel.
- Diet (e.g. ad libitum): Purina Certified Rabbit Chow HF (pellets), ad libitum
- Water (e.g. ad libitum): Automatic watering system, ad libitum
- Acclimation period: 29 days.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): Maintained range of 65 to 71 degrees Fahrenheit
- Humidity (%): Maintained range of 40 to 70% relative humidity.
- Photoperiod (hrs dark / hrs light): Approximately 12 hours light and 12 hours dark by automatic timer.

Type of coverage:

semiocclusive

Preparation of test site:

other: clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): Single 0.5 ml dose of test material.


VEHICLE
Not applicable.

Duration of treatment / exposure:

4 hours.

Observation period:

72 hours.

Number of animals:

6 (3 males, 3 females).

Details on study design:

TEST SITE
- Area of exposure: The day prior to topical administration of the test material, the hair of each rabbit on the dorsal surface from the shoulder region to the lumbar region was closely clipped with an electronic clipper. The skin was left intact. Elizabethan-type collars were placed around the neck of each rabbit at this time to acclimate them to wearing collars.
- Type of wrap if used: The test material was introduced under a gauze patch which was secured with tape. The patch was loosely held in contact with the skin by means of a semi-occlusive dressing for the duration of the exposure period.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): After exposure the dressing and gauze patch were removed. The skin was then washed with distilled water and paper towel to remove any remaining test material.
- Time after start of exposure: 4 hours.


SCORING SYSTEM:
Dermal responses were evaluated approximately 45 minutes, 24, 48 and 72 hours following patch removal. All scoring was made according to the Draize Method of Scoring.

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: Necrosis observed at all time endpoints

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: Necrosis observed at all time endpoints

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: Necrosis observed at all time endpoints

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: Necrosis observed at all time endpoints

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: Necrosis observed at all time endpoints

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: Necrosis observed at all time endpoints apart from 45 minutes

Irritation parameter:

erythema score

Basis:

mean

Remarks:

: Mean result over all 6 animals

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: Necrosis observed at all time endpoints

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

not reversible

Remarks on result:

other: Necrosis observed at all time endpoints

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

not reversible

Remarks on result:

other: Necrosis observed at all time endpoints

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

not reversible

Remarks on result:

other: Necrosis observed at all time endpoints

Irritation parameter:

edema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

not reversible

Remarks on result:

other: Necrosis observed at all time endpoints

Irritation parameter:

edema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

not reversible

Remarks on result:

other: Necrosis observed at all time endpoints

Irritation parameter:

edema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

not reversible

Remarks on result:

other: Necrosis observed at all time endpointsapart from 45 minutes

Irritation parameter:

edema score

Basis:

mean

Remarks:

: Mean result over all 6 animals

Time point:

other: mean of 24, 48 and 72 hours

Score:

2

Max. score:

2

Reversibility:

not reversible

Remarks on result:

other: Necrosis observed at all time endpoints

Irritant / corrosive response data:

All animals survived to study termination. Two animals were noted with their collars off and one animal was noted with its collar in its mouth at the time off undamming.

Signs of dermal corrosion, necrosis, were observed in 5 animals at the 45 minute observation and in all 6 animals at the remaining intervals.

Erythema was noted in all animals during the study. Five animals were noted with severe erythema at the 45 minute observation, while one animal displayed moderate-to-severe erythema. All animals displayed severe erythema at the 24, 48 and 72 hour observations.

Edema was also noted in all animals during the study. At the 45 minute observations five animals were scored with slight edema and one animal was noted with very slight erythema. From 24 hours through to study termination all animals displayed slight edema.

Other effects:

During the test period, atonia was noted for 4 animals, blanching was noted for 3 animals, and leathery skin was noted for 2 animals. One animal was noted to have an area of eschar measuring approximately 3.0 x 2.0 cm on the upper edge of the dose site at the 48 hour observation.

Interpretation of results:

corrosive

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

All animals exhibited necrosis, a sign of dermal corrosion during the test period.

