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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:
10 Oct 2016 - 31 March 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
The study was conducted in accordance with international guidelines and in accordance with GLP. All relevant validity criteria were met.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2016
Report Date:
2018

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
Storage Conditions:Stable at ambient temperature (10-30°C). Store in darkness; may be used/formulated in light.

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Covance Research Product Inc, Denver, PA
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: 2.7 - 3.2 kg
- Fasting period before study: not specified
- Housing: individually housed in suspended wired-bottom cages, absorbent paper was changed at least three times per week.
- Diet (e.g. ad libitum): Fresh PMI Rabbit Chow (Diet No. 5321)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: minimum of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Not stated
- Humidity (%): Not stated
- Air changes (per hr): Not stated
- Photoperiod (hrs dark / hrs light): 12 : 12

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.1 ml equivalent (36 mg)
Duration of treatment / exposure:
one second
Observation period (in vivo):
1, 24, 48 and 72 hours post-instillation.
Duration of post- treatment incubation (in vitro):
n/a
Number of animals or in vitro replicates:
3
Details on study design:
- Main study: An analgesic, Buprenorphine, was administered at 0.1 mg/kg subcutaneously between the shoulder blades approximately one hour prior to instillation of the test article. A dose of 0.1 ml equivalent (36 mg) of TX16352 was placed into the conjunctival sac of one eye of each rabbit. The eyes were examined pre-test and scored by the Draize technique.
- Duration of observation period following administration: up to 72 hours
- Frequency of observations and weighing: Eyes were examined pre-test and scored by the Draize technique at 1, 24, 48 and 72 hours post-instillation.
- Necropsy of survivors performed: yes

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 0
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 0
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 0.67
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 0.33
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 0
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 0
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 0.33
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 0
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 0
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 0
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 0.67
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 0
Remarks on result:
no indication of irritation

Any other information on results incl. tables

Table 2. Result and Discussion

No. of Animals

Time Points

ENDPOINTS

Additional Observations

CORNEA

IRIS

CONJUNCTIVAE

3

1-hour

No opacity

No iritis

Redness, chemosis, discharge

Test article residue in conjunctival sac

24-hours

No opacity

No iritis

Redness, chemosis

None

48-hours

No opacity

No iritis

Redness

None

72-hours

No opacity

No iritis

No irritation

None

Systemic Observations:

Diminished fecal output and feed consumption were observed.

Because transient inappetence is frequently observed in rabbits and other animals following administration of Buprenorphine, and the animal appeared otherwise normal and maintained body weight throughout the study, there is no evidence that this finding is test article-related.

Body Weights:

Two animals’ body weights remained the same. One animal gained weight by study termination.

CONCLUSIONS

OECD 405:Ocular Irritant

EU:Not Classified

GHS:Not Classified

US EPA:Category III

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the condition of the study the test item did not produce any evidence of ocular irritation or corrosivity and therefore does not meet the criteria for classification according to the Globally Harmonized Classification System and to the Regulation (EC) No. 1272/2008, relating to the Classification, Labelling and Packaging of Substances and Mixture.
Executive summary:

OECD 405 - 2016: Three healthy New Zealand White rabbits (two males and one female), free from evidence of ocular irritation and corneal abnormalities, were placed on the study. An analgesic, Buprenorphine, was administered at 0.1 mg/kg subcutaneously between the shoulder blades approximately one hour prior to instillation of the test article. A dose of 0.1 ml equivalent (36 mg) of the test item was placed into the conjunctival sac of one eye of each rabbit. The eyes were examined pre-test and scored by the Draize technique at 1, 24, 48 and 72 hours post-instillation. The control eyes were observed at the same time periods. Sodium fluorescein dye procedures were used at the 24-hour observation interval. Animals were evaluated for mortality, toxicity and pharmacological effects twice daily. Body weights were recorded pre-test and at termination.

Diminished fecal output and feed consumption were observed. Because transient inappetence is frequently observed in rabbits and other animals following administration of Buprenorphine, and the animal appeared otherwise normal and maintained body weight throughout the study, there is no evidence that this finding is test article-related. Two animals’ body weights remained the same. One animal gained weight by study termination. No evidence of corrosively or irritation was observed.

Under the condition of the study the test item did not produce any evidence of ocular irritation or corrosivity and therefore  does not meet the criteria for classification according to the Globally Harmonized Classification System and to the Regulation (EC) No. 1272/2008, relating to the Classification, Labelling and Packaging of Substances and Mixture.