Iron tris(phosphinate)

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Justification for type of information:

data is from safety assesment reports

Data source

Reference

Reference Type:

secondary source

Title:

Ferric phosphate- Toxicological evaluation

Author:

European Food Safety Authority (EFSA)

Year:

2013

Bibliographic source:

Ferric phosphate - RAR - Vol. 3, 2013

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: EC Commission Directive 92/69/EEC, Method B5, Acute Toxicity – Eye irritation

Principles of method if other than guideline:

To assess the extent of ocular damage caused by Ferric phosphate in rabbit eyes

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Iron orthophosphate

EC Number:

233-149-7

EC Name:

Iron orthophosphate

Cas Number:

10045-86-0

Molecular formula:

Fe.H3O4P

IUPAC Name:

Ferric phosphate

Test material form:

solid: crystalline

Details on test material:

Name of the test compound: Ferric orthophosphate
Molecular formula: FePO4
Molecular weight: 154 g/mo/l
Substance type: Inorganic
Physical State: Solid
Lot/Batch no.: 105668
Purity: Minimum 24.8 % Fe
Stability of test compound: Stable under recommended storage conditions (room temp. in the dark)

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Sex: Male
- Source: Charles River UK, Margate, Kent, England
- Age at study initiation: 9 - 11 weeks old at time of dosing
- Weight at study initiation: 1344 – 1935 g (males)
- Fasting period before study: no data available
- Housing: Individually in standard laboratory rabbit housing units
- Diet (e.g. ad libitum): Charles River Breeding and Maintenance Diet for Rabbits, ad libitum
- Water (e.g. ad libitum): Ad libitum access to automated watering system supplied with tap water
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 °C
- Humidity (%):55 ± 15 %
- Air changes (per hr): 15 per hour
- Photoperiod (hrs dark / hrs light): Alternating 12 hour light/dark cycle

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

3.2 mg equivalent to a volume of 0.1 mL

Duration of treatment / exposure:

single exposure

Observation period (in vivo):

The treated eyes were assessed at 1, 24, 48 and 72 hours post-instillation and reactions were graded using the standard Draize scale for ocular reactions

Duration of post- treatment incubation (in vitro):

no data available

Number of animals or in vitro replicates:

3 male rabbits

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): not washed
- Time after start of exposure: no data available

SCORING SYSTEM: The treated eyes were assessed at 1, 24, 48 and 72 hours post-instillation and reactions were graded using the standard Draize scale for ocular reactions

TOOL USED TO ASSESS SCORE: hand-slit lamp / biomicroscope / fluorescein: no data available
Other information: After instillation of the test substance, ocular assessments and clinical observations were performed in the treated eyes for up to 72 hours. Mortality and clinical condition was checked twice daily and rabbits were checked at least once daily for signs of systemic toxicity. Body weights were recorded on the day prior to instillation of ferric phosphate.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Reversibility:

fully reversible within: 72 hours

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Reversibility:

fully reversible within: 72 hours

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

Reversibility:

fully reversible within: 72 hours

Remarks on result:

no indication of irritation

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Reversibility:

fully reversible within: 72 hours

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No signs of systemic toxicity or clinical reaction to treatment were observed. No deaths occurred.
The reactions elicited included iridial and conjunctival changes, generally very slight but including slight chemosis in one rabbit. No corneal opacity was evident and all of the ocular
changes had overtly resolved within 48 -72 hours of dosing.

Applicant's summary and conclusion

Interpretation of results:

other: not irritating

Conclusions:

The reactions elicited included iridial and conjunctival changes, generally very slight
but including slight chemosis in one rabbit. No corneal opacity was evident and all of the ocular changes had overtly resolved within 48 -72 hours of dosing. The mean scores for the group of three rabbits over the 24 - 72 hour assessments were 0,0,0,0.44,0 for corneal opacity, iridial response, conjunctival redness, and conjunctival chemosis respectively.
Based on the scores and reversible reactions, ferric phosphate can be considered to be not irritating to rabbit eyes.

Executive summary:

The ocular irritation potential of the test chemical was assessed in rabbits. The study was performed according to OECD 405 and EC Commission Directive 92/69/EEC, Method B5, Acute Toxicity – Eye irritation Guidelines.3.2 mg equivalent to a volume of 0.1 mL of undiluted test chemical was instilled into the eyes of 3 male New Zealand White rabbits.After instillation of the test substance, ocular assessments and clinical observations were performed in the treated eyes for up to 72 hours. Mortality and clinical condition was checked twice daily and rabbits were checked at least once daily for signs of systemic toxicity. Body weights were recorded on the day prior to instillation of test chemical. The treated eyes were assessed at 1, 24, 48 and 72 hours post-instillation and reactions were graded using the standard Draize scale for ocular reactions

 

The reactions elicited included iridial and conjunctival changes, generally very slight but including slight chemosis in one rabbit. No corneal opacity was evident and all of the ocular changes had overtly resolved within 48 -72 hours of dosing. The mean scores for the group of three rabbits over the 24 - 72 hour assessments were 0,0,0,0.44,0 for corneal opacity, iridial response, conjunctival redness, and conjunctival chemosis respectively.

Based on the scores and reversible reactions, the test chemical can be considered to be not irritating to rabbit eyes.