Registration Dossier

Administrative data

Description of key information

Skin irritation: A number of in vivo studies are available to assess the skin irritation potential of trisodium orthophosphate anhydrous and trisodium orthophosphate dodecahydrate. The study reported by Henderson L (1974) as the key study is conducted according to modern standards and has been chosen as a key study because it has been conducted on the anhydrous form of trisodium orthophosphate. The conclusions made in the key study are supported by a number of reliable supporting studies that have been conducted on trisodium orthophosphate dodecahydrate. The results of this study are sufficient for classification and labelling in accordance with Regulation (EC) No. 1272/2008 (EU CLP). 
Eye irritation: A number of in vivo studies are available to assess the eye irritancy potential of trisodium orthophosphate anhydrous or trisodium orthophosphate dodecahydrate. Two studies (Glaza SM, 1992 and Glaza SM, 1992), conducted on trisodium orthophosphate dodecahydrate have been chosen as a weight of evidence for this endpoint. These studies have been conducted at two different temperatures (10°C and 22°C), both studies indicate that trisodium phosphate is irritating to the eyes but the degree of severity of the effects, in particular with respect to redness of the conjunctivae, varies depending on the temperature of the solution. The supporting data for this are not sufficient for use as key data as no total scores are provided. However, the data does support the conclusion that trisodium orthophosphate is irritating to the eyes.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation / corrosion, other
Remarks:
Study was performed prior to the update of the REACH Regulation and prior to the validation of in vitro test methods.
Type of information:
experimental study
Adequacy of study:
key study
Study period:
No data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Qualifier:
according to
Guideline:
other: FDA revision of the test for primary skin irritants, Part 191, Chapter 1, Title 21.
Deviations:
yes
Remarks:
The proposed test differs from the procedure described in the Hazardous Substances Labeling Act, Part 191.11, Chapter 1, Title 21 in that irritation is determined after a 4-h exposure period, rather than after the previously required 24-h exposure period.
Principles of method if other than guideline:
not applicable
GLP compliance:
no
Remarks:
Study pre-dates GLP
Species:
rabbit
Strain:
not specified
Details on test animals and environmental conditions:
No data
Type of coverage:
not specified
Preparation of test site:
other: Intact skin
Vehicle:
not specified
Controls:
not specified
Amount / concentration applied:
No data
Duration of treatment / exposure:
48 h
Observation period:
96 h
Number of animals:
Six
Details on study design:
No data
Irritation parameter:
other: Primary irritant score
Basis:
other: no data
Time point:
other: 4 h
Score:
0
Max. score:
8
Reversibility:
other: Not applicable
Irritation parameter:
erythema score
Basis:
mean
Remarks:
all animals
Time point:
other: mean 4, 24 and 48 hrs
Score:
0
Max. score:
0
Reversibility:
other: not applicable; no effects noted
Irritation parameter:
edema score
Basis:
mean
Remarks:
all animals
Time point:
other: mean 4, 24 and 48 hrs
Score:
0
Max. score:
0
Reversibility:
other: not applicable; no effects noted
Irritant / corrosive response data:
Rabbits had no edema or erythema at all observation periods.
Other effects:
No data

Table 1. Results of a skin irritation study in rabbits with trisodium phosphate.

Rabbit

No

Erythema-eschar observation

Edema observation

Sum total

Score*

4 h

24 h

48 h

4 h

24 h

48 h

1

0

0

0

0

0

0

0

 

0

 

0

0

0

0

0

0

2

0

0

0

0

0

0

0

 

0

 

0

0

0

0

0

0

3

0

0

0

0

0

0

0

 

0

 

0

0

0

0

0

0

4

0

0

0

0

0

0

0

 

0

 

0

0

0

0

0

0

5

0

0

0

0

0

0

0

0

 

0

0

0

0

0

0

6

0

0

0

0

0

0

0

0

0

0

0

0

0

0

* Sum of individual values for each rabbit divided by 6.

Interpretation of results:
GHS criteria not met
Conclusions:
Trisodium phosphate was not considered to be irritating under the conditions of the study.

This study is considered to be adequate and reliable for use as a key study for this endpoint. The data in the study suggests that under test conditions trisodium phosphate is not irritating to the skin, in accordance with Regulation (EC) No. 1272/2008.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Remarks:
Study was performed prior to the update of the REACH Regulation and prior to the validation of in vitro test methods.
Type of information:
experimental study
Adequacy of study:
key study
Study period:
03-03-92 to 03-26-92
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
See read-across justification report under Section 13 ‘Assessment Reports’.

