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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
03-03-92 to 03-26-92
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study. The study was conducted on crystalline trisodium orthophosphate dodecahydrate which is known to have slighly different physicochemical properties which may result in slightly different effects on the eyes.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report Date:
1992

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EPA OTS 798.4500 (Acute Eye Irritation)
Deviations:
no
Principles of method if other than guideline:
not applicable
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material: Trisodium phosphate dodecahydrate
- Substance type: Solid
- Physical state: White powder
- Analytical purity: 93.5%
- Purity test date: 1992-04-02
- Lot/batch No.: 8288
- Storage condition of test material: At room temperature

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Age at study initiation: Adult
- Weight at study initiation: 2322 to 2600g
- Housing: Individually in screen-bottom cages
- Diet: Measured amount of High Fibre Rabbit Chow.
- Water: Ad libitum
- Acclimation period: At least 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 24 ºC
- Humidity (%): 40 to 52 %


IN-LIFE DATES: From: 1992-03-03 To: 1992-03-26

Test system

Vehicle:
water
Controls:
other: The left eye served as the untreated control.
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.1 mL
- Concentration: 15 % w/v mixture
- The prepared test mixture was kept at 10 ºC during administration
- The pH of the prepared test mixture was determined to be 12.8
Duration of treatment / exposure:
Group 1: Remained unwashed
Group 2: 30 seconds post instillation
Observation period (in vivo):
The treated eyes were observed for ocular irritation at 1, 24, 48, 72 and 96 h, and Days 7 and 14 after treatment.
Animals were weighed just before test material administration and at weekly intervals throughout the study.
Number of animals or in vitro replicates:
Group 1: 6 rabbits
Group 2: 3 rabbits
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: Group 1 remained unwashed. Group 2 was flushed with lukewarm tap water for 1 minute
- Time after start of exposure: 30 sec after instillation of the test material


SCORING SYSTEM: Draize


TOOL USED TO ASSESS SCORE: Sodium fluorescein

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal: F40185
Time point:
other: mean 24, 48 and 72 hr
Score:
1.6
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal: F40186
Time point:
other: mean 24, 48 and 72 hrs
Score:
2.6
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal: F40187
Time point:
other: mean 24, 48 and 72 hrs
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal: F40191
Time point:
other: mean 24, 48 and 72 hrs
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal: F40189
Time point:
other: mean 24, 48 and 72 hrs
Score:
2.3
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal: F40190
Time point:
other: mean 24, 48 and 72 hrs
Score:
2.3
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritant / corrosive response data:
In treated eyes receiving a washout, the test material produced corneal and iridial involvement and slight to moderate conjunctival irritation. Irritation continued to be present in the treated eyes of 4 of the animals in group 1 (unwashed eye) at Day 21 after treatment. All treated eyes of the animals in group 2 (washed eyes) had returned to normal appearance by Day 21 after treatment.
Other effects:
No data

Any other information on results incl. tables

 

Table 2. Average Primary Eye Irritation Score*

 

Observation

period

Average score

Group 1

Group 2

1 h

12.7

9.7

24 h

11.7

9.0

48 h

8.7

8.3

72 h

6.3

4.0

96 h

4.3

2.0

Day 7

3.0

0.7

Day 14

0.0

0.0

*the average primary eye irritation score is the total eye irritation score for all the animals divided by the number of animals (6 or 3) at each observation period.

 

Table 2. Individual eye irritation scores Group 1 (unwashed):      

 

Animal

No.

