Amines, C12-14-alkyl, isooctyl phosphates

Endpoint summary

Description of key information

In vivo skin irritation / corrosion = corrosive OECD 404 Report RCR/029/994915/SE (2000)

In vivo primary dermal irritation study = moderately irritating method comparable to OECD 404 Report 480 -2370 (1986)

In vivo primary eye irritation study = moderately irritating method comparable to OECD 405 Report 480 -2371 (1986)

 

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:

23 November 1999 to 6 December 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted to GLP and in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do no effect the quality of the relevant results.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: New Zealand White rabbits were supplied by Charles River UK Ltd, Margate, Kent, England.
- Age at study initiation: at least 14 weeks old
- Weight at study initiation: At the start of the study the animals weighed 2.8 to 3.1 kg
- Housing: The animals were individually housed in stainless steel cages with perforated floors.
- Diet (e.g. ad libitum): Free access to a standard laboratory rabbit diet (Special Diet Services, Stanrab (P) SQC pellet) was allowed throughout the study. Hay three times / week.
- Water (e.g. ad libitum): Free access to mains drinking water was allowed throughout the study.
- Acclimation period: Twenty days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 21°C
- Humidity (%): 28 to 52%
Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study.
- Photoperiod (hrs dark / hrs light): Lighting was controlled by a time switch to give twelve hours continuous light (0700 - 1900 hours) and twelve hours darkness.

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

0.5 ml of the test substance was administered as supplied

Duration of treatment / exposure:

4 hours

Observation period:

1 hour, 24 hours, 48 hours, 72 hours and on Days 5 to 14.

Number of animals:

3 males

Details on study design:

PROCEDURE:
Approximately 24 hours before the test item application, each rabbit was clipped free of hair from the dorso-lumbar region using electric clippers exposing an area of skin approximately 100 mm x 100 mm.

Approximately 0.5 ml of the test item was applied under a 2-ply 25 mm x 25 mm porous gauze pad to one intact skin site on each animal. Each treatment site was covered with "Elastoplast" elastic adhesive dressing for four hours. The animals were not restrained during the exposure period and were returned to their cages immediately after treatment.

At the end of the exposure period the semi occlusive dressing and gauze were removed from each animal and the treatment site washed with warm water to remove any residual test item. The treated area was blotted dry with absorbent paper.

Examination of the treated skin was made approximately 1 hour following removal of the dressings and 24, 48 and 72 hours after exposure. Additional observations were made for all animals on Days 5 through to 14. Local dermal irritation was assessed using the numerical system, see any other information on materials and methods

Any other skin reactions if present, were also recorded.

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

3687

Time point:

other: Mean of scores at 24, 48 and 72 hours

Score:

4

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Remarks on result:

other: Necrotic patch

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

3687

Time point:

other: Mean of scores at 24, 48 and 72 hours

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

3688

Time point:

other: Mean of scores at 24, 48 and 72 hours

Score:

4

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Remarks on result:

other: Necrotic patch

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

3688

Time point:

other: Mean of scores at 24, 48 and 72 hours

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

3869

Time point:

other: Mean of scores at 24, 48 and 72 hours

Score:

4

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Remarks on result:

other: Necrotic patch

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

3869

Time point:

other: Mean of scores at 24, 48 and 72 hours

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritant / corrosive response data:

Please see attached background information for individual skin reactions.

Severe erythema with slight to moderate oedema and necrotic patches were seen in all three animals. The necrotic patches began sloughing off in two animals on Day 11 revealing new skin underneath. Blanching of the skin and desquamation (characterised by dryness of the skin) were observed in all animals. Reactions gradually ameliorated however very slight to well defined erythema with or without very slight oedema was still evident in all animals at study termination on Day 14.

Other effects:

There were no other signs of toxicity or ill health.

Interpretation of results:

Category 1C (corrosive) based on GHS criteria

Conclusions:

A single semi occlusive application of the test substance to intact rabbit skin for four hours elicited severe dermal irritation with necrotic patches.
The test item meets the criteria for classification according to the Classification, Labelling and Packaging Regulation (CLP) or the Globally Harmonised Classification System.

Executive summary:

Introduction. 

