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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2008-07-15 to 2008-10-24
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report date:
2008

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
changes in air humidity
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
changes in air humidity
Principles of method if other than guideline:
Few times during experiment the relative air humidity was above 70%. It did not influence study course and results.
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Chemical structure
Reference substance name:
iron(3+) sodium 2-({2-[(carboxylatomethyl)[(2-oxidophenyl)methyl]amino]ethyl}[(2-oxidophenyl)methyl]amino)acetate
EC Number:
700-327-5
Cas Number:
1061328-86-6
Molecular formula:
C20H20FeN2NaO6
IUPAC Name:
iron(3+) sodium 2-({2-[(carboxylatomethyl)[(2-oxidophenyl)methyl]amino]ethyl}[(2-oxidophenyl)methyl]amino)acetate
Details on test material:
- Name of test material (as cited in study report): Fe (III) HBED
- Substance type: chelate
- Physical state: microgranulate
- Analytical purity: 8.6% of Fe3+
- Impurities (identity and concentrations): no data
- Composition of test material, percentage of components: no data
Data concerning identity, purity and stability of test item are responsibility of Sponsor.
- Purity test date: 2008-05-26
- Lot/batch No.: 215/P/Fe-HBED
- Expiration date of the lot/batch: not reported
- Stability under test conditions: up to 15.05.2011
- Storage condition of test material: at temp. from -10°C to +30°C
- Other:

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Reproductive Farm of Rabbits, Balice
- Age at study initiation: Two 9-month-old males (rabbit No 1 and No 2) and one 11-month-old male (rabbit no 3)
- Weight at study initiation: rabbit No 1 weighed 3.8 kg, rabbit No 2: 3.7 kg and rabbit No 3: 3.7 kg
- Housing: The animals were kept individually in air-conditioned room in metal cages with dimensions (length x width x height): 60 x 35 x 40 cm.
- 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: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 45-90
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: The test item was applied to rabbits’ skin on: 2008-07-15 (rabbit No 1), 2008-07-22. (rabbit No 2 and No 3). The study was finished on: 2008-07-29 (rabbit No 1) and 2008-08-12 (rabbit No 2 and No 3).

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
water
Remarks:
The test item was moistened with few drops of water, and then laid on the prepared skin
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g (on multilayered gauze patch)

VEHICLE
- Amount(s) applied (volume or weight with unit): The test item was moistened with few drops of water, and then laid on prepared skin of one rabbit
Duration of treatment / exposure:
4 hours
Observation period:
Observations of skin were performed after 1, 24, 48 and 72 hours as well as 7, 14 and 21 days after the end of exposure.
Number of animals:
Two 9-month-old males (rabbit No 1 and No 2) and one 11-month-old male (rabbit no 3) were used in experiment.
Details on study design:

TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- % coverage: 6%
- 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): yes
- Time after start of exposure: 4 hours

SCORING SYSTEM: Skin condition was evaluated according to the scoring system of OECD Guideline No 404 / Method B.4.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: mean value at 24, 48 and 72 hours
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: mean value at 24, 48 and 72 hours
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 21 day
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: mean value at 24, 48 and 72 hours
Score:
1.7
Max. score:
4
Reversibility:
fully reversible within: 21 days
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: mean at 24, 48 and 72 hours
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: mean value at 24, 48 and 72 hours
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: mean value at 24, 48 and 72 hours
Score:
0
Max. score:
4
Remarks on result:
other: no effect
Irritant / corrosive response data:
During reading after 1 hour since the end of exposure, well defined erythema was stated on treated area of skin of all rabbits. No oedema of skin was stated in rabbits.
During reading after 24 hours since the end of exposure, well defined erythema was still observed on treated area of skin of all rabbits. Barely perceptible oedema of skin was stated in rabbit No 1 and No 2.
During reading after 48 hours since the end of exposure, barely perceptible erythema was stated in rabbit No 1 whereas well defined erythema was observed in rabbit No 2 and No 3. No oedema of treated skin was stated.
During readings after 72 hours and 7 days since the end of exposure, barely perceptible erythema of skin was stated in rabbits No 1 and No 3, well defined erythema - in rabbit No 2.
During reading after 14 days since the end of exposure, no pathological changes were stated on treated area of skin of rabbit No 1. Barely perceptible
erythema of skin was stated in rabbits No 2 and No 3.
During reading after 21 days since the end of exposure, no pathological changes were stated on treated area of skin of rabbits.
Other effects:
The animals gained in the body weight: at the end of experiment rabbit No 1 weighed 4.0 kg, rabbit No 2 – 3.8 kg and rabbit No 3 – 3.6 kg.

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test substance is not irritating to skin since mean values for erythema and oedema calculated for each animal for three consecutive days (24, 48 and 72 hours) did not exceed the trigger values leading to classification and labelling according to CLP.
Executive summary:

Acute skin irritation/corrosion study with Fe (III) HBED (CAS 1061328 -86 -6) according to the OECD TG 404 was conducted in 3 White New Zealand rabbits (Gruszka, 2008). The powdered test item in amount of 0.5 g was applied as a single dose to the shaved skin of the rabbits and covered with an appropriate band. The test substance was held 4 hours in contact with the skin by semi-occlusive dressing. Skin condition was evaluated after 1, 24, 48, and 72 hours as well as after 7, 14 and 21 days after the end of exposure. The mean values of the scores for erythema and oedema were calculated for each animal. Erythema and oedema were observed on skin of rabbits. Well-defined erythema was observed in all animals at 1-hour and at 24-hour readings. Erythema became barely perceptible on day 7 in two animals and on day 14 in third animal and was fully reversible within 21 days of observation period. Very slight oedema was noted only in two animals at 24-hour reading and disappeared completely after 48 hours after exposure. No pathological changes were noted on treated skin of animals. Mean scores over 24, 48 and 72 hours for each animal were 1.3, 0.3 and 2.0 for erythema and 0.3, 1.7 and 0.0 for oedema. These values do not exceed cut-off-values defined in the Guidance on the Application of Regulation (EC) No. 1272/2008, and do not trigger classification and labeling as skin irritant.