Executive summary:

The dermal corrosivity potential of the test substance was evaluated following its application to the clipped backs of six New Zealand White rabbits. The test material was administered as a single 0.5 ml dose introduced under a gauze patch which was secured with tape. The patch was loosely held in contact with the skin by means of a semi-occlusive dressing. The dressing remained in place for four hours. After exposure was completed, the dressing and gauze were removed and the test site graded for erythema, edma and other signs of dermal irritation at 45 minutes, 24, 48 and 72 hours following patch removal. All dermal scoring was made according to the Draize method of scoring.

All animals survived to study termination.

All animals exhibited necrosis, a sign of dermal corrosion during the test period.

Erythema was noted in all animals during the test period, ranging from moderate-to-severe to severe. Edema was also noted in all animals ranging from very slight to slight.

Supplemental dermal observations noted over the study period included blanching, eschar, atonia and leathery skin.

Based on these findings, the test substance should be considered corrosive to rabbit skin.

Reference 2

Endpoint:

skin corrosion: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
An in vitro skin irritation study is not required because adequate in vivo data are available (see key study: Plutnick, 1985). As per ECHA Guidance - Chaper R7a: Endpoint specific guidance (v6.0; July, 2017);
"In case an exisiting good quality in vivo skin irritation study is available, its results can be used to fulfil the standard information requirement.."

In the same document; Section 7.2.3; the following is observed regarding the historical use of animal data for skin corrosion/irritation:
"An IATA, which aims at minimisation of animal testing and instead largely relies on internationally approved in vitro tests, has been adopted by the OECD in 2014 as Guidance Document 203 (OECD, 2014b). Thereby, animal models have become unnecessary in most cases when testing for this endpoint." The in vivo skin irritation study used for this endpoint pre dates this OECD Guidance Document (report date: 1985).
Furthermore, also in Section 7.2.3: Data from existing irritation studies in animals must be taken into account before further testing is considered. A quality assessment was performed on the existing study and it was deemed adequate for fulfilling the skin sensitisation endpoint. Therefore, no further testing was required.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Dosing initiated: February 3 1982, Study termination: February 17 1982

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study conducted in accordance with generally accepted scientific principles, possibly with incomplete reporting or methodological deficiencies, which do not affect the quality of the relevant results.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Dutchland Laboratory Animals, Denver, Pennsylvania
- Age at study initiation: Approx 12 weeks
- Weight at study initiation: 2.6 to 3.6 kilograms
- Housing: Individually housed in suspended stainless steel cages (27 x 22 x 14 inches)
- Diet (e.g. ad libitum): Purina Certified Rabbit Chow (ad libitum)
- Water (e.g. ad libitum): Automatic watering system (ad libitum)
- Acclimation period: 30 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): Maintained range of 65 to 71 degrees Fahrenheit during study.
- Humidity (%): Maintained range of 40 to 70% during study.
- Photoperiod (hrs dark / hrs light): 12 hours light, 12 hours dark by automatic timer.

Vehicle:

unchanged (no vehicle)

Controls:

other: The contralateral eye of the animals served as the control.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml of the test material was instilled into the lower conjunctival sac of the right eye of each animal. The upper and lower lids were gently held together for approximately one second to prevent loss of the material. The treated eyes of six animals remained unwashed. Twenty to thirty seconds after instillation, the treated eyes of the three remaining animals were rinsed for one minute with sixty milliliters of lukewarm tap water. The control eyes of these animals were not washed.



VEHICLE
Not applicable.

Duration of treatment / exposure:

14 days.

Observation period (in vivo):

14 days.

Number of animals or in vitro replicates:

9.

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Treated eyes of three animals were rinsed for one minute with sixty ml of lukewarm water.
- Time after start of exposure: Twenty to thirty seconds after installation,


SCORING SYSTEM: Observations for signs of ocular irritation were made at approximately 1, 4, 24, 48 and 72 hours and 4 and 7 days after treatment. Since there were signs of irritation on Day 7, observations were made on Day 14.
Ocular reactions were graded according to the Draize Scale for Scoring Ocular Lesions.


