Acetic acid, oxo-, sodium salt, reaction products with ethylenediamine and hydroxybenzenesulfonic acid monosodium salt, iron sodium salts

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

from 2000-08- 09 to 2000-08-23

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): EDDHAS Fe, sel de K
- Molecular formula (if other than submission substance): C18H14FeN2O12S2(3K)
- Molecular weight (if other than submission substance): 687.3
- Smiles notation (if other than submission substance): O=C(O)C(NCCNC(C(=O)O)c1cc(ccc1(O))S(=O)(=O)O)c2cc(ccc2(O))S(=O)(=O)O
- InChl (if other than submission substance): InChI=1S/C18H20N2O12S2/c21-13-3-1-9(33(27,28)29)7-11(13)15(17(23)24)19-5-6-20-16(18(25)26)12-8-10(34(30,31)32)2-4-14(12)22/h1-4,7-8,15-16,19-22H,5-6H2,(H,23,24)(H,25,26)(H,27,28,29)(H,30,31,32)
- Substance type: Fe chelate
- Physical state: brownish/red powder
- Analytical purity: 55±2%
- Impurities (identity and concentrations): none
- Purity test date: 2000-10-24
- Expiration date of the lot/batch: 2001-01-24
- Stability under test conditions: at least 6 months from receipt (date of receipt: 24 July 2000)
- Storage condition of test material: at room temperature and protected from humidity
- Other:

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Species, strain: rat, Sprague-Dawley ICO: OFA-SD (IOPS Caw)
- Source: Iffa Credo, 69210 LArbresle, France.
- Age at study initiation: 8 weeks old
- Weight at study initiation: 249 ± 8 g for the males and 225 ± 8 g for the females
- Fasting period before study: no
- Housing: during the acclimatization period, one to seven animals of the same sex were housed in polycarbonate cages (48 cm x 27 cm x 20 cm).
During the treatment period, the animals were housed individually in polycarbonate cages (35.5 cm x 23.5 cm x 19.3 cm).
Each cage contained dust-free sawdust (SICSA, 94142 Alfortville, France).
- Diet (e.g. ad libitum): ad libitum, A04 C pelleted diet (UAR, 91360 Villemoisson-sur-Orge, France)
- Water (e.g. ad libitum): drinking water filtered by a FG Millipore membrane (0.22 micron) was provided ad libitum.
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ±2
- Humidity (%): 30 to 70
- Air changes (per hr): approximately 12 cycles/hour of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 2000-08- 09 To: 2000-08-23

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

water

Remarks:

purified by reverse osmosis

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal area (5 cm x 6 cm for the females and 5 cm x 7 cm for the males)
- % coverage: 10
- Type of wrap if used: restraining bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 24 hours

TEST MATERIAL
- For solids, paste formed: yes. A single dose of 2000 mg/kg of the test substance in its original form was placed on a hydrophilic gauze pad pre-moistened with 2 mL of water

VEHICLE
- Amount(s) applied (volume or weight with unit): 2 mL

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

other: the data on historical control rats were used

Details on study design:

- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: The animals were observed frequently during the hours following administration of the test substance, for detection of possible treatment-related clinical signs. Thereafter, observation of the animals was made at least once a day until day 15.
Type, time of onset and duration of clinical signs were recorded for each animal individually. The animals were weighed individually just before administration of the test substance on day 1 and then on days 8 and 15.

- Necropsy of survivors performed: yes. After opening the thoracic and abdominal cavities, a macroscopic examination of the main organs (digestive tract, heart, kidneys, liver, lungs, pancreas, spleen and any other organs with obvious abnormalities) was performed. In case of macroscopic lesions, organ samples were taken and preserved in 10% buffered formalin. No microscopic examination was performed.

- Other examinations performed: From day 2, any local cutaneous reaction was recorded

Statistics:

No

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no findings

Mortality:

No deaths occurred during the study.

Clinical signs:

other: No clinical signs were observed during the study.

Gross pathology:

Macroscopic examination of the main organs of the animals revealed no apparent abnormalities.

Other findings:

No cutaneous reactions were observed.
A slight brownish coloration of the skin which could have masked a possible discrete erythema, was noted in most of the animals on day 2 only.

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the experimental conditions of this study, the dermal LD50 of the test substance Fe3KEDDHSA is higher than 2000 mg/kg in rats.

Executive summary:

The acute dermal toxicity of the test substance Fe3KEDDHSA was evaluated in rats according to OECD TG 402. The test substance in its original form was applied to the skin of one group of ten Sprague-Dawley rats (five males and five females) at the dose of 2000 mg/kg bw. 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. The test site was then covered by a semi-occlusive dressing for 24 hours. 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 subjected to necropsy.

No clinical signs and no deaths were observed during the study. A reduced weight gain was seen in 1/5 females between day 1 and day 8. The overall body weight gain of the other animals was similar to that of historical control animals at the test facility. No cutaneous reactions were observed. A slight brownish coloration of the skin which could have masked a possible discrete erythema, was noted in most of the animals on day 2 only. No apparent abnormalities were observed at necropsy in any animal. Under the experimental conditions of this study, the dermal LD50 of the test substance EDDHAS Fe 3K is detremined to be higher than 2000 mg/kg in rats.