Triiron bis(orthophosphate)

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2015-12-15 to 2016-02-07

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

2012-10-02

Deviations:

yes

Remarks:

application time of fluorescein after test item application was not stated

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Triiron bis(orthophosphate)

EC Number:

239-018-0

EC Name:

Triiron bis(orthophosphate)

Cas Number:

14940-41-1

Molecular formula:

Fe.2/3H3O4P or Fe3(PO4)2

IUPAC Name:

triiron bis(orthophosphate)

Test material form:

solid: particulate/powder

Details on test material:

- State of aggregation: light grey powder

Specific details on test material used for the study:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: 15 - 25 °C, tightly closed
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: test material was ground to a fine dust before application.

Test animals / tissue source

Species:

rabbit

Strain:

other: Zika

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Kaninchenbetrieb Kock, Warnkenhagen, Germany
- Age at study initiation: 14 (one rabbit) and 18 weeks old (two rabbits)
- Weight at study initiation: 3.24 to 4.87 kg
- Housing: single-caged
- Diet (ad libitum): conventional laboratory diet (a half-and-half blend of "Holstenstolz Kaninchenverbrauchsfutter Z, Type 038" and "Rabbit maintenance, MuesliMash")
- Water (ad libitum): tap water (drinking quality)
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 °C (± 3 °C)
- Relative humidity: 30 - 70 %
- Air changes: 15/hour
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

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

Duration of treatment / exposure:

1 hour

Observation period (in vivo):

1, 24, 48 and 72 hours up to 5 (confirmatory test) or 9 days (initial test)

Number of animals or in vitro replicates:

3 female rabbits

Details on study design:

INITIAL AND CONFIRMATORY TEST
The in vivo test was performed initially using one animal. Prior to the initial test the pH of the test substance in water (saturated, sedimented suspension, 5.55 % w/v)) was determined (pH = 7.46).
Becasue of lack of corrosive or severe irritant reactions after the initial test, two additional animals were exposed.

USE OF TOPICAL ANAESTHETICS AND SYSTEMIC ANALGESICS
Approx. 60 minutes prior to test substance application, Alvegesic vet. (concentration: 10 mg/mL) was applied (application volume: 0.3 mg/kg bw).
Approx. five minutes prior to test substance application, one drop of a topical ocular anaesthetic (Proparakain-POS 0.5 %) was applied to each eye.
Four to six hours after test substance application, Alvegesic vet. (concentration: 10 mg/mL) subcutaneous was administered to provide a continued therapeutic level of systemic analgesia. An additional application was not necessary.

REMOVAL OF TEST SUBSTANCE
- Washing: test substance had not been removed from the eye of the test animals by physiological mechanisms at the first observation time, therefore the eyes were rinsed with physiological saline
- Time after start of exposure: 1 hour after treatment

SCORING SYSTEM: according to the Draize scale

TOOL USED TO ASSESS SCORE: slit lamp biomicroscope and fluorescein staining

CLINICAL OBSERVATIONS:
Test animals were evaluated for the entire duration of the study for clinical signs of pain and/or distress at least twice daily, with a minimum of 6 hours between observations, or more often if necessary.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 2

Irritation parameter:

iris score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

3

Remarks on result:

other: moderate conjunctivae redness was observed at the 1 hour observation.

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: Slight chemosis was observed at the 1 hour observation.

Results 5

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 6

Irritation parameter:

iris score

Basis:

mean

Remarks:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 7

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

3

Remarks on result:

other: severe conjunctivae redness was observed at the 1 hour observation.

Results 8

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: Slight chemosis was observed at the 1 hour observation.

Results 9

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 10

Irritation parameter:

iris score

Basis:

mean

Remarks:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 11

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Remarks on result:

other: moderate conjunctivae redness was observed at the 1 hour observation.

Results 12

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: slight chemosis was observed at the 1 hour observation.

Irritant / corrosive response data:

Initial test (one rabbit): reversible signs of eye reactions (conjunctivae redness, chemosis) to the test substance were observed at 1 hour (also at 4 hours and 7 hours) after application.
Confirmatory test (two rabbits): reversible signs of eye reactions (conjunctivae redness, chemosis) to the test substance were observed at 1 hour (also 5 hours and 8 hours) and at 24 hours (one rabbit only) after application.

Other effects:

- Lesions and clinical observations: at the daily observations the animals did not show any other visible clinical symptoms.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The substance is not irritating to the eyes.
According to the EC Regulation No. 1272/2008 and subsequent adaptations, the substance is not classified as an eye irritant.