Copper di(acetate)

Acute Toxicity: oral

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 guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Copper di(acetate)

EC Number:

205-553-3

EC Name:

Copper di(acetate)

Cas Number:

142-71-2

Molecular formula:

Cu(CO2CH3)2

IUPAC Name:

copper di(acetate)

Details on test material:

- Name of test material (as cited in study report): Copper acetate monohydrate
- Analytical purity: 99.9%
- Lot/batch No.: 11.6.1SD
- Storage condition of test material: room temperature in the dark

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories UK Ltd., Oxon, UK.
- Age at study initiation: Eight to twelve weeks.
- Weight at study initiation: 151 - 172 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 killed for humane reasons, during the day of dosing, due to the occurrence of clinical signs of toxicity that exceeded the permitted severity limit.

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 killed for humane reasons, during the day of dosing, due to the occurrence of clinical signs of toxicity that exceeded the severity limit set forth in the UK Home Office Project Licence. There were no deaths at a dose level of 300 mg/kg.

Clinical signs:

other: Signs of systemic toxicity noted in the animal treated at a dose level of 2000 mg/kg were hunched posture, ataxia, pilo-erection, lethargy, decreased respiratory rate and hypothermia. There were no signs of systemic toxicity at a dose level of 300 mg/kg.

Gross pathology:

Abnormalities noted at necropsy of the animal treated at a dose level of 2000 mg/kg were abnormally red lungs, dark liver, dark kidneys, blue coloured fluid and solid contents present in the stomach, epithelial sloughing and dark red gastric mucosa, blue solid substance adhered to the glandular region of the stomach and reddened small intestine. Epithelial sloughing of the gastric mucosa was noted at necropsy of one animal 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:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral median lethal dose (LD50) of copper acetate monohydrate in the female Wistar strain rat was estimated to be in the range of 300 - 2000 mg/kg bodyweight.
Classification according to Directive 67/548/EEC: Harmful (Xn). R22, Harmful if swallowed.
Classification according to CLP/GHS: Acute Tox. 4, H302: Harmful if swallowed.

Executive summary:

A GLP-compliant study was performed to assess the acute oral toxicity of copper acetate 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 furthergroup 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 killed for humane reasons, during the day of dosing, due to the occurrence of clinical signs of toxicity that exceeded the severity limit set forth in the UK Home Office Project Licence. There were no deaths at a dose level of 300 mg/kg. Signs of systemic toxicity in the animal treated at a dose level of 2000 mg/kg were hunched posture, ataxia, pilo-erection, lethargy, decreased respiratory rate and hypothermia. There were no signs of systemic toxicity 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 abnormally red lungs, dark liver, dark kidneys, blue coloured fluid and solid contents present in the stomach, epithelial sloughing and dark red gastric mucosa, blue solid substance adhered to the glandular region of the stomach and reddened small intestine. Epithelial sloughing of the gastric mucosa was noted at necropsy of one animal 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.