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Description of key information

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:
experimental study
Adequacy of study:
key study
Study period:
2006
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:
2002
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
2004
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Version / remarks:
1998
Qualifier:
according to guideline
Guideline:
other: JMAFF Guidelines: Acute Dermal Irritation
Version / remarks:
2000
GLP compliance:
yes
Specific details on test material used for the study:
Since the test substance did not mix with water, the powdery test substance was moistened with watery ethanol (50% w/v) (water, Milli-U, Millipore Corporation, Bedford, USA, ethanol, Merck, Darmstadt, Germany), immediately before application, to ensure close contact with the animal's skin.
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
Animals used within the study were at least 6 weeks old and body weights were at least 1.0 kg.
Identification: Earmark.
A health inspection was performed prior to the commencement of treatment, to ensure that the animals were in a good state of health. Special attention was paid to the skin to be treated, which was intact and free from abnormalities,

Conditions
Animals were housed in a controlled environment, in which optimal conditions were considered to be approximately 15 air changes per hour, a temperature of 21.0 +- 3.0°C (actual range: 20.8 - 22.4°C), a relative humidity of 30-70% (actual range: 46 - 59%) and 12 hours artificial fluorescent light and 12 hours darkness per day.
Accommodation
Individually in labelled cages with perforated floors (Scanbur, Denmark, dimensions 56x44x37.5cm). Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.
Diet
Standard laboratory rabbit diet (Charles River Breeding and Maintenance Diet for Rabbits, Altromin, Lage, Germany) approx. 100 g. per day, Hay (TecniLab-BMI BV, Someren, The Netherlands) was provided at least three times a week.
Water
Free access to tap water.
Results of analysis for each batch of diet (nutrients) and results of quarterly analysis of diet (contaminants) and water were assessed and did not reveal any findings that were considered to have affected the study integrity. All certificates and results of analysis are retained in the NOTOX archives.
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Remarks:
Approximately 24 hours before treatment, the dorsal fur was clipped with electric clippers, exposing an area of approximately 150 cm2 (10x15 cm). To facilitate scoring, treated skin areas were re-clipped at least 3 hours before the observations.
Vehicle:
other: watery ethanol (50% v/v)
Remarks:
ince the test substance did not mix with water, the powdery test substance was moistened with watery ethanol (50% w/v), immediately before application, to ensure close contact with the animal's skin.
Amount / concentration applied:
Each animal was treated by dermal application of 0.5 grams of the test substance. The test substance was moistened with 0.7 ml of the vehicle and applied to the skin of one flank, using a metalline patch" of 2x3 cm. The patch was mounted on Micropore tape", which was wrapped around the abdomen and secured with Coban elastic bandage".
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
3 males
Details on study design:
In the interest of animal welfare and to minimize any testing likely to produce severe responses in animals, a weight of evidence analysis was performed, prior to the start of this in-vivo skin irritation study in rabbit. As recommended in the test guidelines, all available information was evaluated (e.g. existing human and animal data, literature, substance data supplied by the sponsor, analysis of structure activity relationships (SAR), physicochemical properties and reactivity (pH, buffering capacity) and in-vitro, ex-vivo tests and in-vivo tests) to determine the need for in-vivo skin testing. It was concluded that there is need to perform this in-vivo skin irritation study in rabbit in order to establish the possible skin irritating properties of the test substance.

The study was performed in a stepwise manner and was started by treatment of a single rabbit (sentinel). The two other animals were treated in a similar manner three weeks later, after considering the degree of skin irritation observed in the first animal.

Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: not relevant
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: not relevant
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
none
Other effects:
none
Interpretation of results:
GHS criteria not met
Conclusions:
Based on these results v123109 does not have to be classified and has no obligatory labelling requirement for skin irritation according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (New York and Geneva, 2003) and EC criteria for classification and labelling requirements for dangerous substances and preparations (Council Directive 671548/EEC).
Endpoint:
skin corrosion: 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 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
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2006
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:
2002
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
2004
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Version / remarks:
1998
Qualifier:
according to guideline
Guideline:
other: JMAFF guidelines: 'Acute Eye Irritation"
Version / remarks:
2000, inclusing the most recent partial revisions
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Remarks:
Source: Charles River Deutschland, Kissler, Germany
Details on test animals or tissues and environmental conditions:
Age and body weight: Animals used within the study were at least 6 weeks old and body weights were at least 1.0 kg.
Identification: Earmark.

Conditions
Animals were housed in a controlled environment, in which optimal conditions were considered to be approximately 15 air changes per hour, a temperature of 21.0 +- 3.0°C (actual range: 21.0 —22.4°C), a relative humidity of 30-70% (actual range: 47% - 59%) and 12 hours artificial fluorescent light and 12 hours darkness per day.

Accommodation
Individually in labelled cages with perforated floors (Scanbur, Denmark, dimensions 56x44x37.5 cm).
Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.

Diet
Standard laboratory rabbit diet (Charles River Breeding and Maintenance Diet for Rabbits, Altromin, Lage, Germany) approx. 100 g. per day. In addition, hay (TecniLab-BMI BV, Someren, The Netherlands) was provided at least three times weekly.

Water
Free access to tap-water.

Results of analysis for each batch of diet (nutrients) and results of quarterly analysis of diet (contaminants) and water were assessed and did not reveal any findings that were considered to have affected study integrity. All certificates and results of analysis are retained in the NOTOX archives.
Vehicle:
other: The powdery test substance was instilled as delivered by the sponsor.
Amount / concentration applied:
instillation of on average 35.1 (range 35.0-35.3 mg) of test substance (volume of approximately 0.1 ml ) i
Observation period (in vivo):
1, 24, 48 and 72 hours after instillation
Number of animals or in vitro replicates:
3
Details on study design:
The study was performed in a stepwise manner and was started by treatment of a single rabbit (sentinel). The two other animals were treated in a similar manner three weeks later, after considering the degree of eye irritation observed in the first animal.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: not relevant
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
<= 1
Max. score:
1
Reversibility:
fully reversible within:
Remarks:
24 hours
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
<= 1
Max. score:
1
Reversibility:
fully reversible within:
Remarks:
24 hours
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
mean
Time point:
24/48/72 h
Score:
<= 1
Max. score:
1
Reversibility:
fully reversible within:
Remarks:
48 hours
Irritation parameter:
conjunctivae score
Remarks:
Discharge
Time point:
24/48/72 h
Score:
<= 1
Max. score:
1
Reversibility:
fully reversible within:
Remarks:
24 hours
Irritant / corrosive response data:
Instillation of approximately 35 mg of v123109 (a volume of approximately 0.1 ml) into one eye of each of three rabbits resulted in effects on the iris and conjunctivae.
lrldial irritation grade 1 was observed in two animals and had resolved within 24 hours.
The irritation of the conjunctivae consisted of redness, chemosis and discharge and had completely resolved within 48 hours.
No corneal opacity was observed, and treatment of the eyes with 2% fluorescein, 24 hours after test substance instillation revealed no corneal epithelial damage.

There was no evidence of ocular corrosion.
Other effects:
Colouration I Remnants
Remnants of the test substance were present in the eye of one animal on day 1.
Toxicity I Mortality
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred
Interpretation of results:
GHS criteria not met
Conclusions:
Based on these results v123109 does not have to be classified and has no obligatory labelling requirement for eye irritation according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (New York and Geneva, 2003) and EC criteria for classification and labelling requirements for dangerous substances and preparations (Council Directive 67/548/EEC).
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

Justification for classification or non-classification