Benzenamine, reaction products with aniline hydrochloride and nitrobenzene

Endpoint summary

Description of key information

Skin Irritation

Key Study: Allen (1993)

The test material produced a primary irritation index of 0.0 and was classified as a non-irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.

The test material did not produce positive criteria in any rabbit and was considered a non-irritant to rabbit skin.

Supporting Study: Walter (1992)

The test material produced a primary irritation index of 0.2 and was classified as a mild irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.

Eye Irritation

Key Study: Allen (1993)

The test material produced a maximum group mean score of 4.7 and was classified as a minimal irritant (Class 3 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.

 

Supporting Study: Walter (1992)

The test material produced a maximum group mean score of 0.0 and was classified as non-irritating (Class 1 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.

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:

15 December 1992 to 18 January 1993

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted to GLP in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect 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

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: David Percival Ltd., Moston, Sandbach, Cheshire, UK
- Age at study initiation: 12 - 16 weeks
- Weight at study initiation: 2.36 - 2.57 kg
- Housing: individually housed in suspended metal cages
- Diet: ad libitum throughout study
- Water: ad libitum throughout study
- Acclimation period: 5 days minimum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 20°C
- Humidity (%): 55 - 61%
- Air changes (per hr): 15 changes per hour
- Photoperiod (hrs dark / hrs light): continuous 12 hours light and 12 hours darkness

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5g, moistened with 0.5 ml distilled water

Duration of treatment / exposure:

4h

Observation period:

1h, 24 h, 48 h and 72 h post treatment

Number of animals:

2 male, 1 female

Details on study design:

On the day before the test each of a group of three rabbits was clipped free of fur from the dorsal flank area using veterinary clippers. Only animals with a healthy intact epidermis by gross observation were selected for the study.

TEST SITE
A quantity of 0.5 g of the test material, moistened with 0.5 ml of distilled water, was introduced under a 2.5 cm x 2.5 cm gauze patch and placed in position on the shorn skin.
The gauze patch was secured in position with a strip of surgical adhesive tape (BLENDERM: approximate size 2.5 cm x 4.0 cm). The trunk of each rabbit was wrapped in an elasticated corset (TUBIGRIP)

REMOVAL OF TEST SUBSTANCE
Any residual test material was removed by gentle swabbing with cotton wool soaked in distilled water followed by diethyl ether 4 h after the start of exposure.

SCORING SYSTEM: Draize J.H. (1959) Association of Food and Drug Officials of the United States, Austin, Texas, "The Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics":

EVALUATION OF SKIN REACTIONS

Erythema and eschar formation:

No erythema 0
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet redness) or eschar formation (injuries in depth) preventing erythema reading 4

Oedema formation:

No oedema 0
Very slight oedema (barely perceptible) 1
Slight oedema (edges of area well-defined by definite raising) 2
Moderate oedema (edges raised approximately 1 millimetre) 3
Severe oedema (raised more than 1 millimetre and extending beyond the area of exposure) 4

Irritation parameter:

erythema score

Basis:

mean

Remarks:

all animals

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

edema score

Basis:

mean

Remarks:

all animals

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritant / corrosive response data:

Primary irritation index: 0.0; erythema and oedema score: 0.0 for all animals at all time points.
No adverse dermal reactions were noted during the study.

Other effects:

Black-coloured staining was noted at the treatment site of all animals at the 1-hour observation and in two animals at the 24, 48 and 72-hour
observations.

Interpretation of results:

other: Not classified according to EU criteria.

Conclusions:

The test material produced a primary irritation index of 0.0 and was classified as a non-irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.

The test material did not produce positive criteria in any rabbit according to the EEC labelling regulations and was classified as NONIRRITANT to rabbit skin. No symbol and risk phrase are therefore required.

Executive summary:

A study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. The method used followed that described in the OECD Guidelines for Testing of Chemicals 0980 No. 404 "Acute Dermal Irritation/Corrosion".

A single 4-hour, semi-occluded application of the test material to the intact skin of three rabbits produced no adverse dermal reactions.

