Registration Dossier

Administrative data

Description of key information

Based on the results obtained from the structural analogue substance, the test is not considered to be irritant to skin and eye.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
For this endpoint information from a structural similar compound is available. The study for this similar compound was performed according to GLP and the methods applied are fully compliant with OECD TG 404.
See chapter 13 report for a more detailed justification.
Reason / purpose:
read-across source
Related information:
Composition 1
Test material information:
Composition 1
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
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
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
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:
May 25, 2000 - Jun 01, 2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Principles of method if other than guideline:
None
GLP compliance:
yes (incl. certificate)
Test material information:
Composition 1
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Strain: Albino rabbit, Crl:KBL(NZW)BR, female (f)
Source: Charles River Wiga GmbH, Kif3legg
Age: about 33 weeks
Weight: 4,31 kg (3,77-4,76)
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 g
Duration of treatment / exposure:
4 hours
Observation period:
24, 48, 72 hours after removal of patches
Number of animals:
3 female rabbits
Details on study design:
Identification and adaptationHealthy rabbits were allocated to the study group. The animals were kept in the experimental room for more than 7 days to allow for acclimatization.Each animal was uniquely identified by a tattoo in the ear displaying the animal number. Individual cage cards were affixed to each cage displaying the study number, test material, day of treatment, and animal number.Assignment3 female rabbits were used for this studyHousing and dietAll rabbits were housed in an air-conditioned room. Lighting was controlled by a timer to provide a 12-hour light and a 12-hour dark regime. They were kept separately in special rabbit cages (manufacturer: Becker; type K99/30 KU) with plastic grids placed on mobile racks. Temperature and relative humidity were measured using a thermohygrograph. The room temperature varied from 20 to 22°C and the relative humidity from 50 to 64 %. The rabbits received diet for rabbits No. 814, Eberle Nafag ad libitum, and fresh tap water from Makrolon drinking bottles at least three times a week.The diet is checked periodically according to the specifications of the manufacturer by an independent laboratory, approved by the German government. Analysis includes both qualitative and quantitative evaluation for heavy metals, aflatoxins, pesticides, and antibiotics.The drinking water is periodically analyzed according to the national regulations for human drinking water.VehicleName:Aqua pro injectioneGrading scale for evaluation: Erythema and eschar formation Scores--------------------------------------------------No erythema 0Very slight erythema (barely perceptible) 1Well defined erythema 2Moderate to severe erythema 3 Severe erythema (beet redness) to eschar formation preventing grading of erythema 4--------------------------------------------------Maximum possible: 4--------------------------------------------------Edema formation Scores--------------------------------------------------No edema 0Very slight edema (barely perceptible) 1Slight edema (edges of area well defined by definite raising) 2Moderate edema (raised approx. 1 mm) 3 Severe edema (raised more than 1 mm and extending beyond area of exposure) 4--------------------------------------------------Maximum possible: 4--------------------------------------------------Total possible irritation score (maximum): 8Mean score = Mean grading for erythema or edema of all the rabbits per time pointMean cumulative score = Mean grading of all readings for erythema and edema per time pointMean score per animal = Mean grading for each animal of erythema or edema (24, 48, and 72 hours after removal of the patches)
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritant / corrosive response data:
After a single application to the intact dorsal skin of rabbits, for a 4 hours period of exposure under semiocclusive conditions, no signs of irritation were observed in the treated areas.
Other effects:
None

Clinical findings

After a single application to the intact dorsal skin of rabbits, for a 4 hours period of exposure under semiocclusive conditions, no signs of irritation were observed in the treated areas. No signs of clinical toxicity were detected.

Mortality

All animals survived the observation period.

Body weight

Body weight development of the treated rabbits was inconspicuous.

Interpretation of results:
GHS criteria not met
Conclusions:
The test item was not irritating to the skin in this assay. According to the Regulation (EC) No 1272/2008, OJ L 353 the test material should not be classified as a skin irritant.
Executive summary:

Purpose

The purpose of this assay was to identify the skin irritation/corrosion potential of the test item when applied to the intact skin of previously shaven rabbits for a 4 hours period under semiocclusive conditions. This study should provide a rational basis for risk assessment to the irritating potential of the test item in man.