TOOL USED TO ASSESS SCORE: fluorescein

Irritation parameter:

other: necrosis

Basis:

other: necrosis observed in number of test animals (out of 12)

Time point:

other: All timepoints

Score:

12

Max. score:

12

Reversibility:

not reversible

Remarks on result:

other: Necrosis was observed in all animals at all intervals.

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 14 d

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

48 h

Score:

4

Max. score:

4

Reversibility:

not fully reversible within: 14 d

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

72 h

Score:

4

Max. score:

4

Reversibility:

not fully reversible within: 14 d

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 14 d

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

48 h

Score:

4

Max. score:

4

Reversibility:

not fully reversible within: 14 d

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

72 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 14 d

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 14 d

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

48 h

Score:

4

Max. score:

4

Reversibility:

not fully reversible within: 14 d

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

72 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 14 d

Irritation parameter:

chemosis score

Basis:

animal #4

Time point:

24 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 14 d

Irritation parameter:

chemosis score

Basis:

animal #4

Time point:

48 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 14 d

Irritation parameter:

chemosis score

Basis:

animal #4

Time point:

72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 14 d

Irritation parameter:

chemosis score

Basis:

animal #5

Time point:

24 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 14 d

Irritation parameter:

chemosis score

Basis:

animal #5

Time point:

48 h

Score:

4

Max. score:

4

Reversibility:

not fully reversible within: 14 d

Irritation parameter:

chemosis score

Basis:

animal #5

Time point:

72 h

Score:

4

Max. score:

4

Reversibility:

not fully reversible within: 14 d

Irritation parameter:

chemosis score

Basis:

animal #6

Time point:

24 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 14 d

Irritation parameter:

chemosis score

Basis:

animal #6

Time point:

48 h

Score:

4

Max. score:

4

Reversibility:

not fully reversible within: 14 d

Irritation parameter:

chemosis score

Basis:

animal #6

Time point:

72 h

Score:

4

Max. score:

4

Reversibility:

not fully reversible within: 14 d

Irritation parameter:

chemosis score

Basis:

animal: #7

Time point:

24 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 14 d

Irritation parameter:

chemosis score

Basis:

animal: #7

Time point:

48 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 14 d

Irritation parameter:

chemosis score

Basis:

animal: #7

Time point:

72 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 14 d

Irritation parameter:

chemosis score

Basis:

animal: #8

Time point:

24 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 14 d

Irritation parameter:

chemosis score

Basis:

animal: #8

Time point:

48 h

Score:

4

Max. score:

4

Reversibility:

not fully reversible within: 14 d

Irritation parameter:

chemosis score

Basis:

animal: #8

Time point:

72 h

Score:

4

Max. score:

4

Reversibility:

not fully reversible within: 14 d

Irritation parameter:

chemosis score

Basis:

animal: #9

Time point:

24 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 14 d

Irritation parameter:

chemosis score

Basis:

animal: #9

Time point:

48 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 14 d

Irritation parameter:

chemosis score

Basis:

animal: #9

Time point:

72 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 14 d

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

72 h

Score:

> 4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

probability of severe irritation

Remarks:

Score not attributed due to severity of response

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

72 h

Score:

3

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

48 h

Score:

> 4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

probability of severe irritation

Remarks:

Score not attributed due to severity of response

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

cornea opacity score

Basis:

animal #4

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

cornea opacity score

Basis:

animal #5

Time point:

24/48 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

cornea opacity score

Basis:

animal #5

Time point:

72 h

Score:

> 4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

probability of severe irritation

Remarks:

Score not attributed due to severity of response

Irritation parameter:

cornea opacity score

Basis:

animal #6

Time point:

24/48 h

Score:

3

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

cornea opacity score

Basis:

animal #6

Time point:

72 h

Score:

> 4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

probability of severe irritation

Remarks:

Score not attributed due to severity of response

Irritation parameter:

cornea opacity score

Basis:

animal: #7

Time point:

24/48 h

Score:

2

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

cornea opacity score

Basis:

animal: #7

Time point:

72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

cornea opacity score

Basis:

animal: #8

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

cornea opacity score

Basis:

animal: #9

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24 h

Score:

2

Max. score:

2

Reversibility:

not reversible

Irritation parameter:

iris score

Basis:

animal #1

Time point:

48 h

Score:

> 2

Max. score:

2

Reversibility:

not reversible

Remarks on result:

probability of severe irritation

Remarks:

Score not attributed due to severity of response

Irritation parameter:

iris score

Basis:

animal #1

Time point:

72 h

Score:

> 2

Max. score:

2

Reversibility:

not reversible

Remarks on result:

probability of severe irritation

Remarks:

Score not attributed due to severity of response

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

> 2

Max. score:

2

Reversibility:

not reversible

Remarks on result:

probability of severe irritation

Remarks:

Score not attributed due to severity of response

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

> 2

Max. score:

2

Reversibility:

not reversible

Remarks on result:

probability of severe irritation

Remarks:

Score not attributed due to severity of response

Irritation parameter:

iris score

Basis:

animal #4

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

not reversible

Irritation parameter:

iris score

Basis:

animal #5

Time point:

24/48/72 h

Score:

> 2

Max. score:

2

Reversibility:

not reversible

Remarks on result:

probability of severe irritation

Remarks:

Score not attributed due to severity of response

Irritation parameter:

iris score

Basis:

animal #6

Time point:

24/48 h

Score:

2

Max. score:

2

Reversibility:

not reversible

Irritation parameter:

iris score

Basis:

animal #6

Time point:

72 h

Score:

> 2

Max. score:

2

Reversibility:

not reversible

Remarks on result:

probability of severe irritation

Remarks:

Score not attributed due to severity of response

Irritation parameter:

iris score

Basis:

animal: #7

Time point:

24/48/72 h

Score:

> 2

Max. score:

2

Reversibility:

not reversible

Remarks on result:

probability of severe irritation

Remarks:

Score not attributed due to severity of response

Irritation parameter:

iris score

Basis:

animal: #8

Time point:

24/48/72 h

Score:

> 2

Max. score:

2

Reversibility:

not reversible

Remarks on result:

probability of severe irritation

Remarks:

Score not attributed due to severity of response

Irritation parameter:

iris score

Basis:

animal: #9

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

not reversible

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

not reversible

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

not reversible

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

not reversible

Irritation parameter:

conjunctivae score

Basis:

animal #4

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

not reversible

Irritation parameter:

conjunctivae score

Basis:

animal #5

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

not reversible

Irritation parameter:

conjunctivae score

Basis:

animal #6

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

not reversible

Irritation parameter:

conjunctivae score

Basis:

animal: #7

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

not reversible

Irritation parameter:

conjunctivae score

Basis:

animal: #8

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

not reversible

Irritation parameter:

conjunctivae score

Basis:

animal: #9

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not reversible

Irritant / corrosive response data:

Ocular reaction to the test material was severe. Necrosis was observed in all animals at all intervals. In many cases the eye could not be fully evaluated due the severity of response.
Conjuctival responses included: redness scores of ‘3-4’, chemosis scores of ‘2-4’ lending to an increase in severity over time, discharge scores of ‘0-3’, ulceration and necrosis, with seven of the nine rabbits clearing of ulceration after the first two to three observation period.
 Iridial responses could not be evaluated at all in four animals, one being a washed animal, or were either scored at ‘2’ or not evaluated for the remaining five animals.
 Corneal responses included; opacity scores of ‘4’ for one unwashed animal, and for remaining animals ranged from ‘2-4’ or could not be evaluated at some intervals due to the severity of response. Area scores ranged from ‘1-4’. Ulceration of the cornea was scored from ‘0-4’, or could not be evaluated for some intervals due to the severity of response.

