Registration Dossier

Administrative data

Description of key information

Eye: not irritating in rabbits

Skin: not irritating in rabbits (read across)

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:
Oct. 22, 1979 to Nov. 12, 1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
light/dark cycle, observation times, exposure time and the use of both intact and abraded skin.
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Ciba-Geigy Limited (Toxicology GU 2.1)
- Weight at study initiation: 2 to 3 kgs
- Housing: Individually in metal cages
- Diet (e.g. ad libitum): ad libitum standard rabbit food NAFAG No. 814
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 4 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2°C
- Humidity (%): 55 +/- 10%
- Photoperiod (hrs dark / hrs light): 14 hrs dark/ 10 hrs light

Type of coverage:
occlusive
Preparation of test site:
other: Abraded and intact shaved
Vehicle:
other: Propylene glycol and saline (70:30)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Concentration (if solution): 50%
- amount: 0.5 g
Duration of treatment / exposure:
24 hours
Observation period:
7 days
Number of animals:
3 males and 3 females
Details on study design:
TEST SITE
- Area of exposure: 2.5 X 2.5 cm
- Type of wrap if used: impermeable material

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 24 hours

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
Total possible erythema score = 4
Edema formation
No edema = 0
Very slight edema (barely perceptible) = 1
Slight edema (edges of area well defined bydefinite raising) = 2
Moderate edema (raised approximately 1 mm) = 3
Severe edema (raised more than 1 mm and extending beyond area of exposure) = 4
Total possible edema score = 4
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24h, 48h, 72h
Score:
0
Max. score:
4
Remarks on result:
other: for both intact and abraded skin
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24h, 48h, 72h
Score:
0
Max. score:
4
Remarks on result:
other: for both intact and abraded skin
Irritant / corrosive response data:
No erythema or edema was observed on any of the test animals on abraded or intact skin.
Other effects:
None
Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of the present experiment the test article was found to cause no irritation when applied to intact and abraded rabbit skin.
Executive summary:

In a skin irritation study predating GLP the test substance was investigated for dermal effects in rabbits in a test similar to OECD testing guideline 404. An amount of 0.5 g test material was applied to the skin of 3 male and 3 female adult New Zealand White rabbits in an occlusive manner. The protocol differed by additional testing of abraded skin versus intact skin and a prolonged exposure time of 24h was used. Observation was terminated after 7 days which is acceptable as no indication of erythema or erythema was observed during the observation period. All scores for edema and erythema were zero at any time point. Based on the results of this study, the test article is considered to be not irritating to the rabbit 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:
1975
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
according to
Guideline:
other: "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (1959), the US Association of Food and Drug Officials (AFDO).
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
only 7 days of observation
GLP compliance:
no
Species:
rabbit
Strain:
other: Russian breed
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 1.5 to 2 kg
- Housing: individually
- Diet: ad libitum standard rabbit food - NAFAG, Gossau SG
- Water: ad libitum
- Acclimation period: at least 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 1
- Humidity (%): 55 ± 5
- Photoperiod (hrs dark / hrs light): 10/14
Vehicle:
unchanged (no vehicle)
Controls:
other: the untreated eye served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g
Duration of treatment / exposure:
3 animals (males): single application without washing
3 animals (females): single application, washing after 30 seconds
Observation period (in vivo):
7 days
Reading time points: day 1, 2, 3, 4, and 7
Number of animals or in vitro replicates:
3 males and 3 females
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): in 3/6 animals the treated eye was rinsed 10 mL of lukewarm water
- Time after start of exposure: 30 seconds

SCORING SYSTEM: Draize

TOOL USED TO ASSESS SCORE: hand-slit lamp
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
out of all 3 animals
Time point:
other: mean over 24, 48, 72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: eyes not washed out
Irritation parameter:
iris score
Basis:
mean
Remarks:
out of all 3 animals
Time point:
other: mean over 24, 48, 72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Remarks on result:
other: eyes not washed out
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
out of all 3 animals
Time point:
other: mean over 24, 48, 72 h
Score:
0
Max. score:
3
Reversibility:
other: not applicable
Remarks on result:
other: eyes not washed out
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
out of all 3 animals
Time point:
other: mean over 24, 48, 72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: eyes not washed out
Irritant / corrosive response data:
For the animals with eyes rinsed 30 seconds after treatment the same results were observed (scores for: cornea = 0, iris = 0, conjunctivae = 0, and chemosis = 0).
Interpretation of results:
GHS criteria not met
Remarks:
Migrated information
Conclusions:
Based on the results of this study, the test article is considered to be not irritating to the rabbit eye.
Executive summary:

An eye irritation similar to OECD 405 was performed with six female and male rabbits from russian breed. The eyes of three rabbits were left unwashed after application of 0.1 g unchanged test substance and the animals were observed 7 days. The mean scores for the 24, 48 and 72 h reading for conjunctivae redness, iritis, cornea opacity and conjunctivae chemosis were 0 at any reading time point. In three additional rabbits the eyes were rinsed 30 seconds after application of test substance. In this case the same results were observed. This indicates that the substance is not an irritant to the rabbit eye.

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

Additional information

Skin

A valid skin irritation study is available for a structural analogue (see attached read across justification document). In this study, the test substance was investigated for skin irritation in rabbits in a test similar to OECD testing guideline 404. The protocol differed by additional testing of abraded skin versus intact skin and a prolonged exposure time of 24h was used. Observation was terminated after 7 days which is acceptable as no indication of erythema or erythema was observed during the observation period. All scores for edema and erythema were zero at any time point. Based on the results of this study, the test article is considered to be not irritating to the rabbit skin.

In addition to the read across data, a valid study with human volunteers is available for the test article (IBL, 1972, see chapter 7.10.4). In this study, 50 volunteers were tested in a repeated insult patch test. The undiluted test substance (10 mg/cm²) was applied 15 times under occlusive conditions. After each application irritation scores were examined. All subjects showed an irritation score of zero after each application. Therefore it is concluded that the test substance is considered to be not irritant.

In support of these findings is a study result obtained in an animal study performed by IBT. Considering the history of IBT (reporting fake data), the reliability of this study is questionable and an accurate Klimisch rating is impossible. Consequently, the study is rated with K4. However, since falsified data were predominantly reported for studies with repeated exposure, the data from this study was taken into careful consideration. No effects to the skin of rabbits were observed in this study, therefore supporting the findings reported above.

To summarize, based on the data available and taking the read across data into account, the test article is considered to be not irritating to the skin.

Eye

An eye irritation test was performed with six female and male rabbits from Russian breed similar to OECD 405. The eyes of three rabbits were left unwashed after application of 0.1 g unchanged test substance and the animals were observed 7 days. The mean scores for the 24, 48 and 72 h reading for conjunctivae redness, iritis, cornea opacity and conjunctivae chemosis were 0 at any reading time point. In three additional rabbits the eyes were rinsed 30 seconds after application of test substance. In this case the same results were observed. This indicates that the substance is not an irritant to the rabbit eye.

In addition, two studies are available from IBT which revealed minimal to mild ocular effects below the level of regulatory significance and reversible within 7 days the latest. Considering the history of IBT (reporting of fake data), the reliability of these studies is questionable and an accurate Klimisch rating is impossible. Consequently, the study is rated with Klimisch 4. However, since falsified data were predominantly reported for studies with repeated exposure, the data from these studies were taken into careful consideration. They are in support of the data reported by the reliable study and the test substance is therefore considered to be not irritating to the eye.

Justification for classification or non-classification

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for the purpose of classification under Regulation (EC) No.1272/2008. Based on the data, the test substance is not classified as skin or eye irritant.