Registration Dossier

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2010-11-09 to 2010-11-19
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:
2010
Report Date:
2010

Materials and methods

Test guidelineopen allclose all
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)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Test material form:
other: powdered
Details on test material:
- Name of test material (as cited in study report): Cu (II) IDHA
- Substance type: chelate
- Physical state: solid (odourless, blue microgranules)
- Analytical purity: the test item contains 9.82% of copper
- Lot/batch No.: 1/10, date of production: April, 2010
- Expiration date of the lot/batch: April, 2013
- Storage condition of test material: in tightly closed packed at temperature from -10°C to +30°C

Test animals

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)

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:
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

Results and discussion

In vivo

Resultsopen allclose all
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.

Any other information on results incl. tables

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

Applicant's summary and conclusion

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.