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
In accordance with REACH Annex XI, Section 1.5, of Regulation (EC) No. 1907/2006 (REACH) the standard testing regime may be adapted in cases where a grouping or read-across approach has been applied.

The similarities may be based on:
(1) a common functional group
(2) the common precursors and/or the likelihood of common breakdown products via physical or biological processes, which result in structurally similar chemicals; or
(3) a constant pattern in the changing of the potency of the properties across the category

The source substance and the target substance are considered to be similar enough to facilitate read-across for the following reasons because the only difference is that the source is the hydrated form.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
See read-across justification report under Section 13 ‘Assessment Reports’.

3. ANALOGUE APPROACH JUSTIFICATION
See read-across justification report under Section 13 ‘Assessment Reports’.

4. DATA MATRIX
See read-across justification report under Section 13 ‘Assessment Reports’
Reason / purpose:
read-across: supporting information
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
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
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
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal: F40185
Time point:
24/48/72 h
Score:
1.6
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal: F40186
Time point:
24/48/72 h
Score:
2.6
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal: F40187
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal: F40191
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal: F40189
Time point:
24/48/72 h
Score:
2.3
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal: F40190
Time point:
24/48/72 h
Score:
2.3
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
cornea opacity score
Basis:
animal: All 6 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
animal: F40185
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal: F40186
Time point:
24/48/72 h
Score:
0.33
Max. score:
2
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
iris score
Basis:
animal: F40187
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal: F40191
Time point:
24/48/72 h
Score:
0.33
Max. score:
2
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
iris score
Basis:
animal: F40189
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal: F40190
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
chemosis score
Basis:
animal: F40185
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 96 hours
Irritation parameter:
chemosis score
Basis:
animal: F40186
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 96 hours
Irritation parameter:
chemosis score
Basis:
animal: F40187
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal: F40191
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 96 hours
Irritation parameter:
chemosis score
Basis:
animal: F40189
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 96 hours
Irritation parameter:
chemosis score
Basis:
animal: F40190
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 96 hours
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

 

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

Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
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.
Endpoint:
eye irritation: in vivo
Remarks:
Study was performed prior to the update of the REACH Regulation and prior to the validation of in vitro test methods.
Type of information:
experimental study
Adequacy of study:
key study
Study period:
03-03-92 to 03-26-92
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
See read-across justification report under Section 13 ‘Assessment Reports’.

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
In accordance with REACH Annex XI, Section 1.5, of Regulation (EC) No. 1907/2006 (REACH) the standard testing regime may be adapted in cases where a grouping or read-across approach has been applied.

The similarities may be based on:
(1) a common functional group
(2) the common precursors and/or the likelihood of common breakdown products via physical or biological processes, which result in structurally similar chemicals; or
(3) a constant pattern in the changing of the potency of the properties across the category

The source substance and the target substance are considered to be similar enough to facilitate read-across for the following reasons because the only difference is that the source is the hydrated form.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
See read-across justification report under Section 13 ‘Assessment Reports’.

3. ANALOGUE APPROACH JUSTIFICATION
See read-across justification report under Section 13 ‘Assessment Reports’.

4. DATA MATRIX
See read-across justification report under Section 13 ‘Assessment Reports’
Reason / purpose:
read-across: supporting information
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 (incl. certificate)
Species:
rabbit
Strain:
other: Hra: (NZW) SPF
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Age at study initiation: Adult
- Weight at study initiation: 2220 to 2936 g
- 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
Vehicle:
water
Controls:
other: The left eye served as the untreated control.
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.1 mL
- Concentration: 19 % w/v mixture
- The prepared test mixture was kept at 22 ºC during administration
- The pH of the prepared test mixture was determined to be 12.6
Duration of treatment / exposure:
Group 1: Remained unwashed
Group 2: 30 seconds
Observation period (in vivo):
The treated eyes were observed for ocular irritation at 1, 24, 48, 72 and 96 h, and Days 7, 14 and 21 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
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 21 days
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 21 days
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
cornea opacity score
Basis:
animal #4
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 21 days
Irritation parameter:
cornea opacity score
Basis:
animal #5
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 21 days
Irritation parameter:
cornea opacity score
Basis:
animal #6
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 21 days
Irritation parameter:
iris score
Basis:
other: 3 out of 6 animals
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 21 days
Remarks on result:
other: the 3 remaining animals had scores < 1
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #1
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
fully reversible within: 21 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #2
Time point:
24/48/72 h
Score:
2.6
Max. score:
3
Reversibility:
fully reversible within: 21 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #3
Time point:
24/48/72 h
Score:
2.6
Max. score:
3
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #4
Time point:
24/48/72 h
Score:
2.3
Max. score:
3
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #5
Time point:
24/48/72 h
Score:
2.6
Max. score:
3
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #6
Time point:
24/48/72 h
Score:
2.6
Max. score:
3
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 21 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2.6
Max. score:
4
Reversibility:
fully reversible within: 21 days
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.6
Max. score:
4
Reversibility:
fully reversible within: 21 days
Irritation parameter:
chemosis score
Basis:
animal #4
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 21 days
Irritation parameter:
chemosis score
Basis:
animal #5
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 21 days
Irritation parameter:
chemosis score
Basis:
animal #6
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 21 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

