Registration Dossier

Administrative data

Description of key information

Skin irritation:

The potential of test item to cause inflammatory or corrosive changes upon first contact with skin was assessed according to OECD 404. No dermal response was observed at the test site of any animal at any time during the 72 hour observation period.

Under the conditions of this test, the test item was classified as 'non-irritant' to the skin.

Eye irritation: The potential of test item to cause damage to the conjunctiva, iris or cornea was assessed in three New Zealand White rabbits based on OECD 405. Under the conditions of this test, the test item was classified as 'non-irritant' to the eye.

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:
From 1991-08-06 to 1991-08-09
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
GLP study in accordance with recognised test guideline but: Lot/batch No.: not stated Expiration date of the lot/batch: not stated NOTE: study deemed acceptable because spectral data for test item are available, covering approximately before and after the test period - see section 1.4 Analytical Information.
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
1981
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Specific details on test material used for the study:
Purity: Ca. 100%
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Ranch Rabbits, Crawley Down, Sussex, England
- Age at study initiation: 3 months
- Weight at study initiation: 2.72 - 2.89 kg
- Housing: They were housed in suspended stainless steel cages (Type RC10/L) mounted in mobile batteries (Modular Systems and Development Company Limited, London, England). The cages measured 61 x 76 x 46 cm high and were fitted with perforated counter-sunk floor panels.
- Diet (e.g. ad libitum): ad libitum, S. Q. C. Rabbit Diet, Special Diet Services Limited, Witham, Essex, England
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 15 - 23 Target 18
- Humidity (%): Range 40 - 70 Target 55
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: 6 August 1991 To: 9 August 1991
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit):0.5g
Duration of treatment / exposure:
4 hour
Observation period:
72 hours
Number of animals:
Three male rabbits
Details on study design:
TEST SITE
- Area of exposure: 3 x 2 cm
- % coverage: 100
- Type of wrap if used: an unmedicated gauze patch (3 x 2 cm) which was held in place on the left test site by strips of Blenderm (3-M Company). 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 ('Sleek' - T &J Smith and Nephew Limited) at both edges.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes, the treatment sites were then gently washed with warm water and dried with paper towels to remove excess test material adhering to the skin.
- Time after start of exposure: 4 hours


SCORING SYSTEM: Draize

Actual criteria for assessment of skin irritation responses are given in Attached Background Information.
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
Of the three rabbits used under test, none of them showed any response at any time.
Other effects:
No dermal response was observed at the test site of any animal at any time during the 72 hour observation period.
The control sites did not show any response to the control procedure. The mean values for erythema and oedema recorded 24, 48 and 72 hours after treatment did not equal or exceed the EEe limit values considered to indicate a significant inflammatory response to treatment.

Scoring of irritance responses:

Animal Number

Type
of Response

Score after removal of dressings

1 hour

24 hour

48 hour

72 hours

Test site

Control
site

Test site

Control
site

Test site

Control
site

Test site

Control
site

91 1437M

Erythema

0

0

0

0

0

0

0

0

Oedema

0

0

0

0

0

0

0

0

91 1439M

Erythema

0

0

0

0

0

0

0

0

Oedema

0

0

0

0

0

0

0

0

91 1441M

Erythema

0

0

0

0

0

0

0

0

Oedema

0

0

0

0

0

0

0

0

Interpretation of results:
other: not irritating
Conclusions:
Under the conditions of this test, the test item was classified as 'non-irritant' to the skin.
Executive summary:

The potential of test item to cause inflammatory or corrosive changes upon first contact with skin was assessed by semi-occluded application of 0.5 g of the test material to the closely-clipped dorsa of three New Zealand White rabbits for four hours according to OECD 404. Dermal reactions were assessed 1, 24, 48 and 72 hours after removal of the dressings.

No dermal response was observed at the test site of any animal at any time during the 72 hour observation period.

Under the conditions of this test, the test item was classified as 'non-irritant' to the skin.

