Registration Dossier

Administrative data

Description of key information

Based on these results AHU377does not have to be classified and has no obligatory labelling requirement for skin irritation.

Based on the results AHU377 should be classified as : irritating to eyes (Category 2A) and should be labelled as: irritating to eyes (R 36).

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:
8-25 January 2008
Reliability:
1 (reliable without restriction)
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
no
Amount / concentration applied:
0.5 gram
Duration of treatment / exposure:
4 hours
Observation period:
1, 24, 48 and 72 hours after exposure.
Number of animals:
3
Details on study design:
Three rabbits were exposed to 0.5 grams of AHU377, moistened with water by application onto clipped skin for four hours using a semi-occlusive dressing. Skin reactions were assessed 1, 24, 48 and 72 hours after exposure.The skin reactions were assessed approximately 1, 24, 48 and 72 hours after the removal of the dressing and test substance. The irritation scores and a description of all other (local) effects were recorded. Adjacent areas of untreated skin of each animal serve as controls.
The irritation was assessed according to the following numerical scoring system. At each observation, the highest scores given were recorded.

Mortality was checked twice daily. Toxicity was checked at least once daily. Body weight was checked day of treatment (prior to instillation) and at termination.
Irritation parameter:
overall irritation score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
overall irritation score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
overall irritation score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
Based on these results AHU377does 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 67/548/EEC).
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:
Nov 2007 - March 2008
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)
Qualifier:
according to
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Albino rabbit, New Zealand White (SPF-quality)
Location:
Specific Pathogenic Free area: animal room no. 7.
Room temperature:
20.0 to 21.4° C.
Room relative humidity:
29 – 60%.
Lighting cycle:
Fluorescent light for a 12-hour light/12-hour dark cycle.
Animal caging:
Individually housed in labelled cages with perforated floors (Scanbur, Denmark, dimensions 56x44x37.5 cm).
Acclimatization:
Acclimatization period was at least 5 days before start of treatment under laboratory conditions.
Food:
Free access to pelleted diet for rabbits (K-H from SSNIFF® Spezialdiäten GmbH, Soest, Germany). In addition, hay (TecniLab-BMI BV, Someren, The Netherlands) was provided three times a week.
Analysis of food:
Results of analysis for each batch of diet (nutrients and contaminants) and hay were assessed and did not reveal any findings that were considered to have affected the study integrity.
Water:
Free access to tap-water.
Analysis of water:
Certificates of analysis were examined and archived. Analysis of water did not reveal any findings that were considered to have affected study integrity.
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
Animals were treated by instillation of the test substance at a volume of approximately 0.1 ml (on average, 30.5 mg (range 30.1 – 30.9 mg) in the conjunctival sac of one of the eyes after gently pulling the lower lid away from the eyeball.
Duration of treatment / exposure:
Single samples of AHU377 at a volume of approximately 0.1 ml were instilled into one eye of each of three rabbits.
Observation period (in vivo):
Observations were made 1, 24, 48 and 72 hours and 7 and/or 14 Days after instillation.
Number of animals or in vitro replicates:
three rabbits
Details on study design:
Animals were treated by instillation of the test substance at a volume of approximately 0.1 ml (on average, 30.5 mg (range 30.1 – 30.9 mg) in the conjunctival sac of one of the eyes after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second to prevent loss of the test substance. The other eye remained untreated and served as the reference control.
Immediately after the 24-hour observation, a solution of 2% fluorescein (Merck, Darmstadt, Germany) in water (adjusted to pH 7.0) was instilled into both eyes of each animal to quantitatively determine corneal epithelial damage. This procedure was repeated to assess recovery. Any bright green stained area, indicating epithelial damage, was estimated as a percentage of the total corneal area.
Immediately after fluorescein examination on Day 2, the treated eye of animal 681 was rinsed with approx 50 mL tepid tap water, using a velocity of flow, which did not affect the eye, to remove residual test substance. For reference control the other eye was also rinsed.
After the final observation, the animals were sacrificed by intra-venous injection of pentobarbital Euthesate®
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 7 d
Remarks on result:
probability of weak irritation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 14d
Remarks on result:
probability of weak irritation
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 14d
Remarks on result:
probability of weak irritation
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 h
Remarks on result:
probability of weak irritation
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 h
Remarks on result:
probability of weak irritation
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 72
Remarks on result:
probability of weak irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2.3
Max. score:
4
Reversibility:
fully reversible within: 7d
Remarks on result:
probability of mild irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 14d
Remarks on result:
probability of weak irritation
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 14d
Remarks on result:
probability of weak irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
probability of moderate irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
probability of mild irritation
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2.7
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
probability of mild irritation
Irritant / corrosive response data:
There was no evidence of ocular corrosion.
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.
Other effects:
Remnants of the test substance were present in the eye on Days 1 and/or 2.
Interpretation of results:
Category 2A (irritating to eyes) based on GHS criteria
Conclusions:
Based on these results:
- according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2004), AHU377 should be classified as : irritating to eyes (Category 2A).
- according to the EC criteria for classification and labelling requirements for dangerous substances and preparations (Council Directive 67/548/EEC), AHU377 should be labelled as: irritating to eyes (R 36).
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

Based on these results AHU377does 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 67/548/EEC).

Based on these results:

- according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2004), AHU377 should be classified as : irritating to eyes (Category 2A).

- according to the EC criteria for classification and labelling requirements for dangerous substances and preparations (Council Directive 67/548/EEC), AHU377 should be labelled as: irritating to eyes (R 36).