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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:
2018-05-02 to 2018-05-10
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2018
Report Date:
2018

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
2017-10-09
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
signed 2017-05-08

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Details on test material:
- State of aggregation: white powder
Specific details on test material used for the study:
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at +10 °C to +25 °C, in the closed original container in a dry, cool and well-ventilated place.

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Manfred Bauer Kaninchen, Lohe 7/1, 74632 Neuenstein, Germany
- Age at study initiation: approx. 5.5 months
- Weight at study initiation: 3.7 kg
- Housing: kept singly in cages with dimensions of 823 mm x 660 mm x 500 mm (Scanbur, Denmark)
- Diet (ad libitum): commercial diet, ssniff® K-H V2333 (ssniff Spezialdiäten GmbH, Soest, Germany)
- Water (ad libitum): tap water
- Acclimation period: at least 20 adaptation days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 °C ± 3 °C (maximum range)
- Relative humidity: 30 % - 70 % (maximum range)
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg of the test item into the conjunctival sac of the right eye (left eye served as control)
Duration of treatment / exposure:
not applicable
Observation period (in vivo):
prior to administration and 1, 24, 48, and 72 hours after administration
Duration of post- treatment incubation (in vitro):
not applicable
Number of animals or in vitro replicates:
one male rabbit
Details on study design:
INITIAL AND CONFIRMATORY TEST
The test was performed initially using one animal.
Due to absence of a light reflex (iridial response grade 2) the study was terminated 72 hours after the test item administration. No further animal was employed.

USE OF TOPICAL ANAESTHETICS AND SYSTEMIC ANALGESICS:
- topical anaesthetics and systemic analgesics were used according to the procedure recommended by the OECD TG 405.
- approx. sixty minutes prior to test item administration, 0.01 mg Buprenovet®/kg bw were administered by subcutaneous injection to all animals to provide a therapeutic level of systemic analgesia to avoid or minimize pain and distress.
- approx. five minutes prior to the test item administration, two drops of Novesine, a topical anaesthetic, were applied to both eyes of all animals.
- approx. 8 and 24 hours after test administration 0.01 Buprenovet® and Acticam® 0.5 mg/kg, were administered subcutaneously to provide a continued therapeutic level of systemic analgesia.
- thereafter, Buprenovet was administered once every 12 hours, Acticam was administered once every 24 hours until 72 hours after administration of the test item.

REMOVAL OF TEST SUBSTANCE
- Washing: eyes were not rinsed

SCORING SYSTEM: Draize scale
Any further lesions are listed.

TOOL USED TO ASSESS SCORE: slit lamp / fluorescein (starting 24 hours after administration)

OBSERVATIONS
- body weight of the animal was measured at the beginning and at the end of the study.
- behaviour and food consumption were monitored.
- any adverse systemic effects were recorded.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
2
Remarks on result:
other: Due to absence of a light reflex (iridial response grade 2) the study was terminated 72 hours after the test item administration. An absence of a light reflex of the iris are generally not reversible.
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
2.67
Max. score:
3
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
2.67
Max. score:
4
Irritant / corrosive response data:
- mild or moderate corneal opacity (grade 1 or 2) was observed 24 to 72 hours after administration.
- the fluorescein test revealed corneal staining (whole surface; grade 4) 24 to 72 hours after instillation.
- iridial response was not evaluable (grade 2; absence of a light reflex) 24 to 72 hours after administration.
- mild to severe conjunctival redness (grade 1 to 3) was observed 60 minutes until 72 hours after administration.
- moderate chemosis (grade 2 or 3) was observed 24 hours until 72 hours after administration.
- lesions such as an absence of a light reflex of the iris are generally not reversible; hence, the study was stopped 72 hours after administration and the animal was humanely killed.
Other effects:
not specified

Applicant's summary and conclusion

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
The substance causes serious eye damage.
According to Regulation (EC) No 1272/2008 and subsequent adaptations, the substance does require classification as serious eye damaging (Category 1; H318).