Registration Dossier

Administrative data

Description of key information

The registered substance is not irritating to skin and eyes.

Justification for selection of skin irritation / corrosion endpoint:

K1:The study is performed according to OECD guidelines and GLP.

Justification for selection of eye irritation endpoint:

K1:The study is performed according to OECD guidelines and GLP.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
5 October 1992 - 22 October 1992
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study is performed according to OECD guidelines and GLP.
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Rosemead Rabbits, Rosemead, Waltham Abbey, Essex, England
- Age at study initiation: appr. 3 months
- Weight at study initiation: 2.48 - 2.63 kg
- Housing:individually housed in suspended stainless steel cages mounted in mobile batteries (Modular Systems and Development Company Limited, London, England).
- Diet (e.g. ad libitum): ad libitum, standard pelleted rabbit diet (S.Q.C. Rabbit Diet, Special Diets Services Limited, Witham, Essex, England).
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-20
- Humidity (%): 44-52
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light):12/12

IN-LIFE DATES: 5 October 1992 - 22 October 1992
Type of coverage:
semiocclusive
Preparation of test site:
other: clipped
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated flank
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml
- Concentration (if solution):as such
Duration of treatment / exposure:
4 hours
Observation period:
Assessment of skin irritation responses at the control and treated test sites were made 1, 24, 48 and 72 hours after removal of the
bandages.
Number of animals:
3 males
Details on study design:
TEST SITE
- Area of exposure: dorsum
- % coverage: 6x6 cm
- Type of wrap if used: A single dose (0.5 ml) was applied directly to the skin and covered by an unmedicated gauze patch (3 x 2 cm) which was held in place on the left test site by strips of Blenderm (Community Care Products, 3M Health Care, Loughborough, England). The right test site, acting as a control, was covered by a similar semi-occlusive dressing but otherwise remained untreated. Pads of cotton wool and elasticated bandage were used to protect the patches and ensure good contact between the skin and the test material during the four-hour exposure
period. The elasticated bandage was held in place by thin strips of waterproof plaster ('Blenderm') at both edges.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The treatment sites were gently washed with warm water and
dried with paper towels to remove excess test material adhering to the skin.
- Time after start of exposure: The dressings were removed after four hours exposure.

SCORING SYSTEM:
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) to slight eschar formation (injuries in depth) 4

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

Irritation parameter:
erythema score
Basis:
mean
Remarks:
all animals
Time point:
other: 24-48-72 hours
Score:
0.77
Max. score:
4
Reversibility:
fully reversible within: 9 days
Irritation parameter:
edema score
Basis:
mean
Remarks:
all animals
Time point:
other: 24-48-72 hours
Score:
0
Max. score:
4
Irritant / corrosive response data:
Very slight erythema was observed in all rabbits during the first 24 hours after bandage removal, continuing in two rabbits up to the 72 hour examination. The test site of all rabbits was tacky during the first 24 hours of the observation period and in two animals throughout the first week. This effect was considered to have been caused by dose material that remained adhered to the test site after the washing procedure. The test sites of all animals were overtly normal by Day 9. The control sites did not show any response to the control procedure.

Summary of dermal lesions (following 4-h application) on intact skin

 

no.

Effect

Hour

Days after application

Mean score erythema

24/48/72 h

Mean score oedema

24/48/72 h

1

1

2

3

6

9

 

 

1

Erythema/ eschar

Oedema

0

*

0

1

*

0

1

*

0

1

*

0

0

*

0

0

 

0

1

 

 

0

2

Erythema/ eschar

Oedema

1

*

0

1

*

0

0

*

0

0

*

0

0

*

0

0

 

0

0.33

 

 

0

3

Erythema/ eschar

Oedema

1

*

0

1

*

0

1

*

0

1

 

0

0

 

0

    0

 

    0

1

 

 

0

*Test site tacky

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test substance is not irritating to skin. No oedema occured and the mean score for 24-48-72 hours for erythema is =< 1.5 for all animals.
Executive summary:

The potential the substance to cause inflammatory or corrosive changes upon first contact with skin was assessed by semi-occluded application of 0.5 ml of the test material to the closely-clipped dorsa of three New Zealand White rabbits for four hours. Dermal reactions were assessed 1, 24, 48 and 72 hours and six and nine days after removal of the dressings. Very slight erythema was observed in all rabbits during the first 24 hours after bandage removal, continuing in two rabbits up to the 72 hour examination.

Residual dose material adhered to the test site for up to six days. The test sites of all animals were overtly normal by Day 9. The test substance is not irritating to skin.

