Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Skin irritation:  Two in vivo studies are available for skin irritation. The study reported by Warren (2012) as the key study is conducted according to modern guidelines and performed in a GLP accredited facility. The results of this study are sufficient for classification and labelling in accordance with Regulation (EC) No. 1272/2008 (EU CLP). The additional study (Freeman, 1987) is provided to support this conclusion.
Eye irritation: Four studies of varying reliability exist for the endpoint 'eye irritation'. As all available studies were considered to be deficient in some way a weight of evidence approach is used to address this endpoint for tripotassium orthophosphate.
Respiratory tract irritation: No studies exist to show the effects of tripotassium phosphate on the respiratory tract. However, workplace observations suggest the material is irritating to the respiratory tract.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
12 June 2012 - 18 June 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.46 (In Vitro Skin Irritation: Reconstructed Human Epidermis Model Test)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
Date of inspection: 19-21 July 2011, signed 31 August 2011
Species:
other: reconstituted human epidermis model
Strain:
other: reconstituted human epidermis model
Type of coverage:
other: Topical
Preparation of test site:
other: not applicable
Vehicle:
unchanged (no vehicle)
Controls:
other: Control animals are not applicable, however controls were used in the study.
Amount / concentration applied:
The test item was used as supplied.

- Amount(s) applied (volume or weight with unit):
10 ± 2 mg of the test material was applied to the epidermis surface pre-moistened with 5 µl of sterile distilled water.

- Concentration (if solution):
The test material was used as supplied.

VEHICLE
No vehicle used
Duration of treatment / exposure:
15 minutes and 42 hours post-exposure incubation.
Observation period:
Not applicable
Number of animals:
Not applicable
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done):
At the end of the exposure period, each tissue was removed from the well using forceps and rinsed using a wash bottle containing PBS with Ca++ and Mg++. Rinsing was achieved by filling and emptying each tissue insert for approximately 40 seconds using a constant soft stream of PBS to gently remove any residual test material.

- Time after start of exposure:
15 Minutes post exposure

SCORING SYSTEM:
Quantitative MTT Assessment (percentage tissue viability)
For the test material the relative mean tissue viabilities obtained after the 15 minute treatment followed by the 42 hour post-exposure incubation period were compared to the mean of the negative control treated tissues (n=3). The relative mean viabilities were calculated in the following way:

mean OD540 of test material / mean OD540 of negative control x 100 = Relative mean tissue viability (percentage of negative control)

Classification of irritation potential is based upon relative tissue viability following the 15 minute exposure period followed by the 42 hour post-exposure incubation period according to the following:

Mean tissue viability is ≤50% : Irritant (I) R38

Mean tissue viability is >50% : Non-Irritant (NI)
Irritation / corrosion parameter:
% tissue viability
Run / experiment:
mean value - all three tissues
Value:
81.6
Remarks on result:
other:
Remarks:
Basis: mean viability of cells (%). Time point: day 6. Max. score: 100.0. Reversibility: other: not applicable. Remarks: %. (migrated information)

Test Item, Positive Control Item and Negative Control Item

The mean OD540values, standard deviations and tissue viabilities for the test item, negative control item and positive control item are given in Table 1. The mean viabilities and standard deviations of the test item and positive control, relative to the negative control are also given in Table 1.

The relative mean viability of the test item treated tissues was 81.6% after a 15-Minute exposure period.

 

Quality Criteria

The relative mean tissue viability for the positive control treated tissues was 8.6% relative to the negative control treated tissues and the standard deviation value of the percentage viability was 1.0%. The positive control acceptance criterion was therefore satisfied.

The mean OD540 for the negative control treated tissues was 0.659 and the standard deviation value of the percentage viability was 6.2%. The negative control acceptance criterion was therefore satisfied.

The standard deviation calculated from individual percentage tissue viabilities of the three identically treated tissues was 5.2%. The test item acceptance criterion was therefore satisfied.

 

Table 1. Mean OD540Values and Percentage Viabilities for the Negative Control Item, Positive Control Item and Test Item

 

Item

OD540of tissues

Mean OD540of triplicate tissues

± SD of OD540

Relative individual tissue viability (%)

Relative mean viability (%)

± SD of relative mean viability (%)

Negative control item

0.666

0.659

0.041

101.1

100*

6.2

0.696

105.6

0.615

93.3

Positive control item

0.059

0.056

0.006

9.0

8.6

1.0

0.061

9.3

0.049

7.4

Test item

0.560

0.538

0.034

85.0

81.6

5.2

0.499

75.7

0.555

84.2

 

SD = Standard deviation

*= The mean viability of the negative control tissues is set at 100%

Control group shared with Harlan Laboratories Ltd Project numbers 41200853, 41200861,

41200866, 41200871, 41200880, 41200884 and 41201543

The relative mean viability of the test item treated tissues was 81.6% after the 15-minute exposure period.

