Registration Dossier

Administrative data

Description of key information

The test substance was considered to be non-irritating to the skin and eye and no classification is needed.

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:
1999
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
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:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 188719.4
- Expiration date of the lot/batch: November 2003

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at room temperature (ca. 20 °C) away from direct sunlight.
- Stability under test conditions: 24 hours at room temperature in bidistilled water
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Elevage Scientifique des Dombes F-01400 Chatillon sur Chalaronne
- Age at study initiation: 15 weeks
- Weight at study initiation: One male: 2715 g, Two females: 2631 and 2750 g
- Housing: Individually in stainless steel cages with an automatic cleaning system equipped with feed hoppers, drinking water bowls, with wood and haysticks for gnawing.
- Diet: Pelleted standard Provimi Kliba 3410 rabbit maintenance diet, ad libitum (batch no. 63/98).
- Water: Community tap water from Itingen, ad libitum, in water bowls
- Acclimation period: Five days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 ± 3 °C
- Humidity: 40-70 % (values above 70 % during cleaning process possible)
- Air changes: Air-conditioned with 10-15 air changes/h
- Photoperiod: 12 h light/12 h dark cycle

IN-LIFE DATES: From January 18, 1999 to January 21, 1999
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Remarks:
with an electric clipper
Vehicle:
unchanged (no vehicle)
Remarks:
test substance was moistened with bidistilled water before application
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.5 g (per animal)
Duration of treatment / exposure:
4 h
Observation period:
Up to 72 h (The skin reaction was assessed at approximately 1, 24, 48 and 72 h after the removal of the dressing, gauze patch and test substance)
Number of animals:
One male and two females
Details on study design:
Test substance preparation
0.5 g (per animal) of the test substance was weighed and then moistened with bidistilled water before application. Prior to the application the pH of the test substance was determined with pH-Test-Strip (E. Merck, D-64271 Darmstadt / Germany) and was found to be not assessable.

TREATMENT
Approximately three d before treatment, the dorsal fur was clipped with an electric clipper, exposing an area of approximately 100 cm² (10 cm x 10 cm). The skin of the animals was examined approximately 24 h before treatment, and, if necessary, regrown fur was again clipped. Animals with overt signs of skin injury or marked irritation which may have interfered with the interpretation of the results were not used in the test. On the day of treatment, the test substance was applied to approx. 6 cm² of the intact skin of the clipped area. It was covered with a 2.5 cm x 2.5 cm patch of surgical gauze and the gauze was covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and anchored with tape.

REMOVAL OF TEST SUBSTANCE
The duration of treatment was 4 h. Then the dressing was removed and the skin was flushed with lukewarm tap water to clean the application site so that any reactions (erythema) were clearly visible at that time.

SCORING SYSTEM: The skin reaction was assessed according to the numerical scoring system listed in the EEC Commission Directive 92/69/EEC, July 31, 1992
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
IRRITATION: Application of the test substance to healthy intact rabbit skin resulted in a primary irritation score of 0.00. Local signs (mean values from 24 to 72 h) consisted of grade 0.00 erythema and grade 0.00 edema. No signs of irritation were observed.
CORROSION: No irreversible alterations of the treated skin were observed nor were corrosive effects evident on the skin.
Other effects:
VIABILITY/MORTALITY AND CLINICAL SIGNS: No clinical signs of systemic toxicity were observed in the animals during the test and observation period, and no mortality occurred.
COLORATION: Orange staining by the test substance of the treated skin was observed.
BODY WEIGHTS: The body weight of all animals were considered to be within the normal range of variability.

SKIN IRIRITATION SCORES - INDVIDUAL VALUES

Animal Number

Erythema

Edema

 

24 h

48 h

72 h

24 h

48 h

72 h

34 (M)

0

0

0

0

0

0

35 (F)

0

0

0

0

0

0

36 (F)

0

0

0

0

0

0

Interpretation of results:
GHS criteria not met
Conclusions:
FAT 93450/A was considered to be non-irritating to Rabbit skin.
Executive summary:

An in vivo study was conducted to evaluate the skin irritation potential of the test substance, FAT 93450/A (of ca. 96 % purity) in New Zealand White rabbits according to EU Method B.4 and OECD Guideline 404 in compliance with GLP. 500 mg of test substance was applied to a clipped intact skin area of 6 cm2 in each animal under a 2.5 x 2.5 cm2 patch of surgical gauze. The patch was allowed to remain in contact with the skin for 4 h. Then, the dressing was removed and the skin was flushed with lukewarm tap water to clean the application site. Animals were scored for irritation reactions after 1, 24, 48 and 72 h. Animals were also monitored daily for viability, mortality and clinical signs. Body weights were recorded pre-test and at study termination. No dermal reactions (erythema or edema) were observed at 24, 48 and 72 h. No signs of body weight variability, toxicity or mortality were observed in any animal during the study period. Orange staining by the test substance of the treated skin was observed during the study period. Under the study conditions, FAT 93450 was considered to be non-irritating to 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:
1998
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
GLP compliance:
not specified
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Pa 243/244-22 bei 70 Grad getr.

