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

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

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

Adequacy of study:

key study

Study period:

from 2000-07- 27 to 2000-08-15

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 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class 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
- Source: Iffa Credo, 69210 LArbresle, France.
- Age at study initiation: 6 weeks old
- Weight at study initiation: 172 ± 4 g for the males and 139 ± 3 g for the females
- Fasting period before study: The animals were fasted for an overnight period of approximately 18 hours before dosing, but had free access to water. Food was given back approximately 4 hours after administration of the test substance.
- Housing: in polycarbonate cages with stainless steel lid (48 cm x 27 cm x 20 cm). Each cage contained one to seven animals of the same sex during the acclimation period and three rats of the same sex and group during the treatment period. Each cage contained dust-free sawdust (SICSA, 94142 Alfortville, France).
- Diet (e.g. ad libitum): ad libitum, except prior dosing (see above). 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: 2000-07- 27 To: 2000-08-15

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

purified (by reverse osmosis)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: not reported: "The test substance was prepared at the chosen concentration in the vehicle. The test substance preparation was made freshly..."
- Amount of vehicle (if gavage): 10 mL/kg bw

MAXIMUM DOSE VOLUME APPLIED: "The volume administered to each animal was adjusted according to body weight determined on the day of treatment".

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: As the test substance was anticipated to be non-toxic at 2000 mg/kg, a limit test was performed by administering 2000 mg/kg of the test substance to one group of three males. As no deaths occurred, the study was completed by the administration of the dose-level of 2000 mg/kg to one group of three females.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3

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. 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. The body weight gain of the treated animals was compared to that of test facility's control animals with the same initial body weight.
- 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: no

Statistics:

The LD50 (median lethal dose) is the statistically derived single dose of the test substance that can be expected to cause death in 50% of the animals.

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 signs of toxicity

Mortality:

No deaths were observed 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 other findings

Any other information on results incl. tables

Table 1: Individual clinical signs and mortality

Dose (mg/kg)	Time	Animals		Mortality	Clinical signs
		Males	Females
2000	30 min - 1 h	01-02-03	04-05-06	No	None
	2h	01-02-03		No	None
	2h30		04-05-06	No	None
	4h00	01-02-03	04-05-06	No	None
	D2toD 15	01-02-03	04-05-06	No	None
min: minutes h: hour D: day

Table 2: Individual and mean body weight and weekly body weight change of treated rats (g)

Dose mg/kg	Volume		Animals	Days
		Sex
	ml/kg			1	(1)	8	(1)	15
2000	10	Male	01	176	79	255	45	300
			02	171	71	242	53	295
			03	168	86	254	76	330
			M	172	79	250	58	308
			SD	4	8	7	16	19
2000	10	Female	04	141	53	194	31	225
			05	136	60	196	23	219
			06	140	45	185	31	216
			M	139	53	192	28	220
			SD	3	8	6	5	5
(1)  = Body weight gain
M   = Mean
SD  = Standard Deviation

Table 3: Individual macroscopic examinations at necropsy

Dose mg/kg	Time	Animals		Macroscopic abnormalities
		Males	Females
2000	D 15	01-02-03	04-05-06	No apparent abnormalities
D: day

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 oral LD5o of the test substance EDDHAS Fe 3K is higher than 2000 mg/kg in rats. No signs of toxicity were observed at this dose level.

Executive summary:

The acute oral toxicity of the test substance Fe3KEDDHSA was evaluated in rats according to the "Acute Toxic Class Method". The study was conducted in compliance with the OECD TG 423. The test substance was prepared in purified water and was administered by oral route (gavage), with a volume of 10 mL/kg, to groups of fasted Sprague-Dawley rats. As the test substance was anticipated to be non-toxic at 2000 mg/kg, a limit test was performed by administering 2000 mg/kg of the test substance to one group of three males. As no deaths occurred, the study was completed by the administration of the dose-level of 2000 mg/kg to one group of three females. Clinical signs, mortality and body weight gain were checked for a period of up to 14 days following the single administration of the test substance. All animals were subjected to necropsy.

No clinical signs and no mortality were observed in the animals given 2000 mg/kg. The overall body weight gain of the animals was not affected by treatment with the test substance. At necropsy, no apparent abnormalities were observed. Under the experimental conditions of this study, the oral LD50 of the test substance EDDHAS Fe 3K is higher than 2000 mg/kg in rats. No signs of toxicity were observed at this dose-level.