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Administrative data

Description of key information

Skin irritation / corrosion: PDII = 3.8 (OECD 404), Xi, R38

Eye irritation: maximum group mean score = 4.7 (OECD 405)

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
23/01/1991-06/02/1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study (OECD Guideline 404)
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: David Percival Ltd., Moston, sandbach, Cheshire, UK
- Age at study initiation: approximately twelve to sixteen weeks old
- Weight at study initiation: 2.08-2.74 kg
- Housing: The animals were individually housed in suspended metal cages
- Diet: ad libitum (Spillers Rabbit Diet, Dalfety Agriculture Ltd., Almondsbury, Bristol)
- Water: ad libitum, drinking water
- Acclimation period:minimum acclimatisation period of five days


ENVIRONMENTAL CONDITIONS
- Temperature: the animal room was maintained at 17-22°C
- Humidity: 49-61%
- Air changes: approximately 15 changes per hour
- Photoperiod: 12 hrs dark / 12 hrs light

Type of coverage:
semiocclusive
Preparation of test site:
other: clipped
Vehicle:
water
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: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.


Duration of treatment / exposure:
4 hours
Observation period:
1, 24, 48 and 72 hours. Additional observations were made on day 7 and 14 to assess the reversibility of the skin reactions.
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 0.5 g of the test material, moistened with 0.5 ml of distilled water, was introduced under a 2.5 x 2.5 cm gauze patch and placed in position on the shorn skin
- Type of wrap if used: The patch was secured in position with a strip of surgical adhesive tape (BLENDERM: approximate size 2.5 x 4.0 cm). To prevent the animals interfering with the patches, the trunk of each rabbit was wrapped in an elasticated corset (TUBIGRIP) and the animals were returned to their cages for the duration of the exposure period.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): corset and patches were removed from each animal and any residual test material removed by gentle swabbing with cotton wool soaked in distilled water
- Time after start of exposure: four hours


SCORING SYSTEM: according to the scale 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"
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 1, 24, 48, 72 hours
Score:
1 - 2
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 7 days
Max. score:
4
Remarks on result:
other: 7 days: Adverse reactions prevented accurate evaluation of erythema. 9 days: animal killed
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 1, 24, 48, 72 hours
Score:
2
Max. score:
4
Remarks on result:
other: Haemorrhage of the dermal capillaries. Light brown discolouration of the epidermis. Thickening of the skin. Loss of skin elasticity.
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 7, 14 days
Score:
0
Max. score:
4
Reversibility:
other: reversible within 7 days
Remarks on result:
other: Crust formation after 7 d. Reduced fur re-growth after 14 days
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 1, 24, 48, 72 hours
Score:
2
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 7, 14 days
Score:
0
Max. score:
4
Reversibility:
other: reversible after 14 days
Remarks on result:
other: 7 days: adverse reactions prevented evaluation. 14 days: crust formation and reduced fur re-growth
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 1, 24, 48, 72 hours
Score:
1
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 7 days
Max. score:
4
Remarks on result:
other: 7 days: adverse reactions prevented accurate evaluation of oedema. 9 days: animal killed
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 1, 24, 48, 72 hours, 7 & 14 days
Score:
0 - 3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 1, 24, 48, 72 hours, 7 & 14 days
Score:
0 - 3
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: 7 days: adverse reactions prevented accurate evaluation of oedema
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
other: S/6, S = Sum of 24 and 72 hour reading
Time point:
other: 24, 72 hours
Score:
3.8
Max. score:
8
Remarks on result:
other: moderate irritant
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
2
Max. score:
4
Remarks on result:
other: positive criteria
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
1 - 2.3
Max. score:
4
Remarks on result:
other: positive criteria
Irritant / corrosive response data:
Very slight to well-defined erythema was noted at all treated skin sites one hour after patch removal, with well-defined erythema at all treated skin sites at the 24, 48, and 72-hours observations.

