Registration Dossier

Toxicological information

Skin irritation / corrosion

Currently viewing:

Administrative data

Endpoint:
skin irritation: in vivo
Remarks:
study acc. OECD 404 conducted in 1998
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
from 13-08-1998 till 08-09-1998
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
The underlying hypothesis for the read-across is that chelates have the same mode of action based on their ability to chelate, remove or add metal cations to body causing perturbation of body’s micronutrients balance.
The source substance is a chelating agent in a target substance. The only difference between the target and the main source substance is presence of magnessium (Mg) cation instead two Na+ cations. As magnessium is an essential micro element required by all forms of life, is considered not to influence the toxicological activity.
Detailed information about the substances purity and data matric are available in RA Statement (IUCLID 13.2)
Cross-referenceopen allclose all
Reason / purpose:
read-across: supporting information
Reference
Endpoint:
skin irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Study period:
2010-11-09 to 2010-11-19
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: well-documented GLP-Guideline Study
Justification for type of information:
A substantial body of evidence exists that the toxicity profiles of chelates depends mainly on metal ion, its affinity to this metal, and their ability to supply or to sequester it from the body/environment. The source substance has the same chelating agent as in a target substance (MgNa2IDHA). The only difference between the target and the source substance is presence of magnessium (Mg) cation instead Cu2+ cations. As magnessium is an essential micro element required by all forms of life, is considered not to influence the toxicological activity.
Detailed information about the substances purity and data matric are available in RA Statement (IUCLID 13.2)
Reason / purpose:
read-across source
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
other: SOP/T/22: “Acute skin irritation/corrosion study”
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Slovak National Accreditation Service (No. G-024)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Experimental Department of National Research Institute of Animal Production, Balice near Kraków
- Age at study initiation: 9-month-old rabbit female (rabbit No 1), 8.5-month-old male (rabbit No 2) and one 8-month-old male (rabbit No 3)
- Housing: individually in metal cages (60 x 35 x 40 cm). Each cage was equipped with label containing information on number of study protocol, start and end date of experiment (written after termination), sex and animal’s number
- 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): 21 - 23;
- Humidity (%): 47 – 84
- Air changes (per hr): about 16 times/h
- Photoperiod (hrs dark / hrs light): 12 / 12

Study commencement: 09.11.2010.
Experiment: from 09.11.2010. to 12.11.2010. (rabbit No 1)
from 16.11.2010. to 19.11.2010. (rabbit No 2 and No 3)
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:
72 hours
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 with sticking plaster

REMOVAL OF TEST SUBSTANCE
- Washing (if done): residual test item was removed using water
- Time after start of exposure: 4 hours
Irritation parameter:
erythema score
Basis:
mean
Remarks:
for 3 animals
Time point:
other: mean at 24, 48 and 72 hours
Score:
0
Irritation parameter:
edema score
Basis:
mean
Remarks:
for 3 animals
Time point:
other: mean at 24, 48 and 72 hours
Score:
0
Irritant / corrosive response data:
No irritating effects were noted.

Table 1: Summary of Cu (II) IDHA. Acute skin irritation/corrosion on rabbits
Administered amount of test item 0.5 g
Number of rabbit 1 2 3
Sex female male male
Mortality of animals 0/1 0/1 0/1
General clinical signs none none none
Skin erythema in area of treatment none none none
Skin oedema in area of treatment none none none
Other none none none

During the entire experiment, no pathological changes were stated on treated skin of rabbits.

Table 2 - Point evaluation of acute skin irritation/corrosion on rabbits
Acute skin irritation/corrosion on rabbits
Cu (II) IDHA
Rabbit 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 0 0 0 0 0
oedema 0 0 0 0 0
3 erythema 0 0 0 0 0
oedema 0 0 0 0 0

Body weight of animals

At the start of experiment animal No 1 weighed 3.7 kg, animal No 2 – 3.5 kg and animal No 3 – 3.6 kg.