The test material produced a primary irritation index of 0.0 and was classified as a non-irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

11 March 1992 to 14 March 1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted to GLP in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect 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

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: David Percival Ltd., Moston, Sandbach, Cheshire, U.K.
- Age at study initiation: 12-16 weeks
- Weight at study initiation: 2.28 - 2.38 kg
- Housing: suspended metal cages, individually housed
- Diet and water: ad libitum
- Acclimation period: minimum 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-22°C
- Humidity (%): 46-52%
- Air changes (per hr): 15/h
- Photoperiod (hrs dark / hrs light): 12h dark/12 h light

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5g, moistened with 0.5 ml distilled water

Duration of treatment / exposure:

4 hours

Observation period:

Approximately one hour following the removal of the patches and 24, 48 and 72 hours later.

Number of animals:

2 male, 1 female

Details on study design:

On the day before the test each of a group of three rabbits was clipped free of fur from the dorsal flank area using veterinary clippers. Only animals with a healthy intact epidermis by gross observation were selected for the study.

TEST SITE
A quantity of 0.5 g of the test material, moistened with 0.5 ml of distilled water, was introduced under a 2.5 cm x 2.5 cm gauze patch and placed in position on the shorn skin.
The gauze patch was secured in position with a strip of surgical adhesive tape (BLENDERM: approximate size 2.5 cm x 4.0 cm). The trunk of each rabbit was wrapped in an elasticated corset (TUBIGRIP)

REMOVAL OF TEST SUBSTANCE
Any residual test material was removed by gentle swabbing with cotton wool soaked in distilled water followed by diethyl ether 4 h after the start of exposure.

SCORING SYSTEM: Draize J.H. (1959) Association of Food and Drug Officials of the United States, Austin, Texas, "The Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics":

EVALUATION OF SKIN REACTIONS

Erythema and eschar formation:

No erythema 0
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet redness) or eschar formation (injuries in depth) preventing erythema reading 4

Oedema formation:

No oedema 0
Very slight oedema (barely perceptible) 1
Slight oedema (edges of area well-defined by definite raising) 2
Moderate oedema (edges raised approximately 1 millimetre) 3
Severe oedema (raised more than 1 millimetre and extending beyond the area of exposure) 4

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 24, 48 and 72 h

Score:

0.33

Max. score:

1

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: 24, 48 and 72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: 24, 48 and 72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: 24, 48 and 72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: 24, 48 and 72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

edema score

Basis:

animal #3

Time point:

other: 24, 48 and 72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritant / corrosive response data:

Very slight erythma noted at one treatment site at 24h. All treated skin sites appeared normal at 48h.

Other effects:

Black-coloured staining caused by the test material was noted at one treated skin site one hour after patch removal. This did not affect the evaluation of skin responses.

Interpretation of results:

other: Not classified according to EU criteria.

Conclusions:

The test material produced a primary irritation index of 0.2 and was classified as a mild irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.

Executive summary:

A study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. The method used followed that described in the OECD Guidelines for Testing of Chemicals (1981) No. 404 "Acute Dermal Irritation/Corrosion".

A single 4-hour, semi-occluded application of the test material to the intact skin of three rabbits produced an isolated incident of very slight erythema. All treated skin sites appeared normal at the 48-hour observation.

The test material produced a primary irritation index of 0.2 and was classified as a mild irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.

Reference 3

Endpoint:

skin irritation: 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

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

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:

21 December 1992 and 25 December 1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted to GLP in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: David Percival Ltd., Moston, Sandbach, Cheshire, U.K.
- Age at study initiation: 12 - 16 weeks
- Weight at study initiation: 2.76 - 3.24 kg
- Housing: individually housed in suspended metal cages
- Diet and water: ad libitum throughout the study
- Acclimation period: minimum 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 19°C
- Humidity (%): 46 - 54%
- Air changes (per hr): 15/hr
- Photoperiod: 12 hrs dark / 12 hrs light

Vehicle:

unchanged (no vehicle)

Controls:

other: the left eye remained untreated and was used for control purposes.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: A volume of 0.1 ml of the test material, which was found to weigh approximately 41 mg

Duration of treatment / exposure:

The upper and lower lid were held together for about one second immediately after application to prevent loss of the test material. The eye was not washed following application.

Observation period (in vivo):

Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment.

Number of animals or in vitro replicates:

3

Details on study design:

Immediately before the start of the test, both eyes of the provisionally selected test rabbits were examined for evidence of ocular irritation or defect with the aid of a light source from a standard ophthalmoscope. Animals showing evidence of ocular lesions were rejected and replaced.
One rabbit was initially treated. A volume of 0.1 ml of the test material, which was found to weigh approximately 41 mg (as measured by gently compacting the required volume into an adapted syringe) was placed into the conjunctival sac of the right eye, formed by gently pulling the lower lid away from the eyeball. Immediately after administration of the test material, an assessment of the initial pain reaction was made.

