Registration Dossier

Administrative data

Description of key information

The substance is considered to be not irritant to eyes and the skin to rabbits

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:
October 1976
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non-GLP and Pre OECD study. Observation limited to 24 hours and 72 hours after treatement.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
24h application and only 24 and 72h observation.
Principles of method if other than guideline:
The test was carried out according to the method given in the "Hazardous Substances Regulations" under the U.S. Federal Hazardous Substances Labelling Act Sect. 191.11 (February 1965).
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
The rabbits were caged singly in an experimental room maintained at a temperature of 2D°C. (± 1°) and a relatiue humidity of 50-70%. Animals uere exposed to artificial light for 10 hours daily frorn 08.00 - 18.00 hours. A commercial irradiated diet (Styles-Oxoid) was fed ad lib. Sterile filtered water was evailable at all times.
Type of coverage:
occlusive
Preparation of test site:
other: Abraded skin/Intact skin
Vehicle:
other: 50% PEG
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1 mL
- Concentration (if solution): 50%
Duration of treatment / exposure:
24 hours
Observation period:
72 hours
Number of animals:
3 males and 3 females
Details on study design:
TEST SITE
- Area of exposure:2.5 cm2
- Type of wrap if used: aluminium foil secured uith "Sleek"* adhesive taps. Ths test sites uere then couered by a 6" uide "Coban"** self adhesive bandage in order to retain the test substance in close contace uith the skin.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No


SCORING SYSTEM:
Erythema and Eschar Formation
Description Grads
No erythema O
Slight erythema (barely perceptible) 1
Well defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet red) to slight eschar formation 4

Oedema Formation
Description Grade
No oedema 0
Very slight oedema (barely perceptible) 1
Slight oedema (edges of area well defined by definite raising) 2
Moderate oedema (raised approximately 1 mm.) 3
Seuere-oedema (raised more than 1 mm. and extending beyond the area of exposure) 4
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24 and 72 hours aboservations
Score:
0.21
Reversibility:
fully reversible within: 72 hours
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The substance is not considered to be irritant to the skin.
Executive summary:

Six rabbits (3 males and 3 females) were treated during 24 hours under occlusive dressing with 1.0 mL of the substances solution (mixed with a 50% aqueous solution of PEG).

After 24 hours slight erythema uas seen on l/6(intact and abraded sites and very slight oedema on 1/6 intact and 2/6 abraded sites.

After 72 hours, all sites were normal.

Generally, there was no differences-seen in the reactions between intact and abraded sites.

The primary irritation score was 0.2.

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:
October 1976
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Pre-OECD study, non-GLP
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
The rabbits were caged singly in an experimental room maintained at a temperature of 20°C. ( + 1°) and a relative humidity of 50-70%. Animals were exposed to artificial light for 10 hours daily from 08.00 - 18.00 hours. A commercial irradiated diet (Styles-Oxoid) was fed ad lib. Sterile filtered water was available at all times.
Vehicle:
unchanged (no vehicle)
Controls:
other: the right eye served as control
Amount / concentration applied:
100 mg
Duration of treatment / exposure:
Single exposure (The eyelids were held closed for 1 second.)
Observation period (in vivo):
The rabbits were examined 1, 24, 48 and 72 hours after application cf the test compound
Number of animals or in vitro replicates:
3 males and 3 females
Details on study design:
The eyes of the experimental animals were examined and found normal prior to the test. 100mg of the test compound were instilled into the conjunctiual sac of the left eye. The eyelids were then held closed for 1 second. The right eye served as a control. After 30 seconds the compound was, as far as possible, flushed out of the eyes of three of the rabbits with approximately 200 ml. of warm water.
The rabbits were examined 1, 24, 48 and 72 hours after application cf the test compound
Irritation parameter:
conjunctivae score
Basis:
animal #5
Time point:
other: 24 hours
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Irritant / corrosive response data:
Con.junctiva.
A very slight reaction was seen in 3/3 unwashed and 1/3 washed eyes. one hour after the application of the compound.
Only one washed eye was still showing a reaction at 24 hours, but this had returned to normal by 48 hours.

Cornea.
Slight opacity with damage to the surface epithelium was seen transiently at one hour only in one unwashed eye.
Generally, there was uery little difference seen in the reactions between washed and unwashed eyes.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
TK 12 146 is a minimal eye irritant in the albino rabbit.
Executive summary:

Three male rabbits and three female rabbits were used in the test. 100mg of the test compound were instilled into the conjunctiual sac of the left eye. The eyelids were then held closed for 1 second. The right eye served as a control. After 30 seconds the compound was, as far as possible, flushed out of the eyes of three of the rabbits with approximately 200 ml. of warm water.

The rabbits were examined 1, 24, 48 and 72 hours after application of the test compound.

A very slight reaction (redness of the conjunctivae) was seen in 3/3 unwashed and 1/3 washed eyes one hour after the application of the compound.

Only one washed eye was still showing a reaction at 24 hours, but this had returned to normal by 48 hours.

Slight corneal opacity with damage to the surface epithelium was seen transiently at one hour only in one unwashed eye.

Generally, there was uery little difference seen in the reactions between washed and unwashed eyes.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Six rabbits (3 males and 3 females) were treated during 24 hours under occlusive dressing with 1.0 mL of the substances solution (mixed with a 50% aqueous solution of PEG). After 24 hours slight erythema was seen on l/6 (intact and abraded sites and very slight oedema on 1/6 intact and 2/6 abraded sites. After 72 hours, all sites were normal.

Generally, there was no differences-seen in the reactions between intact and abraded sites. The primary irritation score was 0.2. The substance is not considered to be irritating to the skin.

In a eye irritation study three male rabbits and three female rabbits were used. 100mg of the test compound were instilled into the conjunctiual sac of the left eye. The eyelids were then held closed for 1 second. The right eye served as a control. After 30 seconds the compound was, as far as possible, flushed out of the eyes of three of the rabbits with approximately 200 ml. of warm water.

The rabbits were examined 1, 24, 48 and 72 hours after application of the test compound.

A very slight reaction (redness of the conjunctivae) was seen in 3/3 unwashed and 1/3 washed eyes one hour after the application of the compound. Only one washed eye was still showing a reaction at 24 hours, but this had returned to normal by 48 hours.

Slight corneal opacity with damage to the surface epithelium was seen transiently at one hour only in one unwashed eye.

Generally, there was uery little difference seen in the reactions between washed and unwashed eyes. The substance is not considered to be irritant for the eye.


Justification for selection of skin irritation / corrosion endpoint:
Only this study is available

Justification for selection of eye irritation endpoint:
Only this study is available

Justification for classification or non-classification

Based on the above mentioned results the substance does not need to be classified according to CLP regulation (Regulation EC No.1272/2008) and DSD (Directive 67/548/EEC).