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Administrative data

acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From: 2008-07-15 To: 2008-10-24
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference Type:
study report
Report date:

Materials and methods

Test guidelineopen allclose all
according to guideline
OECD Guideline 402 (Acute Dermal Toxicity)
according to guideline
EU Method B.3 (Acute Toxicity (Dermal))
GLP compliance:
Test type:
standard acute method
Limit test:

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:
Cas Number:
Molecular formula:
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

Details on test animals or test system and environmental conditions:
- Source: Institute of Occupational Medicine in Łódź
- Age at study initiation: 10 weeks
- Weight at study initiation: males with the average body weight of 341 g and females with the average body weight of 210 g
- Fasting period before study: no
- Housing: The animals were kept in cages with dimensions (length x width x height): 58 x 37 x 21 cm; with plastic bottom and wired lid. After application of the test item each animal was kept individually in cage. After removal of test item from animals’ skin during the following days of experiment, the rats were kept five per cage, each sex separately. UV-sterilized wooden shavings were used as a bedding
- Diet (e.g. ad libitum): ad libitum. Standard granulated "Murigran" fodder produced by Wytwórnia Koncentratów i Mieszanek Paszowych AGROPOL, Motycz.
- Water (e.g. ad libitum): ad libitum; tap water
- Acclimation period: 5 days

- Temperature (°C): 21-23
- Humidity (%): 40-65
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 2008-09-17 To: 2008-10-01

Administration / exposure

Type of coverage:
unchanged (no vehicle)
the test item was moistened with water and then laid on prepared skin
Details on dermal exposure:

- Area of exposure: back
- % coverage: 10% (42 cm² (males) and 36 cm² (females))
- Type of wrap if used: not reported. The test item was applied to gauze patches, moistened with water and then laid on prepared skin. The gauze
patches were covered with PCV foil and elastic bandage was used to make circular protecting band.

- Washing (if done): yes.The band and gauze patches were taken off and the residual test item was removed using water
- Time after start of exposure: 24 hours


- For solids, paste formed: yes. The test material was moistened with water
Duration of exposure:
24 hours
2000 mg/kg bw
No. of animals per sex per dose:
Control animals:
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 for mortality and morbidity was conducted twice a day or once a day (on days off) during 14-day observation period. After administration of the test item, detailed clinical observations were performed at hour intervals on 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 individually determined for each animal directly before administration of test item (day 0) and then on seventh and fourteenth day - before the finishing of the experiment
- Necropsy of survivors performed: yes. Detailed gross examination of external body surfaces, all apertures, cranial, thoracic and abdominal cavity with content was performed at necropsy
- Other examinations performed: clinical signs, body weight
Not reported

Results and discussion

Effect levels
Dose descriptor:
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
No mortalities were observed during the course of the study
Clinical signs:
other: Clinical signs No clinical changes were observed in the animals. The results of detailed clinical observations are presented in the Table 1 (page 41) as well as in Individual Data Sheets attached to this file (pages 43-62).
Gross pathology:
At necropsy enlargement of left lung and congestion of lungs with inflammatory changes were stated in the female No 5. These changes were not connected with test item. Respiratory system diseases occur quite often in laboratory rats [3]. No pathological changes were stated at necropsy of the remaining animals.
Results of gross examination of animals are presented in Individual Data Sheets attached to this file (pages 43-62).
Other findings:
Following application of test item no pathological changes were stated on the skin of treated animals on the site of application.

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Migrated information Criteria used for interpretation of results: OECD GHS
On the ground of the study, one may state that the median dermal lethal dose (LD50) for Fe (III) HBED is greater than 2000 mg/kg b.w.
Executive summary:
Acute dermal toxicity study with Fe (III) HBED (CAS No. 1061328 -86 -6) was performed in Wistar rats according to the OECD TG 402 (Gruszka, 2008). The test item at dose level of 2000 mg/kg bw was applied to the shaved dorsal skin of 10 rats (5 males and 5 females) once and left for a period of 24 hours under semi-occlusive dressing. Purified water was used in order to moisten the test substance and ensure good contact with the skin as well as to remove residual test substance after removal of the dressing. Clinical signs, mortality and body weight gain were checked for a period of 14 days following the single application of the test substance. All animals were sacrificed after 14 -day observation period and subjected to gross necropsy. Following administration of test item, no changes were stated on skin of animals in the site of test item application. No other clinical changes were stated in animals. All animals survived 14-day period of experiment. At necropsy, enlargement of left lung and congestion of lungs with inflammatory changes (changes independent on test item) were stated in the female No 5. No pathological changes were stated in the remaining animals. On the ground of the study, one may state that the median dermal lethal dose (LD50) for Fe (III) HBED is greater than 2000 mg/kg b.w.