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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:
11 February 2013 - 21 February 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Chemical structure
Reference substance name:
Lanthanum trihydroxide
EC Number:
238-510-2
EC Name:
Lanthanum trihydroxide
Cas Number:
14507-19-8
Molecular formula:
H3LaO3
IUPAC Name:
lanthanum(3+) trihydroxide
Test material form:
other: solid (unspecified)
Details on test material:
- Storage conditions: room temperature in the dark

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Strain: New Zealand White
- Age at study initiation: 12 - 20 weeks
- Weight at study initiation: 2.42 or 2.44 kg
- Housing: The animals were individually housed in suspended cages.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): Free access to mains drinking water.
- Acclimation period: At least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23 °C
- Humidity (%): 30 to 70 %
- Air changes (per hr): At least 15 per hour.
- Photoperiod (hrs dark / hrs light): The lighting was controlled by a time switch to give twelve hours continuous light (0600 to 1800) and twelve hours darkness.

IN-LIFE DATES: From: 11 February 2013 To: 21 February 2013

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: The left eye of each animal remained untreated and was used for control purposes.
Amount / concentration applied:
100 mg
Duration of treatment / exposure:
The upper and lower eyelids were held together for about one second immediately after treatment, to prevent loss of the test material, and then released.
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
2. Initially, one animal was treated; after consideration of the ocular response, a second animal was treated.
Details on study design:
Immediately after administration of the test material, an assessment of the initial pain reaction was made.

SCORING SYSTEM: Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment, according to the Draize numerical evaluation.
Individual bodyweights were recorded on Day 0 (the day of dosing) and at the end of the observation period. Any clinical signs of toxicity, if present, were also recorded.

Draize Scale for Scoring Ocular Irritation

1. CONJUNCTIVAE

Redness (refers to palpebral and bulbar conjunctivae excluding cornea and iris):
Vessels normal 0
Vessels definitely injected above normal 1
More diffuse, deeper crimson red, individual vessels not easily discernible 2
Diffuse beefy red 3

Chemosis:
No swelling 0
Any swelling above normal (includes nictitating membrane) 1
Obvious swelling with partial eversion of lids 2
Swelling with lids about half closed 3
Swelling with lids half closed to completely closed 4

Discharge:
No discharge 0
Any amount different from normal (does not include small amounts observed in inner
canthus of normal animals) 1
Discharge with moistening of the lids and hairs just adjacent to lids 2
Discharge with moistening of the lids and hairs a considerable area around the eye 3

2. IRIS

Values:
Normal 0
Folds above normal, congestion, swelling, circumcorneal injection (any or all
of these or combination of any thereof) iris still reacting to light
(sluggish reaction is positive) 1
No reaction to light, haemorrhage, gross destruction (any or all of these) 2

3. CORNEA

Degree of Opacity (most dense area used):
No opacity 0
Scattered or diffuse areas, details of iris clearly visible 1
Easily discernible translucent areas, details of iris slightly obscured 2
Opalescent areas, no details of iris visible, size of pupil barely discernible 3
Opaque, iris not discernible through the opacity 4

Area of Cornea Involved:
One quarter (or less) but not zero 1
Greater than one quarter but less than half 2
Greater than half but less than three quarters 3
Greater than three quarters, up to whole area 4


TOOL USED TO ASSESS SCORE: Any additional ocular effects were also noted. Examination of the eye was facilitated by the use of the light source from a standard ophthalmoscope.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0.5
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
other: discharge score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
other: not applicable
Irritant / corrosive response data:
Individual scores are given in Table 2.
No corneal effects were noted during the study. Iridial inflammation (Grade 1) was noted in both treated eyes one hour after treatment.
Moderate conjunctival irritation (Grade 2 redness, Grade 2 chemosis and Grade 2 discharge) was noted in both treated eyes one hour after treatment. Minimal conjunctival irritation (Grade 1 redness and Grade 1 chemosis) was noted in both treated eyes at the 24 hour observation. Minimal conjunctival irritation (Grade 1 redness in both treated eyes and Grade 1 chemosis in one treated eye) was noted in both treated eyes at the 48 hour observation.
Both treated eyes appeared normal at the 72 hour observation and the study was therefore terminated.
Other effects:
BODYWEIGHT
Both animals showed expected gain in body weight during the study.

Any other information on results incl. tables

Table 2: Individual Scores for Ocular Irritation

Rabbit Number and Sex

72956 Male

72987 Male

IPR = 2

IPR = 2

Time After Treatment

1 hour

24 hours

48 hours

72 hours

1 hour

24 hours

48 hours

72 hours

Cornea

Degree

Area

 

0

0

 

0

0

 

0

0

 

0

0

 

0

0

 

0

0

 

0

0

 

0

0

Iris

1

0

0

0

1

0

0

0

Redness

2

1

1

0

2

1

1

0

Chemosis

2

1

0

0

2

1

1

0

Discharge

2

0

0

0

2

0

0

0

IPR = Initial pain reaction; a score of 2 indicates slight initial pain. The rabbit blinks and tries to open the eye but reflex closes it.

Applicant's summary and conclusion

Interpretation of results:
other: not classified according to EU criteria
Conclusions:
Under the conditions of this study, the test material requires no classification in accordance with EU criteria.
Executive summary:

The irritancy potential of the test material was assessed in vivo in accordance with the standardised guidelines OECD 405 and EU Method B.5.

A single application of 100 mg of the test material was sequentially administered to the right eye of two New Zealand White rabbits. The treated eyes were not irrigated; the left eye remained untreated and served as the control. The animals were observed for ocular effects 1, 24, 48 and 72 hours after administration of the test material.

The individual mean scores for corneal opacity and iritis were 0.0 for both animals. The individual mean scores for conjunctival redness were 0.7 for both animals. The individual mean scores for chemosis were 0.3 and 0.7. Both treated eyes appeared normal at the 72 hour observation and the study was therefore terminated.

Under the conditions of this study, the test material requires no classification in accordance with EU criteria.