Dipotassium hydrogenorthophosphate

Eye irritation

Administrative data

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:

From: 12/05/1986 To: 15/05/1986

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1986

Report date:

1986

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

minor deviation: The range over which room temperature was maintained was lower than the recommended 20±3°C.

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: FIFRA: Pesticide Assessment Guidelines, Subdivision F; Hazard Evaluation: Human and Domestic Animals; Office of Pesticide and Toxic Substances, November 1982; Section 81-4, Primary Eye Irritation Study,

Deviations:

not specified

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: TSCA; Health Effects Test Guidelines; Office of Toxic Substances, Office of Pesticides and Toxic Substances, US EPA, August 1982, Acute Exposure, Primary Eye Irritation Primary eye irritation

Deviations:

not specified

GLP compliance:

no

Remarks:

Study predates GLP

Test material

Test material information

Constituent 1

Reference substance name:

Dipotassium hydrogenorthophosphate

EC Number:

231-834-5

EC Name:

Dipotassium hydrogenorthophosphate

Cas Number:

7758-11-4

Molecular formula:

H3O4P.2K

IUPAC Name:

dipotassium hydrogen phosphate

Details on test material:

- Name of test material (as cited in study report): Potassium Phosphate Diibasic, K2HPO4 50% Solution (aqueous)
- Substance type: Clear, colourless
- Physical state: Liquid
- Analytical purity: no data
- Lot/batch No.: Carondelet Lab #1
- Storage condition of test material: Room temperature
- Receipt of test material: The test material was received 06/05/1986 from Monsanto Company.

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Hazleton-Dutchland, Inc. Denver, Pennsylvania
- Age at study initiation: Young adults (atleast 8 weeks old at study initiation)
- Weight at study initiation:
- Housing: Individually housed, suspended stainless steel cages.
- Diet (e.g. ad libitum): Lab Rabbit Chow HF (Purina # 5326), ad libitum.
- Water (e.g. ad libitum): Automatic watering system, ad libitum. Municipal water supply (Elizabethtown Water Co.)
- Acclimation period: 21 days, with checks for viability twice daily.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): Temperature was maintained within the range of 60-70°F to the maximum extent possible. (15.5°C-21.1°C)
- Humidity (%): Humidity was kept within the range of 30-70% to the maximum extent possible.
- Air changes (per hr): No data.
- Photoperiod (hrs dark / hrs light): Light cycle: 12 hours light, 12 hours dark (controlled by automatic timer)


IN-LIFE DATES: From: Date of receipt on 21/04/1986 To: Termination 15/05/1986

Test system

Vehicle:

other: The test material was received and administered as 50% solution

Controls:

other: The untreated eye served as control.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): 50%

VEHICLE
- No data.

Duration of treatment / exposure:

24 h

Observation period (in vivo):

3 days.

Number of animals or in vitro replicates:

Six (3 males, 3 females)

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The eyes were rinsed to remove any residual test material.
- Time after start of exposure: 24 h

STUDY DESIGN
- Evaluation of ocular irritation: At 1, 24, 48 and 72 h after treatment

SCORING SYSTEM: At each interval the treated control eyes were examined and scored according to Draize J.H. 1959, The Appraisal of Chemicals in Foods. Drugs and Cosmetics, p 51. Association of Food and Drug Officials of the United States, Austin, Texas. Scores were considered positive under 16 CFR 1500.42.

TOOL USED TO ASSESS SCORE: fluorescein dye was used to confirm presence or absence of corneal ulceration.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.6

Max. score:

3

Reversibility:

fully reversible within: 72 hrs

Results 2

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 72 hrs

Results 3

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.6

Max. score:

3

Reversibility:

fully reversible within: 72 hrs

Results 4

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #4

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 hrs

Results 5

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #5

Time point:

24/48/72 h

Score:

0.6

Max. score:

3

Reversibility:

fully reversible within: 72 hrs

Results 6

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #6

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 hrs

Results 7

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 72 hrs

Results 8

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 72 hrs

Results 9

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 72 hrs

Results 10

Irritation parameter:

chemosis score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 72 hrs

Results 11

Irritation parameter:

chemosis score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 72 hrs

Results 12

Irritation parameter:

chemosis score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 72 hrs

Results 13

Irritation parameter:

iris score

Basis:

other: All 6 animals tested

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 14

Irritation parameter:

cornea opacity score

Basis:

other: all 6 animals tested

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

50% Potassium Phosphate Solution produced mild, transient ocular irritation. Irritation consisted primarily of conjunctival irritation (redness, chemosis, discharge) and iridial changes or iritis, with the most severe effects ocurring at one hour. No significant corneal changes were seen. All six animals were free of ocular irritation within 48 to 72 hours after instillation of the test material.

Other effects:

Animals vocalizing after instillation of the test material are identified in Table 2.

