Lanthanum fluoride

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

11 February 2013 to 21 February 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted to GLP in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

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:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Lanthanum fluoride

EC Number:

237-252-8

EC Name:

Lanthanum fluoride

Cas Number:

13709-38-1

Molecular formula:

F3La

IUPAC Name:

lanthanum fluoride

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Storage conditions: Room temperature in the dark

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Strain: New Zealand White (Hsdlf:NZW)
- Source: Harlan Laboratories UK Ltd., Leicestershire, UK
- Age at study initiation: 12 - 20 weeks
- Weight at study initiation: 2.43 - 2.52 kg
- Housing: individually housed in suspended cages
- Diet: 2930C Teklad Global Rabbit diet, Harlan Laboratories UK Ltd., Oxon, UK, ad libitum
- Water: mains drinking water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 23 °C
- Humidity (%): 30 - 70 %
- Air changes (per hr): at least 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours light
- The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: left eye served as control

Amount / concentration applied:

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

Duration of treatment / exposure:

- Dose administration: Approximately 100 mg of the test material was applied into the conjunctival sac of the right eye of one rabbit by gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second immediately after treatment, to prevent loss of the test material, and then released. The left eye was untreated (control eye).

Observation period (in vivo):

Animals were observed up to 72 hours post administration

Number of animals or in vitro replicates:

One animal initially, followed by a further animal once the irritation potential was fully assessed in the first animal.

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Irrigation was not performed

SCORING SYSTEM:
Immediately after administration of the test material, an assessment of the initial pain reaction was made according to the six point scale (Table 1). Assessment of ocular damage/irritation was made approximately 1, 24, 48 and 72 hours following treatment; the reactions observed were scored in accordance with the criteria of Draize (1977) (Table 2).

TOOL USED TO ASSESS SCORE: Examination of the eye was facilitated by the use of the light source from a standard ophthalmoscope.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: Mean of 24, 48 and 72 hour time points

Score:

0

Max. score:

4

Reversibility:

other: no effect observed

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

other: Mean of 24, 48 and 72 hour time points

Score:

0

Max. score:

4

Reversibility:

other: no effect observed

Results 3

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: Mean of 24, 48 and 72 hour time points

Score:

0

Max. score:

2

Reversibility:

other: no effect observed

Results 4

Irritation parameter:

iris score

Basis:

animal #2

Time point:

other: Mean of 24, 48 and 72 hour time points

Score:

0

Max. score:

2

Reversibility:

other: no effect observed

Results 5

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: Mean of 24, 48 and 72 hour time points

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Results 6

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

other: Mean of 24, 48 and 72 hour time points

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Results 7

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: Mean of 24, 48 and 72 hour time points

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Results 8

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: Mean of 24, 48 and 72 hour time points

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritant / corrosive response data:

No corneal effects were noted during the study. Iridial inflammation (grade 1) was noted in both treated eyes one hour after treatment. Moderate conjunctival irritation (grade 2 redness; grade 2 chemosis; grade 1 or 2 discharge) was noted in both treated eyes one hour after treatment. Minimal conjunctival irritation (grade 1 redness; grade 1 chemosis) was noted in both treated eyes at the 24 hour observation.
Both treated eyes appeared normal at the 48 hour observation and the study was terminated after the 72 hour observation.

Other effects:

Both animals showed expected gain in body weight during the study.

Any other information on results incl. tables

Table 1: Individual Scores for Ocular Irritation

Rabbit Number and Sex	79255 Male				72964 Male
	Initial Pain Reaction (IPR) = 2				Initial Pain Reaction (IPR) = 2
Time After Treatment	1 hour	24 hours	48 hours	72 hours	1 hour	24 hours	48 hours	72 hours
CORNEA
Degree of Opacity	0	0	0	0	0	0	0	0
Area of Cornea Involved	0	0	0	0	0	0	0	0
IRIS	1	0	0	0	1	0	0	0
CONJUCTIVEA
Redness	2	1	0	0	2	1	0	0
Chemosis	2	1	0	0	2	1	0	0
Discharge	1	0	0	0	2	0	0	0

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of the study, the test material only elicited slight reactions in any of the animals during the course of the study that meant the test material does not require classification as an eye irritant.

Executive summary:

The potential of the test material to cause eye irritation was determined in a GLP study which was conducted in accordance with the standardised guidelines OECD 405 and EU Method B.5. Approximately 100 mg of test material was applied into one eye of each of two rabbits and were assessed for up to 72 hours to determine the grade of ocular reaction. No corneal effects were noted during the study. Mild iridial inflammation and moderate conjunctival irritation was noted in both treated eyes one hour after treatment. Minimal conjunctival irritation was noted in both treated eyes at the 24 hour observation. However, both treated eyes appeared normal at the 48 hour observation and the study was terminated after the 72 hour observation.

Under the conditions of the study, the test material only elicited slight reactions in any of the animals during the course of the study that meant the test material does not require classification as an eye irritant.