Ammonium iron(III) trimethylenediaminetetraacetate hemihydrate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

4 April 1991 - 18 April 1991

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was peformed according to OECD guidelines and GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Ammonium iron(III) trimethylenediaminetetraacetate hemihydrate

EC Number:

400-660-3

EC Name:

Ammonium iron(III) trimethylenediaminetetraacetate hemihydrate

Cas Number:

111687-36-6

Molecular formula:

Hill formula: C11 H18 Fe N3 O8 CAS formula: C11 H14 Fe N2 O8.H4N

IUPAC Name:

iron(3+) ammonium 2-({3-[bis(carboxylatomethyl)amino]propyl}(carboxylatomethyl)amino)acetate hydrate

Details on test material:

Name: 1,3-Propylenediaminetetraacetic acid, ferric-ammonium complex (PDTA-FeNH4)
Appearance: fine yellow crystalline powder,
Batch No.: GW-1000

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (U.K.) limited, Margate, Kent, England
- Age at study initiation: ± 4 weeks
- Weight at study initiation: males from 127 - 140 g and for females from 110 - 122 g.
- Fasting period before study: Food was removed from the hoppers at approximately 1700 hours on the day before dos i ng
- Housing: The animals were housed in stainless steel grid cages measuring 54 x 33 x 20 cm (Steven Clarke Fabrications Limited, Alva,
Clackmannanshire, Scotland). The grid floors ensured rapid removal of waste material to undertrays which were cleaned out as necessary. Five animals of the same sex were accommodated in each cage. The cages were suspended in mobile stainless steel racks.
- Diet (e.g. ad libitum): Acommerci ally-avail able compl ete pelleted rodent diet (Laboratory Animal Diet No.1, from Biosure, Manea, Cambridgeshire, England) was fed without restriction, except for the removal of food for approximately 18 hours before administration of the test material.
- Water (e.g. ad libitum): Animals had free access to tap water supplied in a single bottle per cage and re- fill ed as requi red
- Acclimation period:at least five days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-25
- Humidity (%): 40-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: 4 April 1991 - 18 April 1991

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 250 mg/ml
- Amount of vehicle (if gavage): 20 ml/kg body weight

MAXIMUM DOSE VOLUME APPLIED: 20 ml/kg body weight

DOSAGE PREPARATION (if unusual): The dosage was calculated and expressed gravimetrically in terms of the material as received. A fresh formulation of the test material was prepared on the morning of administration and any surplus remaining after dosing was destroyed on the same day. No analyses were undertaken to assess the stabil ity, homogeneity or achieved concentration of the test material in the vehicle.

Doses:

5000 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: The bodyweight of each animal was recorded on the day before dosing and on Days 1, 8 and 15. The test was terminated on the morning of Day 15.
- Necropsy of survivors performed: yes
- Other examinations performed: Three separate inspections were made during the first hour after dosing and two further inspections during the remainder of Day 1. From Day 2 onwards, the animals were inspected twice daily (morning and afternoon). The type, time of onset and duration of reactions to treatment were recorded.

Statistics:

None

Results and discussion

Preliminary study:

A preliminary study was carried out using three groups of one male and one female rat giv~n a single oral administration of PDTA-FeNH4 at dosages of 400, 800 or 2000 mg/kg, at a volume-dosage of 20 ml/kg in purified water. There was no death.

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

There was no death.

Clinical signs:

other: The principal signs of reaction to treatment were staggering gait and piloerection, observed in all animals during the first four days after dosing. One animal also displayed hunched posture on Days 2 and 3 and another animal showed hairloss during the ma

Gross pathology:

Necropsy, on Day 15, revealed no significant macroscopic lesion.

Applicant's summary and conclusion

Interpretation of results:

study cannot be used for classification

Remarks:

Migrated information

Conclusions:

LD50 > 5000 mg/kg bw

Executive summary:

The acute oral toxicity of 1,3-Propylenediaminetetraacetic acid, ferric-ammonium complex, hereafter referred to as PDTA-FeNH4, was investigated in a group of five male and five female CD rats at a dosage of 5000 mg/kg. The animals were starved overnight prior to dosing. The test material was administered at a volume-dosage of 20 ml/kg in purified water. Mortality and signs of reaction to treatment were recorded during a subsequent 14-day observation period. The animals were killed on the following day and subjected to necropsy.

There was no death. Staggering gait and piloerection were observed in all animals during the first four days after treatment. One animal also displayed a hunched posture during this time and one other hairloss during the majority of the first week of observation. All animals were overtly normal during the second week. The animals achieved exepeted bodyweight gains and necropsy revealed no significant macroscopic lesion. Under the conditions of this study, the acute oral median lethal dosage (LD50) of the test material was greater than 5000 mg/kg.