Any other information on results incl. tables

Table 1 - Eye irritation in rabbits, summary of responses.

Animal # / Sex	Cornea		Iris	Conjunctivae
	Opacity	Ulceration		Redness	Chemosis	Necrosis or Ulceration
1 F	-	-	-	-	+	-
2 F	-	-	+	+	+	-
3 M	-	-	+	+	+	-
4 F	-	-	+	+	+	-
5 M	-	-	-	+	+	-
6 M	-	-	+	+	+	-

Table 2 - Individual ocular scores.

^v- animal vocalised after test material administration

f - observation confirmed with fluorescein

Animal 1 - Female^v	Time After Administration (hours)				Positive scores per 16 CFR 1500.42
Conjunctivae scores	1	24	48	72
Redness	1	1	1	0	No
Chemosis	2	1	0	0	Yes
Discharge	2	0	0	0	-
Necrosis (N) / Ulceration (U)	0	0	0	0	No
Iris scores	+	0	0	0	No
Cornea scores
Opacity	0	0	0	0	No
Area	0	0	0	0
Stippling	0	0	0	0
Ulceration	0	0f	0f	0	No
Other	-	-	-	-

Table 2 - continued

Animal 2 - F	Time After Administration (hours)				Positive scores per 16 CFR 1500.42
Conjunctivae scores	1	24	48	72
Redness	2	1	0	0	Yes
Chemosis	2	0	0	0	Yes
Discharge	1	0	0	0	-
Necrosis (N) / Ulceration (U)	0	0	0	0	No
Iris scores	1	0	0	0	Yes
Cornea scores
Opacity	+	0	0	0	No
Area	4	0	0	0
Stippling	0	0	0	0
Ulceration	0	0f	0f	0	No
Other	-	-	-	-

Table 2 - continued

Animal 3 - Male	Time After Administration (hours)				Positive scores per 16 CFR 1500.42
Conjunctivae scores	1	24	48	72
Redness	2	1	1	0	Yes
Chemosis	2	1	0	0	Yes
Discharge	2	0	0	0	-
Necrosis (N) / Ulceration (U)	0	0	0	0	No
Iris scores	1	0	0	0	Yes
Cornea scores
Opacity	0	0	0	0	No
Area	0	0	0	0
Stippling	0	0	0	0
Ulceration	0	0f	0f	0	No
Other	-	-	-	-

Table 2 - continued

Animal 4 - Female	Time After Administration (hours)				Positive scores per 16 CFR 1500.42
Conjunctivae scores	1	24	48	72
Redness	2	2	1	0	Yes
Chemosis	2	1	0	0	Yes
Discharge	3	0	0	0	-
Necrosis (N) / Ulceration (U)	0	0	0	0	No
Iris scores	1	0	0	0	Yes
Cornea scores
Opacity	+	0	0	0	No
Area	4	0	0	0
Stippling	0	0	0	0
Ulceration	0	0f	0f	0	No
Other	-	-	-	-

Table 2 - continued

Animal 5 - Male^v	Time After Administration (hours)				Positive scores per 16 CFR 1500.42
Conjunctivae scores	1	24	48	72
Redness	2	1	1	0	Yes
Chemosis	2	1	0	0	Yes
Discharge	3	0	0	0	-
Necrosis (N) / Ulceration (U)	0	0	0	0	No
Iris scores	+	0	0	0	No
Cornea scores
Opacity	+	+	0	0	No
Area	4	4	0	0
Stippling	1	1	0	0
Ulceration	0	0f	0f	0	No
Other	-	-	-	-

Table 2 - continued

Animal 6 - Male	Time After Administration (hours)				Positive scores per 16 CFR 1500.42
Conjunctivae scores	1	24	48	72
Redness	2	2	1	0	Yes
Chemosis	2	1	0	0	Yes
Discharge	2	0	0	0	-
Necrosis (N) / Ulceration (U)	0	0	0	0	No
Iris scores	1	+	0	0	Yes
Cornea scores
Opacity	+	+	0	0	No
Area	4	4	0	0
Stippling	0	0	0	0
Ulceration	0	0f	0f	0	No
Other	-	-	-	-

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Author's conclusion: 50% Potassium Phosphate Solution produced mild, transient ocular irritation. Irritation consisted primarily of conjunctival irritation (redness, chemosis, discharge) and iridial changes or iritis, with the most severe effects ocurring at one hour. No significant corneal changes were seen. All six animals were free of ocular irritation within 48 to 72 hours after instillation of the test material.

This study considered to be sufficient for classification and labelling due to the minimal effects noted and is therefore submitted as a key study with supporting data also provided to support the conclusions on classification and labelling. Dipotassium hydrogenorthophosphate is not considered to be classified for eye irritation in accordance with Regulation (EC) No. 1272/2008 (EU CLP).