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Animal species / strain quality: Rabbit/New Zealand White
Origin: Dr. K. Thomae GmbH, Biberach, FRG
Age of the animals: Young adult animals
Acclimatization period: at least for 1 week.
Housing: Stainless steel wire mesh cages with grating
Room temperature: 20 - 24 °C
Relative humidity: 30 - 70 %.
Day/night rhythm: 12 h/12 h (6.00 a.m. - 6.00 p.m.I 6.00 p.m. - 6.00 a.m.)
Type of cage: Stainless steel wire mesh cages with grating, floor area: 3000 cm2
No. of animals per cage: Single housing.
Animal identification: Ear tattoo
Bedding: No bedding in the cages; wood shavings in the waste trays.
Drinking water: About 250 ml tap water per animal per day
Diet: Kliba-Labordiaet, Klingentalmuehle AG Kaiseraugst, Switzerland, (about 130 g per animal per day)
Vehicle:
not specified
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.1 ml bulk volume
(about 26 mg of the comminuted test substance)
Duration of treatment / exposure:
The test substance was applied in a single dose to the conjunctival sac of the right eyelid; the substance was washed out with tap water about 24 hours after application (before 24 hour reading).
Observation period (in vivo):
1 h, 24 h, 48 h, 72 h, 8 d and 15 d after application.
Number of animals or in vitro replicates:
3 rabbits
Details on study design:
Both eyes of the animal(s) were examined before application of the test material for signs of pre-existing irritation, reaction or abnormality which would prevent it from being used in the study.
Route of application: The test substance was applied in a single dose to the conjunctival sac of the right eyelid; the substance was washed out with tap water about 24 hours after application (before 24 hour reading).
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
3 rabbits
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
mean
Remarks:
3 rabbits
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 15 d
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.33
Max. score:
3
Reversibility:
fully reversible within: 8 d
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 15 d
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24h

Individual eye scores

Animal No 1

Time point

Cornea

Iris

Conjunctiva (Redness)

Chemosis

After 24 hours

0

0

1

0

After 48 hours

0

0

1

0

After 72 hours

0

0

1

0

Mean (24-72 Hrs)

0

0

1

0

 

Animal No 2

Time point

Cornea

Iris

Conjunctiva (Redness)

Chemosis

After 24 hours

0

0

2

1

After 48 hours

0

0

1

0

After 72 hours

0

0

1

0

Mean (24-72 Hrs)

0

0

1.33

0.33

 

Animal No 3

Time point

Cornea

Iris

Conjunctiva (Redness)

Chemosis

After 24 hours

0

0

2

0

After 48 hours

0

0

2

0

After 72 hours

0

0

2

0

Mean (24-72 Hrs)

0

0

2

0

 

Interpretation of results:
GHS criteria not met
Conclusions:
The test substance Palanil Gelb HM f. ber. t. does not give indication of an irritant property to the eye.
Executive summary:

An eye irritation study was carried out with Palanil Gelb HM f. ber. t. in NZW rabbits as per OECD Guideline 405. The potential of Palanil Gelb HM f. ber. t. to cause damage to the conjunctiva, iris or cornea was assessed in 3 White New Zealand rabbits, subjected to a single ocular application of 0.1 ml bulk volume (about 26 mg) of the test substance. The average score (24 to 72 hours) for irritation was calculated to be 0.0 for corneal opacity and for iris, 1.4 for conjunctival redness and 0.1 for chemosis. The findings were reversible in all animals within 15 days after application; thus the study was terminated. Symptoms observed and described in the respective observations together with the mean scores for irritation do not indicate an irritant property of the test substance to the eye. Under the test conditions chosen and considering the described findings Palanil Gelb HM f. ber. t. does not give indication of an irritant property to the eye.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin Irritation/Corrosion:

In an in vivo skin irritation study, the test substance (of ca. 96 % purity) was assessed in New Zealand White rabbits according to EU Method B.4 and OECD Guideline 404 in compliance with GLP. No dermal reactions (erythema or edema) were observed at 24, 48 and 72 h. No signs of body weight variability, toxicity or mortality were observed in any animal during the study period. Orange staining by the test substance of the treated skin was observed during the study period.

Taking into consideration these findings, FAT 93450/A was considered to be non-irritating to rabbit skin. In the supporting acute dermal irritation/corrosion study (Seifert, 1984), due to intensive staining by the test substance, scoring of the erythema values was not possible till 24h observation. The erythema scored was 0 for all three animals at 48 and 72h observations, while no edema was seen at any of the observations. Hence, it can be concluded, that the test substance is non irritant and not corrosive when applied to the rabbit skin.

Eye Irritation:

The key study was conducted to assess the eye irritancy potential of the test substance (of commercial grade purity) to the eye of New Zealand White rabbits according to OECD Guideline 405. A single ocular dose of 0.1 g of test substance was applied into the conjunctival sac of the right eye of three male animals. The average score (24 to 72 hours) for irritation was calculated to be 0.0 for corneal opacity and for iris, 1.4 for conjunctival redness and 0.1 for chemosis. The findings were reversible in all animals within 15 days after application, indicating that the test substance was non-irritating to the rabbit's eye. Another supporting eye irritation (1984) study demonstrated similar results as the test substance did not give any indication of an irritant property to the eye.

Justification for classification or non-classification

Based on in vivo studies, it can be concluded that no classification for skin and eye effects of the test substance is warranted according to EU CLP.