After consideration of the ocular responses produced in the first treated animal, two additional animals were treated.
Assessment of ocular damage/irritation was made according to the numerical evaluation given below (from Draize J.H. 1959, Association of Food and Drug Officials of the United States, Austin, Texas, "The Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics").

Any other ocular effects were also noted. Examination of the eye was facilitated by use of the light source from a standard ophthalmoscope.

SCORING SYSTEM: Draize Scale for Ocular Irritation.

1. CONJUNCTIVAE
(A) Redness (refers to palpebral and bulbar conjunctivae excluding cornea and iris)
Vessels normal............................................................................................................................................0
Vessels definitely injected above normal................................................................................................1
More diffuse, deeper crimson red, individual vessels not easily discernible....................................2
Diffuse beefy red.........................................................................................................................................3

(B) Chemosis
No swelling..................................................................................................................................................0
Any swelling above normal (includes nictitating membrane).............................................................1
Obvious swelling with partial eversion of lids.......................................................................................2
Swelling with lids about half closed.........................................................................................................3
Swelling with lids half closed to completely closed...............................................................................4

(C) Discharge
No discharge...............................................................................................................................................0
Any amount different from normal (does not include small amounts observed in inner
canthus of normal animals)......................................................................................................................1
Discharge with moistening of the lids and hairs just adjacent to lids...............................................2
Discharge with moistening of the lids and hairs a considerable area around the eye...................3

THE TOTAL SCORE = (A + B + C) x 2 MAXIMUM TOTAL = 20

2. IRIS

(D) Values
Normal.........................................................................................................................................................0
Folds above normal, congestion, swelling, circumcorneal injection (any or all
of these or combination of any thereof) iris still reacting to light
(sluggish reaction is positive).................................................................................................................1
No reaction to light, haemorrhage, gross destruction (any or all of these)....................................2

THE TOTAL SCORE = D x 5 MAXIMUM TOTAL = 10

3. CORNEA

(E) Degree of Opacity (most dense area used)
No opacity...................................................................................................................................................0
Scattered or diffuse areas, details of iris clearly visible......................................................................1
Easily discernible translucent areas, details of iris slightly obscured..............................................2
Opalescent areas, no details of iris visible, size of pupil barely discernible....................................3
Opaque, iris not discernible through the opacity................................................................................4

(F) Area of Cornea Involved
One quarter (or less) but not zero..........................................................................................................1
Greater than one quarter but less than half...........................................................................................2
Greater than half but less than three quarters......................................................................................3
Greater than three quarters, up to whole area.......................................................................................4

THE TOTAL SCORE = (E x F) x 5 MAXIMUM TOTAL = 80

MAXIMUM TOTAL SCORE POSSIBLE = 110

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

(all animals)

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

iris score

Basis:

mean

Remarks:

(all animals)

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

(all animals)

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

(all animals)

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritant / corrosive response data:

No corneal or iridial effects were noted during the study. Minimal to moderate conjunctival irritation was noted in all treated eyes one hour after treatment.
No ocular effects were noted 24 hours after treatment.

Other effects:

Residual test material was noted around the treated eye of all animals throughout the study.

INDIVIDUAL SCORES AND INDIVIDUAL TOTAL SCORES FOR OCULAR IRRITATION

Rabbit Number and Sex (Bodyweight kg)	IPR = 2				IPR = 1				IPR = 1
	7 Female (3.14)				6 Female (3.24)				58 Female (2.76)
Time After Treatment	1 hr	24 hr	48 hr	72 hr	1 hr	24 hr	48 hr	72 hr	1 hr	24 hr	48 hr	72 hr
CORNEA E = Degree of Opacity F = Area of Opacity	0   0	0   0	0   0	0   0	0   0	0   0	0   0	0   0	0   0	0   0	0   0	0   0
Score (E x F) x 5	0	0	0	0	0	0	0	0	0	0	0	0
IRIS D	0	0	0	0	0	0	0	0	0	0	0	0
Score (D x 5)	0	0	0	0	0	0	0	0	0	0	0	0
CONJUNCTIVAE A = Redness B = Chemosis C = Discharge	1 0 0^Re	0 0 0^Re	0 0 0^Re	0 0 0^Re	1 0 1^Re	0 0 0^Re	0 0 0^Re	0 0 0^Re	1 1 2^Re	0 0 0^Re	0 0 0^Re	0 0 0^Re
Score (A + B + C) x 2	2	0	0	0	4	0	0	0	8	0	0	0
Total Score	2	0	0	0	4	0	0	0	8	0	0	0

Key: hr = hour(s)             IPR = initial pain reaction              Re = residual test material around the treated eye

Interpretation of results:

other: Not classified according to EU criteria.

