Ferrate(1-), [[N,N'-1,2-ethanediylbis[N-[[2-(hydroxy-.kappa.O)phenyl]methyl]glycinato-.kappa.N,.kappa.O]](4-)]-, sodium (1:1), (OC-6-13)-

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From: 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 guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

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:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- 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

ENVIRONMENTAL CONDITIONS
- 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:

semiocclusive

Vehicle:

unchanged (no vehicle)

Remarks:

the test item was moistened with water and then laid on prepared skin

Details on dermal exposure:

TEST SITE
- 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.

REMOVAL OF TEST SUBSTANCE
- 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

TEST MATERIAL

- For solids, paste formed: yes. The test material was moistened with water

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

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 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

Statistics:

Not reported

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

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

Remarks:

Migrated information Criteria used for interpretation of results: OECD GHS

Conclusions:

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.