Trisodium orthophosphate

Eye irritation

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

Guideline:

EPA OTS 798.4500 (Acute Eye Irritation)

Deviations:

no

Principles of method if other than guideline:

not applicable

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

trisodium orthophosphate dodecahydrate

IUPAC Name:

trisodium orthophosphate dodecahydrate

Constituent 2

Reference substance name:

Trisodium orthophosphate

EC Number:

231-509-8

EC Name:

Trisodium orthophosphate

Cas Number:

7601-54-9

Molecular formula:

H3O4P.3Na

IUPAC Name:

trisodium phosphate

Constituent 3

Reference substance name:

10101-89-0

EC Number:

600-151-8

Cas Number:

10101-89-0

IUPAC Name:

10101-89-0

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

Results

Results 1

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

Results 2

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

Results 3

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

Results 4

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

Results 5

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

Results 6

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
F40185^u	0	0	0	2^b	1	2^c	10
F40186^u	0	0	1^i	2^b	2	2^c	17
F40187^t	0	0	0	2^b	2	2^c	12
F40191^u	0	0	1^i	2^b	1	2^c	15
F40189^t	0	0	0	2^b	1	2^c	10
F40190^t	0	0	0	2^b	2	2^c	12
Mean							12.7
24 h
F40185	0	0	0	2^b	1	2^c	10
F40186	0	0	1^i	2^b	1	2^c	15
F40187	0	0	0	2^b	2	2^c	12
F40191	0	0	1^i	2^b	1	2^c	15
F40189	0	0	0	2	1	2^c	10
F40190	0	0	0	2^b	1	1^c	8
Mean							11.7
48 h
F40185	0	0	0	2	1	1^c	8
F40186	0	0	0	3^a	1	1^c	10
F40187	0	0	0	2	2	2^c	12
F40191	0	0	0	2	1	0	6
F40189	0	0	0	2	1	1^c	8
F40190	0	0	0	2	1	1^c	8
Mean							8.7
72 h
F40185	0	0	0	1	1	0	4
F40186	0	0	0	3^a	1	0	8
F40187	0	0	0	2	0	0	4
F40191	0	0	0	2	1	0	6
F40189	0	0	0	3^a	1	0	8
F40190	0	0	0	3^a	1	0	8
Mean							6.3
96 h
F40185	0	0	0	1	0	0	2
F40186	0	0	0	3^a	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
F40188^u	0	0	0	2^b	1	1^c	8
F40192^t	0	0	1^i	2^b	1	1^c	13
F40193^u	0	0	0	2^b	1	1^c	8
Mean							9.7
24 h
F40188	0	0	0	2^b	1	1^c	8
F40192	0	0	1^i	2^b	1	0	11
F40193	0	0	0	2^b	1	1^c	9
Mean							9.0
48 h
F40188	0	0	0	2	1	0	6
F40192	0	0	1^i	2	1	0	11
F40193	0	0	0	2	1	1^c	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.