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Toxicological information

Eye irritation

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Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2006
Report date:
2006

Materials and methods

Test guidelineopen allclose all
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

Test material

Constituent 1
Chemical structure
Reference substance name:
N-[4-[(4,6-dimethylpyrimidin-2-yl)sulfamoyl]phenyl]-2-methyl-prop-2-enamide
EC Number:
611-915-5
Cas Number:
59941-98-9
Molecular formula:
C16 H18 N4 O3 S
IUPAC Name:
N-[4-[(4,6-dimethylpyrimidin-2-yl)sulfamoyl]phenyl]-2-methyl-prop-2-enamide
Test material form:
solid: particulate/powder
Remarks:
determined at NOTOX
Details on test material:
pH 6.4 (determined at NOTOX)

Test animals / tissue source

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.

Test system

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.

Results and discussion

In vivo

Resultsopen allclose all
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

Applicant's summary and conclusion

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).