Table 2. Average Primary Eye Irritation Score*

Observation

period

Average score

Group 1

Group 2

1 h

20.5

17.3

24 h

19.0

14.3

48 h

20.2

6.7

72 h

21.3

6.0

96 h

14.8

3.3

Day 7

9.2

2.7

Day 14

4.5

0.7

Day 21

2.5

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 3. Individual eye irritation scores Group 1 (unwashed):

Animal

No.

Cornea

Iris

Conjunctivae

Total

Score*

A

B

C

D

E

F

1 h

F39914t

1

1

1i

3b

3

3c

28

F39937u

1

1

0

2b

3

3c

21

F39939t

0

0

0

2b

1

2c

10

F40197t

1

1

1i

2b

2

2c

22

F40198u

1

1

1i

2b

2

2c

22

F40199u

1

1

1i

2b

2

1c

20

Mean

20.5

24 h

F39914

1

1

1i

3b

3

3c

28

F39937

1

1

0

2b

3

3c

21

F39939

0

0

0

2b

1

1c

8

F40197

1

1

0

2b

1

2c

15

F40198

1

1

1i

2b

2

2c

22

F40199

1

1

1i

2b

2

1c

20

Mean

19.0

Individual eye irritation scores unwashed continued:

Animal

No.

Cornea

Iris

Conjunctivae

Total

Score*

A

B

C

D

E

F

48 h

F39914

1

1

1

3

3

3

28

F39937

1

1

0

3

2

1

17

F39939

0

0

0

3

1

1

10

F40197

1

1

0

2

1

1

13

F40198

1

2

1

3

2

3

31

F40199

1

1

1

3

2

1

22

Mean

20.2

72 h

F39914

1j

1

1i

3a ,b

3

3c

28

F39937

1j

1

1i

3a ,b

3

0

22

F39939

0

0

0

3a ,b

3

0

12

F40197

1j

1

0

3a

2

0

15

F40198

1j

2

1i

3a

2

2c

29

F40199

1j

1

1i

3a

2

1c

22

Mean

21.3

Individual eye irritation scores unwashed continued:

Animal

No.

Cornea

Iris

Conjunctivae

Total

Score*

A

B

C

D

E

F

96 h

F39914

1j

1

0

3a

2

0

15

F39937

1j

1

0

3a

1

0

13

F39939

0

0

0

3a

1

0

8

F40197

1j

1

0

3a

1

0

13

F40198

1j

1

1i

3a

2

0

20

F40199

1j

1

1i

3a

2

0

20

Mean

14.8

Day 7

F39914

1n

1

0

2a

1

0

11

F39937

1j

1

0

2

1

0

11

F39939

0

0

0

3a

1

0

8

F40197

0

0

0

2

0

0

4

F40198

1j

1

0

3a

1

0

13

F40199

0

0

0

3a

1

0

8

Mean

9.2

Day 14

F39914

0

0

0

1

0

0

2

F39937

1

1

0

2

0

0

9

F39939

0

0

0

2

0

0

4

F40197

0

0

0

1

0

0

2

F40198

0

0

0

2

0

0

4

F40199

0

0

0

3a

0

0

6

Mean

4.5

Day 21

F39914

0

0

0

0

0

0

0

F39937

1j, n

1

0

1

0

0

7

F39939

0

0

0

1

0

0

2

F40197

0

0

0

0

0

0

0

F40198

0

0

0

1

0

0

2

F40199

0

0

0

2

0

0

4

Mean

2.5

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

j: Corneal epithelial peeling

n: Corneal neovascularization

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):

Animal

No.

