Registration Dossier

Toxicological information

Eye irritation

Currently viewing:

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Between 31 May 2011 and 14 June 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well performed GLP and OECD guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011
Report date:
2011

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Deviations:
no
GLP compliance:
yes

Test material

Constituent 1
Reference substance name:
Manganese Oxalate, dihydrate
IUPAC Name:
Manganese Oxalate, dihydrate

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
- Animals: Young Adult New Zealand White Rabbit, SPF
- Rationale: Recognized by international guidelines as a recommended test system.
- Breeder: Charles River Deutschland GmbH, Stolzenseeweg 32-36, 88353 Kisslegg, Germany
- Number of Animals: 3 males
- Age (when treated): 14 - 17 weeks
- Body Weight Range (when treated): 2787 - 2880 g
- Identification: By unique cage number and corresponding ear number.
- Randomization: Selected by hand at time of delivery. No computer generated randomization program.
- Acclimatization: Under laboratory conditions after health examination. Only animals without any visual signs of illness were used for the study.
- Conditions: Standard Laboratory Conditions. Air-conditioned with 10-15 air changes per hour, and continuously monitored environment with a room temperature of 17-23 °C and a relative humidity between 30-70%, automatically controlled light cycle of 12 hours light and 12 hours dark and music played during the daytime light period.
- Accommodation: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls.
- Diet: Pelleted standard Teklad Global High Fiber Rabbit Diet 2031C (batch no. 80/10, Provimi Kliba AG, 4303 Kaiseraugst, Switzerland) was available ad libitum. Results of analyses for contaminants are archived at Harlan Laboratories Ltd. A piece of wood (batch no. 122201, imported by Indulab AG, Gams, Switzerland from ABEDD® - LAB & VET GmbH, 1160 Vienna, Austria) and a haystick 4642 (batch no. 37/10, Provimi Kliba AG, 4303 Kaiseraugst, Switzerland) were also provided for environmental enrichment.
- Water: Community tap water from Füllinsdorf ad libitum. Results of bacteriological, chemical and contaminant analyses are archived at Harlan Laboratories Ltd.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: The right eye remained untreated and was used for control purposes.
Amount / concentration applied:
0.1g /animal
Duration of treatment / exposure:
single application into the left eye
Observation period (in vivo):
Approximately 1 hour and 24, 48 and 72 hours as well as 7 days following treatment
Number of animals or in vitro replicates:
3 animals were tested in total. (After consideration of the ocular responses produced in the first treated animal, two additional animals were treated. )
Details on study design:
Due to the tabular nature of this information & to retain the integrity & coherence of the original Harlan Laboratories Ltd. Study report D26206 please see section “Any other information on materials and methods incl. tables”

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Remarks:
opacity
Basis:
animal: 94 male
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: Reversibility: no effects observed
Irritation parameter:
cornea opacity score
Remarks:
opacity
Basis:
animal: 95 male
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: Reversibility: no effects observed
Irritation parameter:
cornea opacity score
Remarks:
opacity
Basis:
animal: 96 female
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: Reversibility: no effects observed
Irritation parameter:
iris score
Remarks:
light reflex
Basis:
animal: 94 male
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0
Max. score:
2
Reversibility:
other: Reversibility: no effects observed
Irritation parameter:
iris score
Remarks:
light reflex
Basis:
animal: 95 male
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0
Max. score:
2
Reversibility:
other: Reversibility: no effects observed
Irritation parameter:
iris score
Remarks:
light reflex
Basis:
animal: 96 female
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0
Max. score:
2
Reversibility:
other: Reversibility: no effects observed
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal: 94 male
Time point:
other: Mean of 24, 48 and 72 hours
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal: 95 male
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal: 96 female
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
animal: 94 male
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
animal: 95 male
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: score = 1 at 1-hour reading
Irritation parameter:
chemosis score
Basis:
animal: 96 female
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: score = 1 at 1-hour reading
Irritant / corrosive response data:
Eye Reactions:
The instillation of Manganese Oxalate Dihydrate into the eye resulted in moderate reddening of the conjunctivae and sclerae in all animals 1 hour after treatment. The same severity of the conjunctivae persisted in all three animals at the 24 hours while the severity slightly decreased in the sclerae and was recorded as slight in all three animals. One animal (No. 94) was still slightly reddened in the conjunctivae 48 hours after treatment while no animal was affected anymore in the sclerae. A slight conjunctival chemosis and slight discharge were seen in all animals 1 hour after treatment. The chemosis and discharge persisted as slight in one animal (no. 94) 24 hours later and fully disappeared thereafter. All these effects were reversible and were no longer evident 48 (Nos. 95 and 96) or 72 hours (animal no. 94) after treatment. No abnormal findings were observed for the cornea and iris including iris light reflex.
No corrosion was observed. No staining of the treated eyes by the test item was observed.
Test item remnants were observed in the treated eyes of all animals at the 1-hour reading. The remnants were still present in one animal (No. 94) at the 24 hours.
Thus, the test item did not induce significant or irreversible damage to the rabbit eye.
The mean score was calculated separately for each animal across three scoring times (24, 48 and 72 hours after instillation) for corneal opacity, iris including iris light reflex, redness and chemosis of the conjunctivae, respectively. The individual mean scores for corneal opacity and iris including iris light reflex were 0.00 for all three animals. The individual mean scores for reddening of the conjunctivae were 1.00, 0.67 and 0.67 and for conjunctival chemosis were 0.33, 0.00 and 0.00.
Other effects:
Viability/Mortality: No intercurrent deaths occurred during the course of the study
Clinical signs: No clinical signs were recorded throughout the entire observation period.
Body weights: The body weights were within the range commonly recorded for this strain and age.