Very slight to moderate oedema was noted at all treated skin sites one and 24 hours after patch removal with very slight to slight oedema at the 48 and 72-hour observations.
Other effects:
Other adverse skin reactions noted at one treated skin site at this time were haemorrhage of dermal capillaries, light brown discolouration of the epidermis, thickening of the skin and loss of elasticity. Crust formation was noted at the 7 day observation. Hardened light brown-coloured scabs and thickening of the skin were noted at two treated skin sites at the 7 day observation. These reactions prevented accurate evaluation of erythema and oedema. Crust formation and/or reduced re-growth of fur was noted at two treated skin sites at the 14-day observation.

Key to tables:

Br = light brown discolouration of the epidermis

Cf = crust formation

Fr = reduced fur re-growth

Hd = haemorrhage of dermal capillaries

Le = loss of skin elasticity

Sp = hardened light brown-coloured scab

Th = thickening of the skin

?e = adverse reactions prevented accurate evaluation of erythema

?Od = adverse reactions prevented accurate evaluation of oedema

Individual skin reactions

Skin reaction

Observation time 

Individual Scores – Rabbit Number and Sex (Bodyweight Kg)

 

 

 

191 Female

(2.08)

196Female

(2.74)

204 Male

(2.44)

Total

Erythema/eschar formation 

1 h 

1

2 Hd

2

(5)

 

24 h 

2

2 Hd

2

6

 

48 h 

2

2 Br

2

(6)

 

72 h 

2

2 BrThLe

6

 

7 days 

?eSpTh

0 Cf

?eSpTh

(0-8)

 

14 days

-

0Fr

0CfFr

(0)

Oedema formation 

1 h 

1

3

3

(7)

 

24 h 

1

3

3

7

 

48 h 

1

2

2

(5)

 

72 h 

1

2

1

4

 

7 days 

?Od

0

?Od

(0-8)

 

14 days

-

0

0

(0)

Sum of 24 and 72-Hour readings (S): 23

Primary Irritation Index (S/6): 23/6 = 3.8

Classification: Moderate irritant

( ) = total values not used for calculation of primary irritation index

- = animal killed

Individual daily and individual mean scores

Skin reaction

Reading (h)

Individual Scores – Rabbit Number and Sex (Bodyweight Kg)

 

191 Female

(2.08)

196 Female 

(2.74)

204 Male

(2.44)

 Erythema/eschar formation 

24

2

2

2

 

48

2

2

2

 

72

2

2

 Total

 

6

6

 Mean Score

 

2.0+

2.0+

2.0+ 

 Oedema formation 

24

1

3

3

 

48

1

2

2

 

72

1

2

1

 Total

 

3

7

6

 Mean Score

 

1.0

2.3+

2.0+

+ = positive criteria

Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
The test material produced a primary irritation index of 3.8 and was classified as moderate irritant to rabbit skin according to the Draize Classification scheme. No corrosive effects were noted. The test material produced positive criteria in 3/3 rabbits according to the EEC labelling regulations and was classified as irritant to rabbit skin. The symbol "Xi" and risk phrase R38 "irritating to skin" 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 (1981) No. 404 "Acute Dermal Irritation/Corrosion" referenced as Method B4 in Commission Directive 84/449/EEC (which constitutes Annex V of Council Directive 67/548/EEC.

The results may be used as a basis for classification and labelling under Annex VI of Council Directive 67/548/EEC (as adapted to technical progress by Commission Directive 83/467/EEC).

A single 4 -hour, semi-occluded application of the test material to the intact skin of three rabbits produced well-defined erythema and very slight to moderate oedema. Other adverse skin reactions noted were haemorrhage of the dermal capillaries, light brown discolouration of the epidermis, thickening of the skin, loss of skin elasticity, crust formation, hardened light brown-coloured scab and reduced re-growth of fur.