The study was performed to assess the irritancy potential of the test item to the skin of the New Zealand White rabbit. The method was designed to be compatible with the following:

- OECD Guidelines for the Testing of Chemicals No. 404 “Acute Dermal Irritation/Corrosion” (adopted 17 July 1992)

- Method B4 Acute Toxicity (Skin Irritation) of Commission Directive 92/69/EEC

- EPA Health Effects Test Guidelines OPPTS 870.2500 Acute Dermal Irritation EPA 712 -C-98 -196 (August 1998)

Results. 

A single 4-hour, semi-occluded application of the test item to the intact skin of three rabbits for four hours elicited severe dermal irritation with necrotic patches.

Conclusion. 

The test item is classified as corrosive according to the Classification, Labelling and Packaging Regulation (CLP) or the Globally Harmonised Classification System.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

29/04/1986 to 06/05/1986

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

Study carried out according to company protocols comparable to guideline study

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Young adult male and female albino New Zealand rabbits obtained from Clerco Research Farm, Cincinnati, OH, USA
- Housing: The animals were housed individually in stainless steel cages with wire mesh floors.
- Diet (e.g. ad libitum): Purina Certified Rabbit Chow 5322 was fed throughout the study.
- Water (e.g. ad libitum): Free access to filtered tap water was provided through an automatic watering system.
- Acclimation period: 7 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 67 ± 5 F
- Humidity (%): 30 - 70%
- Ventilation: The animal room was well ventilated and air conditioned
- Photoperiod (hrs dark / hrs light): lighting was controlled by automatic timers to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.5ml

Duration of treatment / exposure:

4 hours

Observation period:

Test Sites were evaluated following test article removal at 30 -60 minutes, 24 hours, 48 hours, 72 hours and on Days 4 to 7

Number of animals:

3 males and 3 females

Details on study design:

TEST SITE
- Area of exposure: 2.5cm2
- Type of wrap if used: gauze wrapping with impervious binder consiting of plastic wrap, adhesive tape and masking tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): wiped with gauze sponge moistened with deionised water
- Time after start of exposure: after 4 hour exposure period

OBSERVATION TIME POINTS
(indicate if minutes, hours or days):; 30 -60 minutes, 24 hours, 48 hours, 72 hours and on Days 4 to 7

SCORING SYSTEM:
- Method of calculation: Draize J H

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24 h

Score:

ca. 2

Max. score:

4

Reversibility:

other:

Remarks:

Within the 7 day observation period this was not reversible

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

48 h

Score:

ca. 2

Max. score:

4

Reversibility:

other:

Remarks:

Within the 7 day observation period this was not reversible

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

72 h

Score:

ca. 2

Max. score:

4

Reversibility:

other:

Remarks:

Within the 7 day observation period this was not reversible

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

7 d

Score:

ca. 2

Max. score:

4

Reversibility:

other:

Remarks:

Within the 7 day observation period this was not reversible

Remarks on result:

other: Desquamation observed

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24 h

Score:

ca. 3

Max. score:

4

Reversibility:

other:

Remarks:

Within the 7 day observation period this was not reversible

Irritation parameter:

edema score

Basis:

animal #1

Time point:

48 h

Score:

ca. 3

Max. score:

4

Reversibility:

other:

Remarks:

Within the 7 day observation period this was not reversible

Irritation parameter:

edema score

Basis:

animal #1

Time point:

72 h

Score:

ca. 3

Max. score:

4

Reversibility:

other:

Remarks:

Within the 7 day observation period this was not reversible

Irritation parameter:

edema score

Basis:

animal #1

Time point:

7 d

Score:

ca. 1

Max. score:

4

Reversibility:

other:

Remarks:

Within the 7 day observation period this was not reversible

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24 h

Score:

ca. 2

Max. score:

4

Reversibility:

other:

Remarks:

Within the 7 day observation period this was not reversible

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

48 h

Score:

ca. 2

Max. score:

4

Reversibility:

other:

Remarks:

Within the 7 day observation period this was not reversible

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

72 h

Score:

ca. 2

Max. score:

4

Reversibility:

other:

Remarks:

Within the 7 day observation period this was not reversible

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

7 d

Score:

ca. 1

Max. score:

4

Reversibility:

other:

Remarks:

Within the 7 day observation period this was not reversible

Remarks on result:

other: Desquamation observed

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24 h

Score:

ca. 3

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

edema score

Basis:

animal #2

Time point:

48 h

Score:

ca. 3

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

edema score

Basis:

animal #2

Time point:

72 h

Score:

ca. 3

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

edema score

Basis:

animal #2

Time point:

7 d

Score:

ca. 0

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24 h

Score:

ca. 2

Max. score:

4

Reversibility:

other:

Remarks:

Within the 7 day observation period this was not reversible

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

48 h

Score:

ca. 2

Max. score:

4

Reversibility:

other:

Remarks:

Within the 7 day observation period this was not reversible

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

72 h

Score:

ca. 2

Max. score:

4

Reversibility:

other:

Remarks:

Within the 7 day observation period this was not reversible

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

7 d

Score:

ca. 1

Max. score:

4

Reversibility:

other:

Remarks:

Within the 7 day observation period this was not reversible

Remarks on result:

other: Desquamation observed

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24 h

Score:

ca. 2

Max. score:

4

Reversibility:

other:

Remarks:

Within the 7 day observation period this was not reversible

Irritation parameter:

edema score

Basis:

animal #3

Time point:

48 h

Score:

ca. 3

Max. score:

4

Reversibility:

other:

Remarks:

Within the 7 day observation period this was not reversible

Irritation parameter:

edema score

Basis:

animal #3

Time point:

72 h

Score:

ca. 3

Max. score:

4

Reversibility:

other:

Remarks:

Within the 7 day observation period this was not reversible

Irritation parameter:

edema score

Basis:

animal #3

Time point:

7 d

Score:

ca. 1

Max. score:

4

Reversibility:

other:

Remarks:

Within the 7 day observation period this was not reversible

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

24 h

Score:

ca. 2

Max. score:

4

Reversibility:

other:

Remarks:

Within the 7 day observation period this was not reversible

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

48 h

Score:

ca. 1

Max. score:

4

Reversibility:

other:

Remarks:

Within the 7 day observation period this was not reversible

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

72 h

Score:

ca. 1

Max. score:

4

Reversibility:

other:

Remarks:

Within the 7 day observation period this was not reversible

Remarks on result:

other: Desquamation observed

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

7 d

Score:

ca. 1

Max. score:

4

Reversibility:

other:

Remarks:

Within the 7 day observation period this was not reversible

Remarks on result:

other: Desquamation observed

Irritation parameter:

edema score

Basis:

animal #4

Time point:

24 h

Score:

ca. 2

Max. score:

4

Reversibility:

fully reversible within: 5 days

Irritation parameter:

edema score

Basis:

animal #4

Time point:

48 h

Score:

ca. 1

Max. score:

4

Reversibility:

fully reversible within: 5 days

Irritation parameter:

edema score

Basis:

animal #4

Time point:

72 h

Score:

ca. 1

Max. score:

4

Reversibility:

fully reversible within: 5 days

Irritation parameter:

edema score

Basis:

animal #4

Time point:

7 d

Score:

ca. 0

Max. score:

4

Reversibility:

fully reversible within: 5 days

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

24 h

Score:

ca. 1

Max. score:

4

Reversibility:

other:

Remarks:

Within the 7 day observation period this was not reversible

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

48 h

Score:

ca. 1

Max. score:

4

Reversibility:

other:

Remarks:

Within the 7 day observation period this was not reversible

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

72 h

Score:

ca. 1

Max. score:

4

Reversibility:

other:

Remarks:

Within the 7 day observation period this was not reversible

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

7 d

Score:

ca. 1

Max. score:

4

Reversibility:

other:

Remarks:

Within the 7 day observation period this was not reversible

Remarks on result:

other: Desquamation observed

Irritation parameter:

edema score

Basis:

animal #5

Time point:

24 h

Score:

ca. 1

Max. score:

4

Reversibility:

fully reversible within: 1 day

Irritation parameter:

edema score

Basis:

animal #5

Time point:

48 h

Score:

ca. 0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #5

Time point:

72 h

Score:

ca. 0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #5

Time point:

7 d

Score:

ca. 0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

24 h

Score:

ca. 2

Max. score:

4

Reversibility:

fully reversible within:

Remarks:

7 days

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

48 h

Score:

ca. 2

Max. score:

4

Reversibility:

fully reversible within:

Remarks:

7 days

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

72 h

Score:

ca. 2

Max. score:

4

Reversibility:

fully reversible within:

Remarks:

7 days

Remarks on result:

other: Desquamation observed

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

7 d

Score:

ca. 0

Max. score:

4

Remarks on result:

other: Desquamation observed

Irritation parameter:

edema score

Basis:

animal #6

Time point:

24 h

Score:

ca. 2

Max. score:

4

Reversibility:

fully reversible within:

Remarks:

6 days

Irritation parameter:

edema score

Basis:

animal #6

Time point:

48 h

Score:

ca. 2

Max. score:

4

Reversibility:

fully reversible within:

Remarks:

6 days

Irritation parameter:

edema score

Basis:

animal #6

Time point:

72 h

Score:

ca. 2

Max. score:

4

Reversibility:

fully reversible within:

Remarks:

6 days

Irritation parameter:

edema score

Basis:

animal #6

Time point:

7 d

Score:

ca. 0

Max. score:

4

Irritant / corrosive response data:

See attached background information.
Well defined to moderate erythema and very slight to moderate edema was observed for all anials after test item removal.

Other effects:

All animals survived the study period and were free from overt toxic signs.

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

Under the conditions of the study the test article was considered to be moderatly irritating.

Executive summary:

Introduction

A primary dermal irritation study was performed to evaluate the irritancy potential of the test item to the skin of the New Zealand White rabbit. 

Method

The test item was applied to 1 intact test site on each of 6 rabbits and covered with impervious bandages for 4 hours. After which the test sites were wiped clean of residual test material and evaluated for erythema, edema and other lesions at 30 - 60 minutes, at 24, 48 and 72 hours and on days 4 to 7.

Results

Well defined to moderate erythema and slight to moderate edema was observed for all animals. Desquamation was noted at the test sites of 2 animals at 72 hours, 4 animals at Day 4 and 5 and for all animals on Days 6 and 7. Dermal reactions decreased in severity from 24 hours to day 7.

No mortalities occurred during the study and all animals were free of overt signs of toxicity.

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Young adult male and female albino New Zealand rabbits obtained from Clerco Research Farm, Cincinnati, OH, USA
- Housing: The animals were housed individually in stainless steel cages with wire mesh floors.
- Diet (e.g. ad libitum): Purina Certified Rabbit Chow 5322 was fed throughout the study.
- Water (e.g. ad libitum): Free access to filtered tap water was provided through an automatic watering system.
- Acclimation period: 7 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 67 ± 5 F
- Humidity (%): 30 - 70%
- Ventilation: The animal room was well ventilated and air conditioned
- Photoperiod (hrs dark / hrs light): lighting was controlled by automatic timers to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

Vehicle:

unchanged (no vehicle)

Controls:

other:

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied : 0.1ml

Observation period (in vivo):

1hr, 24, 48 and 72 hours and 7 days after instillation of the test item

Number of animals or in vitro replicates:

3 males and 3 females

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Eyes were not washed after treatment


SCORING SYSTEM: Draize

TOOL USED TO ASSESS SCORE: A pocket flashlight without magnification was used at all evaluation intervals. A 2% sodium Fluorescein solution in deionised water was used at all evaluations except for those done at 1 hour after instillation.

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24 h

Score:

ca. 1

Max. score:

4

Reversibility:

fully reversible within:

Remarks:

7 days

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

48 h

Score:

ca. 1

Max. score:

4

Reversibility:

fully reversible within:

Remarks:

7 days

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

72 h

Score:

ca. 1

Max. score:

4

Reversibility:

fully reversible within:

Remarks:

7 days

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

7 d

Score:

ca. 0

Max. score:

4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24 h

Score:

ca. 1

Max. score:

2

Reversibility:

fully reversible within:

Remarks:

48 hours

Irritation parameter:

iris score

Basis:

animal #1

Time point:

48 h

Score:

ca. 0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #1

Time point:

72 h

Score:

ca. 0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #1

Time point:

7 d

Score:

ca. 0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24 h

Score:

ca. 3

Max. score:

3

Reversibility:

fully reversible within:

Remarks:

7 days

Remarks on result:

other: Blistering of conjunctiva observed

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

48 h

Score:

ca. 2

Max. score:

3

Reversibility:

fully reversible within:

Remarks:

7 days

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

72 h

Score:

ca. 2

Max. score:

3

Reversibility:

fully reversible within:

Remarks:

7 days

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

7 d

Score:

ca. 0

Max. score:

3

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24 h

Score:

ca. 2

Max. score:

4

Reversibility:

fully reversible within:

Remarks:

7 days

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

48 h

Score:

ca. 1

Max. score:

4

Reversibility:

fully reversible within:

Remarks:

7 days

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

72 h

Score:

ca. 1

Max. score:

4

Reversibility:

fully reversible within:

Remarks:

7 days

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

7 d

Score:

ca. 0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24 h

Score:

ca. 1

Max. score:

4

Reversibility:

fully reversible within:

Remarks:

48 hours

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

48 h

Score:

ca. 0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

72 h

Score:

ca. 0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

7 d

Score:

ca. 0

Max. score:

4

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24 h

Score:

ca. 1

Max. score:

2

Reversibility:

fully reversible within:

Remarks:

48 hours

Irritation parameter:

iris score

Basis:

animal #2

Time point:

48 h

Score:

ca. 0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #2

Time point:

72 h

Score:

ca. 0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #2

Time point:

7 d

Score:

ca. 0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24 h

Score:

ca. 3

Max. score:

3

Reversibility:

fully reversible within:

Remarks:

7 days

Remarks on result:

other:

Remarks:

Blistering observed

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

48 h

Score:

ca. 2

Max. score:

3

Reversibility:

fully reversible within:

Remarks:

7 days

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

72 h

Score:

ca. 2

Max. score:

3

Reversibility:

fully reversible within:

Remarks:

7 days

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

7 d

Score:

ca. 0

Max. score:

3

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24 h

Score:

ca. 2

Max. score:

4

Reversibility:

fully reversible within:

Remarks:

72 hours

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

48 h

Score:

ca. 1

Max. score:

4

Reversibility:

fully reversible within:

Remarks:

72 hours

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

72 h

Score:

ca. 0

Max. score:

4

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

7 d

Score:

ca. 0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24 h

Score:

ca. 1

Max. score:

4

Reversibility:

fully reversible within:

Remarks:

7 days

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

48 h

Score:

ca. 1

Max. score:

4

Reversibility:

fully reversible within:

Remarks:

7 days

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

72 h

Score:

ca. 1

Max. score:

4

Reversibility:

fully reversible within:

Remarks:

7 days

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

7 d

Score:

ca. 0

Max. score:

4

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24 h

Score:

ca. 1

Max. score:

2

Reversibility:

fully reversible within:

Remarks:

72 hours

Irritation parameter:

iris score

Basis:

animal #3

Time point:

48 h

Score:

ca. 1

Max. score:

2

Reversibility:

fully reversible within:

Remarks:

72 hours

Irritation parameter:

iris score

Basis:

animal #3

Time point:

72 h

Score:

ca. 0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #3

Time point:

7 d

Score:

ca. 0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24 h

Score:

ca. 3

Max. score:

3

Reversibility:

fully reversible within:

Remarks:

7 days

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

48 h

Score:

ca. 3

Max. score:

3

Reversibility:

fully reversible within:

Remarks:

7 days

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

72 h

Score:

ca. 3

Max. score:

3

Reversibility:

fully reversible within:

Remarks:

7 days

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

7 d

Score:

ca. 0

Max. score:

3

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24 h

Score:

ca. 2

Max. score:

4

Reversibility:

fully reversible within:

Remarks:

7 days

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

48 h

Score:

ca. 3

Max. score:

4

Reversibility:

fully reversible within:

Remarks:

7 days

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

72 h

Score:

ca. 3

Max. score:

4

Reversibility:

fully reversible within:

Remarks:

7 days

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

7 d

Score:

ca. 0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #4

Time point:

24 h

Score:

ca. 2

Max. score:

4

Reversibility:

fully reversible within:

Remarks:

7 days

Irritation parameter:

cornea opacity score

Basis:

animal #4

Time point:

48 h

Score:

ca. 2

Max. score:

4

Reversibility:

fully reversible within:

Remarks:

7 days

Irritation parameter:

cornea opacity score

Basis:

animal #4

Time point:

72 h

Score:

ca. 2

Max. score:

4

Reversibility:

fully reversible within:

Remarks:

7 days

Irritation parameter:

cornea opacity score

Basis:

animal #4

Time point:

7 d

Score:

ca. 0

Max. score:

4

Remarks on result:

other: Pannus observed

Irritation parameter:

iris score

Basis:

animal #4

Time point:

24 h

Score:

ca. 1

Max. score:

2

Reversibility:

fully reversible within:

Remarks:

7 days

Irritation parameter:

iris score

Basis:

animal #4

Time point:

48 h

Score:

ca. 1

Max. score:

2

Reversibility:

fully reversible within:

Remarks:

7 days

Irritation parameter:

iris score

Basis:

animal #4

Time point:

72 h

Score:

ca. 1

Max. score:

2

Reversibility:

fully reversible within:

Remarks:

7 days

Irritation parameter:

iris score

Basis:

animal #4

Time point:

7 d

Score:

ca. 0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

animal #4

Time point:

24 h

Score:

ca. 3

Max. score:

3

Reversibility:

fully reversible within:

Remarks:

7 days

Remarks on result:

other: blistering observed

Irritation parameter:

conjunctivae score

Basis:

animal #4

Time point:

48 h

Score:

ca. 2

Max. score:

3

Reversibility:

fully reversible within:

Remarks:

7 days

Irritation parameter:

conjunctivae score

Basis:

animal #4

Time point:

72 h

Score:

ca. 2

Max. score:

3

Reversibility:

fully reversible within:

Remarks:

7 days

Irritation parameter:

conjunctivae score

Basis:

animal #4

Time point:

7 d

Score:

ca. 0

Max. score:

3

Irritation parameter:

chemosis score

Basis:

animal #4

Time point:

24 h

Score:

ca. 3

Max. score:

4

Reversibility:

fully reversible within:

Remarks:

7 days

Irritation parameter:

chemosis score

Basis:

animal #4

Time point:

48 h

Score:

ca. 2

Max. score:

4

Reversibility:

fully reversible within:

Remarks:

7 days

Irritation parameter:

chemosis score

Basis:

animal #4

Time point:

72 h

Score:

ca. 2

Max. score:

4

Reversibility:

fully reversible within:

Remarks:

7 days

Irritation parameter:

chemosis score

Basis:

animal #4

Time point:

7 d

Score:

ca. 0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #5

Time point:

24 h

Score:

ca. 1

Max. score:

4

Reversibility:

not fully reversible within:

Remarks:

7 days

Irritation parameter:

cornea opacity score

Basis:

animal #5

Time point:

48 h

Score:

ca. 2

Max. score:

4

Reversibility:

not fully reversible within:

Remarks:

7 days

Irritation parameter:

cornea opacity score

Basis:

animal #5

Time point:

72 h

Score:

ca. 2

Max. score:

4

Reversibility:

fully reversible within:

Remarks:

7 days

Irritation parameter:

cornea opacity score

Basis:

animal #5

Time point:

7 d

Score:

ca. 2

Max. score:

4

Reversibility:

not fully reversible within:

Remarks:

7 days

Remarks on result:

other: Pannus observed

Irritation parameter:

iris score

Basis:

animal #5

Time point:

24 h

Score:

ca. 1

Max. score:

2

Reversibility:

fully reversible within:

Remarks:

7 days

Irritation parameter:

iris score

Basis:

animal #5

Time point:

48 h

Score:

ca. 1

Max. score:

2

Reversibility:

fully reversible within:

Remarks:

7 days

Irritation parameter:

iris score

Basis:

animal #5

Time point:

72 h

Score:

ca. 1

Max. score:

2

Reversibility:

fully reversible within:

Remarks:

7 days

Irritation parameter:

iris score

Basis:

animal #5

Time point:

7 d

Score:

ca. 0

Max. score:

2

Reversibility:

fully reversible within:

Remarks:

7 days

Irritation parameter:

conjunctivae score

Basis:

animal #5

Time point:

24 h

Score:

ca. 3

Max. score:

3

Reversibility:

not fully reversible within:

Remarks:

7 day observation period

Remarks on result:

other: bistering observed

Irritation parameter:

conjunctivae score

Basis:

animal #5

Time point:

48 h

Score:

ca. 3

Max. score:

3

Reversibility:

not fully reversible within:

Remarks:

7 days

Irritation parameter:

conjunctivae score

Basis:

animal #5

Time point:

72 h

Score:

ca. 3

Max. score:

3

Reversibility:

not fully reversible within:

Remarks:

7 days

Irritation parameter:

conjunctivae score

Basis:

animal #5

Time point:

7 d

Score:

ca. 1

Max. score:

3

Reversibility:

not fully reversible within:

Remarks:

7 days

Irritation parameter:

chemosis score

Basis:

animal #5

Time point:

24 h

Score:

ca. 4

Max. score:

4

Reversibility:

not fully reversible within:

Remarks:

7 days

Irritation parameter:

chemosis score

Basis:

animal #5

Time point:

48 h

Score:

ca. 4

Max. score:

4

Reversibility:

not fully reversible within:

Remarks:

7 days

Irritation parameter:

chemosis score

Basis:

animal #5

Time point:

72 h

Score:

ca. 4

Max. score:

4

Reversibility:

not fully reversible within:

Remarks:

7 days

Irritation parameter:

chemosis score

Basis:

animal #5

Time point:

7 d

Score:

ca. 2

Max. score:

4

Reversibility:

not fully reversible within:

Remarks:

7 days

Irritation parameter:

cornea opacity score

Basis:

animal #6

Time point:

24 h

Score:

ca. 1

Max. score:

4

Reversibility:

fully reversible within:

Remarks:

7 days

Irritation parameter:

cornea opacity score

Basis:

animal #6

Time point:

48 h

Score:

ca. 1

Max. score:

4

Reversibility:

fully reversible within:

Remarks:

7 days

Irritation parameter:

cornea opacity score

Basis:

animal #6

Time point:

72 h

Score:

ca. 1

Max. score:

4

Reversibility:

fully reversible within:

Remarks:

7 days

Irritation parameter:

cornea opacity score

Basis:

animal #6

Time point:

7 d

Score:

ca. 0

Max. score:

4

Irritation parameter:

iris score

Basis:

animal #6

Time point:

24 h

Score:

ca. 1

Max. score:

2

Reversibility:

fully reversible within:

Remarks:

48 hours

Irritation parameter:

iris score

Basis:

animal #6

Time point:

48 h

Score:

ca. 0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #6

Time point:

72 h

Score:

ca. 0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #6

Time point:

7 d

Score:

ca. 0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

animal #6

Time point:

24 h

Score:

ca. 3

Max. score:

3

Reversibility:

fully reversible within:

Remarks:

7 days

Irritation parameter:

conjunctivae score

Basis:

animal #6

Time point:

48 h

Score:

ca. 2

Max. score:

3

Reversibility:

fully reversible within:

Remarks:

7 days

Irritation parameter:

conjunctivae score

Basis:

animal #6

Time point:

72 h

Score:

ca. 2

Max. score:

3

Reversibility:

fully reversible

Remarks:

7 days

Irritation parameter:

conjunctivae score

Basis:

animal #6

Time point:

7 d

Score:

ca. 0

Max. score:

3

Irritation parameter:

chemosis score

Basis:

animal #6

Time point:

24 h

Score:

ca. 2

Max. score:

4

Reversibility:

fully reversible within:

Remarks:

7 days

Irritation parameter:

chemosis score

Basis:

animal #6

Time point:

48 h

Score:

ca. 2

Max. score:

4

Reversibility:

fully reversible within:

Remarks:

7 days

Irritation parameter:

chemosis score

Basis:

animal #6

Time point:

72 h

Score:

ca. 1

Max. score:

4

Reversibility:

fully reversible within:

Remarks:

7 days

Irritation parameter:

chemosis score

Basis:

animal #6

Time point:

7 d

Score:

ca. 0

Max. score:

4

Irritant / corrosive response data:

See attached background information.

Other effects:

No mortalities and no abnormal clinical signs were observed during the study.

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

Under the conditions of the study the test article was considered to be moderatly irritating.

Executive summary:

Introduction

The study was performed to evaluate the primary eye irritancy potential of the test item. 

Method

After instillation of 0.1ml the test item to the right eye of 6 rabbits the eyes were examined for ocular irritation and lesions at 1 hour, 24 hour, 48 hour , 72 hours and a 7 day interval.

Results

Incidences of redness, chemosis, discharge and iritis were observed together with blistering of the conjuntivae, white discharge, opacities, positive fluorescein staining and pannus. The test article was considered to be moderately irritating.

No mortalities occurred during the study and all animals were free of overt signs of toxicity.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Additional information

Two in vivo dermal irritation studies and one in vivo eye study are available. The most recent in vivo dermal irritation study was considered the most reliable and was used for classification. This study showed the substance to be corrosive. The substance can therefore be considered to lead to serious eye damage.

Justification for classification or non-classification

According to the criteria for classification and labelling of substances and mixtures (Regulation (EC) No. 1272/2008), the substance qualifies for classification as Skin Corrosive 1C, H314: Eye Damage 1, H318.