Potassium pentahydrogen bis(phosphate)

Endpoint summary

Description of key information

Skin irritation: One key study is available. The study is conducted according to appropriate 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).
Eye irritation: One key study is available. The study is conducted according to appropriate 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).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Remarks:

In vivo. 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: 19/04/2006 To: 22/04/2006

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

(2002)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Version / remarks:

(1998)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Part B.4 (Skin Irritation), Directive 2004/73/EC (2004)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Robinson Services, Inc. Clemmons, NC on April 12, 2006.
- Age at study initiation: The animals are described as young adult rabbits
- Weight at study initiation:
- Housing: The animals were singly housed in suspended stainless steel caging with mesh floors. Litter paper was placed beneath the cage and was changed at least three times per week.
- Diet (e.g. ad libitum): Pelleted Purina Rabbit Chow #5326
- Water (e.g. ad libitum):Filtered tap water was supplied ad libitum by an automatic water dispensing system.
- Acclimation period: 7 days
- Other: 1 male and 2 females were tested. Females assigned to test were nulliparous and non-pregnant.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-22°C
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hrs light/ dark cycle.


IN-LIFE DATES: From: 12/04/2006 To: 22/04/2006

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

water

Controls:

not specified

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.56 gram
- Concentration (if solution): 90% w/w

VEHICLE
- The vehicle was distilled water
- A dry paste was formed.

Duration of treatment / exposure:

4 hours

Observation period:

72 hours after removal of patches containing the test material.

Number of animals:

Three (1 male and 2 females)

Details on study design:

TEST SITE
The test material (moistened to a 90% w/w aqueous suspension) was placed on a 1"x1", 4-ply gauze pad and applied to one 6cm² intact dose site on each animal. The pad and the entire trunk of the animal were then wrapped with semi-occlusive 3-inch micropore tape. Elizabethan collars were placed on each rabbit.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The pads and collars were removed and the test sites were gently cleansed of any residual test substance.
- Time after start of exposure: 4 hours

SCORING SYSTEM: Draize, J.H., Woodard, G. and Calvery, H.O. Methods for the study of irritation and toxicity of susbtances applied topically to the skin and mucous membranes. J. Pharm. Exp. Ther. 1944; 82:377-390.

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 hrs

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:

other: all animals tested

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

See Tables 1 and 2.
Within one hour after patch removal, all three treated sites exhibited very slight erythema. The overall incidence and severity of irritation decreased with time. All animals were free of dermal irritation by 48 hours.

Other effects:

None - all animals appeared active and healthy during the study.

Table 1 - Individual skin irritation scores

Results given in the format 'erythema/edema'

Animal #	Sex	Time after patch removal
		30-60 min	24 hrs	48 hrs	72 hrs
16475	F	1/0	1/0	0/0	0/0
16476	M	1/0	0/0	0/0	0/0
16477	F	1/0	0/0	0/0	0/0
Total		3/0	1/0	0/0	0/0
Mean		1.0/0	0.3/0	0/0	0/0

Table 2: Summary of primary skin irritation scores (average value for three rabbits)

	Time after patch removal
Erythema	1.0	0.3	0	0
Edema	0	0	0	0
Total (PDI)^a	1.0	0.3	0	0

^a– PDI = Average Erythema + average Edema

Interpretation of results:

GHS criteria not met

Conclusions:

The author reports that under the conditions of this study, PeKacid is classified as slightly irritating to the skin according to U.S. EPA Addendum 3 on data reporting to pesticide assessment guidelines; Dermal Irritation, January 1988.

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) No1272/2008 (EU CLP). Potassium pentahydrogen bis(phosphate) is not considered to be irritating to the skin.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Remarks:

In vivo. 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:

2005-09-27 to 2006-07-07

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Robinson Services, Inc. Clemmons, NC.
- Age at study initiation: Young adult
- Housing: The animals were singly housed in suspended stainless steel caging with mesh floors which conform to the size recommendations in the most recent Guide for the Care and Use of Laboratory Animals DHEW (NIH). Litter paper was placed beneath the cage and was changed at least 3 times per week.
- Diet: Pelletted Purina Rabbit Chow #5326
- Water: Filtered tap water was supplied ad libitum by an automatic water dispensing system.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 23 ºC
- Photoperiod: 12 h light/dark cycle

IN-LIFE DATES: From: 2006-04-27 To: 2006-05-04

Vehicle:

unchanged (no vehicle)

Controls:

other: The other eye of each rabbit remained untreated with the test substance and served as a control.

Amount / concentration applied:

one-tenth of a gram

Duration of treatment / exposure:

Test substance was not removed

Observation period (in vivo):

7-days post instillation

Number of animals or in vitro replicates:

Three

Details on study design:

SCORING SYSTEM: scored according to Draize. The classification of eye scores was by the system of Kay and Calandra.