At the end of experiment animal No 1 weighed 3.6 kg, animal No 2 – 3.5 kg and animal No 3 – 3.6 kg

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
During readings no pathological changes were stated on treated skin of rabbits. The test item Cu (II) IDHA does not irritate skin of rabbits.
Executive summary:

A study was undertaken to investigate the skin irritation potential of Cu (II) IDHA in New Zealand White rabbits (OECD 404; Kropidło, 2010, Report No. DDR-15/10). A dose of 0.5 g then was applied to a shaved, unabraded site on one animal. The powdered test item was applied in amount of 0.5 g as a single dose (applied first to multilayered gauze patch with dimensions of 2.5 x 2.5 cm, moistened with few drops of water and then laid on prepared skin) to shaved skin of one animal (rabbit No 1) and covered with appropriate band. The area of skin surface treated with the test item was about 6 cm². The gauze patches were covered with PCV foil and fixed with sticking plaster. The rabbits trunk was covered with lignin and elastic bandage was used to make circular protecting band. After an exposure time of 4 hours, the band and gauze patches were taken off and the residual test item was removed using water. The animal was observed for 72 hours. After evaluation of treated skin, in order to confirm irritation or its lack, the test item was applied to skin of another two animals (rabbit No 2 and No 3) for 4 hours. The test sites were then evaluated in accordance with the method of Draize at 1 hour, 24, 48 and 72 hours.

General clinical observations for morbidity and mortality of all animals were performed daily during the entire experiment. Detailed clinical observations of treated skin were performed after 1, 24, 48 and 72 hours since the end of exposure. Body weight of animals was determined directly before administration on day of administration of test item (day 0) and on last day of experiment. During readings no pathological changes were stated on treated skin of rabbits. No mortality or effects on body weight were observed. The test item Cu (II) IDHA does not irritate skin of rabbits.

Based on the results of this study this substance is not classified as a skin irritant in accordance with EU CLP Regulation (EC) No. 1272/2008.

Reason / purpose:
read-across: supporting information
Reference
Endpoint:
skin irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Study period:
23.05 - 27.06.2007
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: well-documented GLP-Guideline Study
Justification for type of information:
A substantial body of evidence exists that the toxicity profiles of chelates depends mainly on metal ion, its affinity to this metal, and their ability to supply or to sequester it from the body/environment. The source substance has the same chelating agent as in a target substance (MgNa2IDHA). The only difference between the target and the source substance is presence of magnessium (Mg) cation instead Fe3+ cations. As magnessium is an essential micro element required by all forms of life, is considered not to influence the toxicological activity.
Detailed information about the substances purity and data matric are available in RA Statement (IUCLID 13.2)
Reason / purpose:
read-across source
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Three white rabbits of New Zealand strain coming from conventional Reproductive Farm of Rabbits, Balice were used in the test.
The rabbits were quarantined for at least 5 days and observed carefully during this time.
One 5.5-month-old male rabbit weighing 4,02 kg and two 6 and 5-month-old female rabbits weighing 2.99 kg and 3.11 kg were used in the study.

During quarantine and experiment the animals were kept in air-conditioned rooms with the following parameters:
- temperature: 18 - 22 °C;
- relative air humidity: 50 - 80%;
- artificial fluorescent lighting: 12 hours light / 12 hours darkness.
The animals were kept individually in metal cages with dimensions: 60 x 35 x 40 cm. Each cage was equipped with label containing information on study protocol number, start date of the experiment, sex and animal number.

The animals were given ad libitum standard granulated fodder "LSK" produced by Wytwórnia Koncentratów i Mieszanek Paszowych AGROPOL, Motycz and drinking tap water.
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g unchanged test material
Duration of treatment / exposure:
4 hours
Observation period:
Observations of skin were performed after 1, 24, 48 and 72 hours as well as 7 days since the end of exposure.
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: about 6 cm2.
- Type of wrap if used: The
gauze patches were covered with PCV foil and fixed with sticking plaster. The rabbit’s trunk was covered with lignin and elastic bandage was used to make circular protecting band.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): After 4 hours of exposure, the band and gauze patches were taken off and the residual test material was removed using water.
- Time after start of exposure: 4 h
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 72h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 72 h
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 48h
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 72h
Score:
0
Max. score:
1
Reversibility:
fully reversible within: 24h
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 72h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 72h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 72h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritant / corrosive response data:
During observation after 1 hour since the end of exposure, faint erythema (barely visible) was stated on treated skin of all three rabbits.
During observation after 24 hours since the end of exposure, faint erythema (barely visible) was stated on treated skin of rabbits No 1 and 2. No pathological changes on skin of rabbit No 3 were noticed.

During observation after 48 and 72 hours since the end of exposure faint erythema (barely visible) was observed on treated skin of rabbit No 1. Rabbit No 2 showed no pathological changes.
During observation after 7 days no pathological changes on treated skin of rabbit No 1 were stated.
Other effects:
At the start of the experiment rabbit No 1 weighed 4.02 kg, rabbit No 2 - 2.99 kg while rabbit No 3 - 3.11 kg. At the end of the experiment body weight of rabbits amounted: rabbit No 1 – 4.1 kg, rabbit No 2 – 3.11 kg and rabbit No 3 – 3.27 kg.

