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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:
17 November 2017 - 06 December 2017
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 guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
2012
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Version / remarks:
August 1998
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
May 2008
Deviations:
no
Qualifier:
according to
Guideline:
other: Appendix to Director General Notification, No. 12-Nousan-8147. Agricultural Production Bureau, Ministry of Agriculture, Forestry and Fisheries of Japan (JMAFF)
Version / remarks:
November 2000, including the most recent revisions.
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
- Physical appearance: pale yellow liquid
- Storage conditions: at room temperature

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Charles River France, L’Arbresle, France
- Age at study initiation: approximately 13-16 weeks old
- Weight at study initiation: 3168 to 3616 g
- Housing: individually, in cages with perforated floors
- Diet: Pelleted diet for rabbits (Global Diet 2030 Teklad®, Mucedola, Milanese, Italy), once daily throughout the study period. Hay was fed in addition.
- Water: municipal tap-water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS (set to maintain)
- Temperature (°C): 18-24 (actual: 20)
- Humidity (%): 40-70 (actual: 65-67)
- Air changes (per hr): >= 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 20 November 2017 to 06 December 2017

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
- Test item: 0.1 mL
- Buprenorphine 0.01 mg/kg bw (1 hour prior and 1 hour after application of the test item and at the end of the first day) was administered for pain management as well as two drops of the topical anaesthetic 0.5% proparacaine hydrochloric ophthalmic solution (five minutes prior to application of the test item)
Duration of treatment / exposure:
Single treatment followed by observations at 1, 24, 48 and 72 hours and/or 14 days after instillation
Observation period (in vivo):
14 days
Number of animals or in vitro replicates:
3 males in a stepwise manner: starting with one animal and followed by treatment of two additional animals two weeks later.
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM: according to Draize

TOOL USED TO ASSESS SCORE: 2% fluorescein in water (pH adjusted to 7.0)

OBSERVATIONS:
- Mortality/moribundity checks: throughout the study, animals were observed for general health/mortality and moribundity twice daily, in the morning and at the end of the working day.
- Clinical observations: postdose observations were performed once daily throughout the study; the observation period was 72 hours for two animals and 7 days for one animal.
- Body weights: animals were weighed individually on day 1 (predose) and on the day of the final observation.
- Irritation: the eyes of each animal were examined approximately 1, 24, 48 and 72 hours and, for one animal, 7 days after instillation of the test item. The irritation scores and a description of all other (local) effects were recorded.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no applicable
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.7
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.7
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritant / corrosive response data:
Instillation of the test item into one eye of each of three rabbits resulted in irritation of the conjunctivae, which consisted of redness, chemosis and discharge. The irritation had completely resolved within 72 hours in two animals and within 7 days in the other animal.

No iridial irritation or corneal opacity was observed, and treatment of the eyes with 2% fluorescein 24 hours after test item instillation revealed no corneal epithelial damage.
Other effects:
- Coloration/remnants: No staining of (peri) ocular tissues by the test item was observed and no test item remnants were seen.
- Toxicity/mortality: No signs 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
Remarks:
Not classified according to Regulation (EC) No. 1272/2008
Conclusions:
Based on the results of an in vivo eye irritation study, performed according to OECD guideline 405 and GLP principles, X-19657 is not irritant to the eyes and is not classified for eye irritation according to GHS and Regulation (EC) No. 1272/2008.