Dimanganese trioxide

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2009-11-03 to 2009-12-24

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

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:

manganese oxide

IUPAC Name:

manganese oxide

Constituent 2

Reference substance name:

1344-43-0

Cas Number:

1344-43-0

IUPAC Name:

1344-43-0

Constituent 3

Reference substance name:

Manganese oxide

EC Number:

215-695-8

EC Name:

Manganese oxide

IUPAC Name:

215-695-8

Details on test material:

- Name of test material: MnO
- Substance type: Green powder
- Physical state: Solid
- Impurities (identity and concentrations): MnO2 0.46%, Fe 56 ppm, Ins. ac. 15 %, H2O at 105 °C 0.01%
- Composition of test material, percentage of components: Mn 77.8%
- Purity test date: 24/09/08
- Lot/batch No.: 104833-06
- Storage condition of test material: 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
- Source: Harlan Laboratories U.K. Limited, Hillcrest, Belton, Loughborough, UK
- Age at study initiation: 12 to 20 weeks old
- Weight at study initiation: 2.49 to 2.90 kg
- Housing: Animals were housed individually in suspended cages.
- Diet : Free access to 2030 Teklad Global Rabbit diet (Harlan Teklad, Blackthorn, Bicester, Oxon, UK).
- Water : Free access to mains drinking water
- Acclimation period: A minimum of 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23 °C
- Humidity (%): 30 to 70%
- Air changes (per hr): At least 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hour cycle.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 100 mg

Duration of treatment / exposure:

single treatment

Observation period (in vivo):

Animals were assessed up to 72 hours after exposure (assessments were made at 1, 24, 48 and 72 hours post treatment).

Number of animals or in vitro replicates:

3 animals in total (1 animal used in the initial test, with further 2 animals in the main test)

Details on study design:

APPLICATION OF TEST SUBSTANCE:
Initially a single rabbit was treated with 100 mg of test material. The test material was administered into the conjunctival sac of the right eye, formed by gently pulling the lower lid away from the eyeball. The upper and lower eyelids were held together for about one second immediately after treatment to prevent loss of test material and then released. The left eye served as a control and remained untreated. Immediately after administration of the test material and assessment of the initial pain reaction was made. After consideration of the ocular responses produced in the first treated animal, two additional animals were treated.

SCORING SYSTEM:
Assessment of ocular damage/irritation was made 1, 24, 48 and 72 hours post dosing using the scoring system from Draize J.H. (1977) “Dermal and Eye Toxicity Tests” In: Principles and Procedures for Evaluating the Toxicity of Household Substances, National Academy of Sciences, Washington DC p. 48 to 49. Any other ocular effects were also noted at this point along with any clinical signs of toxicity if present. Individual body weights were recorded on day 0 and 3. For scoring see Table 1 in box 'Any other information on materials & methods incl. tables'.

TOOL USED TO ASSESS SCORE: standard ophthalmoscope

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Results 5

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Results 6

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Remarks on result:

no indication of irritation

Results 8

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Remarks on result:

no indication of irritation

Results 9

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Remarks on result:

no indication of irritation

Results 10

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

no indication of irritation

Results 11

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

no indication of irritation

Results 12

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Eye irritation scores were recorded at 1, 24, 48, and 72 hours after treatment. No corneal damage or iridial inflammation was seen throughout the observation period. Slight irritating effects on conjunctivae were observed 1 and 24 hours in all animals, which were fully reversible within 48 hours.

Other effects:

Some green staining of the fur around the eyes was noted in all animals.

Any other information on results incl. tables

Table 1: Individual Scores and Individual Total Scores for Ocular Irritation

Rabbit Number and Sex	68643 Male				68649 Male				68667 Male
Time After Treatment	1 Hr	24 Hrs	48 Hrs	72 Hrs	1 Hr	24 Hrs	48 Hrs	72 Hrs	1 Hr	24 Hrs	48 Hrs	72 Hrs
Cornea
E = Degree of opacity	0	0	0	0	0	0	0	0	0	0	0	0
F = Area of Cornea Involved	0	0	0	0	0	0	0	0	0	0	0	0
Iris
D	0	0	0	0	0	0	0	0	0	0	0	0
Conjunctivae
A = Redness	2	1	0	0	2	1	0	0	2	1	0	0
B = Chemosis	2	1	0	0	2	1	0	0	2	1	0	0
C = Discharge	2Sf	1	0	0	1Sf	0Sf	0	0	1Sf	0Sf	0	0

Sf = Green coloured staining of the fur around the treated eye

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

In conclusion, in an acute eye irritation/corrosion study according to OECD 405, manganese oxide is not an eye-irritant.

Executive summary:

In a primary eye irritation study according to guideline OECD 405, 100 mg of manganese oxide (77% Mn content) was instilled into the conjunctival sac of one eye of each of three young adult New Zealand White rabbits (males). Animals were observed for 72 hours. Irritation was scored by the method of Draize. Only very mild conjunctival reactions were observed, which were fully reversible within 48 hours. In this study, manganese oxide is not an eye irritant.