Quality criteria: The quality criteria required for acceptance of results in the test were satisfied.

Direct MTT Reduction

An assessment found the test item was able to directly reduce MTT. Therefore, an additional procedure using water-killed tissues was performed during the determination of skin irritation potential. However, the results obtained showed a negligible degree ofinterference due to direct reduction of MTT occurred. It was therefore considered unnecessary to use the results of the water-killed tissues for quantitative correction of results or for reporting purposes.

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of the study tripotassium orthophosphate is considered to be a non-irritant.
This study is conducted according to an appropriate validated in vitro guideline and under the conditions of GLP and therefore the study is considered to be acceptable and to adequately satisfy both the guideline requirement and the regulatory requirement (Regulation (EC) No. 1907/2006; REACH) as a key study for this endpoint. In addition, the data is considered to be adequate and reliable for classification and labelling in accordance with Regulation (EC) No. 1272/2008 (EU CLP). Tripotassium orthophosphate is not considered to be classified in accordance with Regulation (EC) No. 1272/2008 (EU CLP).
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:
weight of evidence
Study period:
No data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
according to guideline
Guideline:
other: Code of Federal Regulation, Section 1500.42
Deviations:
not specified
GLP compliance:
not specified
Remarks:
Study pre-dates GLP
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Zartman Farms, Douglassville, Pa.
- Weight at study initiation: 2.0 to 2.5 kg
- Housing: Housed and fed individually
Vehicle:
not specified
Controls:
other: The untreated right eye served as a control for each animal.
Amount / concentration applied:
0.1 mL
Duration of treatment / exposure:
7 days
Observation period (in vivo):
No data
Number of animals or in vitro replicates:
7
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: Not done

SCORING SYSTEM: according to the Federal Register 38 (187) 27019 an animal should be considered as exhibiting a positive reasion if the test stubstace produced at any of the readings, ulceration of the cornea (other than a fine stippling); or opacity of the cornea (other than a slight duling of the normal lustre); or inflammation of the iris (other than a slight deepening of the folds, or rugae, or a slight circumcorneal injection of the blood vessels); or if such substances produce in the conjunctivae (excluding the cornea and iris) an obvious swelling with partial eversion or the lids or a diffuse crimson red with vessles not easily discernible.
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
other: all animals tested (#1-6)
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
other: all animals tested (#1-6)
Time point:
24/48/72 h
Score:
2.6
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
other: all animals tested (#1-6)
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
other: animal #1, 3, 4 and 6
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
3.6
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
animal #5
Time point:
24/48/72 h
Score:
3.33
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritant / corrosive response data:
All of the test animals exhibited severe irritation at 24, 48 and 72 h. At 4 days, four animals exhibited moderate irritation and two animals exhibited severe irritation. All animals exhibited moderate irritation at 7 days.
Other effects:
No data

Eye irritation in rabbits:

Animal No.

Cornea

A x B x 5

Iris

A x 5

Conjunctivae

(A + B + C) x 2

Total score

per animal

A

B

A

A

B

C

24 h

1

3

4

2

3

3

2

85

2

4

4

2

3

3

2

106

3

3

4

2

3

3

2

86

4

3

4

2

3

3

2

86

5

4

4

2

3

3

2

106

6

3

4

2

3

3

2

86

48 h

1

3

4

2

3

3

2

86

2

4

4

2

3

3

2

106

3

3

4

2

3

3

2

86

4

3

4

2

3

3

2

86

5

3

4

2

3

3

2

86

6

3

4

2

3

3

2

86

72 h

1

3

4

2

3

2

3

86

2

3

4

2

3

2

3

86

3

3

4

2

3

2

3

86

4

3

4

2

3

2

3

86

5

3

4

2

3

2

3

86

6

3

4

2

3

2

3

86

4 days

1

2

4

2

3

2

3

66

2

3

4

2

3

2

3

86

3

2

4

2

3

2

2

64

4

2

4

2

3

2

2

64

5

3

4

2

3

2

2

84

6

2

4

2

2

2

2

62

7 days

1

2

4

2

2

2

2

62

2

2

4

2

2

2

2

62

3

2

4

2

2

2

2

62

4

2

4

2

2

2

2

62

5

2

4

2

2

2

2

62

6

2

4

2

2

2

2

62

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
The test material produced moderate to severe irritation for 7 days when instilled into the eye and not washed out.