Conclusions:

The test material produced a maximum group mean score of 4.7 and was classified as a minimal irritant (Class 3 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.

Executive summary:

A study was performed to assess the irritancy potential of the test material to the eye of the New Zealand White rabbit. The method used followed that described in the OECD Guidelines for Testing of Chemicals (1987) No. 405 "Acute Eye Irritation/Corrosion".

A single application of the test material to the non-irrigated eye of three rabbits produced minimal to moderate conjunctival irritation. No ocular effects were noted 24 hours after treatment.

The test material produced a maximum group mean score of 4.7 and was classified as a minimal irritant (Class 3 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

18 March 1992 to 22 March 1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted to GLP in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: David Percival Ltd., Moston, Sandbach, Cheshire, U.K.
- Age at study initiation: 12 - 16 wks
- Weight at study initiation: 2.28 - 2.60 kg
- Housing: individually housed in suspended metal cages
- Diet and water: ad libitum throughout study
- Acclimation period: 5 days minimum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 21°C
- Humidity (%): 48 - 56 %
- Air changes (per hr): 15/hr
- Photoperiod: 12 hrs dark / 12 hrs light

Vehicle:

unchanged (no vehicle)

Controls:

other: the left eye remained untreated and was used for control purposes.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml, which was found to weight approximately 59.7 mg

Duration of treatment / exposure:

The upper and lower lid were held together for about one second immediately after application to prevent loss of the test material. The eye was not washed following application.

Observation period (in vivo):

Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment.

Number of animals or in vitro replicates:

3

Details on study design:

Immediately before the start of the test, both eyes of three provisionally selected test rabbits were examined for evidence of ocular irritation or defect with the aid of a light source from a standard ophthalmoscope. Animals showing evidence of ocular lesions were rejected and replaced.
One rabbit was initially treated. A volume of 0.1 ml of the test material, which was found to weigh approximately 59.7 mg (as measured by gently compacting the required volume into an adapted syringe) was placed into the conjunctival sac of the right eye, formed by gently pulling the lower lid away from the eyeball. Immediately after administration of the test material, an assessment of the initial pain reaction was made.

After consideration of the ocular responses produced in the first treated animal, two additional animals were treated.
Assessment of ocular damage/irritation was made according to the numerical evaluation given below (from Draize J.H. 1959, Association of Food and Drug Officials of the United States, Austin, Texas, "The Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics").

Any other ocular effects were also noted. Examination of the eye was facilitated by use of the light source from a standard ophthalmoscope.

SCORING SYSTEM: Draize Scale for Ocular Irritation.

1. CONJUNCTIVAE
(A) Redness (refers to palpebral and bulbar conjunctivae excluding cornea and iris)
Vessels normal............................................................................................................................................0
Vessels definitely injected above normal................................................................................................1
More diffuse, deeper crimson red, individual vessels not easily discernible....................................2
Diffuse beefy red.........................................................................................................................................3

(B) Chemosis
No swelling..................................................................................................................................................0
Any swelling above normal (includes nictitating membrane).............................................................1
Obvious swelling with partial eversion of lids.......................................................................................2
Swelling with lids about half closed.........................................................................................................3
Swelling with lids half closed to completely closed...............................................................................4

(C) Discharge
No discharge...............................................................................................................................................0
Any amount different from normal (does not include small amounts observed in inner
canthus of normal animals)......................................................................................................................1
Discharge with moistening of the lids and hairs just adjacent to lids...............................................2
Discharge with moistening of the lids and hairs a considerable area around the eye...................3

THE TOTAL SCORE = (A + B + C) x 2 MAXIMUM TOTAL = 20

2. IRIS

(D) Values
Normal.........................................................................................................................................................0
Folds above normal, congestion, swelling, circumcorneal injection (any or all
of these or combination of any thereof) iris still reacting to light
(sluggish reaction is positive).................................................................................................................1
No reaction to light, haemorrhage, gross destruction (any or all of these)....................................2