Chelate with name: Fe (III) IDHA, Point evaluation of acute skin irritation/corrosion study for rabbits

Rabbit No

Observation type

Evaluation after

Average after 24, 48 and 72 h

1 h

24h

48h

72 h

7 days

1

erythema

1

1

1

1

0

1

oedema

0

0

0

0

0

0

2

erythema

1

1

0

0

-

0.3

oedema

0

0

0

0

-

0

3

erythema

1

0

0

0

-

0

oedema

0

0

0

0

-

0

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test item Fe (III) IDHA does not irritate skin of rabbits.
Executive summary:

Acute skin irritation/corrosion study of Chelate with name: Fe (III) IDHA for rabbits was performed according to OECD Guideline for Testing of Chemicals No 404/Method B.4. as well as Principles of Good Laboratory Practice (GLP - OECD, 1997). The study was performed with white rabbits of New Zealand strain. The tested substance was administered in amount of 0.5 g as a single dose to shaved skin of three rabbits and covered with appropriate band. The exposure time was 4 hours. After 1, 24, 48, 72 hours and 7 days since the end of exposure skin condition was examined. During observations all test rabbits showed changes on skin in form of erythema.

Classification of the test material was performed according to Regulation 1272/2008. Taking into account the obtained results, one may state that Chelate with name: Fe (III) IDHA does not irritate skin of rabbits.

Reason / purpose:
read-across: supporting information
Reference
Endpoint:
skin irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Study period:
2013-11-06 to 2013-11-11
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: well-documented GLP-Guideline Study
Justification for type of information:
A substantial body of evidence exists that the toxicity profiles of chelates depends mainly on metal ion, its affinity to this metal, and their ability to supply or to sequester it from the body/environment. The source substance has the same chelating agent as in a target substance (MgNa2IDHA). The only difference between the target and the source substance is presence of magnessium (Mg) cation instead Mn2+ cations. As magnessium is an essential micro element required by all forms of life, is considered not to influence the toxicological activity.
Detailed information about the substances purity and data matric are available in RA Statement (IUCLID 13.2)
Reason / purpose:
read-across source
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
other: SOP/T/22: “Acute skin irritation/corrosion study”
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Bureau for chemical substances (Registration No. B/2012/DPL
Species:
rabbit
Strain:
New Zealand White
Details on test animals 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
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
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: mean at 24, 48 and 72 hours
Score:
0
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: mean at 24, 48 and 72 hours
Score:
0
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
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: mean at 24, 48 and 72 hours
Score:
0
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: mean at 24, 48 and 72 hours
Score:
0
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.

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
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.

Reason / purpose:
read-across: supporting information
Reference
Endpoint:
skin irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Study period:
2008
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
A substantial body of evidence exists that the toxicity profiles of chelates depends mainly on metal ion, its affinity to this metal, and their ability to supply or to sequester it from the body/environment. The source substance has the same chelating agent as in a target substance (MgNa2IDHA). The only difference between the target and the source substance is presence of magnessium (Mg) cation instead Zn2+ cations. As magnessium is an essential micro element required by all forms of life, is considered not to influence the toxicological activity.
Detailed information about the substances purity and data matric are available in RA Statement (IUCLID 13.2)
Reason / purpose:
read-across source
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Principles of method if other than guideline:
Odchylenia od wytycznej/metody.

W trakcie badania wilgotność względna powietrza kilkakrotnie przekroczyła wartość 70 %. Nie miało to wpływu na przebieg i wyniki badania. Nie stwierdzono innych odchyleń od wytycznej / metody.
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Zwierzęta.
W doświadczeniu użyto trzech królików białych rasy nowozelandzkiej pochodzących z Instytutu Zootechniki w Balicach.
Króliki przeszły minimum 5-dniowy okres kwarantanny, w czasie którego były pod stałą obserwacją [SPR/T/6].
W dniu przyjęcia zwierząt do kwarantanny wykonano ogólne badanie lekarsko-weterynaryjne, a przed wprowadzeniem do doświadczenia u zwierząt wykonano szczegółowe badanie lekarsko-weterynaryjne [SPR/T/46]. Do doświadczenia wprowadzono zwierzęta nie wykazujące żadnych objawów klinicznych.Wszystkie zwierzęta były indywidualnie oznaczone [SPR/T/7].W doświadczeniu użyto trzech samców w wieku: królik nr 1 - 9 miesięcy, królik nr 2 - 7 miesięcy i królik nr 3 - 11 miesięcy.

