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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:
Final report: 04-APR-1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
No certificate of analysis for the test substance.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1980
Report date:
1980

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
other: Draize method
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
4 animals, observation period of 7 days
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Terbium trinitrate
EC Number:
233-138-7
EC Name:
Terbium trinitrate
Cas Number:
10043-27-3
Molecular formula:
HNO3.1/3Tb
IUPAC Name:
terbium trinitrate
Test material form:
other: colourless liquid
Details on test material:
- Name of test material (as cited in study report): Nitrate de terbium

Test animals / tissue source

Species:
rabbit
Strain:
other: New Zealand
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2 kg to 3 kg

IN-LIFE DATES: From: 10-MAR-1980 To: 01-APR-1980

No other information were available.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
not required
other: The right eye, which remained untreated, served as control
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.1 mL introduced into the conjunctival sac of the left eye
Duration of treatment / exposure:
Single conjunctival instillation
Observation period (in vivo):
1 hour, 1, 2, 3, 4 and 7 days after instillation
Number of animals or in vitro replicates:
4 rabbits per treatment group
Details on study design:
TREATMENT PROCEDURE
0.1 mL of test item as such was placd into the conunctival sac of the left eye of each animal.

REMOVAL OF TEST SUBSTANCE
- Washing: one treatment group without washing and one treatment group with washing 30 seconds after instillation

SCORING 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

- 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, crimsom 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 ncitating 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

The coefficients of the conjunctival damage, the iris damage and the corneal damage allow to determine 3 indices of ocular irritation:
- the individual eye irritation index (= IEI), the maximum value of which equals 110, is equal to each time, for each rabbit, to 2 (A + B + C) + 5A1 + 5A2B2
- the mean ocular irritation index (= MOI) is the average, at each time, of the IEI of the 4 treated rabbits;
- the acute eye irritation index (= AEI) is the highest MOI obtained within 7 days of observation.
The interpretation of the results is made from these 3 index and is drawn from KAY and CALANDRA (J. Soc. Cosmet. Chem., 13, 281 (1962): "Interpretation of eye-irritation tests").

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: mean score 24, 48 and 72 hours
Score:
3.33
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: Presence of a membrane on half of the corneal surface at 24 hours
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: mean score 24, 48 and 72 hours
Score:
1
Max. score:
2
Reversibility:
not reversible
Remarks on result:
other: Circumcorneal injections + congestion of the iris
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: mean score 24, 48 and 72 hours
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: Presence of a whitish humor on the edge of the eyelids at 24 hours
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: mean score 24, 48 and 72 hours
Score:
2.66
Max. score:
3
Reversibility:
not reversible
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: mean score 24, 48 and 72 hours
Score:
3
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: mean score 24, 48 and 72 hours
Score:
0.33
Max. score:
2
Reversibility:
not reversible
Remarks on result:
other: At 24 and 48 hours, impossible read due to corneal opacification. At 72 hours, circumcorneal injections + congestion of the iris (score = 1)
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: mean score 24, 48 and 72 hours
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: Presence of a whitish humor on the edge of the eyelids at 24 and 48 hours
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: mean score 24, 48 and 72 hours
Score:
2.66
Max. score:
3
Reversibility:
not reversible
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: mean score 24, 48 and 72 hours
Score:
2.33
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: mean score 24, 48 and 72 hours
Score:
1
Max. score:
2
Reversibility:
not reversible
Remarks on result:
other: Circumcorneal injections + congestion of the iris
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: mean score 24, 48 and 72 hours
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: Presence of a whitish humor on the edge of the eyelids at 24 and 48 hours
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: mean score 24, 48 and 72 hours
Score:
2.66
Max. score:
3
Reversibility:
not reversible
Irritation parameter:
cornea opacity score
Basis:
animal #4
Time point:
other: mean score 24, 48 and 72 hours
Score:
3
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: Presence of a membrane on half of the corneal surface at 24 hours
Irritation parameter:
iris score
Basis:
animal #4
Time point:
other: mean score 24, 48 and 72 hours
Score:
1
Max. score:
2
Reversibility:
other: impossible read due to corneal opacification
Remarks on result:
other: At 24 and 48 hours, Circumcorneal injections + congestion of the iris. At 72 hours, impossible read due to corneal opacification
Irritation parameter:
chemosis score
Basis:
animal #4
Time point:
other: mean score 24, 48 and 72 hours
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: Presence of a whitish humor on the edge of the eyelids at 24 hours
Irritation parameter:
conjunctivae score
Basis:
animal #4
Time point:
other: mean score 24, 48 and 72 hours
Score:
2.66
Max. score:
3
Reversibility:
not reversible
Irritant / corrosive response data:
Chemosis (grade 4), enanthema (score 1 - 3), congestion of iris (score 1 - 2) and corneal opacity (score 2 - 4) were observed in all animals at 1h and remained present at the end of the observation study (day 7).