Study design

To test for primary skin irritation, the test item was mixed with some drops of Aqua pro injectione to ensure good contact to the skin. Afterwards the test material was spread onto patches and applied to the intact skin of three previously shaven rabbits for a 4 hours period under semiocclusive conditions. The first examination of the treated skin sites followed 1 hour after removal of the patches. Then, examinations were performed daily for further 7 days.

Results

Under the conditions of the present study no signs of irritation were seen. The evaluation of all animals yields a zero mean score.

Conclusion

The test item was not irritating to the skin in this assay. According to the Regulation 1272/2008 the test material should not be classified as a skin irritant.

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

Eye irritation

Link to relevant study records

Referenceopen allclose all

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
Interpretation of results:
GHS criteria not met
Endpoint:
eye irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
For this endpoint information from a structural similar compound is available. The study for this similar compound was performed according to GLP and the methods applied are fully compliant with OECD TG 405.
See chapter 13 report for a more detailed justification.
Reason / purpose:
read-across source
Related information:
Composition 1
Test material information:
Composition 1
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Interpretation of results:
GHS criteria not met
Conclusions:
For this endpoint information from a structural similar compound is available. The study for this similar compound was performed according to GLP and the methods applied are fully compliant with OECD TG 405. The source compound was negative in this assay. See chapter 13 report for a more detailed justification.
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
May 25, 2000 - Jun 01, 2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Principles of method if other than guideline:
None
GLP compliance:
yes (incl. certificate)
Test material information:
Composition 1
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Strain: Albino rabbit, Crl:KBL(NZW)BR, female (f)
Source: Charles River Wiga GmbH, Kifßlegg
Age: about 33 weeks
Weight: 4,31 kg (3,68-5,05)
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.1 g test material
Duration of treatment / exposure:
0.1 g test material was instilled into the conjunctival sac of the left eye of each animal by gently pulling the lower lid away from the eyeball to form a cup into which the test material was placed. The right eye remained untreated and served as control. After instillation, the eyelids were closed for about 30 seconds.
Observation period (in vivo):
1 hour after treatment, after 24, 48, and 72 hours, then daily up to day 8
Number of animals or in vitro replicates:
3 female rabbits
Details on study design:
-- Identification and adaptationHealthy rabbits were allocated to the study group. The animals were kept in the experimental room for more than 7 days to allow for acclimatization. Each animal was uniquely identified by a tattoo in the ear displaying the animal number. Individual cage cards were affixed to each cage displaying the study number, test material, day of treatment, and animal number.-- Assignment3 female rabbits were used for this study.-- Housing and dietAll rabbits were housed in an air-conditioned room. Lighting was controlled by a timer to provide a 12-hour light and a 12-hour dark regime.They were kept separately in special rabbit cages (manufacturer: Becker; type K99/30 KU) with plastic grids placed on mobile racks. Temperature and relative humidity were measured using a thermohygrograph. The room temperature varied from 20 to 22 °C and the relative humidity from 50 to 64 %. The rabbits received diet for rabbits No. 814, Eberle Nafag ad libitum, and fresh tap water from Makrolon drinking bottles at least three times a week.The diet is checked periodically according to the specifications of the manufacturer by an independent laboratory, approved by the German government. Analysis includes both qualitative and quantitative evaluation for heavy metals, aflatoxins, pesticides, and antibiotics.The drinking water is periodically analyzed according to the national regulations for human drinking water.-- PreparationBefore the application, the test material was ground in a mortar using a pestle.–- Administration and dose levelTo ensure that only rabbits with normal eyes were included in the study, approximately 24 hours before treatment ophthalmological examinations were performed after instillation of a 0.15 % fluorescein solution (Dr. Thilo & Co.) using an ophthalmoscope according to Eisenhut (Basel). Animals with eye defects, injury or irritation were excluded.0.1 g test material was instilled into the conjunctival sac of the left eye of each animal by gently pulling the lower lid away from the eyeball to form a cup into which the test material was placed. The right eye remained untreated and served as control. After instillation, the eyelids were closed for about 30 seconds.-- Observation for clinical symptomsThe rabbits were examined for eye irritation and for changes in behavior and general condition 1 hour after treatment, after 24, 48, and 72 hours, then daily up to day 8 of the experimental part.Eye changes were evaluated according to the DRAIZE- , OECD- and EEC recommendations.-- Evaluation of eye reactions- Cornea ScoresA) Opacity-degree of density (area most dense taken for reading)No ulceration or opacity 0Scattered or diffuse areas of opacity (other than slight dullingof normal lustre), details of iris clearly visible 1Easily discernible translucent area, details of iris slightly obscured 2Nacrous area, no details of iris visible, size of pupil barely discernible 3Opaque cornea, iris not discernible through the opacity 4B) Area of cornea involved not evaluated (Rating according to the DRAIZE method)- IrisA) Normal 0 Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperemia, or injection, any of these or combination of any thereof, iris still reacting to light (sluggish reaction is positive) 1 No reaction to light, hemorrhage, gross destruction (any or all of these) 2 - Conjunctivae ScoresA) Redness (refers to palpebral and bulbar conjunctivae, cornea and iris)Blood vessels normal 0Some blood vessels definitely hyperemic (injected) 1Diffuse, crimson color, individual vessels not easily discernible 2Diffuse beefy red 3B) Chemosis: lids and/or nictating membranesNo swelling 0Any swelling above normal (includes nictating membranes) 1Obvious swelling with partial eversion of lids 2Swelling with lids about half closed 3Swelling with lids more than half closed 4C) Discharge (Rating according to the DRAIZE method ) No discharge 0 Any amount different from normal (does not include small amounts observed in inner canthus of normal animals) 1Discharge with moistening of the lids and hairs just adjacent to lids 2Discharge with moistening of the lids and hairs, and of a considerable area around the eye 3Mean score of all animals = Mean grading for irritations of cornea, iris, and conjunctivae per time pointMean score per animal = Mean grading for each animal of irritations of cornea, iris, and conjunctivae (1, 24, 48, and 72 hours after application)Maximum value = Maximum grading of a sign of irritation within a period
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritant / corrosive response data:
No signs of irritation were observed at the cornea and iris. The conjunctivae showed redness (score 1) on day 1 (1 hour) of the study. Later on no signs of irritation were observed. The untreated eyes were unchanged.
Other effects:
No signs of clinical toxicity were detected.