Any other information on results incl. tables

Results:

Animal

Number

Sex

Evaluation

Interval*

Corneal

Opacity

Area of

Corneal Opacity

Iris Light Reflex

Conjunctivae

Sclera

Ocular Discharge

Test Item

Remnants

Redness

Chemosis

94

M

1 hour

0

0

0

2

1

2

1

X

95

M

0

0

0

2

1

2

1

X

96

F

0

0

0

2

1

2

1

X

94

M

24 hours

0

0

0

2

1

1

1

X

95

M

0

0

0

2

0

1

0

96

F

0

0

0

2

0

1

0

94

M

48 hours

0

0

0

1

0

0

0

95

M

0

0

0

0

0

0

0

96

F

0

0

0

0

0

0

0

94

M

72 hours

0

0

0

0

0

0

0

95

M

0

0

0

0

0

0

0

96

F

0

0

0

0

0

0

0

94

M

7 days

0

0

0

0

0

0

0

95

M

0

0

0

0

0

0

0

96

F

0

0

0

0

0

0

0

 * Examinations were performed at the specified times after instillation of the test item.

 X = present

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based upon Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008, the test item does not have to be classified with respect to eye irritation.
Executive summary:

The primary eye irritation potential of Manganese Oxalate Dihydrate was investigated according to OECD test guideline no. 405. The test item was applied by instillation of 0.1 g into the left eye of each of three young adult New Zealand White rabbits. Scoring of irritation effects was performed approximately 1, 24, 48 and 72 hours as well as 7 days after test item instillation.

The instillation of Manganese Oxalate Dihydrate into the eye resulted in slight to moderate reddening of the conjunctivae and sclerae as well as slight conjunctival chemosis and discharge. These effects were reversible and were no longer evident 7 days after treatment for all animals, the end of the observation period. No abnormal findings were observed for the cornea and iris including iris light reflex. No corrosion was observed. No staining of the treated eyes by the test item was observed. Test item remnants were observed in the treated eyes. No clinical signs were observed.

Thus, the test item did not induce significant or irreversible damage to the rabbit eye.

 

The mean score was calculated separately for each animal across three scoring times (24, 48 and 72 hours after instillation) for corneal opacity, iris including iris light reflex, redness and chemosis of the conjunctivae, respectively. The individual mean scores for corneal opacity and iris including iris light reflex were 0.00 for all three animals. The individual mean scores for reddening of the conjunctivae were 1.00, 0.67 and 0.67 and for conjunctival chemosis were 0.33, 0.00 and 0.00.

 

Based upon the referred classification criteria (Regulation (EC) No 1272/2008 of the European Parliament and of the Council of16 December 2008), Manganese Oxalate Dihydrate does not have to be classified with respect to eye irritation.