Registration Dossier

Administrative data

Description of key information

Skin irritation / corrosion:
For the test item a relative absorbance value of 92.2% was found in the In vitro Skin Irritation Test (Human skin Model Test). This value is well above the threshold for irritancy of <=50%.
In an acute dermal toxicity study no signs of skin corrosion were observed.
Thus, the test item did not induce significant or irreversible damage to the skin.
Eye irritation:
The individual mean scores for corneal opacity and iris were 0.00 for all three animals. The individual mean scores for the conjunctivae were 1.00, 0.67 and 0.67 for reddening, and 0.33, 0.00 and 0.00 for chemosis respectively. These effects were fully reversible and were no longer evident 72 hours after treatment. No corrosion was observed at any of the measuring intervals. No staining of the treated eyes by the test item and no clinical signs were observed.
Thus, the test item did not induce significant or irreversible damage to the rabbit eye.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well performed GLP and OECD guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
Deviations:
no
GLP compliance:
yes
Amount / concentration applied:
Approximately 10 mg of the neat test item were applied to each of triplicate EPISKIN (Skinethic) tissues. In order to improve contact and to guaranty a uniform and complete coverage of the epidermis, the test material was wetted with 15 µL deionised water.
Duration of treatment / exposure:
The skin equivalents were exposed to the test item for 15 minutes. Afterwards the test items was washed off and the equivalents were incubated for further 42 hours.
Details on study design:
Approximately 10 mg of the neat test item were applied to each of triplicate EPISKIN (Skinethic) tissues. In order to improve contact and to guaranty a uniform and complete coverage of the epidermis, the test material was wetted with 15 µL deionised water.

The test item and the positive and negative controls were washed off the skin tissues after 15 minutes treatment. After further incubation for about 42 hours the tissues were treated with the MTT solution for 3 hours following approximately 69 hours extraction of the colorant from the cells. The amount of extracted colorant was determined photometrically at 570 nm.
Irritation / corrosion parameter:
% tissue viability
Run / experiment:
mean of 3 runs
Value:
92.2
Vehicle controls validity:
valid
Positive controls validity:
valid
Other effects / acceptance of results:
After treatment with the test item Manganese Oxalate Dihydrate the relative absorbance values decreased slightly to 92.2%. This value is well above the threshold for irritancy of ≤ 50%. Therefore, the test item is not considered to possess an irritant potential.

Results after treatment with Manganese Oxalate Dihydrate

 

Dose group

Treat-ment Interval

Absor-bance 570 nm
Tissue 1*

Absor-bance 570 nm
Tissue 2*

Absor-bance 570 nm
Tissue 3*

Mean Absor-bance of 3 Tissues

Relative Absor-bance [%] Tissue 1, 2, 3**

Stan-dard De-viation [%]

Rel. Absor-bance

[% of Negative Control]***

Negative Control

15 min

1.079

0.873

1.021

0.991

108.9
88.1
103.0

10.7

100.0

Positive Control

15 min

0.390

0.324

0.208

0.308

39.4
32.7
21.0

9.3

31.0

Test Item

15 min

0.778

1.015

0.948

0.914

78.5
102.4
95.7

12.3

92.2

*        Mean of two replicate wells after blank correction

**      relative absorbance per tissue [rounded values]: (100 x (absorbance tissue )) / (mean absorbance negetive control)

***    relative absorbance per treatment group [rounded values]: (100 x (mean absorbancetest item)) / (mean absorbancenegetive control)

Optical evaluation of the MTT-reducing capacity of the test item after 1 hour incubation with MTT-reagent did not show blue colour.

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
In conclusion, it can be stated that in this study and under the experimental conditions reported, the test item Manganese Oxalate Dihydrate is non irritant to skin.
Executive summary:

This in vitro study was performed to assess the irritation potential of Manganese Oxalate Dihydrate by means of the Human Skin Model Test.

Three tissues of the human skin model EpiSkin™ were treated with the test item, the negative or the positive control for 15 minutes.

Approximately 10 mg of the neat test item were applied to each of triplicate tissues. In order to improve contact and to guaranty a uniform and complete coverage of the epidermis, the test material was wetted with 15 µL deionised water.

The test item and the positive and negative controls were washed off the skin tissues after 15 minutes treatment. After further incubation for about 42 hours the tissues were treated with the MTT solution for 3 hours following approximately 69 hours extraction of the colorant from the cells. The amount of extracted colorant was determined photometrically at 570 nm.

10 µL of either the negative control (deionised water) or the positive control (5% Sodium lauryl sulfate) were applied to each tissue.

After treatment with the negative control the absorbance values were well within the required acceptability criterion of mean OD 0.6 till ≤1.5 for the15 minutes treatment interval thus showing the quality of the tissues.

Treatment with the positive control induced a decrease in the relative absorbance as compared to the negative control to 31.0% thus ensuring the validity of the test system.

The standard deviations between the % variabilities of the test item, the positive and negative controls were below 13% (threshold of the "OECD Guideline for the Testing of Chemicals 439: In vitro Skin Irritation: Reconstructed Human Epidermis Test Method”: 18%), thus ensuring the validity of the study.

After treatment with the test item Manganese Oxalate Dihydrate the relative absorbance values decreased slightly to 92.2%. This value is well above the threshold for irritancy of50%. Therefore, the test item is not considered to possess an irritant potential.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
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
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
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.
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”
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.

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

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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for selection of skin irritation / corrosion endpoint:
Skin corrosion / irritation of the test item was tested according to OECD guidelines 435 and 439.
A qualifiying test (prerequisite of OECD 435) revealed that the test sytem was not suitable for the test item. Therefore this test was discontinued.
Only one evaluable study remaining.

Justification for selection of eye irritation endpoint:
Eye irritation of the test item was tested according to OECD guidelines 437 and 405. Both studies revealed negative results (not irritating). Thus the higher tier in vivo study was selected as key study.

Justification for classification or non-classification

The relative absorbance value determined for skin irritation is above the defined threshold value and the mean scores determined for serious eye damage/eye irritation are below the respective threshold values.

Based on the findings of these studies and of an acute dermal toxicity study corrosive effects on skin can be excluded as well.

Since these findings do not meet the criteria for classification according to the rules laid down in Directive 67/548/EEC and in Regulation (EC) No 1272/2008, classification is not warrantable.