Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2006-12-20 to 2007-01-23
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report Date:
2007

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Statement of GLP Compliance No. G 024 (Slovak National Accreditation Service); Statement of GLP Compliance No. 4/2006/DPL
Test type:
fixed dose procedure
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
other: microgranules
Details on test material:
- Name of test material (as cited in study report): Fe (III) IDHA
- Substance type: chelate
- Physical state: solid (odourless, green microgranules)

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Institute of Occupational Medicine in Łódź, Poland
- Age and weight at study initiation: Pilot study: 10 week (dose of 2,000 mg/kg bw). Main experiment: 11 weeks (average body weight of 188.5 g).
- Fasting period before study: yes. The day before the experiment was due to commence, some 18 hours before administration of the analysed material, the animals were deprived of feed, being left with only water. Feed was made available again 3 hours after administration of the analysed substance.
- Housing: The animals were kept in plastic cages with metal wire covers, with the following dimensions (length x width x height): 58 x 37 x 21 cm.
During the experiment, the animals were kept in cages individually (initial study) and in groups of four (main study).
- Diet (e.g. ad libitum): ad libitum (standard granulated "Murigran" laboratory feed, manufactured by Wytwórnia Koncentratów i Mieszanek Paszowych AGROPOL of Motycz
- Water (e.g. ad libitum): ad libitum (tap water)
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-21
- Humidity (%): 45-71
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES:
The analysed substance was administered to the rats on the following days: 20.12.2006. (1 female – initial experiment, dose of 2,000 mg/kg of body mass), 04.01.2007 (4 females – experiment proper, dose of 2000 mg/kg of body mass). The experiment was terminated on the following days: 03.01.2007. (1 female – initial experiment, dose of 2000 mg/kg of body mass), 23.01.2007. (4 females – experiment proper, dose of 2000 mg/kg of body mass), respectively.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 1 ml of the water solution of the analysed substance contained: 400 mg of the substance (dose of 2,000 mg/kg of body mass).
- Amount of vehicle (if gavage): 0.5 mL per 100 g of the body weight.

- Rationale for the selection of the starting dose: During the initial experiment, one female received a dose of 2,000 mg/kg of body mass of the analysed substance. During the 14 day observation period were not observed the symptoms of toxicity. The female survived the 14-day observation period.
On the basis of the initial experiment, during the experiment proper the analysed substance was administered to four successive females in a dose of 2000 mg/kg of body mass.
Doses:
Initial experiment: 2000 mg/kg bw;
Main strudy: 2000 mg/kg bw
No. of animals per sex per dose:
Initial experiment: 2000 mg/kg bw - one animal;
Main strudy: 2000 mg/kg bw - four animals
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: An assessment of the general condition of the animals, i.e. observation of all animals in terms of incidence and mortality, was performed twice daily throughout the 14-day duration of the experiment. Detailed clinical observations were performed on the day of administration of the analysed substance (day 0), 10, 30 and 60 minutes after administration, and subsequently every hour over a period of 5 hours from the time of administration. On successive days of the 14-day period of the experiment – once daily.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight.

Results and discussion

Preliminary study:
Following the single administration of the analysed substance at the dose of 2,000 mg/kg of body weight to one female (initial experiment), no symptoms of toxicity were observed during the 14-day period of observation. The animal survived the 14-day period of observation.
Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: based on mortality, clinical signs and findings at necropsy at 2000 mg/kg bw
Mortality:
No mortality occured during the 14-day observation period.
Clinical signs:
After a single administration of test substance to one female at a dose of 2000 mg / kg b.w. (preliminary experience), during the 14-day period of observation there was no diagnosed with symptoms of toxicity. The female survived the 14-day observation period.
After a single administration of a test substance following four females at a dose of of 2000 mg / kg b.w. (Experience appropriate), during the 14-day observation period also there were no signs of toxicity. Females survived the 14-day period observation.
Body weight:
No body weight increase disorders were observed.
Gross pathology:
Macroscopic studies did not find any pathological changes in the test animals.





Any other information on results incl. tables

Table 1. Clinical signs.

Dose

(mg/kg bw)

Day following administra

tion

Number of live animals

 

 

Rat No

 

 

 

 

 

 

 

 

 

1 *

2

3

4

5

 

 

 

 

 

 

 

 

 

0

5

BZ

BZ

BZ

BZ

BZ

 

 

1

5

BZ

BZ

BZ

BZ

BZ

 

 

2

5

BZ

BZ

BZ

BZ

BZ

 

 

3

5

BZ

BZ

BZ

BZ

BZ

 

2000

4

5

BZ

BZ

BZ

BZ

BZ

 

5

5

BZ

BZ

BZ

BZ

BZ

 

 

6

5

BZ

BZ

BZ

BZ

BZ

 

 

7

5

BZ

BZ

BZ

BZ

BZ

 

 

8

5

BZ

BZ

BZ

BZ

BZ

 

 

9

5

BZ

BZ

BZ

BZ

BZ

 

 

10

5

BZ

BZ

BZ

BZ

BZ

 

 

11

5

BZ

BZ

BZ

BZ

BZ

 

 

12

5

BZ

BZ

BZ

BZ

BZ

 

 

13

5

BZ

BZ

BZ

BZ

BZ

 

 

14

5

BZ

BZ

BZ

BZ

BZ

 

 

 

 

 

 

 

 

 

 

* females from the initial experiment

BZ = without change

Table 2. Body weights

Dose

mg/kg of body mass

Rat no.

Day of experiment

Difference

14 – 0

0

7

14

2000

1*

2

3

4

5

198

179

174

189

174

233

206

225

211

222

241

225

232

216

232

52

35

42

33

41

* females from the initial experiment

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category V
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the mortality, clinical signs and findings at necropsy in five animal dosed by 2000 mg/kg bw, LD50 is considered to be over 2000 mg/kg bw that corresponds to Cat. 5 (not clasified) in accordance with the ECHA guidance on the Application of the CLP Criteria (2013).
Executive summary:

A study was conducted to test oral toxicity potential of Fe(III)IDHA in rats. Following the single administration of the analysed substance in a dose of 2,000 mg/kg b.w. to a single female, no symptoms of toxicity were observed during the 14-day period of observation. The female survived the 14-day period of observation. Following the single administration of the analysed substance in a dose of 2,000 mg/kg bw to four successive females, no symptoms of toxicity were observed during the 14-day period of observation. The females survived the 14-day observation period. All the animals were put down following the 14-day period of observation and subsequently underwent autopsies and macroscopic studies. No pathological changes were found during the macroscopic study in the studied animals.