Reaction mass of disodium [2,2'-(imino-kappaN)dibutanedioato-kappa2O1,O4(4-)]manganese(2-) and sodium sulphate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2013-11-06 to 2013-11-11

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: well-documented GLP-Guideline Study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: SOP/T/22: “Acute skin irritation/corrosion study”

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Bureau for chemical substances (Registration No. B/2012/DPL

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of disodium [2,2'-(imino-kappaN)dibutanedioato-kappa2O1,O4(4-)]manganese(2-) and sodium sulphate

EC Number:

939-867-3

Cas Number:

666748-58-9

Molecular formula:

MnC8H7NO8Na2

IUPAC Name:

Reaction mass of disodium [2,2'-(imino-kappaN)dibutanedioato-kappa2O1,O4(4-)]manganese(2-) and sodium sulphate

Constituent 2

Reference substance name:

Manganese chelate of sodium salt N-[1,2 dicarboxyethyl] D,L aspartic acid

IUPAC Name:

Manganese chelate of sodium salt N-[1,2 dicarboxyethyl] D,L aspartic acid

Constituent 3

Reference substance name:

Mn (II) IDHA

IUPAC Name:

Mn (II) IDHA

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): Mn (II) IDHA
- Substance type: chelate
- Physical state: solid (odourless, white microgranules)
- Analytical purity: contains 9.07% of Mn+2 (content 56.7% of MnIDHA, 40% of Na2SO4, and 3% of H2O (humidity))
- Lot/batch No.: 6/13, date of production: June, 2013
- Expiration date of the lot/batch: June, 2016
- Storage condition of test material: at temperature between 0 – 30°C

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Experimental Department of National Research Institute of Animal Production, Balice near Kraków
- Age at study initiation: 6-month-old – rabbit No. 1 and 6.5-month-old – rabbit No. 2, and on one 9-month-old female – rabbit No. 3
- Housing: individually in metal cages (60 x 35 x 40 cm (length x width x height)). Each cage was equipped with a label containing the number of the study protocol, the dates of the experiment commencement and termination, and sex and number of the animal.
- Diet (e.g. ad libitum): ad libitum; standard granulated "LSK" fodder produced by Wytwórnia Koncentratów i Mieszanek Paszowych AGROPOL, Motycz
- Water (e.g. ad libitum): ad libitum; tap water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 22;
- Humidity (%): 45 – 65
- Air changes (per hr): about 16 times/h
- Photoperiod (hrs dark / hrs light): 12 / 12

Start of the study: 04.11.2013
Start of the experimental phase: 06.11.2013
End of the experimental phase: 11.11.2013

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.5 g (powdered test item)

Duration of treatment / exposure:

4 hours

Observation period:

1, 24, 48, and 72 hours after the end of the exposure

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 6 cm²
- Type of wrap if used: The gauze patches were covered with PCV foil and fixed using a non-irritating sticking plaster

REMOVAL OF TEST SUBSTANCE
- Washing (if done): residual test item was removed using water
- Time after start of exposure: 4 hours

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: mean at 24, 48 and 72 hours

Score:

0

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: mean at 24, 48 and 72 hours

Score:

0

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: mean at 24, 48 and 72 hours

Score:

0.3

Max. score:

1

Reversibility:

fully reversible within: 48 hours

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: mean at 24, 48 and 72 hours

Score:

0

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: mean at 24, 48 and 72 hours

Score:

0

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Time point:

other: mean at 24, 48 and 72 hours

Score:

0

Irritant / corrosive response data:

During the reading which took place 1 hour after the end of the exposure, no pathological changes on the treated skin of rabbit No. 1 were stated. Very slight (barely perceptible) erythema was stated in rabbit No. 2 and 3.
During the reading which took place 24 hours after the end of the exposure, no pathological changes were stated in rabbits No. 1 and 2. Very slight (barely perceptible) erythema was still observed in rabbit No. 3.
During the reading which took place 48 and 72 hours after the end of the exposure, no pathological changes on the treated skin of the rabbits were stated.

Any other information on results incl. tables

Table 1: Summary of results:

Administered volume of test item	0.5 mL
Number of rabbit	1	2	3
Sex	male	male	female
Mortality of animals	0/1	0/1	0/1
General clinical signs	none	none	none
Skin erythema in the treatment area	none	very slight (barely perceptible) after 1 hour	very slight (barely perceptible) after 1 hour and 24 hours
Skin oedema in the treatment area	none	none	none
Other	none	none	none

Body weight of the animals

At the start of the experiment, animal No. 1 weighed 3.3 kg, animal No. 2 weighed 3.6 kg and animal No. 3 weighed 4.3 kg. On the last day of the experiment, animal No. 1 weighed 3.4 kg, animal No. 2 weighed 3.7 kg and animal No. 3 weighed 4.3 kg.

Interpretation of the study results

On the grounds of the study, the test item, i.e. Mn (II) IDHA can be classified to the following categories:

- does not irritate the rabbit skin – according to the Annex to the Decree of the Minister of Health of August 10, 2012 on classification of chemical substances and mixtures (Journal of Laws, item 1018),

- is beyond categorization – according to the Regulation (EC) No. 1272/2008 of the European Parliament and of the Council of December 16, 2008 on classification, labelling, and packaging of substances and mixtures, amending and repealing Directives 67/548/EEC and 1999/45/EC and amending Regulation (EC) No. 1907/2006.

The detailed results of the study based on the scoring system presented in the OECD Guideline No. 404 / EU Method B.4. are given in Table 2.

Table 2 - Point evaluation of acute skin irritation/corrosion on rabbits
Acute skin irritation/corrosion on rabbits
Cu (II) IDHA
Animal No	Observation type	Evaluation after				Average after24, 48and72hours
		1hour	24hours	48hours	72hours
1	erythema	0	0	0	0	0
	oedema	0	0	0	0	0
2	erythema	1	0	0	0	0
	oedema	0	0	0	0	0
3	erythema	1	1	0	0	0.3
	oedema	0	0	0	0	0

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The observations of the treated skin revealed some changes in the form of barely perceptible erythema. The test item Mn (II) IDHA does not irritate skin of rabbits.

Executive summary:

A study was undertaken to investigate the skin irritation potential of Mn (II) IDHA in New Zealand White rabbits (OECD 404; Sornat, 2013, Report No. DDR-15/13). The study commenced with a sighting study on one animal. The powdered test item was applied in an amount of 0.5 g once to the shaved skin of one animal (rabbit No. 1) and covered with an appropriate band. The exposure lasted 4 hours. After evaluation of treated skin, in order to confirm irritation or its absence, the test item was applied to the skin of the next two animals (rabbit No. 2 and No. 3) for 4 hours in order to confirm its irritant properties. The procedure was the same as in case of rabbit No. 1. General clinical observations of the animals for morbidity and mortality were performed daily during the entire experiment. Detailed clinical observations of the treated skin were performed 1, 24, 48, and 72 hours after the end of the exposure. Body weights of the animals were determined on the administration day (day 0), i.e. directly before the administration, and on the last day of the experiment. After the observation period, the animals were euthanized.

The observations of the treated skin revealed some changes in the form of barely perceptible erythema.