Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin corrosion: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
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:
weight of evidence
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
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 eye irritation study in the 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 and in vivo tests) to determine the need for in vivo eye testing. The in vitro Bovine Corneal Opacity and Permeability (BCOP) study (NOTOX project 498487) showed that the test substance was non-irritating. This negative BCOP result should be confirmed in an in vivo eye irritation study. Based on the available information, it was concluded that there is need to perform this in vivo eye irritation study in rabbit in order to establish the possible eye irritating properties of the test substance.
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Qualifier:
according to guideline
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nohsan, Notification No. 8147, April 2011; including the most recent partial revisions.
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
- Albino rabbit
- Source: Charles River France, L'Arbresle Cedex, France
- Male animals
- Animals used within the study were at least 6 weeks old and body weights were at least 1.0 kg
- 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 ± 3.0oC (actual range: 18.8 – 21.1oC), a relative humidity of 40-70% (actual range: 26 - 69%) and 12 hours artificial fluorescent light and 12 hours darkness per day.
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
18.6 mg (range 18.5 - 18.7 mg) of the test substance (a volume of approximately 0.1 mL)
Observation period (in vivo):
Mortality/Viability: twice daily.
Toxicity: at least once daily.
Body Weight: day of treatment (prior to instillation) and after the final observation.
Necropsy: no necropsy was performed according to protocol.
Irritation: the eyes of each animal were examined approximately 1, 24, 48 and 72 hours and 7 and/or 14 days after instillation of the test substance. The irritation scores and a description of all other (local) effects were recorded.
Number of animals or in vitro replicates:
3
Details on study design:
The other eye remained untreated and served as the reference control.
Diet: Pelleted diet for rabbits (Global Diet 2030 from Harlan Teklad®, Mucedola, Milanese, Italy) approximately 100 grams per day. Hay (TecniLab-BMI BV, Someren, The Netherlands) and wooden sticks (Swedish aspen wood, Bioservices, Uden, The Netherlands) were available during the study period
Water Free access to tap water.
Irritation parameter:
cornea opacity score
Basis:
mean
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 - <= 1
Max. score:
1
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
iris score
Basis:
animal: 2 and 3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Remarks:
redness, chemosis and discharge
Basis:
animal #1
Time point:
24/48/72 h
Score:
< 2
Max. score:
2
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: Reversibility based on worst parameter, being redness.
Irritation parameter:
conjunctivae score
Remarks:
redness, chemosis and discharge
Basis:
animal: 2 and 3
Time point:
24/48/72 h
Score:
< 2
Max. score:
2
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Reversibility based on worst parameter, being redness.
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
>= 1 - <= 2
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal: 2 and 3
Time point:
24/48/72 h
Score:
>= 0 - <= 1
Max. score:
1
Reversibility:
fully reversible within: 48 hours
Irritant / corrosive response data:
Corrosion: there was no evidence of ocular corrosion.
Coloration / Remnants: remnants of the test substance were present in the eye on Day 1.
Other effects:
Toxicity / 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, CH03220 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 (2011),
- Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and
mixtures.
Executive summary:

Acute eye irritation/corrosion study with CH03220 in the rabbit.

The study was carried out based on the guidelines described in: OECD No.405 (2002) "Acute Eye Irritation / Corrosion"
EC, No 440/2008, B5: "Acute Toxicity: Eye Irritation/Corrosion" EPA, OPPTS 870.2400 (1998): "Acute Eye Irritation"

JMAFF guidelines (2000); including the most recent partial revisions.

Single samples of approximately 19 mg of CH03220 (a volume of approximately 0.1 mL) were instilled into one eye of each of three rabbits. Observations were made 1, 24, 48 and 72 hours and 7 and/or 14 days after instillation.

Instillation of the test substance resulted in effects on the iris (one animal) and conjunctivae (three animals). Iridial irritation grade 1 was observed in one animal only and and resolved within 72 hours. The irritation of the conjunctivae consisted of redness, chemosis and discharge and completely resolved within 7 days in two animals and within 14 days in the other animal.

Remnants of the test substance were present in the eye on Day 1.

Based on these results, CH03220 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 (2011),
- Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and

mixtures.

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