Dipotassium hydrogenorthophosphate

Endpoint summary

Description of key information

Skin irritation: Four in vivo studies are available for skin irritation. The study reported by Freeman (1987) 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) and as such dipotassium hydrogenorthophosphate is not classified for skin irritation. The additional studies ( Blaszcak DL, 1986, Bullock, 1972 and Becker, 1975) are provided to support this conclusion. 
Eye irritation: Three in vivo studies are available for eye irritation. The key study (Blaszcak, 1986) is conducted to a protocol similar to modern day guidelines. The results are deemed sufficient for classification and labelling in accordance with Regulation (EC) No. 1272/2008 (EU CLP). The supporting studies (Freeman C, 1987 and Parke G, 1975) support the conclusions made from the data in the key study. 

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin 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:

No data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

other: no data

Deviations:

not applicable

Principles of method if other than guideline:

Dipotassium phosphate at dosage levels of 300 and 20 mg/kg was in contact with the skin for 24 h under an occlusive wrap. Observations were conducted at approximately 3 h on the day of dosing and daily thereafter for 14 days.

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hazleton Researach Animals, Inc., Denver, Pennsylvania.
- Age at study initiation: young adult
- Weight at study initiation: 2.10 to 2.65 kg
- Housing: individually housed in stainless steel rabbit cages with DACB cageboard bedding used in litter pans.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 68 - 77 ºF
- Humidity (%): 28 - 44 %
- Photoperiod (hrs dark / hrs light): 12 h fluorescent light and 12 h dark

Type of coverage:

occlusive

Preparation of test site:

other: clipped

Vehicle:

physiological saline

Controls:

not specified

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 300 mg/kg and 20 mg/kg

Duration of treatment / exposure:

24 h

Observation period:

14 days

Number of animals:

5 animals

Details on study design:

TEST SITE
- Area of exposure: the trunk from the scapular to the pelvic floor.
- Type of wrap if used: 8 ply 4 x 4 inch gauze pad held in place with hypoallergenic tape. The test site was occluded with impervious plastic sheeting.


REMOVAL OF TEST SUBSTANCE
- Washing: the test site was wiped with clean gauze moistened with methanol, then rinsed with tap water.
- Time after start of exposure: approximately 24 h after application.


SCORING SYSTEM: Draize

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 hrs

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0.6

Max. score:

4

Reversibility:

fully reversible within: 72 hrs

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 72 hrs

Irritation parameter:

edema score

Basis:

other: all animals tested

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

Slight erythema was noted on the test sites of three rabbits in the 300 mg/kg group. All irritation resolved by day 4.

Other effects:

There were no treatment-related deaths, clinical signs, changes in body weight or treatment-related observations at necropsy.

Individual scores (300 mg/kg bw)

Animal #	ER	ED	O
24 hr
B5917M	0	0	0
B5918M	0	0	0
B5851M	1	0	0
B5905M	1	0	0
B5888M	1	0	0
Irritation score: 0.6/8.0
48 hr
B5917M	0	0	0
B5918M	0	0	0
B5851M	1	0	0
B5905M	1	0	0
B5888M	0	0	0
Irritation score: 0.4/8.0
72 hr
B5917M	0	0	0
B5918M	0	0	0
B5851M	1	0	0
B5905M	0	0	0
B5888M	0	0	0
Irritation score: 0.2/8.0
Day 4
B5917M	0	0	0
B5918M	0	0	0
B5851M	0	0	0
B5905M	0	0	0
B5888M	0	0	0
Irritation score: 0.0/8.0

Primary skin irritation scores for each group:

Scoring interval	Dosage level
	300 mg/kg	20 mg/kg
24 h	0.6 / 8.0	0 / 8.0
48 h	0.4 / 8.0	0 / 8.0
72 h	0.2 / 8.0	0 / 8.0
Day 4	0 / 8.0	0 / 8.0
Day 7	0 / 8.0	0 / 8.0
Day 14	0 / 8.0	0 / 8.0
Primary irritation Index	0.4 / 8.0	0.8 / 8.0

Mean body weights ± SD

Dosage level (mg/kg)	Body weights ± SD (kg)
	Day
	0	7	14
300	2.26 ± 0.223	2.31 ± 0.179	2.38 ± 0.169
20	2.23 ± 0.094	2.19 ± 0.218	2.15 ± 0.063

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of the study the authors concludes that the test material is temporarily approximated to be minimally irritating (300 mg/kg) and non-irritating (20.0 mg/kg).
This study has been selected as the key study because the results are sufficient in order to derive a reliable conclusion on classification and labelling in accordance with Regulation EC (No.) 1272/2008 (EU CLP). Dipotassium hydrogenorthophosphate is not considered to be classified according to Regulation (EC) No. 1272/2008 (EU CLP).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

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

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.

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

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

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

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.

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

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

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

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

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

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

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

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 72 hrs

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

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

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

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

Irritation parameter:

iris score

Basis:

other: All 6 animals tested

Time point:

24/48/72 h

Score:

0

Max. score:

2

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.

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	-	-	-	-

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).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Justification for classification or non-classification

The data available for skin and eye irritation of dipotassium hydrogenorthophosphate conclude that no classification is required according to regulation (EC) No. 1272/2008 (EU CLP). It is not considered scientifically justified on ethical grounds to repeat in vivo studies for these endpoints as the data provided is sufficient.