THE TOTAL SCORE = D x 5 MAXIMUM TOTAL = 10

3. CORNEA

(E) Degree of Opacity (most dense area used)
No opacity...................................................................................................................................................0
Scattered or diffuse areas, details of iris clearly visible......................................................................1
Easily discernible translucent areas, details of iris slightly obscured..............................................2
Opalescent areas, no details of iris visible, size of pupil barely discernible....................................3
Opaque, iris not discernible through the opacity................................................................................4

(F) Area of Cornea Involved
One quarter (or less) but not zero..........................................................................................................1
Greater than one quarter but less than half...........................................................................................2
Greater than half but less than three quarters......................................................................................3
Greater than three quarters, up to whole area.......................................................................................4

THE TOTAL SCORE = (E x F) x 5 MAXIMUM TOTAL = 80

MAXIMUM TOTAL SCORE POSSIBLE = 110

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

(all animals)

Time point:

other: 24, 48 and 72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

iris score

Basis:

mean

Remarks:

(all animals)

Time point:

other: 24, 48 and 72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

(all animals)

Time point:

other: 24, 48 and 72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

(all animals)

Time point:

other: 24, 48 and 72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritant / corrosive response data:

No adverse ocular effects were noted during the study.

Other effects:

Residual test material was noted around the treated eye of all animals throughout the study.

Interpretation of results:

other: Not classified according to EU criteria.

Conclusions:

The test material produced a maximum group mean score of 0.0 and was classified as non-irritating (Class 1 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.

Executive summary:

A study was performed to assess the irritancy potential of the test material to the eye of the New Zealand White rabbit. The method used followed that described in the OECD Guidelines for Testing of Chemicals (1987) No. 405 "Acute Eye Irritation/Corrosion".

A single instillation of the test material to the non-irrigated eye of three rabbits produced no adverse ocular effects during the study.

The test material produced a maximum group mean score of 0.0 and was classified as non-irritating (Class 1 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.

Reference 3

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

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

In the absence of any other factors key studies have been selected based on aniline content of the batches tested. Batches with known aniline content are judged to be key and in cases where two batches of known aniline content have been tested the one with the higher content is considered key.

Skin Irritation

Key Study: Allen (1993)

A study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. The method used followed that described in the OECD Guidelines for Testing of Chemicals 0980 No. 404 "Acute Dermal Irritation/Corrosion". The study was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997).

A single 4-hour, semi-occluded application of the test material to the intact skin of three rabbits produced no adverse dermal reactions.

The test material produced a primary irritation index of 0.0 and was classified as a non-irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.

 

Supporting Study: Walter (1992)

A study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. The method used followed that described in the OECD Guidelines for Testing of Chemicals (1981) No. 404 "Acute Dermal Irritation/Corrosion". The study was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997).

A single 4-hour, semi-occluded application of the test material to the intact skin of three rabbits produced an isolated incident of very slight erythema. All treated skin sites appeared normal at the 48-hour observation.

The test material produced a primary irritation index of 0.2 and was classified as a mild irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.

Eye Irritation

Key Study: Allen (1993)

A study was performed to assess the irritancy potential of the test material to the eye of the New Zealand White rabbit. The method used followed that described in the OECD Guidelines for Testing of Chemicals (1987) No. 405 "Acute Eye Irritation/Corrosion". The study was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997).

A single application of the test material to the non-irrigated eye of three rabbits produced minimal to moderate conjunctival irritation. No ocular effects were noted 24 hours after treatment.

The test material produced a maximum group mean score of 4.7 and was classified as a minimal irritant (Class 3 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.

 

Supporting Study: Walter (1992)

A study was performed to assess the irritancy potential of the test material to the eye of the New Zealand White rabbit. The method used followed that described in the OECD Guidelines for Testing of Chemicals (1987) No. 405 "Acute Eye Irritation/Corrosion". The study was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997).

A single instillation of the test material to the non-irrigated eye of three rabbits produced no adverse ocular effects during the study.

The test material produced a maximum group mean score of 0.0 and was classified as non-irritating (Class 1 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.

Justification for classification or non-classification

The registered substance does not meet the criteria for classification for irritation according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.