The test material produced a primary irritation index of 3.8 and was classified as moderate irritant to rabbit skin according to the Draize Classification scheme. No corrosive effects were noted. The test material was also classified as irritant according to the EEC labelling regulations. The symbol "Xi" and risk phrase R38 "irritating to skin" are therefore required.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study (OECD 405)
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: David Percival Ltd., Moston, Sandbach, Cheshire, UK
- Age at study initiation: approximately twelve to sixteen weeks old
- Weight at study initiation: 2.64-3.14 kg
- Housing: The animals were individually housed in suspended metal cages
- Diet: ad libitum (Spillers Rabbit Diet, Dalgety Agriculture Ltd., Almondsbury, Bristol)
- Water: ad libitum, drinking water
- Acclimation period:minimum acclimatisation period of five days

Immediately before the start of the test, both eyes of the 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.

ENVIRONMENTAL CONDITIONS
- Temperature: the animal room was maintained at 18-20°C
- Humidity: 49-61%
- Air changes: approximately 15 changes per hour
- 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:
A volume of 0.1 ml of the test material, which was found to weigh approximately 67 mg (as measured by gently compacting the required volume into an adapted syringe
Duration of treatment / exposure:
1 second
Observation period (in vivo):
1, 24, 48 and 72 hours
Number of animals or in vitro replicates:
3
Details on study design:
The test material was placed into the conjunctival sac of the right eye, formed by gently pulling the lower lid away from the eyeball. The upper and lower eyelids were held together for about one second immediately after application, to prevent loss of the test material, and then released. Immediately after administration of the test material, an assessment of the initial pain reaction was made.

SCORING SYSTEM: Assessment of ocular damage/irritation was made according to the numerical evaluation given by 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 adverse ocular effects were also noted.

TOOL USED TO ASSESS SCORE: Examination of the eye was facilitated by use of the light source from a standard ophthalmoscope
Irritation parameter:
cornea opacity score
Remarks:
E = degree of opacity
Basis:
animal: #1, #2, #3
Time point:
other: 1, 24, 48, 72 hours
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Remarks:
F = area of opacity
Basis:
animal: #1, #2, #3
Time point:
other: 1, 24, 48, 72 hours
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
animal: #1, #2, #3
Time point:
other: 1, 24, 48, 72 hours
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Remarks:
A = redness
Basis:
animal: #1, #2, #3
Time point:
other: 1, 24, 48, 72 hours
Score:
0 - 2
Max. score:
3
Reversibility:
fully reversible
Remarks:
2 animals: within 24 hours. 1 animal: within 48 hours
Irritation parameter:
chemosis score
Remarks:
B = Conjunctivae chemosis
Basis:
animal: #1, #2, #3
Time point:
other: 1, 24, 48, 72 h
Score:
0 - 1
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Irritation parameter:
conjunctivae score
Remarks:
C = discharge
Basis:
animal: #1, #2, #3
Time point:
other: 1, 24, 48, 72 hours
Score:
0
Max. score:
3
Irritant / corrosive response data:
No adverse corneal or iridial effects were noted during the study.
Minimal conjunctival irritation was noted in all treated eyes one hour after treatment and in one treated eye at the 24-hour observation.
All treated eyes appeared normal 48 hours after treatment.

Individual total scores and group mean scores for ocular irritation

Rabbit number and sex

Individual total scores at:

1 hr

24 hr

48 hr

72 hr

172 Female

4

0

0

0

193 Female

4

0

0

0

154 Male

6

2

0

0

Group total

14

2

0

0

Group mean score

4.7

1 hr

0.7

24 hr

0.0

48 hr

0.0

72 hr

Individual & mean scores for cornea, iris & conjunctivae required for EEC labelling regulations

Rabbit number and sex               (bodyweight Kg)

Time after treatment

Corneal opacity

Iridial inflammation

Conjunctival redness

Conjunctival chemosis

172 Female

(3.14)

