Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
no study available

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:
Start of Treatment: 04 May 2011; End of Experiment: 18 May 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Performed according to GLP, OECD Guidelines followed and no deviations reported
Justification for data waiving:
other:
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
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)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: S&K - LAP Kft.
2173 Kartal, Császár út 135, Hungary
- Age at study initiation: ~ 11 weeks old (young adult)
- Weight at study initiation:
- beginning of the life phase: 2607 - 2629 g
- end of the life phase: 3260 - 3550 g
- Housing: Rabbits were individually housed in AAALAC approved metal wire rabbit cages. Cages were of an open wire structure and cages were placed together to allow some social interaction with rabbit(s) in adjoining cages
- Diet (e.g. ad libitum): Animal received PURINA Base - Lap gr. diet for rabbits produced by AGRIBRANDS Europe Hungary PLC, H-5300 Karcag, Madarasi road, Hungary, ad libitum. Contents of PURINA Base-Lap gr. diet for rabbits see in Appendix 4 of attached report.
- Water (e.g. ad libitum): The animals received municipal tap water, as for human consumption, ad libitum, from an automatic system. The quality control analysis is performed once every three months and microbiological assessment is performed monthly, by Veszprém County Institute of State Public Health and Medical Officer Service (ANTSZ, H-8201 Veszprém, Jozsef A.u.36., Hungary). The quality control results are retained in the archives of LAB Research Ltd.
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 30 – 70 (relative humidity)
- Air changes (per hr): 15-20 air exchanges/hour
- Photoperiod (hrs dark / hrs light): Light 12 hours daily, from 6.00 a.m. to 6.00 p.m

The environmental parameters were recorded twice daily during the study.
Vehicle:
unchanged (no vehicle)
Controls:
other: contralateral eye
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): A single dose of 0.1 g of the solid test item KS-235 was administered to each animal
Duration of treatment / exposure:
1 hour
Observation period (in vivo):
The eyes were examined at 1, 24, 48, 72 hours, 1 week and 2 weeks after treatment. The duration of the observation period was sufficient to identify reversibility or irreversibility of changes. Any clinical signs of toxicity or signs of ill- health during the study were recorded.

At the end of the observation period, each animal was sacrificed by intramuscular injections of CP-Ketamin 10% and CP-Xylazin 2% followed by iv. Euthasol® 40% anaesthesia (see details in attached report). Death was verified by checking pupil and cornea reflex, absence of respiration and pulse.

Individual body weight was recorded at the beginning and end of the experiment (see Table 3 of attached report).
Number of animals or in vitro replicates:
3 males
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): The treated eye of the rabbits was rinsed with physiological saline solution.
- Time after start of exposure: at 1 hour after application

SCORING SYSTEM: The eye irritation scores were evaluated according to the scoring system by Draize (1977) and OECD 405 (24 April 2002) shown in Appendix 1 of attached report.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0.9
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Irritant / corrosive response data:
The eyes were examined at 1, 24, 48, 72 hours and 1 and 2 weeks after the application.
- Initial Pain Reaction (IPR) (score 2 or 3) was observed in two animals.
- One hour after the application, conjunctival redness (score 1 or 2) was observed in all animals and discharge (score 2) was seen in all rabbits.
- At 24 hours after treatment, conjunctival redness (score 1 or 2) was observed in all animals and discharge (score 3) was seen in two rabbits.
- At 48 hours after treatment, conjunctival redness (score 1) was observed in two animals and discharge (score 1 or 3) was seen in two rabbits.
- At 72 hours after treatment, conjunctival redness (score 1) was observed in one animal and discharge (score 1 or 3) was seen in two rabbits.
- At one week after treatment, conjunctival redness (score 1) was observed in one animal and discharge (score 1) was seen in one rabbit.
- At two weeks after treatment, there were no clinical signs observed.
- The animal’s individual mean scores (considering readings at 24, 48 and 72 hours after the treatment) were as follows:
 
Chemosis: 0.00, 0.00, 0.00
Discharge: 0.00, 1.67, 3.00
Redness: 0.33, 1.00, 1.33
Cornea opacity: 0.00, 0.00, 0.00
Iris: 0.00, 0.00, 0.00

MORTALITY: There was no mortality observed during the study.

 

BODY WEIGHTS: The body weight and body weight change were considered to be normal with no indication of treatment related effect.

 

CLINICAL OBSERVATION:

- General daily examination: There were no clinical signs observed that could be related to treatment.

- As there were no clinical signs observed, the study was terminated after the two weeks observation.

- During the study, the control eye of all animals was symptom-free. The general state and behaviour of animals were normal throughout the study period.

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test item KS-235 (Batch No.: 91014), applied to rabbits’ eye mucosa, caused significant conjunctival irritant effects which were reduced at 1 week after application. The effects were fully reversible within 2 weeks.

According to Regulation (EC) No 1272/2008, KS-235 does not require classification as an eye irritant.
Executive summary:

An acute eye irritation study of the test item KS-235 was performed in New Zealand White rabbits. The irritation effects of the test item were evaluated according to the Draize method (OECD No.: 405, 2002).

                  

The test item was placed into the conjunctival sac of the left eye of each animal. The untreated right eye served as control. An amount of 0.1 g of the test item was administered as a single dose. The treated eye of the rabbits was rinsed at 1 hour after application with physiological saline solution.

 

The eyes were examined at 1, 24, 48, 72 hours and 1 and 2 weeks after the application. Initial Pain Reaction (IPR) (score 2 or 3) was observed in two animals.

 

One hour after the application, conjunctival redness (score 1 or 2) was observed in all animals and discharge (score 2) was seen in all rabbits.

 

At 24 hours after treatment, conjunctival redness (score 1 or 2) was observed in all animals and discharge (score 3) was seen in two rabbits.

 

At 48 hours after treatment, conjunctival redness (score 1) was observed in two animals and discharge (score 1 or 3) was seen in two rabbits.

 

At 72 hours after treatment, conjunctival redness (score 1) was observed in one animal and discharge (score 1 or 3) was seen in two rabbits.

 

At one week after treatment, conjunctival redness (score 1) was observed in one animal and discharge (score 1) was seen in one rabbit.

 

At two weeks after treatment, there were no clinical signs observed.

 

As there were no clinical signs observed, the study was terminated after the two weeks observation.

 

During the study, the control eye of all animals was symptom free.

The general state and behaviour of animals were normal throughout the study period.

 

The body weight changes were considered to be normal during the study period.

 

The animal’s individual mean scores (considering readings at 24, 48 and 72 hours after the treatment) were as follows:

 

chemosis: 0.00, 0.00, 0.00

discharge: 0.00, 1.67, 3.00

redness: 0.33, 1.00, 1.33

cornea opacity: 0.00, 0.00, 0.00

iris: 0.00, 0.00, 0.00

 

The test item KS-235 (Batch No.: 91014), applied to rabbits’ eye mucosa, caused significant conjunctival irritant effects which were reduced at 1 week after application. The effects were fully reversible within 2 weeks.

 

According to Regulation (EC) No 1272/2008, KS-235 does not require classification as an eye irritant.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

Justification for selection of eye irritation endpoint:
According to Regulation (EC) No 1272/2008, KS-235 does not require classification as an eye irritant.

The test item KS-235 (Batch No.: 91014), applied to rabbits’ eye mucosa, caused significant conjunctival irritant effects which were reduced at 1 week after application. The effects were fully reversible within 2 weeks.

Justification for classification or non-classification