Reaction mass of copper oxide and manganese dioxide

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

02 November 2009 to 19 November 2009.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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 dioxide

EC Number:

215-202-6

EC Name:

Manganese dioxide

Cas Number:

1313-13-9

Molecular formula:

MnO2

IUPAC Name:

Manganese dioxide

Test material form:

solid: particulate/powder

Details on test material:

Sponsor's identification : MnO2
Purity : 97.6%
Batch number : 103721-02
Description : black powder
Date received : 8 September 2008
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
- Source: Harlan Laboratories U.K. Limited, Hillcrest, Belton, Loughborough, UK
- Weight at study initiation: 2.31 to 2.82 kg
- Housing: The animals were individually housed in suspended cages
- Diet: Free access to mains drinking water and food (2030 Teklad Global Rabbit diet supplied by Harlan Teklad, Blackthorn, Bicester, Oxon, UK) was allowed throughout the study.
- Water:Free access to mains drinking water was allowed throughout the study.
- Acclimation period: of at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23°C
- Humidity (%): 30 to 70% respectively
- Air changes (per hr): The rate of air exchange was at least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): A volume of 0.1 mL of the test material, which was found to weigh approximately 32 mg
- Concentration (if solution): A volume of 0.1 mL of the test material, which was found to weigh approximately 32 mg

VEHICLE
Not applicable

Duration of treatment / exposure:

72 hours

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

3

Details on study design:

APPLICATION OF TEST SUBSTANCE:
Initially a single rabbit was treated with 0.1 mL (32 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 an 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:
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:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effect

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: no effect

Results 3

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritant / corrosive response data:

Individual and group mean scores for ocular irritation are given in Table 1 and Table 2 (all tables are in the any other information on results section).
Black staining of the fur was noted around all treated eyes throughout the study.
No corneal or iridial effects were noted during the study.
Moderate conjunctival irritation was noted in all treated eyes one hour after treatment (score 2 for conjunctival redness and chemosis, respectively), with minimal conjunctival irritation noted at the 24-hour observation (score 1 for conjunctival redness and chemosis, respectively). All treated eyes appeared normal at the 48-hour observation.

Other effects:

Individual bodyweights and bodyweight changes are given in Table 3. All animals showed expected gain in bodyweight during the study.

Any other information on results incl. tables

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

Rabbit Number and Sex	68633 Male				68650 Male				68672 Male
	IPR= 2				IPR= 2				IPR= 2
Time After Treatment	1 Hour	24 Hours	48 Hours	72 Hours	1 Hour	24 Hours	48 Hours	72 Hours	1 Hour	24 Hours	48 Hours	72 Hours
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	1Sf	0Sf	0Sf	0Sf	1Sf	0Sf	0Sf	0Sf	1Sf	0Sf	0Sf	0Sf
Score (A + B + C) x 2	10	4	0	0	10	4	0	0	10	4	0	0
Total Score	10	4	0	0	10	4	0	0	10	4	0	0

IPR= Initial pain reaction

Sf = Black staining of the fur around treated eye

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
68633 Male	10	4	0	0
68650 Male	10	4	0	0
68672 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
68633Male	2.31	2.37	0.06
68650Male	2.82	2.85	0.03
68672Male	2.55	2.57	0.02

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

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 material 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 conjunctival irritation was noted in all treated eyes one hour after treatment with minimal conjunctival irritation noted at the 24-hour observation. All treated eyes appeared normal at the 48-hour observation.

Therefore, under the conditions of the study the test material was determined to be not irritating to eyes.