Potassium pentahydrogen bis(phosphate)

Eye irritation

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Potassium pentahydrogen bis(phosphate)

EC Number:

238-961-5

EC Name:

Potassium pentahydrogen bis(phosphate)

Cas Number:

14887-42-4

Molecular formula:

H 5 K O 8 P 2

IUPAC Name:

potassium pentahydrogen diphosphate

Constituent 2

Reference substance name:

14487-42-4

Cas Number:

14487-42-4

IUPAC Name:

14487-42-4

Details on test material:

- Name of test material: Pekacid
- Lot No.: #0001
- Physical state: White crystalline powder
- PSL reference no.: 060214-3H
- Storage conditions: At room temperature
- Composition: The product is an inorganic phosphate salt. See methods table.
- pH: 2.2 (1 % water)
- Solubility: Fully soluble in water
- Stability: The test substance was expected to be stable for the duration of the test.
- Expiration date: 2007-12-31

Test animals / tissue source

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

Test system

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.

Results and discussion

In vivo

Results

Results 1

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

Results 2

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

Results 3

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

Results 4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 7 days

Results 5

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 7 days

Results 6

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

Results 7

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

Results 8

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

Results 9

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

Results 10

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

Results 11

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 12

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.

Any other information on results incl. tables

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.

Applicant's summary and conclusion

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).