Registration Dossier

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:
other: Study conducted in compliance with Good laboratory Practice and internationally accepted guidelines.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012

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)
Test type:
fixed dose procedure
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Copper iodide.
- Analytical purity: 99.7%
- Lot/batch No.: 108701/2 REACH STANDARD 290911
- Storage condition of test material: room temperature in the dark

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Ltd., Oxon, UK.
- Age at study initiation: Eight to twelve weeks.
- Weight at study initiation: 150 - 192 grams
- Fasting period before study: Overnight.
- Housing: The animals were housed in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes.
- Diet (e.g. ad libitum): ad libitum.
- Water (e.g. ad libitum): ad libitum.
- Acclimation period: At least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25°C
- Humidity (%): 30 to 70%
- Air changes (per hr): 15.
- Photoperiod (hrs dark / hrs light): 12 hours dark/12 hours light.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 30 mg/ml and 200 mg/ml
- Amount of vehicle (if gavage): 10 ml/kg
- Justification for choice of vehicle: Arachis oil BP was used because the test item did not dissolve/suspend in distilled water.

MAXIMUM DOSE VOLUME APPLIED:

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Using available information on the toxicity of the test item, 2000 mg/kg was chosen as
the starting dose.
Doses:
Following a sighting test with single animals at dose levels of 2000 mg/kg and 300 mg/kg, a further group of four fasted females was given a single oral dose of test item, as a suspension in arachis oil BP, at a dose level of 300 mg/kg bodyweight.
No. of animals per sex per dose:
See Doses.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing: Clinical observations were made ½, 1, 2, and 4 hours after dosing and then daily for up to fourteen days. Morbidity and mortality checks were made twice daily. Individual bodyweights were recorded on Day 0 (the day of dosing) and on Days 7 and
14 or at death.
- Necropsy of survivors performed: yes.
- Other examinations performed: clinical signs, body weight.

Results and discussion

Preliminary study:
The animal treated at a dose level of 2000 mg/kg was found dead five days after dosing. There were no deaths at a dose levelof 300 mg/kg.
Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
300 - 2 000 mg/kg bw
Based on:
test mat.
Mortality:
The animal treated at a dose level of 2000 mg/kg was found dead five days after dosing. There were no deaths at a dose levelof 300 mg/kg.
Clinical signs:
Signs of systemic toxicity noted in the animal treated at a dose level of 2000 mg/kg were hunched posture, pilo-erection, tiptoe gait, diarrhoea and
red/brown staining around the snout. Diarrhoea andwetness of the ano-genital region were noted during the day of dosing in two animals treated at a dose level of 300 mg/kg. There were no signs of systemic toxicity noted in the remaining animals treated at a dose level of 300 mg/kg.
Body weight:
Surviving animals showed expected gains in bodyweight.
Gross pathology:
Abnormalities noted at necropsy of the animal treated at a dose level of 2000 mg/kg were dark liver, haemorrhagic and thickened gastric mucosa and thickened non-glandular epithelium of the stomach. Pale liver or patchy pallor of the liver was noted at necropsy of two animals treated at a dose level of 300 mg/kg. No abnormalities were noted at necropsy of the remaining animals treated at a dose level of 300 mg/kg.
Other findings:
None.

Any other information on results incl. tables

Individual bodyweights and bodyweight changes at dose levels of 2000 mg/kg and 300 mg/kg respectively are shown in Tables 1 and 2 (attached).

Applicant's summary and conclusion

Interpretation of results:
other: Acute Tox. 4, H302: Harmful if swallowed.
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The acute oral median lethal dose (LD50) of copper iodide in the female Wistar strain rat was estimated to be in the range of 300 - 2000 mg/kg bodyweight (CLP/GHS - Acute Tox. 4, H302: Harmful if swallowed.). The test item was also classified as harmful according to Appendix 4 of Method B1 bis Acute Toxicity (Oral) of Commission Regulation (EC)No. 440/2008.
Executive summary:

A GLP-compliant study was performed to assess the acute oral toxicity of copper iodide in the Wistar strain rat. The method was designed to be compatible with OECD Guideline 420 and EUMethod B.1 bis. Following a sighting test at dose levels of 2000 mg/kg and 300 mg/kg, a further group of four fasted females was given a single oral dose of test item, as a suspension in arachis oil BP, at a dose level of 300 mg/kg bodyweight. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

The animal treated at a dose level of 2000 mg/kg was found dead five days after dosing. There were no deaths at a dose levelof 300 mg/kg. Signs of systemic toxicity noted in the animal treated at a dose level of 2000 mg/kg were hunched posture, pilo-erection, tiptoe gait, diarrhoea and red/brown staining around the snout. Diarrhoea and wetness of the ano-genital region were noted during the day of dosing in two animals treated at a dose level of 300 mg/kg. There were no signs of systemic toxicity noted in the remaining animals treated at a dose level of 300 mg/kg. Surviving animals showed expected gains in bodyweight. Abnormalities noted at necropsy of the animal treated at a dose level of 2000 mg/kg were dark liver, haemorrhagic and thickened gastric mucosa and thickened non-glandular epithelium of the stomach. Pale liver or patchy pallor of the liver was noted at necropsy of two animals treated at a dose level of 300 mg/kg. No abnormalities were noted at necropsy of the remaining animals treated at a dose level of 300 mg/kg.

The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be in the range of 300 - 2000 mg/kg bodyweight (CLP/GHS − Acute Tox. 4, H302: Harmful if swallowed.). The test item was also classified as harmful according to Appendix 4 of Method B1 bis Acute Toxicity (Oral) of Commission Regulation (EC)No. 440/2008.