Registration Dossier

Diss Factsheets

Toxicological information

Acute Toxicity: oral

Currently viewing:

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
between 9 March 2004 to 12 July 2004
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of relevant results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2004
Report date:
2004

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
Remarks:
U.S. EPA Good Laboratory Practice Standards, Toxic Substances Control Act (TSCA), 40 CFR Part 792, OECD Principles of Good Laboratory Practice (as revised 1997), ENV/MC/CHEM (98) 17 and NIER Public notice no.1998-41, under Toxic Chemicals Control)
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Reference substance name:
Iron dichloride
EC Number:
231-843-4
EC Name:
Iron dichloride
Cas Number:
7758-94-3
IUPAC Name:
iron(2+) dichloride
Details on test material:
Identity: Iron dichloride (CAS No.: 7758-94-3)
Lot number: 23828CB
Purity: 98%
Storage conditions: Room temperature
Appearance: Tan powder
Stability: Stable

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Orient Co. Ltd., Korea
- Age at study initiation: Approximately 8 weeks of age
- Weight at study initiation: Mean of 163.9 g
- Fasting period before study: Fasted overnight prior to dosing
- Housing: Individually housed in stainless steel cages with wire mesh floors
- Diet: ad libitum access to certified rodent diet (2014C, lot 111703MA, Teklad global 14% Protein Rodent diet, Harlan Teklad, USA)
- Water: ad libitum access to filtered/UV-treated tap water
- Acclimation period: seven days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.5 - 25.6°C during acclimation, 20.9 - 25.4°C during study
- Humidity (%): 28.8 - 58.1% during acclimation, 32.7 - 63.8 during study
- Air changes (per hr): not stated in report
- Photoperiod (hrs dark / hrs light): automatically controlled to provide 12 hours of artifical light (08:00 - 20:00 hours, 150 - 300 Lux)

IN-LIFE DATES: From: Study initiation on March 9th 2004 To: Experimental phase completion on April 20th 2004

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 80% of intended final volume
- Amount of vehicle (if gavage): 10 ml/kg bodyweight
- Justification for choice of vehicle: not stated in report
- Lot/batch no. (if required): 122KO131
- Purity: not stated in report

MAXIMUM DOSE VOLUME APPLIED: based on 10 ml/kg bodyweight

DOSAGE PREPARATION (if unusual): not applicable

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: no available information on the test article, so the starting dose of 300 mg/kg bw was selected.
Doses:
300 mg/kg bw as starting dose.
2000 mg/kg as limiting dose
No. of animals per sex per dose:
6 females at 300 mg/kg
3 females at 2000 mg/kg
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: checked at least once daily for any mortality. Individually observed hourly for the first 4 hours after dosing, then daily once for a total of 14 days. Bodyweights were recorded on Day 1 (prior to dosing), Days 8 and 15 (prior to necropsy).
- Necropsy of survivors performed: yes
- Other examinations performed: Changes in skin and fur, eyes and mucous membrane, and also respiratory, circulatory, autonomic and central nervous systems, and somatomotor activity and behavious pattern.
Statistics:
No statistical analysis was performed because of the small sample size and absence of controls.

Results and discussion

Preliminary study:
not applicable
Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LD50
Effect level:
500 mg/kg bw
Based on:
test mat.
Remarks:
FeCl2
Sex:
female
Dose descriptor:
LD50
Effect level:
220 mg/kg bw
Based on:
element
Remarks:
Fe
Mortality:
All animals in the 2000 mg/kg bw dose group were found dead on Day 1 and one animal who received 300 mg/kg bodyweight was found dead on Day 2.
Clinical signs:
Hypoactivity, piloerection, prone position, reddish change and edema on ears, fore-legs and hind-legs were oberseved in all animals at 2,000 mg/kg bw. in the 300 mg/kg bw dose group, all animals showed hypoactivity and piloerection on Day 1. The one dead animal from the 300 mg/kg bw group showed dyspnea, prone position, incomplete eyelid opening and hypothermia on Day 1. These signs were considered the signs of pain and distress related with administration of the test article. some animals who received 300 mg/kg bw had soft stools on Day 2.

At 2000 mg/kg bw, nasal discharge (reddish or clear), was observed in all animals.
Body weight:
All surviving animals had normal bodyweight gain during the study.
Gross pathology:
Hemorrhage on lymphatic nodes, stomach and intestine in all animals and hemorrhage on the thymus of one animal was observed. one animal showed hypertrophy of the pancreas and one other exhibited hypertrophy of the spleen.
At 300 mg/kg bw, hemorrhage on lymphatic nodes and intestine were observed in the one animal that died during the study.
Other findings:
- Organ weights: not recorded
- Histopathology: not recorded
- Potential target organs: pancreas, spleen, somach and intestines
- Other observations: none

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In conclusion, all animals recieved 2,000 mg/kg bodyweight and one animal recieved 300 mg/kg bodyweight was found dead related wiith administration of test article.

The test article will be classified into category 4 (LD50: 300 - 2000 mg/kg) according to the OECD Harmonised Integrated Classification System. The test material is also classified as R22 - Harmful if swallowed according to the Dangerous Substances Directive.
According to this result, the acute lethal oral dose (LD50 cut off values) to rats of the test article, iron dichloride was considered to be 500 mg/kg bodyweight under the conditions of this study (Acute Toxic Class Method).

Executive summary:

This study was performed to assess the acute toxicity of the test article, iron dichloride (CAS No.: 7758 -94 -3) by single oral gavage administration to Sprague-Dawley rats and to classify according to the criteria from the OECD Harmonised Integrated Classification system, ENV/JM/MONO (2001) 6 (14 August 2001). Mortality, clinical signs and bodyweight changes were monitored throughout the study. All animals were examined macroscopically.

According to the test guideline, three fasted female rats were used for each step. The starting dose of 300 mg/kg bw was selected. Three additinal rats were also dosed at this level as results at the starting dose indictaed mortality was not observed. The third step was a limit dose of 2000 mg/kg bw. Because all animals were found dead after this dosing, the study was completed.

All animals who received 2000 mg/kg bodyweight were found dead on Day 1 and one animal in the second group of 300 mg/kg bw was found dead on Day 2.

Hypoactivity, piloerection, prone position, reddish change and edema on ears, fore-legs and hind-legs were oberseved in all animals at 2,000 mg/kg bw. In the 300 mg/kg bw dose group, all animals showed hypoactivity and piloerection on Day 1. The one dead animal from the 300 mg/kg bw group showed dyspnea, prone position, incomplete eyelid opening and hypothermia on Day 1. These signs were considered the signs of pain and distress related with administration of the test article. Some animals who received 300 mg/kg bw had soft stools on Day 2.

All surviving animals had normal bodyweight gains during the study.

At 2000 mg/kg bw, nasal discharge (reddish or clear) was observed externally in all animals. Hemorrhage on lymphatic nodes, stomach and intestine in all animals and hemorrhage on the thymus of one animal was observed. One animal showed hypertrophy of the pancreas and one other exhibited hypertrophy of the spleen. At 300 mg/kg bw, hemorrhage on lymphatic nodes and intestine were observed in the one animal that died during the study.

At 2000 mg/kg bw, nasal discharge (reddish or clear), was observed in all animals.