Eye alterations

Clinical findings

No signs of irritation were observed at the cornea and iris. The conjunctivae showed redness (score 1) on day 1 of the study. Later on no signs of irritation were observed. The untreated eyes were unchanged.

No signs of clinical toxicity were detected.

Mortality

All animals survived the observation period.

Body weight

Body weight development of the treated rabbits was inconspicuous.

Interpretation of results:
GHS criteria not met
Conclusions:
The test material has not to be regarded as an irritant for the eyes.
Executive summary:

Purpose

The purpose of this primary eye irritation assay was to provide information on possible health hazards in case of acute eye contact with a test material and serve as a a rational basis for risk assessment to the eye irritating potential of the test item in man.

Study design

The test material was tested for its toxicological properties. For the test of primary eye irritation, 0.1 g of the ground test material was applied into the conjunctival sac of rabbits.

The first examination of the eyes followed 1 hour after instillation. The examinations were performed daily for further 7 days.

Results

No signs of irritation were observed at the cornea and iris. The conjunctivae showed redness (score 1) on day 1 of the study. Later on no signs of irritation were observed. The untreated eyes were unchanged.

Conclusion

The test material has not to be regarded as an irritant for the eyes.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

Based on the results obtained from the structural analogue substance, the test item is not considered to be classified and labelled for skin and eye irritation/corrosion according to Regulatio (EC) No 1272/2008.