The study meets generally accepted scientific standards; however substance identity is not adequately reported (although company records indicate the substance to be tripotassium orthophosphate) and as such this study is not considered to be acceptable for use as a stand-alone source of data but is considered acceptable for use as part of a weight of evidence approach in accordance with Annex XI, section 1.2 of Regulation (EC) No. 1907/2006 (REACH).
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:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Qualifier:
no guideline followed
Principles of method if other than guideline:
No details on methodology included within study report.
GLP compliance:
not specified
Species:
rabbit
Strain:
not specified
Details on test animals or tissues and environmental conditions:
No data
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied : 10 mg
Duration of treatment / exposure:
No data
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
2 per treatment
Details on study design:
No data
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
based on total scores from 2 animals
Time point:
24 h
Score:
10
Max. score:
80
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: Response noted in 1 animal
Irritation parameter:
iris score
Basis:
mean
Remarks:
based on total scores from 2 animals
Time point:
24 h
Score:
5
Max. score:
10
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: Response noted in 1 animal
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
based on total scores from 2 animals
Time point:
24 h
Score:
18
Max. score:
20
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: Response recorded in 2 animals
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
based on total scores from 2 animals
Time point:
24 h
Score:
16
Max. score:
20
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: Response noted in 2 animals
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
based on total scores from 2 animals
Time point:
24 h
Score:
15
Max. score:
80
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: Response noted in 1 animal
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
based on total scores from 2 animals
Time point:
24 h
Score:
13
Max. score:
20
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: Response noted in 2 animals
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
2 animals
Time point:
24/48/72 h
Reversibility:
not reversible
Remarks on result:
probability of moderate irritation
Irritation parameter:
iris score
Basis:
mean
Remarks:
2 animals
Time point:
24/48/72 h
Reversibility:
fully reversible
Remarks on result:
probability of moderate irritation
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
2 animals
Time point:
24/48/72 h
Reversibility:
not reversible
Remarks on result:
probability of moderate irritation
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
2 animals
Time point:
24/48/72 h
Reversibility:
not reversible
Remarks on result:
probability of moderate irritation
Irritant / corrosive response data:
Erythema, oedema and discharge were recorded as local effects.
Other effects:
No data

Table 1: In vivo eye irritation results in rabbits for tripotassium phosphate

 

Dose/Response Data

Eye Structure

Number Responding/Mean Score for 2 Rabbits

24 Hours

48 Hours

72 Hours

Cornea

1/10

1/10

1/15

Iris

1/5

1/5

0/0

Conjunctivae

2/18

2/16

2/13

Interpretation of results:
GHS criteria not met
Conclusions:
The paper concludes that the irritant rating of tripotassium orthophosphate in rabbits in a moderate irritant. Observations were only recorded for 72 hours and as such an indication of the reversibility of the effects is not available.

In accordance with Regulation (EC) No. 1272/2008 (EU CLP) it is not possible to reliably assign a classification on the basis of the results reported in this study report, however the study indicates that tripotassium orthophosphate is potentially corrosive to the eyes and as such this study is considered acceptable for use as part of a weight of evidence approach in accordance with Annex XI, section 1.2 of Regulation (EC) No. 1907/2006 (REACH).


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:
weight of evidence
Study period:
No data
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Qualifier:
according to guideline
Guideline:
other: No data
Deviations:
not applicable
Principles of method if other than guideline:
Test substance was applied as a finely ground sample equivalent to 0.1 mL - 40 mg sample to the eyes of rabbits for 1 minute and for 24 h.
GLP compliance:
no
Remarks:
Study pre-dates GLP
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
No data
Vehicle:
not specified
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: dosage equivalent to 0.1 mL / volume - 40 mg sample
Duration of treatment / exposure:
1 min or 24 h
Observation period (in vivo):
1 minute exposure: 10 days
24 h exposure: 24 h
Number of animals or in vitro replicates:
Three
Details on study design:
No data
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
24 h
Max. score:
110
Reversibility:
not reversible
Remarks on result:
other: 24 h exposure: Corrosive
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
24 h
Score:
21.3
Max. score:
110
Reversibility:
fully reversible
Remarks on result:
other: 1 minute exposure
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Reversibility:
not reversible
Remarks on result:
other: corrosive
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Reversibility:
not reversible
Remarks on result:
other: corrosive
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Reversibility:
not reversible
Remarks on result:
other: corrosive
Irritation parameter:
chemosis score
Basis:
animal: All animals
Time point:
24/48/72 h
Reversibility:
not reversible
Remarks on result:
other: corrosive
Irritant / corrosive response data:
1 minute exposure
Immediate: discomfort was severed with pawing, squealing, thrashing about the stocks, and eyes tightly closed.
10 min: Slight erythema, copious discharge.
1 h: severe erythema, very slight edema, copious discharge.
24 h: Area of barely perceptible corneal dullness in one instance, iris congestion, severe erythema (necosis in conjunctival sac), very slight to slight edema, copious discharge containing white exudate.
40 - 168 h: gradual improvement.
168 h - 10 d: all scored zero.

