Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
May, 29 - June, 12, 2007
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:
2007
Report Date:
2007

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
GLP compliance:
yes (incl. certificate)
Remarks:
Statement of GLP Compliance No G-024 issued by Slovac National Accreditation Service; Statement of GLP Compliance No 4/2006/DPL issued by Bureau for Chemical Substances and Preparations
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
other: microgranules
Details on test material:
- Name of test material (as cited in study report): Fe(III)IDHA
- Substance type: chelate
- Physical state: green microgranules

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Institute of Occupational Medicine in Łódz kept in conventional type.
- Age at study initiation: 10-week-old male rats and 11-weekold females
- Weight at study initiation: male rats with the average body weight of 287 g and females with the average body weight of 194 g
- Fasting period before study: no
- Housing:
- Diet (e.g. ad libitum): standard granulated "Murigran" fodder produced by Wytwórnia Koncentratów i Mieszanek Paszowych AGROPOL, Motycz
- Water (e.g. ad libitum): tap water
- Acclimation period: yes

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 - 23 °C;
- Humidity (%): 48 - 80
- Photoperiod (hrs dark / hrs light): artificial, fluorescent lighting: 12 hours light / 12 hours darkness

The animals were kept in cages with plastic bottom and wired lid, with dimensions: (length x width x height) 58 x 37 x 21 cm. Following administration of the test material on animals skin, each one was kept individually per cage. After removal of the test material from animals skin, during the following days of experiment the rats were kept five per cage, each sex separately.

Wooden UV-sterilized shavings were used as a litter. Each cage was equipped with label containing information on name of test material, study code, used dose, start date and planned ending date of the experiment, animal sex and animal numbers.

IN-LIFE DATES: From: To:
The experiment was started on May 29th, 2007 (males and females) and ended on June 12th, 2007.

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
The day before the test back and sides of animals were shaved with electric razor on skin surface area of about 4 x 6 cm. Only those animals that showed no macroscopically visible irritation or damages of skin were used for the experiments. The animals were not starved prior to the experiment.

The undiluted test material was applied to the dorsal skin of 10 rats (5 males and 5 females) in dose of 2000 mg/kg b.w. The area of skin treated with the test material was about 6 cm2. The test material was applied to gauze patches and then laid on the prepared skin. The gauze patches were covered with PCV foil and elastic bandage was used to make circular protecting band. After 24 hours the band and gauze patches were taken off and the residual test material was removed using water.
Duration of exposure:
24 hours
Doses:
2000 mg/kg b.w.
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Evaluation of general condition of animals, i.e. observation of all animals in regards to mortality and morbidity was conducted twice a day during 14-day observation period. Following administration of the test material, detailed clinical observations were performed in hour intervals during the day of administration (day 0). Since the first till the 14th day of observation period detailed clinical observations were performed once a day.
Body weight of animals was determined individually for each animal directly before administration of the test material (day 0) and then on seventh andfourteenth day - before the finishing of the experiment.
- Necropsy of survivors performed: yes
- Other examinations performed: After opening of thorax and abdomen macroscopic examination of internal organs was performed.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
All rats survived the 14-day observation period.
Clinical signs:
During 14-day experiment period no changes on skin or in behavior of test animals were stated.
Body weight:
During 14-day experiment period all animals showed body weight gains.
Gross pathology:
No pathological changes were stated in animals during macroscopic examination.

Any other information on results incl. tables

Chelate with name: Fe (III) IDHA Acute dermal toxicity study for rats – clinical signs – overall list

Dose

(mg/kg

b.w.)

Sex

Day after

administration

No of

alive

animals

Rat No

 

1

2

3

4

5

 

 

 

2000

Males

0

5

NC

NC

NC

NC

NC

 

1

5

NC

NC

NC

NC

NC

 

2

5

NC

NC

NC

NC

NC

 

3

5

NC

NC

NC

NC

NC

 

4

5

NC

NC

NC

NC

NC

 

5

5

NC

NC

NC

NC

NC

 

6

5

NC

NC

NC

NC

NC

 

7

5

NC

NC

NC

NC

NC

 

8

5

NC

NC

NC

NC

NC

 

9

5

NC

NC

NC

NC

NC

 

10

5

NC

NC

NC

NC

NC

 

11

5

NC

NC

NC

NC

NC

 

12

5

NC

NC

NC

NC

NC

 

13

5

NC

NC

NC

NC

NC

 

14

5

NC

NC

NC

NC

NC

 

Females

0

5

NC

NC

NC

NC

NC

 

 

1

5

NC

NC

NC

NC

NC

 

2

5

NC

NC

NC

NC

NC

 

3

5

NC

NC

NC

NC

NC

 

4

5

NC

NC

NC

NC

NC

 

5

5

NC

NC

NC

NC

NC

 

6

5

NC

NC

NC

NC

NC

 

7

5

NC

NC

NC

NC

NC

 

8

5

NC

NC

NC

NC

NC

 

9

5

NC

NC

NC

NC

NC

 

10

5

NC

NC

NC

NC

NC

 

11

5

NC

NC

NC

NC

NC

 

12

5

NC

NC

NC

NC

NC

 

13

5

NC

NC

NC

NC

NC

 

14

5

NC

NC

NC

NC

NC

 

NC – no changes

Chelate with name: Fe (III) IDHA Acute dermal toxicity study for rats – body weight of animals (g)

Dose

(mg/kg

b.w.)

Sex

Rat No

Day

Difference

 

 

0

7

14

14 - 0

 

 

 

 

 

 

2000

Males

1

260

281

302

42

 

2

299

308

326

27

 

3

285

293

315

30

 

4

300

316

345

45

 

5

293

309

332

39

 

 

 

 

 

 

 

 

 

1

191

206

209

18

 

Females

 

2

191

203

215

24

 

3

194

203

211

17

 

4

198

207

216

18

 

5

195

199

218

23

 

 

 

 

 

 

 

 

 

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Taking into account the obtained results one may state that the median dermal acute dose (LD50) for Chelate with name: Fe (III) IDHA is higher than 2000 mg/kg b.w.
Executive summary:

Acute dermal toxicity study of Chelate with name: Fe (III) IDHA for rats was performed according to the OECD Guideline for Testing of Chemicals No 402/ Method B.3 as well as Principles of Good Laboratory Practice (GLP - OECD, 1997). The test material was given to 10 rats (5 males and 5 females) to shaved dorsal skin in single dose of 2000 mg/kg b.w. for 24 hours. During 14-day observation period no changes on skin or in behavior were stated in test animals. All animals survived 14- day experiment period. All animals which were euthanized after 14-day observation period were dissected and studied macroscopically. Macroscopic examination showed no pathological changes in test animals. Taking into account the obtained results one may state that median dermal acute dose (LD50) for Chelate with name: Fe (III) IDHA is higher than 2000 mg/kg b.w.