Sex

Pre-

initiation

Observation period

72 h

Day 7

Day 14

Day 21

F39914

Female

Neg

Pos (20 %)

Neg

Neg

Neg

F39937

Female

Neg

Pos (15 %)

Pos (10 %)

Pos (10 %)

Pos (< 5 %)

F39939

Female

Neg

Neg

Neg

Neg

Neg

F40197

Male

Neg

Pos (20 %)

Neg

Neg

Neg

F40198

Male

Neg

Pos (30 %)

Pos (15 %)

Neg

Neg

F40199

Male

Neg

Pos (20 %)

Neg

Neg

Neg

Neg: Negative stain retention

Pos: Positive stain retention (area of cornea involved)

Table 5. Individual eye irritation scores for group 2 (washed):

Animal

No.

Cornea

Iris

Conjunctiva

Total

score*

A

B

C

D

E

F

1 h

F40202u

1j

1

1i

2b

2

2c

22

F40201t

0

0

1i

2b

2

2c

17

F40200t

0

0

1i

2b

1

1c

13

Mean

17.3

24 h

F40202

1j

1

1i

2b

1

1c

18

F40201

0

0

1i

2b

2

2c

17

F40200

0

0

0

2b

1

1c

8

Mean

14.3

48 h

F40202

0

0

0

2

1

0

6

F40201

0

0

0

2

1

1c

8

F40200

0

0

0

2

1

0

6

Mean

6.7

72 h

F40202

0

0

0

2

1

0

6

F40201

0

0

0

2

1

0

6

F40200

0

0

0

2

1

0

6

Mean

6.0

96 h

F40202

0

0

0

1

0

0

2

F40201

0

0

0

1

0

0

2

F40200

0

0

0

2

1

0

6

Mean

3.3

Day 7

F40202

0

0

0

1

0

0

2

F40201

0

0

0

1

0

0

2

F40200

0

0

0

2

0

0

4

Mean

2.7

Day 14

F40202

0

0

0

0

0

0

0

F40201

0

0

0

0

0

0

0

F40200

0

0

0

1

0

0

2

Mean

0.7

Day 21

F40202

0

0

0

0

0

0

0

F40201

0

0

0

0

0

0

0

F40200

0

0

0

0

0

0

0

Mean

0.0

A: Cornea - degree of opacity

B: Cornea - area of involvement

C: Iris - degree of 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]

b: Blanching

c: Clear discharge

i: Injected

j: Corneal epithelial peeling

u: Excessive pawing at the treated eye after instillation

t: No pain response after test material instillation

Table 6. Sodium fluorescein examination (washed):

Animal

No.

Sex

Observation Period

Pre-

initiation

72 h

Day 7

Day 14

Day 21

F40202

Male

Neg

Neg

Neg

Neg

Neg

F40201

Female

Neg

Neg

Neg

Neg

Neg

F40200

Female

Neg

Neg

Neg

Neg

Neg

Neg: Negative stain retention

Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
The test substance produced moderate to severe conjunctival irritation in unwashed eyes. In eyes receiving washout, the test material produced corneal and iridial involvement and slight to moderate conjunctival irritation.Some minor redness was noted up to day 21 however, in conjunction with the other key study a classification of corrosive is not considered to be necessary as the substance tested (trisodium orthophosphate dodecahydrate) is a crystalline form is more difficult to dissolve in solution and therefore it is likely that the persistent redness is due to crystaline material irritating the mucosa of the eye as opposed to the local effects of the substance itself.

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.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Justification for classification or non-classification

Skin irritation: The data available for trisodium orthophosphate suggests no classification according to Regulation (EC) No 1272/2008 (EU CLP). However, workplace observations have noted that under certain conditions (for example; humidity) local irritation when the material is placed in contact with the skin occurs and for that reason and in accordance with the hazard evaluation guidelines set out in the Guidance to Regulation (EC) No 1272/2008 trisodium phosphate is considered to be irritating to the skin (category 2).

Eye irritation: All available studies indicate that trisodium orthophosphate is irritating to the eyes and therefore classification as a category 2 eye irritant is proposed.

Respiratory irritation: Respiratory irritation has been noted in worker populations exposed to trisodium orthophosphate via the inhalation route and therefore a classification of STOT-SE category 3 for respiratory tract irritation is proposed.