Ammonium iron(III) citrate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

Data is from experimental study report.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1997

Report date:

1997

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: EEC Guidelines (B.1)

Principles of method if other than guideline:

The purpose of the study was to evaluate the acute oral toxicity of the test article in rats.

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Ammonium iron(III) citrate

EC Number:

214-686-6

EC Name:

Ammonium iron(III) citrate

Cas Number:

1185-57-5

Molecular formula:

C6H8O7.xFe.xH3N

IUPAC Name:

Ammonium iron (III) citrate

Details on test material:

- Name of test material (IUPAC name): 2-Hydroxypropane-1,2,3-tricarboxylate, ammonium iron (3+) salt
- Common name: Ferric ammonium citrate
- Molecular formula: C6H8O7.xFe.xH3N
- Molecular weight: 264.9979 g/mol
- Smiles notation: N.[Fe+3].OC(=O)CC(O)(CC(=O)O)C(=O)O
- InChl: 1S/C6H8O7.Fe.H3N/c7-3(8)1-6(13,5(11)12)2-4(9)10;;/h13H,1-2H2,(H,7,8)(H,9,10)(H,11,12);;1H3/q;+3;
- Substance type: Organic

Test animals

Species:

rat

Strain:

Sprague-Dawley

Remarks:

Cri: CD (SD) BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Italia S.p.A. Via Indipendenza, 11 22050 CALCO (Lecco) Shipping slips No.s 6603 (October 3. 1997) and 6984 (October 17, 1997)
- Age at study initiation: no more than three months
- Weight at study initiation: Males: 217-241 2 Females: 200-219 g
- Fasting period before study:
- Housing: 5 animals/sex/cage in air-conditioned room.
- Diet (e.g. ad libitum): GLP 4RF21 top certificate pelleted diet produced by Charles River Italia's feed licencee Mucedola S.rl.. Settimo Milanese,ad libitum
- Water (e.g. ad libitum): from the municipal water main system, ad libitum
- Acclimation period: at least 5 days before the start of the test.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ±2
- Humidity (%): 55% ± 10
- Air changes (per hr): about 20 / hour filtered on HEPA 99.97%
- Photoperiod (hrs dark / hrs light): 12 hour cycle (7 a.m. - 7 p.m. )
-Animal identification: by appropriately coloring different areas of the limbs. Cage card gave experiment number, dosage group, sex and date of administration.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg

DOSAGE PREPARATION (if unusual): one group of 5 rats/sex, randomly selected, was administered a dosage of 2000 mg/kg (limit dose) of the test article. The volume of administration was 1.44 ml/kg. The density of the test article is 1.39 g/ml.

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 males + 5 females treated at 2000 mg/kg

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:twice pre-trial (at randomization and on day 1 just before administration) and on days 3, 8 and 14. On day 1 the animals were weighed after a 16-hour fasting period.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights

Statistics:

no data

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 mortality was observed.

Mortality:

No deaths occurred in the treated animals of either sex. The LD50 was not calculated and it was considered higher than 2000 mg/kg.

Clinical signs:

other: No clinical changes were seen in the animals.

Gross pathology:

At the autopsy carried out at the end of the observation period, no appreciable macroscopic findings were evident in any treated rat.

Applicant's summary and conclusion

Interpretation of results:

other: Not Classified

Conclusions:

No deaths or clinical signs occurred in the treated animals. Body weight growth of the treated animals was normal during the observation period. At the final killing no appreciable macroscopic findings were evident in any animal.In conclusion, the LD50 of the test article, when administered to rats as a single dose by oral route, was higher than 2000 mg/kg. At this dose the compound did not induce mortality or apparent signs of toxicity in the treated rats.

Executive summary:

An acute oral toxicity study of test chemical was conducted in Sprague Dawley Crl:CD(SD) BR rats 5 males and 5 females) in accordance with the OECD Guideline 401 (Acute Oral Toxicity) and EEC Guidelines (B.1).

 

The test article was administered undiluted as supplied at the dosage of 2000 mg/kg. The volume of administration was 1.44 ml/kg (the density of the test article is 1.39 g/ml).

 

All rats were treated after a 16-hour fasting period. The day of treatment was considered day 1 of the study. The animals were weighed twice before treatment (at randomization and on day 1 just before treatment) and on days 3, 8 and 14. They were clinically observed for 14 days following the treatment. On day 15 the rats were killed (fasted overnight) by excision of the femoral arteries after i.p. overdosage anesthesia with 5% sodium pentobarbital and were subjected to a thorough autopsy.

 

No deaths or clinical signs occurred in the treated animals. Body weight growth of the treated animals was normal during the observation period. At the final killing no appreciable macroscopic findings were evident in any animal.

 

In conclusion, the LD50 of the test article, when administered to rats as a single dose by oral route, was higher than 2000 mg/kg. At this dose the compound did not induce mortality or apparent signs of toxicity in the treated rats.