24 hr

0

0

0

0

48 hr

0

0

0

0

72 hr

0

0

0

0

Total

 

0

0

0

0

Mean

 

0.0

0.0

0.0

0.0

193 Female

(2.64)

24 hr

0

0

0

0

48 hr

0

0

0

0

72 hr

0

0

0

0

Total

 

0

0

0

0

Mean

 

0.0

0.0

0.0

0.0

154 Male

(2.84)

24 hr

0

0

1

0

48 hr

0

0

0

0

72 hr

0

0

0

0

Total

 

0

0

1

0

Mean

 

0.0

0.0

0.3

0.0

Interpretation of results:
GHS criteria not met
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.
The test material did not produced positive criteria in any rabbit according to the EEC labelling regulations and was classified as non-orritant to the rabbit eye. No symbol and risk phrase are therefore required.
Executive summary:

A study was performed to assess the irritancy potential of the test material, DTBH, 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" referenced as Method B5 in Commission Directive 84/449/EEC (which constitutes Annex V of Council Directive 67/548/EEC).

The results may be used as a basis for classification and labelling under Annex VI of Council Directive 67/548/EEC (as adapted to technical progress by Commission Directive 83/467/EEC).

A single application of the test material to the non-irrigated eye of three rabbits produced minimal conjunctival irritation. All treated eyes appeared normal 48 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. The test material was also classified as non-irritant according to the EEC labelling regulations. No symbol and risk phrase are required.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation / corrosion:

Skin irritation / corrosion: The test material was evaluated for its irritancy potential to the skin of the New Zealand White rabbit. The test material produced a primary irritation index of 3.8 and was classified as moderate irritant to rabbit skin according to the Draize Classification scheme. No corrosive effects were noted. The test material was also classified as irritant according to the EEC labelling regulations. The symbol "Xi" and risk phrase R38 "irritating to skin" are therefore required.

Test method:

The method used followed that described in the OECD Guidelines for Testing of Chemicals (1981) No. 404 "Acute Dermal Irritation/Corrosion" referenced as Method B4 in Commission Directive 84/449/EEC (which constitutes Annex V of Council Directive 67/548/EEC.

The results may be used as a basis for classification and labelling under Annex VI of Council Directive 67/548/EEC (as adapted to technical progress by Commission Directive 83/467/EEC).

A single 4 -hour, semi-occluded application of the test material to the intact skin of three rabbits produced well-defined erythema and very slight to moderate oedema. Other adverse skin reactions noted were haemorrhage of the dermal capillaries, light brown discolouration of the epidermis, thickening of the skin, loss of skin elasticity, crust formation, hardened light brown-coloured scab and reduced re-growth of fur.

Eye irritation:

The test material was evaluated for its irritancy potential to the eye of the New Zealand White rabbit. 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. The test material was also classified as non-irritant according to the EEC labelling regulations. No symbol and risk phrase are required.

Test method:

The method used followed that described in the OECD Guidelines for testing of Chemicals (1987) No. 405 "Acute Eye Irritation/Corrosion" referenced as Method B5 in Commission Directive 84/449/EEC (which constitutes Annex V of Council Directive 67/548/EEC).

The results may be used as a basis for classification and labelling under Annex VI of Council Directive 67/548/EEC (as adapted to technical progress by Commission Directive 83/467/EEC).

A single application of the test material to the non-irrigated eye of three rabbits produced minimal conjunctival irritation. All treated eyes appeared normal 48 hours after treatment.

Justification for classification or non-classification

Skin irritation / corrosion:

In accordance with EU CLP (Regulation (EC) No. 1272/2008) the test material was classified as irritant. A signal word 'Warning' and H-sentence H315 "Causes skin irritation" are therefore required.

Eye irritation:

In accordance with EU CLP (Regulation (EC) No. 1272/2008) the test material was classified as non-irritant. No symbol and risk phrase are required.