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Description of key information

Skin irritation (OECD 404, RL1): 2 m and 1 f, not irritating

Eye irritation (OECD 405, RL1): 2 m and 1 f, not irritating

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
17.04.-09.05.1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
Acute dermal irritancy/corrosivity, OECD 1981
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: SAVO-Ivanovas, Kisslegg
- Age at study initiation: about 17 - 19 weeks
- Housing: Healthy young rabbits were allocated to the different groups. The animals were kept in the experimental room for more than 7 days to allow for acclimatization. All rabbits were housed in an air-conditioned room of 39 m2 (No. 123) in the rabbit experimental station with daylight. They were kept separately in cages type KK 017 (floor area: 75 x 54.5 = 4087 cm2, height: 38 cm; manufacturer: Hulskamp) on metal grids. The paper underneath the cages was changed three times a week. The cages were machine-cleaned before the start of the study. The temperature varied from 21 to 24°C and the humidity from 43 to 64 %. The measurements were carried out using a thermohygrograph (type 252, Wilhelm Lambrecht KG, Göttingen).
- Diet: The rabbits received Altromin Standard Diet TPF(R) 2113, pellets and acidified, fully demineralized water from an automatic drinking device ad libitum. The diet is checked periodically by an independent and German Government approved testing laboratory, according to the regulations of the manufacturer. Analysis includes both qualitative and quantitative evaluation for heavy metals, aflatoxins, pesticides, and antibiotics. Drinking water employed in this type of study is regularly investigated microbiologically. The analytical results show that the limits set by German regulations for animal feed have not been exceeded..

Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5 g
Duration of treatment / exposure:
4 h
Observation period:
7 days
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: left and right side of the animals' back
- Type of wrap if used: polyethylene foil which was kept in place by a leather sleeve

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes (any test material on the left site was wiped off)
- Time after start of exposure: 4 hours

OBSERVATION TIME POINTS
(indicate if minutes, hours or days) : 1 hour after removal of the patches, and then daily for a period of further 7 days

SCORING SYSTEM:
- Method of calculation: according to DRAIZE
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 5 days
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Other effects:
There was no mortality and no clinical signs of toxicity were observed during the study period. The body weight gains were within the normal ranges during the study period.
Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of the present study, the GHS critera for skin irritation were not met. The test animals did not show a score between 2.3 and 4, but of 1 or less after exposion.
Executive summary:

To test for primary skin irritation, 0.5 g of the test material was mixed with some drops of Aqua pro injectione to ensure good contact with the skin. Afterwards the test material was spread onto 4 cm2 patches and applied to the intact skin of previously shaven rabbits for a 4 hours period under occlusive conditions. The first examination of the treated skin sites followed 1 hour after removal of the patches. Thereafter, examinations were performed daily for further 7 days. Under the conditions of the present study, the criteria for classification according to GHS are not met. Therefore, the test item is not considered to be irritating to skin.

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

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
17.04.-09.05.1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
1987
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: SAVO-Ivanovas, Kisslegg
- Age at study initiation: about 17 - 19 weeks
- Housing: Healthy young rabbits were allocated to the different groups. The animals were kept in the experimental room for more than 7 days to allow for acclimatization. All rabbits were housed in an air-conditioned room of 39 m2 (No. 123) in the rabbit experimental station with daylight. They were kept separately in cages type KK 017 (floor area: 75 x 54.5 = 4087 cm2, height: 38 cm; manufacturer: Hulskamp) on metal grids. The paper underneath the cages was changed three times a week. The cages were machine-cleaned before the start of the study. The temperature varied from 21 to 24°C and the humidity from 43 to 64 %. The measurements were carried out using a thermohygrograph (type 252, Wilhelm Lambrecht KG, Göttingen).
- Diet: The rabbits received Altromin Standard Diet TPF(R) 2113, pellets and acidified, fully demineralized water from an automatic drinking device ad libitum. The diet is checked periodically by an independent and German Government approved testing laboratory, according to the regulations of the manufacturer. Analysis includes both qualitative and quantitative evaluation for heavy metals, aflatoxins, pesticides, and antibiotics. Drinking water employed in this type of study is regularly investigated microbiologically. The analytical results show that the limits set by German regulations for animal feed have not been exceeded..
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.1 g
Duration of treatment / exposure:
After instillation the eyelids were closed for about 30 seconds. Rinsing of the eyes was not performed.
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
3
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
After single instillation of 0.1 g test item, into the conjunctival sac of the left eye, without rinsing, no irritation of the cornea and iris was observed. Examination of the conjunctivae revealed redness
(score 1), chemosis in 1 animal (score 2 = positive effect), and discharge (score 1 or 2) at the first reading. At the second reading only redness (score 1) was seen in 1 animal. Later, no irritation was seen. The chemosis at the first reading was probably due to incidental mechanical irritation. According to these results the test material is not regarded as an irritant.
Other effects:
There was no mortality and no signs of toxicity were observed during the study period. The body weight gains were within the normal ranges during the study period.
Interpretation of results:
GHS criteria not met
Conclusions:
The test item is not irritating to eye.
Executive summary:

The test item was tested for its eye irritating properties. For the test of primary eye irritation, 0.1 g of the test material was applied into the conjunctival sac of rabbits. The first examination of the eyes followed 1 hour after instillation. The other examinations were performed daily for further 7 days.

Examination of the conjunctivae revealed redness (score 1), chemosis in 1 animal (score 2 = positive effect), and discharge (score 1 or 2) at the first reading. At the second reading only redness (score 1) was seen in 1 animal. Later on no irritation was seen. The chemosis at the first reading was probably due to incidental mechanical irritation. According to these results the test material is not regarded as an irritant.

Endpoint:
eye irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In vivo skin irritation study

To test for primary skin irritation, 0.5 g of the test material was mixed with some drops of Aqua pro injectione to ensure good contact with the skin. Afterwards the test material was spread onto 4 cm2 patches and applied to the intact skin of previously shaven rabbits for a 4 hours period under occlusive conditions. The first examination of the treated skin sites followed 1 hour after removal of the patches. Thereafter, examinations were performed daily for further 7 days. Under the conditions of the present study, the criteria for classification according to GHS are not met. Therefore, the test item is not considered to be irritating to skin.

In vivo eye irritation study

The test item was tested for its eye irritating properties. For the test of primary eye irritation, 0.1 g of the test material was applied into the conjunctival sac of rabbits. The first examination of the eyes followed 1 hour after instillation. The other examinations were performed daily for further 7 days. Examination of the conjunctivae revealed redness (score 1), chemosis in 1 animal (score 2 = positive effect), and discharge (score 1 or 2) at the first reading. At the second reading only redness (score 1) was seen in 1 animal. Later on no irritation was seen. The chemosis at the first reading was probably due to incidental mechanical irritation. According to these results the test material is not regarded as an irritant.

Justification for classification or non-classification

The available data on skin and eye irritation do not meet the criteria for classification according to Regulation (EC) 1272/2008.