Cornea

Iris

Conjunctivae

Total

Score*

A

B

C

D

E

F

1 h

F40185u

0

0

0

2b

1

2c

10

F40186u

0

0

1i

2b

2

2c

17

F40187t

0

0

0

2b

2

2c

12

F40191u

0

0

1i

2b

1

2c

15

F40189t

0

0

0

2b

1

2c

10

F40190t

0

0

0

2b

2

2c

12

Mean

12.7

24 h

F40185

0

0

0

2b

1

2c

10

F40186

0

0

1i

2b

1

2c

15

F40187

0

0

0

2b

2

2c

12

F40191

0

0

1i

2b

1

2c

15

F40189

0

0

0

2

1

2c

10

F40190

0

0

0

2b

1

1c

8

Mean

11.7

48 h

F40185

0

0

0

2

1

1c

8

F40186

0

0

0

3a

1

1c

10

F40187

0

0

0

2

2

2c

12

F40191

0

0

0

2

1

0

6

F40189

0

0

0

2

1

1c

8

F40190

0

0

0

2

1

1c

8

Mean

8.7

72 h

F40185

0

0

0

1

1

0

4

F40186

0

0

0

3a

1

0

8

F40187

0

0

0

2

0

0

4

F40191

0

0

0

2

1

0

6

F40189

0

0

0

3a

1

0

8

F40190

0

0

0

3a

1

0

8

Mean

6.3

96 h

F40185

0

0

0

1

0

0

2

F40186

0

0

0

3a

1

0

8

F40187

0

0

0

2

0

0

4

F40191

0

0

0

2

0

0

4

F40189

0

0

0

2

0

0

4

F40190

0

0

0

 2

0

0

4

Mean

4.3

Day 7

F40185

0

0

0

0

0

0

0

F40186

0

0

0

2

0

0

4

F40187

0

0

0

2

0

0

4

F40191

0

0

0

2

0

0

4

F40189

0

0

0

2

0

0

4

F40190

0

0

0

1

0

0

2

Mean

3.0

Day 14

F40185

0

0

0

0

0

0

0

F40186

0

0

0

0

0

0

0

F40187

0

0

0

0

0

0

0

F40191

0

0

0

0

0

0

0

F40189

0

0

0

0

0

0

0

F40190

0

0

0

0

0

0

0

Mean

0

Table 3. Individual eye irritation scores for group 2 (washed):

Animal

No.

Cornea

Iris

Conjunctiva

Total

score*

A

B

C

D

E

F

1 h

F40188u

0

0

0

2b

1

1c

8

F40192t

0

0

1i

2b

1

1c

13

F40193u

0

0

0

2b

1

1c

8

Mean

9.7

24 h

F40188

0

0

0

2b

1

1c

8

F40192

0

0

1i

2b

1

0

11

F40193

0

0

0

2b

1

1c

9

Mean

9.0

48 h

F40188

0

0

0

2

1

0

6

F40192

0

0

1i

2

1

0

11

F40193

0

0

0

2

1

1c

8

Mean

8.3

72 h

F40188

0

0

0

2

0

0

4

F40192

0

0

0

1

0

0

2

F40193

0

0

0

2

1

0

6

Mean

4.0

96 h

F40188

0

0

0

1

0

0

2

F40192

0

0

0

1

0

0

2

F40193

0

0

0

1

0

0

2

Mean

2.0

Day 7

F40188

0

0

0

1

0

0

2

F40192

0

0

0

0

0

0

0

F40193

0

0

0

0

0

0

0

Mean

0.7

Day 14

F40188

0

0

0

0

0

0

0

F40192

0

0

0

0

0

0

0

F40193

0

0

0

0

0

0

0

Mean

0.0

A: Cornea - degree of opacity

B: Cornea - area of involvement

C: Iris - degreeof iridial irritation

D: Conjunctivae - redness

E: Conjunctivae - Chemosis

F: Conjunctivae - Discharge

*: total score = (A x B x 5)+ (C x 5) + [(D + E + F) x 2].

a: Petite haemorrhaging

b: Blanching

c: Clear discharge

i: Injected

t: No pain response after test material instillation

u: Excessive pawing at the treated eye after test material instillation

 

Table 4. Sodium fluorescein examination (unwashed & washed):

Animal

No.

Sex

Pre-

initiation

Observation period

72 h

Day 7

Day 14

F40185

Male

Neg

Neg

Neg

Neg

F40186

Male

Neg

Neg

Neg

Neg

F40187

Male

Neg

Neg

Neg

Neg

F40191

Male

Neg

Neg

Neg

Neg

F40189

Female

Neg

Neg

Neg

Neg

F40190

Female

Neg

Neg

Neg

Neg

Neg: Negative stain retention

Applicant's summary and conclusion

Interpretation of results:
Category II
Remarks:
Migrated information 4/6 rabbits showed conjuntival redness scores of ≥2 Criteria used for interpretation of results: EU
Conclusions:
Author's conclusions: The test material, trisodium phosphate dodecahydrate (prepared as a saturated solution at 10°C), when evaluated for it's primary eye irritation potential in rabbits, produced iridial involvement and moderate to severe conjunctival irritation in unwashed eyes. In treated eyes receiving a washout, the test material produced iridal involvement and slight to moderate conjunctival irritation. All treated eyes were normal by day 14.

This study is considered to be reliable and relevant to support the classification of trisodium orthophosphate as irritating to the eyes (Cat 2) as part of a weight of evidence approach.