Potassium dihydrogenorthophosphate

Endpoint summary

Description of key information

Skin irritation: Three in vivo studies are available for skin irritation. The study reported by Freeman (1990) 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 studies (Birch, 1972 and Birch, 1973) are provided to support this conclusion. 
Eye irritation: Two in vivo studies are available for eye irritation. The key study (Freeman C, 1986) is conducted to a protocol similar to modern day guidelines and was performed in a GLP accredited facility. Despite only having assessed the eyes of two animals, the results are deemed sufficient for classification and labelling in accordance with Regulation (EC) No. 1272/2008 (EU CLP). The supporting study (Birch MD, 1973) supports the use of 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:

Rabbits were treated topically on each of two test sites and coverd with gauze patches and the trunk of the animal was wrapped with a piece of cheesecloth for 4 h after which the animals were unwrapped and the test material removed. Approximately 30 min after the end of the exposure period, the test sites were scored for irritation using the method of Draize.

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Haxleton Research Animals, Inc., Denver, Pennsylvania.
- Age at study initiation: young adult
- Weight at study initiation: 2.6 to 2.75 kg
- Housing: individually housed in stainless steel cages wiht DACB cageboard bedding in the litter pans
- Diet: no data
- Water: no data
- Acclimation period:


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 68 to 72 ºC
- Humidity (%): 51 - 66 %
- Air changes (per hr): no data
- Photoperiod: 12 h fluorescent light and 12 h dark cycle


IN-LIFE DATES: no data

Type of coverage:

semiocclusive

Preparation of test site:

other: clipped free of hair

Vehicle:

physiological saline

Controls:

not specified

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g of test material moistened with physiological saline
- Concentration (if solution): no data


VEHICLE
- Amount(s) applied (volume or weight with unit): no data
- Concentration (if solution):no data
- Lot/batch no. (if required): no data
- Purity:no data

Duration of treatment / exposure:

4 h

Observation period:

3 days

Number of animals:

Three

Details on study design:

TEST SITE
- Area of exposure: the clipped area extended from the scapular to the pelvic region. One test site was located on each side of the spinal column.
- % coverage: no data
- Type of wrap if used: 8 ply 2x 2 inch gauze pad secured to each test site with hypoallergenic tape. The entire trunk of the animal was wrapped with a semi-occlusive cheesecloth bandage.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): test sites were wiped with clean gauze moistened with methanol and then rinsed with tap water.
- Time after start of exposure:


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:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

No irritation was noted on any of the test sites during any of hte scoring intervals, and the test was terminated following the 72-h scoring.

Other effects:

All animals remained healthy throughout the study.

Group irritation scores for each scoring interval

Scoring interval	Irritation score
4.5 h	0
24 h	0
48 h	0
72 h	0
Primary irritation index	0/8.0

Pretest examination

Animal #	Body weight (kg)	Test sites
B7853F	2.70	N
B7854F	2.75	N
B7843M	2.60	N

N - normal

Individual skin scores

Animal #	Left			Right
	ER	ED	O	ER	ED	O
4.5 h
B7853F	0	0	0	0	0	0
B7854F	0	0	0	0	0	0
B7843M	0	0	0	0	0	0
Irritation score	0 / 8.0
24 h
B7853F	0	0	0	0	0	0
B7854F	0	0	0	0	0	0
B7843M	0	0	0	0	0	0
Irritation score	0 / 8.0
48 h
B7853F	0	0	0	0	0	0
B7854F	0	0	0	0	0	0
B7843M	0	0	0	0	0	0
Irritation score	0 / 8.0
72 h
B7853F	0	0	0	0	0	0
B7854F	0	0	0	0	0	0
B7843M	0	0	0	0	0	0
Irritation score	0 / 8.0

ER - erythema/eschar

ED - edema

O - other comments

F - female

M - male

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study the test material is non-irritating to intact skin when applied topically to rabbits.

