Manganese carbonate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

7 December 2009 to 17 December 2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study conducted 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. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

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 carbonate

EC Number:

209-942-9

EC Name:

Manganese carbonate

Cas Number:

598-62-9

Molecular formula:

CH2O3.Mn

IUPAC Name:

manganese(2+) carbonate

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material: MnCO3
- Substance type: Kight brown powder
- Physical state: Solid
- Impurities (identity and concentrations): MnO2 0.18 %, Ins HCl 20 ppm, S total 0.144%, H2O at 105 °C 1.31 %
- Composition of test material, percentage of components: Mn 77.8 %
- Purity test date: 29/09/08
- Lot/batch No.: 08793
- 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: 2.67 to 2.78 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 SUBSTANCE
- Amount(s) applied: 100 mg

Duration of treatment / exposure:

Up to 72 hours

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:

1 animal was initially treated, with a further two animals

Details on study design:

APPLICATION OF TEST SUBSTANCE:
Initially a single rabbit was treated with 100 mg of test substance. The test substance 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 substance and then released. The left eye served as a control and remained untreated. Immediately after administration of the test substance 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 JH (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 bodyweights were recorded on day 0 and 3. The numerical values corresponding to each animal, tissue and observation time were recorded. These scores were then assessed using a modified version of the system described by Kay JH and Calandra JC (1962), J. Soc. Cosmet. Chem. 13, 281-289. If evidence of irreversible ocular damage is noted, the test material will be classified as corrosive to the eye.


TOOL USED TO ASSESS SCORE: standard ophthalmoscope

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

80

Reversibility:

other: not applicable

Remarks on result:

other: No corneal effects observed

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

10

Reversibility:

other: not applicable

Remarks on result:

other: No iridial effects observed

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

4

Max. score:

20

Reversibility:

fully reversible within: 48 hours

Results 4

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Results 5

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Results 6

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Results 7

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Results 8

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Results 9

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Results 10

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 h

Remarks on result:

no indication of irritation

Results 11

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 h

Remarks on result:

no indication of irritation

Results 12

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 h

Remarks on result:

no indication of irritation

Results 13

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Remarks on result:

no indication of irritation

Results 14

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Remarks on result:

no indication of irritation

Results 15

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

The test substance produced a maximum group mean score of 10.0

To calculate the maximum group mean score, encompassing all reactions, the following equations were used:
Cornea = (E x F) x 5
Where:
E = Degree of opacity
F = Area of Cornea Involved

Iris = (D x 5)

Conjunctivae = (A + B + C) x 2
Where:
A = Redness
B = Chemosis
C = Discharge

Any other information on results incl. tables

Measurement of pH

The pH of the test substance was determined prior to commencement of the study and found to be as follows:

  

Preparation	pH Measurement
	immediately	after 10 minutes
10 % w/w aqueous preparation of the test substance	7.9	7.9

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

Rabbit Number and Sex	68709 Male				68732 Male				68733 Male
	IPR = 2				IPR = 3				IPR = 2
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
Score (E x F) x 5	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
Score (D x 5)	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	1	0	0	0	1	0	0	0	1	0	0	0
Score (A + B + C) x 2	10	4	0	0	10	4	0	0	10	4	0	0
Total Score	10	6	0	0	10	4	0	0	10	4	0	0

  IPR = Initial pain reaction

 

Table 2: Individual Total Scores and Group Mean Scores for Ocular Irritation

Rabbit Number and Sex	Individual Total Scores At:
	1 Hour	24 Hours	48 Hours	72 Hours
68709 Male	10	4	0	0
68732 Male	10	4	0	0
68733 Male	10	4	0	0
Group Total	30	12	0	0
Group Mean Score	10.0	4.0	0.0	0.0

 

 

Table 3:Individual Bodyweights and Bodyweight Changes

 

Rabbit Number and Sex	Individual Bodyweight (kg)		Bodyweight Change (kg)
	Day 0	Day 3
68643 Male	2.78	2.92	0.14
68649 Male	2.70	2.79	0.09
68667 Male	2.67	2.73	0.06

 

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Slight conjunctival redness and chemosis (score 1) was observed 24 hours following administration of the test substance; all treated eyes appeared normal 48 hours after administration. Under the conditions of the study the test material was determined to be not irritating to eyes.

Executive summary:

The eye irritation potential of the test substance was investigated in vivo in a study which was conducted under GLP conditions and in accordance with the standardised guidelines OECD 405 and EU Method B.5.

No corneal or iridial effects was noted during the study. Moderate conjuctival irritation was noted in all treated eyes one hour after treatment with minimal conjunctival irritation noted at the 24-hour observation. Under the conditions of the study the test material was determined to be not irritating to eyes.