TOOL USED TO ASSESS SCORE: High-intensity white light (Mag Lite) and the fluorescein dye evaluation procedure described below.

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.66

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.66

Max. score:

4

Reversibility:

fully reversible within: 4 days

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.66

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 7 days

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 7 days

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.66

Max. score:

2

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.66

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.66

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.66

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritant / corrosive response data:

Within 24 h of test substance instillation, all three treated eyes exhibited corneal opacity, iritis and conjuncitvitis. The overall incidence and severity of irritation decreased gradually thereafter. All animals were free of ocular irritation by Day 7 (study termination).

Other effects:

All animals appeared active and healthy during the study. Apart from the eye irritation noted below, there were no other signs of gross toxicity, adverse pharmacologic effects or abnormal behaviour.

Individual scores for ocular irritation:

Rabbit No. 16540 (male)
	Hours				Days
	1	24	48	72	4	7
I.Cornea
A. Opacity	1	1*	1	0*	0	0
B. Area	1	1	1	4	4	4
(A x B) x 5	5	5	5	0	0	0
II. Iris
A. Values	1	1	1	1	0	0
A x 5	5	5	5	5	0	0
III. Conjunctivae
A. Redness	2	2	2	2	1	0
B. Chemosis	2	2	2	1	0	0
C. Discharge	3	3	2	1	1	0
(A + B + C) x 2	14	14	12	8	4	0
Total	24	24	22	13	4	0
Rabbit No. 16541 (female)
I.Cornea
A. Opacity	1	1*	1	0*	0	0
B. Area	1	1	1	4	4	4
(A x B) x 5	5	5	5	0	0	0
II. Iris
A. Values	1	1	1	1	0	0
A x 5	5	5	5	5	0	0
III. Conjunctivae
A. Redness	2	2	2	2	1	0
B. Chemosis	2	2	2	2	1	0
C. Discharge	2	2	1	1	0	0
(A + B + C) x 2	12	12	10	10	4	0
Total	22	22	20	15	4	0
Rabbit No. 16542 (male)
I.Cornea
A. Opacity	1	1*	1	0*	0	0
B. Area	1	1	1	4	4	4
(A x B) x 5	5	5	5	0	0	0
II. Iris
A. Values	0	1	1	0	0	0
A x 5	0	5	5	0	0	0
III. Conjunctivae
A. Redness	2	2	2	1	1	0
B. Chemosis	2	2	2	1	0	0
C. Discharge	3	2	1	1	1	0
(A + B + C) x 2	14	12	10	6	4	0
Total	19	22	20	6	4	0

* 2 % ophthalmic fluorescein sodium used to evaluate the extent or verify the absene of corneal opacity.

Classification of eye irritation scores:

MMTS	Irritation classification	Requirement for maintenance of classification
0.0 – 0.5	Non	Up to 0.5 at 1 h with zeros at 24 h; otherwise increase 1 level.
0.6 – 2.5	Practically non	with zeros at 24 h; otherwise increase 1 level.
2.6 – 15.0	Minimally	with zeros at 48 h; otherwise increase 1 level.
15.1 – 25.0	Mildly	with zeros at 96 h; otherwise increase 1 level.
25.1 – 50.0	Moderately	With 7 day mean ≤ 20 and individual total scores ≤ 10 in at least 60 % of the rabbits with no total score > 30; otherwise increase 1 level.
50.1 – 80.0	Severely	With 7 day mean ≤ 40 and individual total scores ≤ 30 in at least 60 % of the rabbits with no total score > 60; otherwise increase 1 level.
80.1 – 100.0	Extremely	With 7 day mean ≤ 80 and individual total scores ≤ 60 in at least 60 % of the rabbits with no total score > 100; otherwise increase 1 level.
100.1 - 110	Maximally	With 7 day mean > 80 and individual total scores > 60 in at least 60 % of the rabbits; otherwise decrease 1 level.

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

Under the conditions of the study, Pekacid is classified as irritating to the eyes, in accordance with Regulation (EC) No. 1272/2008. 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).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Justification for classification or non-classification

Skin irritation: The data available to assess the skin irritation potential of potassium pentahydrogen bis(phosphate) concludes 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 this endpoint as the data provided is sufficient.

Eye irritation: The data available to assess the eye irritation potential of potassium pentahydrogen bis(phosphate) concludes that the substance is classified as irritating to eyes, category 2 in accordance with Regulation (EC) No. 1272/2008 (EU CLP). It is not considered scientifically justified on ethical grounds to repeat in vivo studies for this endpoint as the data provided is sufficient.