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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:
March 31, 2014 - April 21, 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study has been performed according to OECD and/or EC guidelines and according to GLP principles.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report Date:
2014

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:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
(2008)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Version / remarks:
(1998)
Deviations:
no
Qualifier:
according to
Guideline:
other: Food and Agricultural Materials Inspection Centre (FAMIC), 12 Nohsan, Notification No. 8147, April 2011; including the most recent partial revisions.
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): SrHPO4
- Description: White powder

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
- Source: Charles River France, L'Arbresle Cedex, France
- Age at study initiation: 12 - 13 weeks old
- Weight at study initiation: 2.9 - 3.1 kg
- Housing: Individually housed in cages with perforated floors.
- Diet: Free access to pelleted diet for rabbits (Global Diet 2030 Harlan Teklad, Italy). Hay and wooden sticks were available during the study period.
- Water: Free access to tap water.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 – 24
- Humidity (%): 40 - 70
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: One eye of each animal remained untreated and served as the reference control.
Amount / concentration applied:
TEST MATERIAL- Amount(s) applied (volume or weight with unit):
average 98.6 mg (range: 98.4 mg – 98.8 mg) (a volume of approximately 0.1 mL)
Duration of treatment / exposure:
Single instillation on Day 1.
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
3 males
Details on study design:
STUDY DESIGN
The study was performed in a stepwise manner and was started by treatment of a single rabbit (sentinel). The two other animals were treated in a similar manner two weeks later, after considering the degree of eye irritation observed in the first animal.

PREEMPTIVE PAIN MANAGEMENT
One hour prior to instillation of the test substance, buprenorphine (Buprenodale®, Dechra Ltd., Stokeon-Trent, United Kingdom) 0.01 mg/kg was administered by subcutaneous injection in order to provide a therapeutic level of systemic analgesia. Five minutes prior to instillation of the test substance, two drops of the topical anesthetic lidocaïne eyedrops (AST Farma BV, Oudewater, The Netherlands) were applied to both eyes.

TREATMENT
After instillation of the test substance, as such, in the conjunctival sac of one of the eyes, the lids were gently held together for about one second to prevent loss of the test substance. Immediately after the 1 hour observation, the treated eye was rinsed with approximately 50 mL tepid tap water, using a velocity of flow which did not affect the eye, to remove any visible residual test substance. For reference control the other eye was also rinsed. Immediately after the 24-hour observation, a solution of 2% fluorescein in water (adjusted to pH 7.0) was instilled into both eyes of each animal to quantitatively determine corneal epithelial damage. Immediately after fluorescein examination on Day 2, in order to provide a continued level of systemic analgesia, buprenorphine 0.01 mg/kg and meloxicam 0.5 mg/kg were administered by subcutaneous injection.

REMOVAL OF TEST SUBSTANCE
-Washing (if done): Yes, immediately after the 1 hour observation, with approximately 50 mL tepid tap water

OBSERVATIONS
- 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
- Irritation:
The eyes of each animal were examined approximately 1, 24, 48 and 72 hours and 7 days after instillation of the test substance.
The irritation scores and a description of all other (local) effects were recorded. The irritation was assessed according to OECD 405.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Remarks:
(opacity)
Basis:
animal: #1, #2 and #3
Time point:
other: Mean value of score at 24, 48 and 72 h after installation
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
animal: #1, #2 and #3
Time point:
other: Mean value of score at 24, 48 and 72 h after installation
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal: #1, #2 and #3
Time point:
other: Mean value of score at 24, 48 and 72 h after installation
Score:
1.3
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal: #1 and #3
Time point:
other: Mean value of score at 24, 48 and 72 h after installation
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: Mean value of score at 24, 48 and 72 h after installation
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritant / corrosive response data:
Instillation resulted in effects on the iris and conjunctivae. Iridial irritation grade 1 was observed in all animals and resolved within 24 hours. The irritation of the conjunctivae consisted of redness, chemosis and discharge and completely resolved within 7 days in all animals. No corneal opacity was observed, and treatment of the eyes with 2% fluorescein 24 hours after instillation revealed no corneal epithelial damage. There was no evidence of ocular corrosion.
Other effects:
- Remnants of the test substance were present in the eye on Day 1 in all animals
- No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In an eye irritation study with rabbits, performed according to OECD/EC test guidelines, limited irritation was observed.
Executive summary:

In an eye irritation study in rabbits, conducted in accordance with OECD 405 (2012) and according to GLP principles, single samples of approx. 98 mg of the substance (a volume of approximately 0.1 mL) were instilled into one eye of each of three male rabbits. Observations were made 1, 24, 48 and 72 hours and 7 days after instillation. Instillation resulted in effects on the iris and conjunctivae. Iridial irritation grade 1 was observed in all animals and resolved within 24 hours. The irritation of the conjunctivae consisted of redness, chemosis and discharge and was completely resolved within 7 days in all animals. Based on the results of this study, the substance does not need to be classified for eye irritation/corrosion in accordance with the CLP Regulation.