Warunki przetrzymywania zwierząt.

W okresie kwarantanny i doświadczenia zwierzęta przebywały w klimatyzowanym pomieszczeniu o następujących parametrach:
- temperatura powietrza 20 - 22 °C
- wilgotność względna powietrza 50 - 90 %
- oświetlenie sztuczne, jarzeniowe; cykl oświetlenia: 12 godzin jasno - 12 godzin ciemno [SPR/T/9].
Zwierzęta przetrzymywano pojedynczo w metalowych klatkach, o wymiarach (długość x szerokość x wysokość): 60x35x40 cm. Każda klatka wyposażona była w wywieszkę zawierającą: numer protokołu badania, datę założenia i zakończenia doświadczenia, płeć i numer zwierzęcia [SPR/T/22].

Pasza i woda.
Zwierzętom podawano bez ograniczeń granulowaną standardową paszę laboratoryjną „LSK", produkowaną przez Wytwórnię Koncentratów i Mieszanek Paszowych AGROPOL z Motycza oraz wodę wodociągową [SPR/T/15].

Przygotowanie zwierząt.

W przeddzień rozpoczęcia doświadczenia, maszynką elektryczną do strzyżenia, usunięto zwierzętom sierść na grzbiecie i obu bokach na dostatecznie dużej powierzchni. Do doświadczenia użyto tylko tych zwierząt, których skóra była nie uszkodzona i nie wykazywała cech przekrwienia [SPR/T/22].


Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
yes
Amount / concentration applied:
Badany materiał, po roztarciu na proszek, naniesiono w ilości 0,5 g na kilkuwarstwowy płatek gazy o wymiarach 2,5 * 2,5 cm, zwilżono kilkoma kroplami wody. Następnie płatek gazy nałożono na skórę jednego królika (królik nr 1). Narażana powierzchnia skóry królika wynosiła ok. 6 cm2. Gazę osłonięto folią PCW i przytwierdzono do skóry przylepcem. Tułów królika owinięto warstwą ligniny oraz zabezpieczono elastyczną opaską i przylepcem. Po 4-godzinnym okresie narażania, przylepiec i płatek gazy zdjęto, a pozostałość badanego materiału usunięto ze skóry przy pomocy wody.
Duration of treatment / exposure:
4 godziny
Observation period:
Obserwacje i wycena.

Obserwacji skóry dokonano po 1, 24, 48 i 72 godzinach od zakończenia narażania [SPR/T/22].
Stan skóry oceniano według skali punktowej, na podstawie Wytycznej OECD nr 404 / Metody B.4. (Załącznik 6).
Wyniki badania oceniono według Załącznika do Rozporządzenia Ministra Zdrowia z dnia 2 września 2003 r. w sprawie kryteriów i sposobu klasyfikacji substancji i preparatów chemicznych (Dz.U. Nr 171, poz. 1666).
Number of animals:
3 szt.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
>= 0 - <= 1
Max. score:
1
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
>= 0 - <= 1
Max. score:
1
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0

5.5. Data rozpoczęcia i zakończenia doświadczenia.

 

Badany materiałnałożono na skórękrólików w dniu: 15.07.2008. (królik nr 1) oraz 22.07.2008. (królik nr 2 i nr 3). Doświadczenie zakończono w dniu 18.07.2008. (królik nr 1), oraz 25.07.2008. (królik nr 2 i nr 3).

 

 

6.   Wyniki.

 

6.1. Wyniki działania drażniącego/żrącego.

 

W trakcie odczytu po 1 godzinie od zakończenia narażania, na skórze w miejscu nałożenia badanego materiału, u królika nr 2 stwierdzono bardzo słaby (ledwo dostrzegalny) rumień. U pozostałych królików zmian patologicznych na skórze nie stwierdzono.

W trakcie odczytu po 24 godzinach od zakończenia narażania, na skórze dwóch królików (królik nr 2 i nr 3) stwierdzono bardzo słaby (ledwo dostrzegalny) rumień. U królika nr 1 nie stwierdzono zmian.

W trakcie odczytu po 48 godzinach od zakończenia narażania, u królików nie stwierdzono jużzmian patologicznych na narażanej skórze.

W trakcie odczytu po 72 godzinach od zakończenia narażania, u królików nie stwierdzono zmian patologicznych na narażanej skórze.