Other effects:

Corneal prolusions, deterioration of eyelids, eyes held shut by discharge and discharges of red, white and yellow-green were along the supplement observations noted.

Interpretation of results:

corrosive

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Ocular reaction to the test material was severe. Necrosis was observed in all animals at all intervals. In many cases the eye could not be fully evaluated due the severity of response.

Executive summary:

The eye irritation potential of the test substance was evaluated following a single application to the right eye of nine New Zealand White rabbits. Three of the nine animals had their eyes flushed with lukewarm water for approximately one minute, starting at about 20 to 30 seconds after instillation. For ocular lesions were performed at 1, 4, 24, 48 and 72 hours and at Days 4, 7 and 14 post-instillation. Ocular reactions were graded according to the Draize Scale for Scoring Ocular Lesions.

 

Ocular reaction to the test material was severe. Necrosis was observed in all animals at all intervals. In many cases the eye could not be fully evaluated due the severity of response. Corneal prolusions, deterioration of eyelids, eyes held shut by discharge and discharges of red, white and yellow-green were along the supplement observations noted.

 

Conjuctival responses included: redness scores of ‘3-4’, chemosis scores of ‘2-4’ lending to an increase in severity over time, discharge scores of ‘0-3’, ulceration and necrosis, with seven of the nine rabbits clearing of ulceration after the first two to three observation period.

 

Iridial responses could not be evaluated at all in four animals, one being a washed animal, or were either scored at ‘2’ or not evaluated for the remaining five animals.

 

Corneal responses included; opacity scores of ‘4’ for one unwashed animal, and for remaining animals ranged from ‘2-4’ or could not be evaluated at some intervals due to the severity of response. Area scores ranged from ‘1-4’. Ulceration of the cornea was scored from ‘0-4’, or could not be evaluated for some intervals due to the severity of response.

Reference 2

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
An in vitro eye irritation study is not required because adequate in vivo data are available (Kapp, 1982).

An in vitro eye irritation study is not required because adequate in vivo data are available (see key study: Plutnick, 1985). As per ECHA Guidance - Chaper R7a: Endpoint specific guidance (v6.0; July, 2017);
"For existing [animal] data, the use of methods other than those specified in the Annex to the EU Test Methods Regulation, or corresponding OECD methods may be accepted on a case-by-case basis". In this case, an OECD 405 study was performed.

Furthermore, also in Section 7.2.7: Data from existing irritation studies in animals must be taken into account before further testing is considered. A quality assessment was performed on the existing study and it was deemed adequate for fulfilling the skin sensitisation endpoint. Therefore, no further testing was required.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin Corrosion:

Four skin irritation/corrosion studies were performed and all four showed corrosive effects to the skin. Corrosive effects were noted after exposure times of 30 minutes, 1 hour and 4 hours. Non-reversible skin reactions and necrosis (a sign of dermal irritation) was observed in animals in all studies.

The substance has therefore been classified as skin corrosive Category 1A.

Eye corrosion:

Ocular reaction to the test material was severe. Necrosis was observed in all animals at all intervals. In many cases the eye could not be fully evaluated due the severity of response.

The substance meets the criteria for classification as Serious Eye Damage 1, but as the substance is already classified as skin corrosive Category 1a, then serious damage to the eyes is implicit and there is no need to proceed with classification for eye effects.

Justification for selection of skin irritation / corrosion endpoint:
Key study for endpoint.

Justification for selection of eye irritation endpoint:
Key study for endpoint.

Effects on skin irritation/corrosion: corrosive

Effects on eye irritation: corrosive

Justification for classification or non-classification

The test substance meets the criteria to be classified as skin corrosive, Category 1A. The substance also meets the criteria for classification as Serious Eye Damage 1, but as the substance is already classified as skin corrosive Category 1A, then serious damage to the eyes is implicit and there is no need to proceed with classification for eye effects.

The substance must also be labelled with the supplementary label EUH071: Corrosive to the respiratory tract. This is required for substances classified as corrosive, where no acute inhalation data are available and the substance may be inhaled.