24 h exposure
Immediate: discomfort was severe with pawing, squealing, thrashing about the stocks, and eyes tightly closed.
10 min: severe erythema, very slight edema, copious discharge.
1 h: severe erythema, very slight to slight edema, copious discharge.
24 h: corrosive
Other effects:
No data

One minute exposure:

Hour

1

24

48

72

120

168

Structure

Cornea

Iris

Conjunctivae

Cornea

Iris

Conjunctivae

Cornea

Iris

Conjunctivae

Cornea

Iris

Conjunctivae

Cornea

Iris

Conjunctivae

Cornea

Iris

Conjunctivae

Animal No.

1

0

0

14

0

5

14

0

0

10

0

0

10

0

0

6

0

0

4

2

0

0

14

0

5

14

0

0

10

0

0

10

0

0

6

0

0

4

3

0

0

14

5

5

16

5

5

16

0

5

14

0

5

8

0

0

6

Mean / 110

 

14.0

 

21.3

 

15.3

 

13.0

 

8.3

 

4.6

No data for 24 h exposure.

Interpretation of results:
study cannot be used for classification
Conclusions:
The study report indicates that tripotassium phosphate was corrosive when applied as a finely ground sample to rabbits eyes at a dosage equivalent to 0.1 mL/ volume - 40 mg sample for 24 h. After an application of 1 minute the author concluded the material was a mild irritant.


In accordance with Regulation (EC) No. 1272/2008 (EU CLP) it is not possible to reliably assign a classification on the basis of the results reported in this study report, however the study indicates that tripotassium orthophosphate is potentially corrosive to the eyes and as such this study is considered acceptable for use as part of a weight of evidence approach in accordance with Annex XI, section 1.2 of Regulation (EC) No. 1907/2006 (REACH).
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:
other: Reported in secondary literature (review paper)
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Qualifier:
according to guideline
Guideline:
other: no data
Deviations:
not specified
Principles of method if other than guideline:
4 New Zealand White rabbits were dosed with 0.1g of test material (neat) in the right eye. The left eye was used as the control eye.
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
No data
Vehicle:
unchanged (no vehicle)
Controls:
other: left eye served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g
Duration of treatment / exposure:
Washed: 20-30 seconds
Unwashed: 22 days
Observation period (in vivo):
22 days
Number of animals or in vitro replicates:
4
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): the right eyes of 2 out of the 4 tested animals were washed with 100 mL of tap water
- Time after start of exposure: 20-30 seconds after treatment

SCORING SYSTEM: Draize JH, Woodward Fand Calvery HO (1944) J Pharmacol. Exp. ther. 83: 387.

Irritation parameter:
overall irritation score
Remarks:
Draize score
Basis:
other: unwashed (2 animals)
Time point:
24 h
Score:
75
Max. score:
110
Reversibility:
not fully reversible within: 22 days
Irritation parameter:
overall irritation score
Remarks:
Draize score
Basis:
other: unwashed (2 animals)
Time point:
48 h
Score:
85
Max. score:
110
Reversibility:
not fully reversible within: 22 days

Table 1. Results

Test compound

Treatment

Eye irritancy

Draize scores (110 maximum)

24 hr

48 hr

22 days

Tripotassium phosphate

Unwashed

Extreme

75

85

16

Washed

Moderate

46

48

9

Interpretation of results:
study cannot be used for classification
Conclusions:
The authors conclude that tripotassium orthophosphate is extremely irritating to the unwashed eyes of New Zealand White rabbits. As the study does not provide individual eye scores or detailed results and as only 2 animals were tested, it is not sufficient to conclude on classification and labelling in accordance with Regulation (EC) No. 1272/2008 (EU CLP). However, this study is considered acceptable for use as part of a weight of evidence approach in accordance with Annex XI, section 1.2 of Regulation (EC) No. 1907/2006 (REACH).
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

Skin irritation: In accordance with Regulation (EC) No 1272/2008 (EU CLP) tripotassium orthophosphate is not considered to be classified for skin irritation.

Eye irritation: All available studies indicate that tripotassium orthophosphate is corrosive to the eyes and therefore classification as a category 1 corrosive is proposed in accordance with Regulation (EC) No. 1272/2008 (EU CLP).

Respiratory irritation: Respiratory irritation has been noted in worker populations exposed to tripotassium orthophosphate via the inhalation route and therefore a classification of STOT-SE category 3 for respiratory tract irritation is proposed in accordance with Regulation (EC) No. 1272/2008 (EU CLP).