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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:
4th October 2000 - 13th October 2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted to GLP in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001
Report Date:
2001

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: 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: particulate/powder
Remarks:
migrated information: powder
Details on test material:
Ta2O5
Tantalum Pentoxide Grade LT

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Harlan UK Ltd., Bicester, Oxon, England
- Age at study initiation: at least 12 weeks
- Weight at study initiation: 2.5 - 3.0 kg
- Housing: housed individually in metal cages with perforated floors.
- Diet (e.g. ad libitum): ad libitum. standard laboratory rabbit diet (Special Diet Services STANRAB (P) SQC pellet) was provided. The batch of diet used for the study was analysed by the supplier for nutrients, possible contaminants and micro-organisms likely to be present in the diet and which, if in excess of specified amounts, might have an undesirable effect on the test system. The animals were fed hay on arrival and subsequently three times a week.
- Water (e.g. ad libitum): ad libitum. The water supplied to Huntingdon Life Sciences by Anglian Water was potable water for human consumption. Anglian Water takes its guidelines on water quality from the EEC directive relating to water for human consumption (80/778/EEC) and conforms to the United Kingdom Water Act 1989 and subsequent amendments. Results of routine physical and chemical examination of drinking water at consumers' taps, as conducted by the supplier, are made available to Huntingdon Life Sciences Ltd. as quarterly summaries.
- Acclimation period: minimum 5 days
During the acclimatisation and study period the animals were given small (approximately 5 cm x 2 cm x 2 cm) soft white untreated wood blocks for environmental enrichment.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 ± 2°C
- Humidity (%):30 to 70%. relative
- Photoperiod (hrs dark / hrs light): 12 hours of artificial light (0600 - 1800 hours) in each 24-hour period.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: The contralateral eye remained untreated
Amount / concentration applied:
100 mg was placed in the lower everted lid of one eye of each animal
Duration of treatment / exposure:
single exposure, no washing
Observation period (in vivo):
Examination of the eyes was made after 1 hour and 1, 2 and 3 days (equivalent to approximately 24, 48 and 72 hours) after instillation.
Number of animals or in vitro replicates:
3
Details on study design:
TREATMENT PROCEDURE
The eyes of each animal were examined prior to instillation of the test substance to ensure that there was no pre-existing corneal damage, iridial inflammation or conjunctival irritation.

One animal was treated in advance of the other two, to ensure that if a severe response was produced, no further animals would be exposed.
In compliance with the study guideline, the weight of the test substance which when gently compacted occupied a volume of 0.1 mL was measured.
On all occasions, as the volume of 0.1 mL of the test substance exceeded 100 mg, 100 mg only was placed in the lower everted lid of one eye of each animal.
The eyelids were then gently held together for one second before releasing. The contralateral eye remained untreated.

OBSERVATIONS
-Clinical signs:
All animals were observed daily for signs of ill health or toxicity.

-Ocular responses:
Examination of the eyes was made after 1 hour and 1, 2 and 3 days (equivalent to approximately 24, 48 and 72 hours) after instillation. Observation of the eyes was aided by the use of a handheld light.

-Ocular irritation was assessed using the prescribed numerical system:

-Cornea Opacity: degree of density (area most dense taken for reading):
No ulceration or opacity 0
Scattered or diffuse areas of opacity (other than slight dulling of normal lustre), details of iris clearly visible 1
Easily discernible translucent areas, details of iris slightly obscured 2
Nacreous areas, no details of iris visible, size of pupil barely discernible 3
Opaque cornea, iris not discernible through the opacity 4

-Area of cornea involved:
None 0
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

-Iris:
Normal 0
Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia or injection,
any 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

Conjunctivae Redness: (refers to the most severe reading of palpebral and bulbar conjunctivae, as compared to the control eye)
Blood vessels normal 0
Some blood vessels definitely hyperaemic (injected) 1
Diffuse, crimson colour, individual vessels not easily discernible 2
Diffuse beefy red 3

Chemosis: (lids and/or nictating membranes)
No swelling 0
Any swelling above normal (includes nictating membranes) 1
Obvious swelling with partial eversion of lids 2
Swelling with lids about half-closed 3
Swelling with lids more than half-closed 4

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: Mean overall score for 24, 48, 72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Time point:
other: Mean overall score for 24, 48, 72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: Mean overall score for 24, 48, 72 h
Score:
0
Max. score:
3
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: Mean overall score for 24, 48, 72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
Transient hyperaemia of the blood vessels of the conjunctivae was seen in two animals, resolving completely by one day after instillation.
No ocular reactions were observed in the remaining animal throughout the duration of the study.
Other effects:
No corneal damage or iridial inflammation was observed.

Transient hyperaemia of the blood vessels of the conjunctivae was seen in two animals, resolving completely by one day after instillation.
No ocular reactions were observed in the remaining animal throughout the duration of the study.

Any other information on results incl. tables

Table 1: Ocular reactions

Rabbit no. & sex

Region of eye

1 h

Day after installation

1

2

3

 

 

1392 Male*

Cornea

Density

0

0

0

0

Area

0

0

0

0

Iris

0

0

0

0

Conjunctiva

Redness

1

0

0

0

Chemosis

0

0

0

0

 

 

1462 Male

Cornea

Density

0

0

0

0

Area

0

0

0

0

Iris

0

0

0

0

Conjunctiva

Redness

0

0

0

0

Chemosis

0

0

0

0

 

 

1463 Male

Cornea

Density

0

0

0

0

Area

0

0

0

0

Iris

0

0

0

0

Conjunctiva

Redness

1

0

0

0

Chemosis

0

0

0

0

*Pilot animal

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
A single instillation of the test substance into the eye of the rabbit elicited transient, very slight conjunctival irritation in two animals. No ocular reactions were observed in the remaining animal throughout the duration of the study.
Executive summary:

A study was performed to assess the eye irritation potential of Ta2O5 to the rabbit eye, using New Zealand White rabbits. The test was performed to GLP standard and followed the below listed guidelines:

EEC Methods for the determination of toxicity, Annex to Directive 92/69/EEC (Official Journal No. L383A, 29.12.92), Part B, Method B.5. Acute toxicity (eye irritation).

OECD Guideline for the Testing of Chemicals No. 405, "Acute Eye Irritation/Corrosion", Adopted 24 February 1987.

EPA Health Effects Test Guidelines OPPTS 870.2400 Acute Eye Irritation EPA 712-C-98-195. August 1998.

 

Three rabbits were each administered a single ocular dose of 100 mg of the test substance (as a volume of 0.1 mL exceeded 100 mg) and observed for three days after instillation.

 

A single instillation of the test substance into the eye of the rabbit elicited transient, very slight conjunctival irritation in two animals. Responses had resolved by one day after instillation. No ocular reactions were observed in the remaining animal throughout the duration of the study.