Calcium hydrogenorthophosphate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

19 January 2011 - 22 January 2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Deviations:

yes

Remarks:

Specific information related to the characterisation of the test substance as received and as tested is the responsibility of the study Sponsor.

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

Specific information related to the characterisation of the test substance as received and as tested is the responsibility of the study Sponsor.

Test guideline 3

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

Specific information related to the characterisation of the test substance as received and as tested is the responsibility of the study Sponsor.

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Calcium hydrogenorthophosphate

EC Number:

231-826-1

EC Name:

Calcium hydrogenorthophosphate

Cas Number:

7757-93-9

Molecular formula:

CaHPO4

IUPAC Name:

calcium hydrogen phosphate

Constituent 2

Reference substance name:

231-827-1

IUPAC Name:

231-827-1

Constituent 3

Reference substance name:

Calcium bis(dihydrogenorthophosphate)

EC Number:

231-837-1

EC Name:

Calcium bis(dihydrogenorthophosphate)

Cas Number:

7758-23-8

Molecular formula:

CaH4O8P2

IUPAC Name:

calcium dihydrogen phosphate

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: 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 (Natl. Res. Council, 1996). Litter paper was placed beneath the cage and was changed at least 3 times a week.
- Diet: ad libitum; Pelleted Purina Rabbit Chow #5326
- Water: ad libitum, filter tap water was dispensed by an automatic dispensing system.
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-22
- Humidity (%):31-45
- Air changes (per hr): 14
- Photoperiod (hrs dark / hrs light): 12 hr light/dark cycle

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg

Duration of treatment / exposure:

4 hours

Observation period (in vivo):

1, 24, 48 and 72 hours

Number of animals or in vitro replicates:

3

Details on study design:

The left eye of each rabbit was left untreated and served as a control.

SCORING SYSTEM: Ocular irritation was evaluated using a high intensity white light (Mag Lite) in accordance with Draize et al (1944) at 1, 24, 48 and 72 hours post-installation. A fluorescein dye procedure was used in the treated eye at 24 hours to evaluate the absence of corneal damage.

TOOL USED TO ASSESS SCORE: fluorescein and high-intensity white light.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Time point:

24/48/72 h

Score:

0.44

Max. score:

3

Reversibility:

fully reversible within: 72 hrs

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritant / corrosive response data:

There was no irititis observed in any treated eye during this study. One hour post-instillation, all three rabbits exhibited corneal opacity and ‘positive’ conjunctivitis. The overall incidence and severity of irritation decreased with time. All animals were free of ocular irritation by 72 hours.

Other effects:

Apart from the ocular irritation noted above, the animals appeared active and healthy during the study. There were no signs of acute toxicity, abnormal behaviour or adverse pharmacologic effects.

Any other information on results incl. tables

Table 1. Individual scores for ocular irritation

	Rabbit No. 3401 (F)				Rabbit No. 3402 (F)				Rabbit No. 3403 (F)
Observation time	1h	24h	48h	72h	1h	24h	48h	72h	1h	24h	48h	72h
Cornea
Opacity	1	0^1	0	0	1	0^1	0	0	1	0^1	0	0
Area	2	4	4	4	1	4	4	4	1	4	4	4
Iris	0	0	0	0	0	0	0	0	0	0	0	0
Conjunctivae
Redness	2	1	1	0	2	1	0	0	2	1	0	0
Chemosis	1	0	0	0	1	0	0	0	1	0	0	0
Discharge	2	1	0	0	2	1	0	0	2	1	0	0

¹2% ophthalmic fluorescein sodium used to evaluate the absence of corneal opacity

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study dicalcium phosphate (with 10% monocalcium phosphate) was determined to be not classified in accordance with the Guidance on the application of Regulation (EC) No. 1272/2008 (EU CLP).
This study is considered to be acceptable and reliable for use as a key study and for classification and labelling in accordance with Regulation (EC) No. 1272/2008 (EU CLP).