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

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 1992-07-27 to 1992-07-31
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
GLP study in accordance with recognised test guideline but: Lot/batch No.: not stated Expiration date of the lot/batch: not stated NOTE: study deemed acceptable because spectral data for test item are available, covering approximately before and after the test period - see section 1.4 Analytical Information.
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
1987
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
1984
Deviations:
no
GLP compliance:
yes
Specific details on test material used for the study:
Purity: Ca. 100%
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: 4 - 4 1/2 months
- Weight at study initiation: 3.31 - 3.52 kg
- Housing: Individually in suspended stainless steel cages (Type RC10/L/TR6) monted in mobile batteries (Modular Sysytems and Development Company Limited, London, England). The cages measured 61 x 76 x 46 cm high and were fitted with perforayed countersunk floor panels. A tray beneath the floor was lined with absorbent paper which was changed regularly.
- Diet (e.g. ad libitum): Animals had free access to food hoppers containing standard pelleted rabbit diet, (S.Q.C. Rabbit Diet - Special Diets Services
Limited, Witham, Essex, England). The manufacturer supplied analytical data with each batch of diet supplied. This included the concentration of nutritional components, aflatoxins and selected heavy metals, pesticides and micro-organisms. The diet contains no added antibiotic or other chemotherapeutic or prophylactic treatment.
- Water (e.g. ad libitum): The rabbits had free access to tap water taken from the public supply
- Acclimation period: Three weeks.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): Target value 18ºC, actual range 15ºC to 23ºC
- Humidity (%): Target value 55% RH, actual range 40% - 70% RH
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 / 12


IN-LIFE DATES: From: 27 July 1992 To 31 July 1992
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
100 mg of unchanged substance was instilled into the right eye.
Duration of treatment / exposure:
Indeterminate
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
3 animals were used in this study
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): No


SCORING SYSTEM: Darize
Refer to Attached Background Information for details of the scoring system used.

TOOL USED TO ASSESS SCORE: Ophthalmoscope
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
other: for all three animal tested
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
other: for all three animal tested
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
>= 0.3 - <= 0.7
Max. score:
2
Reversibility:
fully reversible within: 72h
Remarks on result:
other: for all three animal tested
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
1
Reversibility:
not fully reversible within: 24h
Remarks on result:
other: for all three animal tested
Irritant / corrosive response data:
A crimson-red conjunctival appearance, very slight chemosis and very slight discharge were observed in all animals one hour after instillation of test item. Injection of the conjunctival blood vessels persisted up to the 48 hour observation.
The eyes of all rabbits were overtly normal by the 72 hour examination.
Other effects:
Instillation of the test material caused a very slight or slight initial pain response.

Individual scores:

Animal No.

cornea opacity

iris

conjunctivae

chemosis

1h

24h

48h

72h

1h

24h

48h

72h

1h

24h

48h

72h

1h

24h

48h

72h

27TK333M

0

0

0

0

0

0

0

0

2

1

1

0

1

0

0

0

27TK336M

0

0

0

0

0

0

0

0

2

1

0

0

1

0

0

0

27TK337M

0

0

0

0

0

0

0

0

2

1

1

0

1

0

0

0

Interpretation of results:
other: not irritating
Conclusions:
Under the conditions of the test, the test item was classified as 'non-irritant' to the eye.
Executive summary:

The potential of test item to cause damage to the conjunctiva, iris or cornea was assessed in three New Zealand White rabbits, each subject to single ocular instillation of 100 mg of the test material according to OECD 405. Ocular reactions were examined 1, 24, 48 and 72 hours after treatment. Crimson-red conjunctival appearance and very slight chemosis and discharge were observed in all animals one hour after instillation. Injection of the conjunctival blood vessels persisted up to the 48 hour observation. The eyes of all rabbits were overtly normal by the 72 hour examination. Instillation of the test material caused a very slight or slight initial pain response. Under the conditions of this test, the test item was classified as 'non-irritant' to the eye.

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

Skin irritation: OECD 404, mean erythema scores at 24, 48 and 72 hours: 0; mean oedema scores at 24, 48 and 72 hours: 0

According to Regulation (EC) No 1272/2008, table 3.2.2, this substance should not be classified for this endpoint.

Eye irritation: OECD 405, Mean scores at 24, 48 and 72 hours:

Corneal opacity: 0.0, 0.0, 0.0; iritis: 0.0, 0.0, 0.0; conjunctivae: 0.7, 0.3, 0.7; chemosis: 0.0, 0.0, 0.0

Reversibility: The eyes of all rabbits were overtly normal by the 72 hour examination.

According to Regulation (EC) No 1272/2008, table 3.3.1 and 3.3.2, this substance should not be classified for this endpoint.