Szczegółowe wyniki badania, w oparciu o skalępunktowąwg Wytycznej OECD nr 404/ Metody B.4., przedstawiono w Tabeli 1 (strona 51).

6.2.    Masa ciała zwierząt.

 

W dniu rozpoczęcia doświadczenia masa ciała królików wynosiła: 3,8 kg (królik nr 1), 3,8 kg (królik nr 2) i 3,7 kg (królik nr 3).

W dniu zakończenia doświadczenia masa ciała królików wynosiła: 3,9 kg (królik nr 1), 3,8 kg (królik nr 2) i 3,7 kg (królik nr 3).

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Executive summary:

Na podstawie przeprowadzonego badania i według Załącznika do Rozporządzenia Ministra Zdrowia z dnia 2 września 2003 r. w sprawie kryteriów i sposobu klasyfikacji substancji i preparatów chemicznych (Dz.U. Nr 171 poz. 1666) można stwierdzić,żeZn (II) IDHAnie drażni skóry królików

Reason / purpose:
data waiving: supporting information
Reference
Endpoint:
skin corrosion: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid

Test animals

Species:
rabbit
Strain:
Himalayan
Details on test animals and environmental conditions:
lnitial age: approx. 4 months
Body weight at start of study: 2.0 - 2.1 kg
ldentification: by tattooed number assigned by the lohndorf breeding station and continuous number 1 - 3
Duration of adaptation : at least 20 days
Administration route: dermal application to the shaved intact dorsal skin (semi-occlusive procedure)

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
water
Remarks:
aqua ad iniectabilia
Controls:
yes
Amount / concentration applied:
500 mg/patch and animal, once epicutaneous
{4000 mg of the test compound were mixed with 1 ml aqua ad iniectabilia, 625 mg of this paste were applied per animal (il, 500 mg test compound/animall)
Duration of treatment / exposure:
4 hours
Observation period:
72 h
Number of animals:
3 male rabbits
Details on study design:
Approximately 24 hours before the test, the fur was removed by shaving from the dorsal area of the trunk of the animals. Care was taken to avoid abrading the skin. Only animals with healthy intact skin were used.
A dose of 500 mg was applied to the test site (area: approx. 6 cm 2). Pulverised solids were moistened sufficiently with water to ensure good contact with the skin. The test substance was applied to the test site and then covered with a gauze patch. The patch was held in contact with the skin by means of a semi-occlusive dressing for the duration of the exposure period. The surrounding untreated skin served as a control.
Exposure time was four hours. During the exposure the animals were kept in com­ fortable restrainers.
Examination of the skin: the skin sites were evaluated immediately before the applica­ tion of the test substance. After the 4-hour exposure period the patch was removed and the skin sites were evaluated. Scores were taken 60 minutes, 24, 48 and 72 hours after patch removal.
The evaluation of the skin irritation was based on the grading given in the Appendix 1 to this report.
Based on most recent guidelines the skin reactions are monitored until the changes observed have completely subsided, however for not more than 14 days after application. Animals that do not reveal any lesions anymore for 24 hours following the first 72 hours of observation are sacrificed.
General criteria: body weight of all animals was measured at the beginning of the study.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
0
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
0
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
0
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
0
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
0
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
0
Irritant / corrosive response data:
Under the present test conditions none of the three rabbits exposed for 4 hours to 500 mg lminodisuccinic acid, sod,um salt IIDS, Na-Salz)/patch and anirnal (semi­ occlusive condition) showed any substance·related lesions at the examination time­ points 60 min. 24, 48 and 72 hours after patch removal.

There were no systemie intolerance reactions.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
IDS, sodium salt was non-irritating to skin.
Executive summary:

Test system              acute skin irritation, Patch·Test, in rabbits, semi-occlusive, according to EC guideline B.4. and OECD guideline404

Test substance      lminodisuccinic acid, sodium salt (IDS.Na·Salz)

Under the present test conditions none of the three rabbits exposed for 4 hours  to 500 mg iminodisuccinic acid, sodium salt {IDS, Na-Salz)/patch and animal (semi­ occlusive condition) showed any substance-related lesions at the exarnination time· points 60 min, 24. 48 and 72 hours after patch removal. Them were no systemic intolerance reactions.

According to the Regulation 1272/2008 and its subsequent amendments on the approximation of the laws, regulations and administrative provision relating to the classification, packaging and labelling of dangerous substances and the results obtained under the present testconditions lminodisuccinic acid, sodium salt (IDS, Na-Salzl) was non-irritatingto skin, hence, no labelling is required.