Any other information on results incl. tables

Table 1 : Results (without rinsing)

 

Evaluation of effects

1 hour

D1

D2

N° of rabbits

147

148

149

150

147

148

149

150

147

148

149

150

Conjunctiva

A) Chemosis

0 - 4

4

4

4

4

4£

4£

4£

4£

4

4£

4£

4

B) Discharge

0 - 3

1

1

1

1

2

2

3

2

3

3

3

3

C) Enanthema

0 - 3

1

1

1

1

2

2

2

2

3

3

3

3

(A+B+C) x 2

(max. = 20)

12

12

12

12

16

16

18

16

20

20

20

20

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Direct photomotor reflex of pupil (§)

N¥

N¥

N

N¥

N¥

N¥

N¥

N¥

N¥

Rɸ

N¥

Rɸ

Iris

Congestion

0 – 2

1α

1α

1α

1α

1α

1α

1α

1α

1α

1α

1α

1α

x 5

(max. = 10)

5

5

5

5

5

5

5

5

5

5

5

5

(§) N = Normal – R = Reduced – No reflex

Cornea

A) Opacity

0 – 4

2

2

2

2

4β

2

2

2β

3

3

2

3

B) Area affected

1 – 4

3

3

3

4

1

4

4

4

3

4

4

1

A x B x 5

(max. = 80)

30

30

30

40

20

40

40

40

45

60

40

15

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Individual ocular irritation score IOI

(max. 110)

47

47

47

57

41

61

63

61

70

85

65

40

Observations:

£: Presence of a whitish humor on the edge of the eyelids.

¥: Permanent myosis with preservation of direct photomotor reflex.

ɸ: Permanent myosis with solw-motion photomotor reflex.

α: Circumcorneal injections + congestion of the iris.

β: Presence of a membrane on half of the corneal surface.

Mean score per zone

Conj. + Iris + Corn.

Conj. + Iris + Corn.

Conj. + Iris + Corn.

12.00

5.00

32.50

16.50

5.00

35.00

20.00

5.00

40.00

Mean ocular irritation score MOI

Standard deviation S

 

 

49.50

5.00

 

 

56.50

10.38

 

 

65.00

18.71

Evaluation of effects

D3

D4

D7

N° of rabbits

147

148

149

150

147

148

149

150

147

148

149

150

Conjunctiva

A) Chemosis

0 - 4

4

4

4

4

4

4

4

4

4£

4£

4£

4£

B) Discharge

0 - 3

3

3

2

2

2

2

2

2

1

1

1

1

C) Enanthema

0 - 3

3

3

3

3

3

3

3

3

3

3

3

3

(A+B+C) x 2

(max. = 20)

20

20

18

18

18

18

18

18

16

16

16

16

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Direct photomotor reflex of pupil (§)

Rɸ

?

Rɸ

Rɸ

Rɸ

?

Rɸ

?

Nul

?

Nul

?

Iris

Congestion

0 – 2

1α

?

1α

1α

1α

?

1α

?

2

?

2

?

x 5

(max. = 10)

5

?

5

5

5

?

5

?

10

?

10

?

(§) N = Normal – R = Reduced – No reflex

Cornea

A) Opacity

0 – 4

3

4

2

3

3

4

3

4

4x

4

4

4x

B) Area affected

1 – 4

4

4

4

4

4

4

3

4

3

4

3

4

A x B x 5

(max. = 80)

60

80

40

60

60

80

45

80

60

80

60

80

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Individual ocular irritation score IOI

(max. 110)

95

100

63

83

83

98

68

98

86

96

86

96

Observations:

£: Presence of a whitish humor on the edge of the eyelids.

ɸ: Permanent myosis with solw-motion photomotor reflex.

?: Impossible read due to corneal opacification.

α: Circumcorneal injections + congestion of the iris.

x: Well-defined neovascularization.

Mean score per zone

Conj. + Iris + Corn.

Conj. + Iris + Corn.

Conj. + Iris + Corn.

19.00

3.75

60.00

18.00

2.50

66.25

16.00

5.00

70.00

Mean ocular irritation score MOI

Standard deviation S

 

 

≥ 82.75

15.20

 

 

≥ 86.75

14.36

 

 

≥ 91.00

5.77

Given the importance of lesions in the eye, some readings could not be performed normally.

As a result, two types of calculations have been performed:

-         On the one hand, assuming that the impossible readings are negative (= 0), which makes it possible to determine a MINIMUM VALUE.

-         And on the other hand, by attributing to these readings the highest possible score, which determines the MAXIMUM VALUE.

Table 2: Summary of various MOI

 

 

Time after instillation

 

 

1 hour

D1

D2

D3

D4

D7

Product instilled as is

(without rinsing)

MIN

49.50

56.50

65.00

82.75

86.75

91.00

(IOAm)

MAX

85.25

91.75

96.00

(IOAM)

Minimum Acute Eye Irritation Index (AEI): 91.00 at D7

Maximum Acute Eye Irritation Index (AEI): 96.00 at D7

 

Applicant's summary and conclusion

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
Under the test conditions, Terbium trinitrate is considered as extremely irritant to the eye.
Executive summary:

An eye irritation study was performed with Terbium trinitrate in rabbits. The method followed was similar to the OECD Guideline 405 and the study was not performed in accordance with GLP. A single dose of Terbium trinitrate in its original form was introduced into the conjunctival sac of the left eye of 4 rabbits/groups. The right eye was not treated and served as control. The eyes were not rinsed after administration of Terbium trinitrate for one treatment group and the eyes were rinsed 30 seconds after administration of Terbium trinitrate for the other treatment group

Ocular reactions were observed 1 hour and 1, 2, 3, 4 and 7 days after the administration.

Chemosis (grade 4), enanthema (score 1 - 3), congestion of iris (score 1 - 2) and corneal opacity (score 2 - 4) were observed in all animals at 1h and remained present at the end of the observation study (day 7).

Terbium trinitrate has induced irreversible effects on the rabbit eyes and is therefore classified as category 1 according to the UN GHS and CLP criteria.