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Toxicological information

Eye irritation

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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:
11/08/1986 - 25/08/1986
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1987

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Tetrapotassium pyrophosphate
EC Number:
230-785-7
EC Name:
Tetrapotassium pyrophosphate
Cas Number:
7320-34-5
Molecular formula:
H4O7P2.4K
IUPAC Name:
tetrapotassium diphosphate
Details on test material:
- Name of test material (as cited in study report): Tetrapotassium pyrophosphate
- Substance type: White granules
- Physical state: Solid
- Analytical purity: >99%
- Stability under test conditions: Stable indefinitely
- Storage condition of test material: Room temperature
- Other:
Formulation: Technical
Reference #: 600G5028W
FMC-T#: 425
Date received: 05/03/1986

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Hazleton Research Animals, Inc., Denver, Pennsylvania on July 16th, 1986
- Age at study initiation: The animals were young.
- Weight at study initiation: 2.53-2.67 kg
- Housing: Individual stainless steel cages, DAGB cageboard bedding was used in litter pans.
- Diet (e.g. ad libitum): Purina High Fiber Rabbit Chow 5326, ad libitum
- Water (e.g. ad libitum): fresh tap water ad libitum
- Acclimation period: July 16th 1986 - August 7th 1986


ENVIRONMENTAL CONDITIONS
- Temperature (°F): 68 - 75 °F
- Humidity (%): 50 - 64 %
- Photoperiod (hrs dark / hrs light): 12 hours fluorescent light, 12 hours dark cycle.


IN-LIFE DATES: From: 16/07/1986 To: 25/08/1986

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: yes, the untreated left eyes served as controls.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.10 gram
Duration of treatment / exposure:
washed eyes: exposure was 20-30 seconds before the eye were rinsed.
not washed: The test material was not removed by any external processes.
Observation period (in vivo):
13 days
Number of animals or in vitro replicates:
4
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): 2 of the 4 animals had their eye washed, the remaining 2 did not.
- Time after start of exposure: 20-30 seconds after treatment.
- The washed eyes were rinsed with 100 mL of tap water for 1 minute.

SCORING SYSTEM: Eyes were assessed for irritation using the method of Draize.


TOOL USED TO ASSESS SCORE: The eyes were examined with the aid of 2% fluorescein dye. Test eyes which retained fluorescein at 24 hours were examined with dye at subsequent assessment times until corneal irritation was no longer observed or dye was no longer retained.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.6
Max. score:
4
Reversibility:
fully reversible within: 13 days
Remarks on result:
other: unwashed eyes
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
other: unwashed eyes
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #1
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
fully reversible within: 13 days
Remarks on result:
other: unwashed eyes
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 13 days
Remarks on result:
other: unwashed eyes
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: Unwashed eyes
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
other: unwashed eyes
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: 13 days
Remarks on result:
other: unwashed eyes
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 13 days
Remarks on result:
other: unwashed eyes
Irritant / corrosive response data:
Several hours after instillation, severe hemorrhagic conjunctivitis was noted in both unwashed eyes, one of which also had iritis; washed eyes had moderate conjunctivitis. Within 24 hours, hemorrhagic conjunctivitis was present in all eyes and slight corneal opacities were evident in both unwashed eyes. Irritation gradually resolved, and by day 4 both of the washed eyes had recovered; unwashed eyes had mild conjunctival redness and discharge. By day 13, both of the unwashed eyes had recovered and the test was terminated.

Washing the eyes with tap water shortly after exposure decreased both the severity and the duration of the irritation observed.
Other effects:
All animals remained healthy during study.

Any other information on results incl. tables

Table 1 - Eye scores per animal

Animal

Time point

Cornea opacity / area

Iris iritis

Conjunctiva

Cornea stain / area

Other

redness

chemosis

discharge

#1

Male

Unwashed eye

1 h

0/0

0

3

2

3

-

Ch*

24 h

1/1

0

3

3

3

+/1

Ch

48 h

1/1

0

3

2

3

+/1

Ch

72 h

0/0

0

3

1

3

0/0

Ch

Day 4

0/0

0

2

0

2

-

Ch

Day 7

0/0

0

1

0

1

-

Ch

Day 10

0/0

0

0

0

1

-

0

Day 13

0/0

0

0

0

0

-

0

 

#2

Male

Unwashed eye

1 h

0/0

1

3

2

3

-

Ch

24 h

1/1

0

3

1

3

+/1

Ch

48 h

0/0

0

2

0

3

0/0

Ch

72 h

0/0

0

2

0

3

-

Ch

Day 4

0/0

0

2

0

3

-

Ch

Day 7

0/0

0

0

0

1

-

0

Day 10

0/0

0

0

0

1

-

0

Day 13

0/0

0

0

0

0

-

0

 

#3

Male

washed eye

1 h

0/0

0

0

2

3

-

0

24 h

0/0

0

1

0

1

0/0

Ch

48 h

0/0

0

1

0

0

-

Ch

72 h

0/0

0

0

0

0

-

0

Day 4

0/0

0

0

0

0

-

0

Day 7

0/0

0

0

0

0

-

0

Day 10

0/0

0

0

0

0

-

0

Day 13

0/0

0

0

0

0

-

0

 

 

 

 

 

 

 

 

 

#4

Male

washed eye

1 h

0/0

0

0

2

3

-

0

24 h

0/0

0

1

1

2

0/0

Ch

48 h

0/0

0

1

0

0

-

Ch

72 h

0/0

0

1

0

0

-

0

Day 4

0/0

0

1

0

0

-

0

Day 7

0/0

0

1

0

0

-

0

Day 10

0/0

0

1

0

0

-

0

Day 13

0/0

0

1

0

0

-

0

* Ch - hemorrhagic conjunctiva

Table 2 - Primary eye irritation indexes

Scoring intervals

Unwashed

Washed

1h

18.5

10.0

24 h

21.0

6.0

48 h

15.5

2.0

72 h

12.0

1.0

Day 4

9.0

0

Day 7

3.0

0

Day 10

2.0

0

Day 13

0

0

Applicant's summary and conclusion

Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
Under the conditions of this study, the author states that the test material is temporarily approximated to be moderately irritating to unwashed eyes and mildly irritating to washed eyes.

Study is conducted according to the appropriate guidelines (EU AND US) and under the conditions of GLP. This study is considered to be acceptable and to adequately satisfy both the guideline requirement and the regulatory requirement for this endpoint.
In addition this study is considered to be acceptable for classification under Regulation (EC) No. 1272/2008 (EU CLP) as Irritating to eyes (Category 2) as 2 animals exhibited a positive response of conjunctival oedema (chemosis) of ≥2 calculated as a mean score following grading at 24, 48 and 72 hours.
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 effects noted and is therefore submitted as a key study with supporting data also provided to support the conclusions on classification and labelling.

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