Registration Dossier

Administrative data

Description of key information

Skin irritation
The key study was carried out following a method similar or equivalent to EU Method B.4 and OECD Guideline 404 (Acute Dermal Irritation / Corrosion). A group of six albino rabbits was treated with the test item (occlusive with 4 h exposure). No skin irritation was noted in any of the six animals at any of the observations at 4, 24, 48 and 72 h. A primary irritation index of 0.0 was obtained following observations at 4, 24, 48 and 72 h. The test article was therefore regarded as a non-irritant. The test item did not produce a corrosive response as defined by the Code of Federal Regulations Title 49, Part 173, 1276. Results obtained were confirmed in several supporting studies.
Respiratory irritation
No indication of respiratory irritation from handling and use.
Eye irritation
The key study was carried out according to OECD Guideline 405 (Acute Eye Irritation / Corrosion). A group of 3 rabbits (New Zealand White) were administered 0.1 g of test item into one eye. The untreated eye served as control. Treated eyes were not washed following application. Animals were observed 1, 24, 48 and 72 hours as well as 7 days after treatment.
Under the conditions of this experiment, the test item was found to cause moderate irritation when applied to the rabbit eye mucosa. No discoloration of the cornea and conjunctivae which could be related to effects of the test article was observed. No corrosion was observed at each of the measuring intervals. The body weight gain of all rabbits was similar. No systemic effects were observed.
Similar results were obtained in several supporting studies.

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non-GLP study.
Qualifier:
equivalent or similar to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: Individual body weights were within the range 2.2 - 3.0 kg.
- Housing: The animals were caged individually in grid floor cages.
- Diet: Ad libitum
- Water: Ad libitum
- Acclimation period: The animals were acclimatised to the laboratory environment for a minimum of 7 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Not controlled, but min. 14 °C
- Humidity (%): Not controlled
- Air changes: Fan controlled air circulation
- Photoperiod: natural lighting conditions supplemented with fluorescent lighting during the working hours (8.45 to 17.00)

IN-LIFE DATES: From: 09.1979 To: 09.1979
Type of coverage:
occlusive
Preparation of test site:
other: intact and abraded
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g.
- The test article was moistened with water for administration.
Duration of treatment / exposure:
Portions of the test article (0.5 g) were applied to one intact and one abraded site on each animal and covered with patches of gauze. Four hours after treatment the wrappings and collars were removed.
Observation period:
Immediately after removal of the wrappings the skin reactions on both the intact and abraded sites were scored. Following this initial reading the test sites were washed with warm water to prevent further exposure to the test article. The evaluation of the skin reactions was repeated 24, 48 and 72 hours after treatment.
Number of animals:
Six New Zealand White rabbits were used for the study.
Details on study design:
TEST SITE
- Area of exposure: 25 mm x 25 mm
- % coverage: 100
- Type of wrap if used: A small plug of cotton wool weighing approximately one g was placed over the top of the pads to achieve uniform pressure over the whole treated surface. The pads were held in place by a strip of adhesive impermeable plaster. An Elizabethan collar was placed around the neck of each animal to prevent removal of the wrapping.

REMOVAL OF TEST SUBSTANCE
- Washing: Yes, washed with warm water
- Time after start of exposure: 4 h

SCORING SYSTEM: U. S. Food and Drug Administration "Appraisal of the Safety Chemicals in Foods, Drugs and Cosmetics," 1959
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 4, 24, 48, 72
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 4, 24, 48, 72
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 4, 24, 48, 72
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 4, 24, 48, 72
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritant / corrosive response data:
A primary irritation index of 0.0 was obtained. The test article is therefore regarded as a non irritant. No skin reactions were noted in any of the animals during the observation period.
The test article did not produce a corrosive response as defined by the Code of Federal Regulations, Title 49, Part 173, 1976. No evidence of tissue destruction was noted during the observation period.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
A primary skin irritation and corrosivity study was performed in the albino rabbit on the test item. No skin irritation was noted in any of the six animals at any of the observations at 4, 24, 48 and 72 h. A primary irritation index of 0.0 was obtained. The test article was therefore regarded as a non-irritant. The test item did not produce a corrosive response as defined by the Code of Federal Regulations Title 49, Part 173, 1276.
Executive summary:

A study similar or equivalent to EU Method B.4 and OECD Guideline 404 (Acute Dermal Irritation / Corrosion) was carried out. A group of six albino rabbits was treated with the test item (occlusive with 4 h exposure). No skin irritation was noted in any of the six animals at any of the observations at 4, 24, 48 and 72 h. A primary irritation index of 0.0 was obtained following observations at 4, 24, 48 and 72 h. The test article was therefore regarded as a non-irritant. The test item did not produce a corrosive response as defined by the Code of Federal Regulations Title 49, Part 173, 1276.

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
Reliability:
1 (reliable without restriction)
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
RCC AG
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Age at study initiation: 14 - 15 weeks
- Weight at study initiation: 2.7 - 3.0 kg
- Housing: Stainless steel cages
- Diet: Ad libitum
- Wate: Ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 +/- 2 °C
- Humidity: 55 /+- 10 %
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: 16 Aug. 1983 To: 23 Aug. 1983
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.1 g/animal
Duration of treatment / exposure:
Eyes were not rinsed after treatment.
Observation period (in vivo):
The eyes were examined and the grade of ocular reactions recorded at 1, 24, 48, 72 hours and at 7 days after treatment.
Number of animals or in vitro replicates:
3 (2 males/1 female)
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: Eyes were not rinsed

SCORING SYSTEM:
- Draize, 1959. Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, Association of Food and Drug Officials of the United States.
- ETAD (Ecological And Toxicological Association of the Dye Stuffs Manufacturing Industry) Methods 001-003 (1979)
- VCI (Verband Der Chemischen Industrie, BRD) Sicherheitsdatenblatt

TOOL USED TO ASSESS SCORE:
- Hand-slit lamp
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: 24, 48 and 72 hours
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: 24, 48 and 72 hours
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: 24, 48 and 72 hours
Score:
0.33
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
1.67
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: 24, 48 and 72 hours
Score:
2.33
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: 24, 48 and 72 hours
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
1.33
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: 24, 48 and 72 hours
Score:
1.33
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: 24, 48 and 72 hours
Score:
0.67
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritant / corrosive response data:
IRRITATION
The test item showed irritation when applied on the rabbit eye mucosa.
COLORATION
No discoloration of the cornea and conjunctivae related to effects of the test article was observed in the rabbits during the treatment and observation intervals.
CORROSION
No corrosion of the cornea was observed at each of the measuring intervals.
Other effects:
BODY WEIGHTS
The body weight gain of all rabbits was similar.
TOXIC SYMPTOMS
No acute toxicological signs were observed in the animals during the test period, and no mortality occurred.
NECROPSY
Due to the results obtained, no macroscopic organ examination was indicated.
Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this experiment the test item was found to cause a moderate irritation when applied to the rabbit eye mucosa. No discoloration of the cornea and conjunctivae which could be related to effects of the test article was observed. No corrosion was observed at each of the measuring intervals.
The maximum mean total score was found to be: 4.9 (unrinsed eyes). The body weight gain of all rabbits was similar. No systemic effects were observed.
Executive summary:

A study according to OECD Guideline 405 (Acute Eye Irritation / Corrosion) was carried out. A group of 3 rabbits (New Zealand White) were administered 0.1 g of test item into one eye. The untreated eye served as control. Treated eyes were not washed following application. Animals were observed 1, 24, 48 and 72 hours as well as 7 days after treatment.

Under the conditions of this experiment, the test item was found to cause moderate irritation when applied to the rabbit eye mucosa. No discoloration of the cornea and conjunctivae which could be related to effects of the test article was observed. No corrosion was observed at each of the measuring intervals. The body weight gain of all rabbits was similar. No systemic effects were observed.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Effects on eye irritation: moderately irritating

Justification for classification or non-classification

Based on the data available the substance is classified and labeled as Eye irritation category 2, H319 Causes serious eye irritation according to Regulation 1272/2008/EEC (CLP) and Irritating Xi, R36 Irritating to eyes according to Directive 67/548/EEC (DSD).