Endpoint:
skin corrosion: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
5 October 1992 - 6 November 1992
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study is performed according to OECD guidelines and GLP.
Qualifier:
according to
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: Rosemead Rabbits, Rosemead, Waltham Abbey, Essex, England.
- Age at study initiation: The rabbits were approximately three and a half to four months old.
- Weight at study initiation: 3.12 - 3.35 kg
- Housing:individually in suspended stainless steel cages mounted in mobile batteries (Modular Systems and Development Company Limited, London, England).
- Diet (e.g. ad libitum): ad libitum, standard pelleted rabbit diet, (S.Q.C. Rabbit Diet - Special Diets Services Limited, Witham, Essex, England).
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-20
- Humidity (%): 49-58
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: 5 October 1992 - 6 November 1992
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eye
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
- Concentration (if solution): as such
Duration of treatment / exposure:
single instillation in one eye
Observation period (in vivo):
The behaviour of each rabbit was observed for several minutes immediately following instillation of the test material to allow assessment of the initial pain response. The animals were returned to their cages and checked at least twice during the first hour after dosing, at regular intervals throughout the day and daily to ensure that the treated eye was not subject to infection or causing distress. Ocular reactions to treatment were assessed 1, 24, 48 and 72 hours after treatment.
Number of animals or in vitro replicates:
3
Details on study design:
SCORING SYSTEM:
Cornea: degree of density (area most dense taken for reading)
0 No ulceration or opacity
1 Scattered or diffuse areas of opacity (other than slight dulling of normal lustre), details of iris clearly visible
2 Easily discernible translucent areas, details of iris slightly obscured
3 Nacrous areas, no details of iris visible, size of pupil barely discernible
4 Opaque cornea, iris not discernible through the opacity

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

Iris
0 Normal
1 Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia or injection, any of these or combination of any thereof, iris still reacting to light (sluggish reaction is positive)
2 No reaction to light, haemorrhage, gross destruction (any or all of these)

Conjunctivae
Redness (refers to palpebral and bulbar conjunctivae cornea and iris)

0 Blood vessels normal
1 Some blood vessels definitely hyperaemic
(injected)
2 Diffuse, crimson colour, individual vessels not easily discernible
3 Diffuse, beefy red

Chemosis (lids and/or nictitating membranes)
0 No swelling 0
1 Any swelling above normal (includes nictitating membranes)
2 Obvious swelling with partial eversion of lids
3 Swelling with lids about half-closed
4 Swelling with lids more than half-closed

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


TOOL USED TO ASSESS SCORE: ophthalmoscope
Irritation parameter:
overall irritation score
Basis:
mean
Remarks:
all animals
Time point:
other: 24-48-72 hours
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: Conjunctival effects were observed after 1 hour.
Irritant / corrosive response data:
Injection of the conjunctival blood vessels was observed in all rabbits during the first hour following instillation Trigonox 141. Very slight discharge and very slight chemosis were also observed in two of these rabbits at this time. The test eyes of all rabbits were overtly normal at the 24 hour examination.
Instillation of the test material caused practically no initial pain response.

Rabbit No and sex

Region of the eye

Hours after instillation

Average 24-48-72 hours

1

24

48

72

 

1-m

Cornea

Degree of opacity

0

0

0

0

0

Area

0

0

0

0

0

 

Iris

0

0

0

0

0

 

Conjunctivae

Redness

1

0

0

0

0

 

 

Chemosis

0

0

0

0

0

 

 

Discharge

0

0

0

0

0

2-m

Cornea

Degree of opacity

0

0

0

0

0

Area

0

0

0

0

0

 

Iris

 

0

0

0

0

0

 

Conjunctivae

Redness

1

0

0

0

0

 

 

Chemosis

1

0

0

0

0

 

 

Discharge

1

0

0

0

0

3-m

Cornea

Degree of opacity

0

0

0

0

0

Area

0

0

0

0

0

 

Iris

 

0

0

0

0

0

 

Conjunctivae

Redness

1

0

0

0

0

 

 

Chemosis

1

0

0

0

0

 

 

Discharge

1

0

0

0

0

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The mean values for ocular lesions recorded 24, 48 and 72 hours after treatment did not equal or exceed the CLP C&L limits.
Executive summary:

The potential to cause damage to the conjunctiva, iris or cornea was assessed in three New Zealand White rabbits, each subjected to a single ocular instillation of 0.1 ml of the test material. Ocular reactions were assessed 1, 24, 48 and 72 hours after treatment. Injection of the conjunctival blood vessels was observed in all rabbits during the first hour following instillation. Very slight discharge and very slight chemosis were also observed in two of these rabbits at this time. The test eyes of all rabbits were overtly normal at the 24 hour examination. Instillation of the test material caused practically no initial pain response.

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

Justification for classification or non-classification

Based on the results an in vivo skin and eye irritation study in rabbits, the data is conclusive but not sufficient for classification for these endpoints.