This study is conducted according protocols comparable to the appropriate guidelines (EU ) and under the conditions of GLP. Minor deviations are noted however, the study is considered to be acceptable and to adequately satisfy both the guideline requirement and the regulatory requirement as a key study for this endpoint.
Potassium dihydrogenorthophosphate 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:

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: no data

Deviations:

not applicable

Principles of method if other than guideline:

The test substance was instilled into the test eyes of 4 New Zealand white rabbits at a dose of 0.1 g. Two rabbits remained unwashed, while the eyes of the remaining rabbits were washed with tap water 20 - 30 sec after treatment. Eyes were assessed for irritation using the method of Draize up to 72 h after instillation.

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Hazleton Reseach Animals, Inc., Denver, Pennsylvania.
- Age at study initiation: young adult
- Weight at study initiation: 2.53 to 3.09 kg
- Housing: individually housed in stainless steel cages. DACB cageboard bedding was used in the litter pans.
- Diet: ad libitum
- Water: ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 71 to 74 ºF
- Humidity (%): 61 %
- Photoperiod (hrs dark / hrs light): 12 h dark / 12 h light

Vehicle:

unchanged (no vehicle)

Controls:

other: the left eye of each rabbit served as a control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g per test eye

Duration of treatment / exposure:

The eyes were washed 20 - 30 seconds after instillation for 2 rabbits
The eyes of two rabbits remained unwashed

Observation period (in vivo):

72 h

Number of animals or in vitro replicates:

4

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: gently washed with 100 mL of tap water at a rate of approximately 100 mL/min.
- Time after start of exposure: 20 - 30 sec after instillation of the test substance


SCORING SYSTEM: Draize


TOOL USED TO ASSESS SCORE: after 24 h examination with a penlight type light, the eyes were examined with the aid of 2 % sodium fluorescein dye.

Irritation parameter:

cornea opacity score

Basis:

other: both animals tested

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

other: both animals tested

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

other: both animals tested

Time point:

24/48/72 h

Score:

0

Max. score:

3

Irritation parameter:

chemosis score

Basis:

other: both animals tested

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

1 h after dosing, all eyes exhibited slight chemosis and / or severe discharge. Within 24 h, all irritation had resolved and the test was terminated following the 72 h scoring. Washing the eyes with tap water shortly after exposure had no significant effect on the irritation observed at the 1-h scoring.

Other effects:

All animals remained healthy throughout the study.

The primary irritation indexes for the unwashed and washed eyes at each time interval

Scoring interval	Unwashed	Washed
1 h	8.0	7.0
24 h	0	0
48 h	0	0
72 h	0	0

Eye examination individual eye scores

Animal No.	Cornea	Iris	Conjunctiva
	Opacity/Area	Iritis	Redness	Chemosis	Discharge
1 hour
B5504F	0/0	0	0	1	3
B5506F	0/0	0	0	1	3
B5508F (w)	0/0	0	0	0	3
B5509F (w)	0/0	0	0	1	3
Primary eye irritation index – unwashed 8.0/110, washed 7.0/110.
24 hour
B5504F	0/0	0	0	0	0
B5506F	0/0	0	0	0	0
B5508F (w)	0/0	0	0	0	0
B5509F (w)	0/0	0	0	0	0
Primary eye irritation index – unwashed 0.0/110, washed 0.0/110.
48 hour
B5504F	0/0	0	0	0	0
B5506F	0/0	0	0	0	0
B5508F (w)	0/0	0	0	0	0
B5509F (w)	0/0	0	0	0	0
Primary eye irritation index – unwashed 0.0/110, washed 0.0/110.
72 hour
B5504F	0/0	0	0	0	0
B5506F	0/0	0	0	0	0
B5508F (w)	0/0	0	0	0	0
B5509F (w)	0/0	0	0	0	0
Primary eye irritation index – unwashed 0.0/110, washed 0.0/110.

(w) - washed

Interpretation of results:

GHS criteria not met

Conclusions:

Authors conclusion: Under the conditions of this study the test material is non-irritating to both unwashed and washed eyes.

Although the study has only been conducted on two animals (unwashed eyes) it is 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. Potassium dihydrogenorthophosphate 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 potassium dihydrogenorthophosphate 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.