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Toxicological information

Acute Toxicity: oral

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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:
1994

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Dicopper chloride trihydroxide
EC Number:
215-572-9
EC Name:
Dicopper chloride trihydroxide
Cas Number:
1332-65-6
Molecular formula:
ClCu2H3O3
IUPAC Name:
dicopper chloride trihydroxide
Details on test material:
- Name of test material (as cited in study report): Copper oxychloride.
- Composition of test material, percentage of components: Not stated.
- Lot/batch No.: 3/0369

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
The rats were housed in groups of five by sex, acclimatised, and fasted overnight prior to dosing. Food was returned four hours after dosing.
Initial body weights were 127 to 204 grams.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on oral exposure:
VEHICLE
- Amount of vehicle (if gavage): 10 mg/kg bw.
Doses:
Dose levels (based on a range-finding study) were 1000, 1400, 1800 and 2200 mg/kg bw.
No. of animals per sex per dose:
Groups of five males and five females.
Control animals:
no
Details on study design:
Animals were observed frequently on the day of dosing and then once daily for the 14 day post-dosing period. Animals were weighed prior to administration and after 7 days (on Day 8) and after 14 days (on Day 15) or at death. Decedents and animals surviving to 14 days were subject to gross necropsy.

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
1 083 mg/kg bw
Based on:
test mat.
95% CL:
239 - 1 355
Sex:
female
Dose descriptor:
LD50
Effect level:
1 854 mg/kg bw
Based on:
test mat.
95% CL:
1 398 - 4 909
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 398 mg/kg bw
Based on:
test mat.
95% CL:
1 018 - 1 706
Mortality:
There were two male mortalities but no female mortalities at 1000 mg/kg bw. At higher doses, the frequency of mortality increased and all males and three females died (or were killed in extremis) following 1800 and 2200 mg/kg bw. The deaths occurred between Day 2 and Day 7. Refer to Table 1.
Clinical signs:
There was a variety of clinical signs recorded including piloerection, nasal discharge, ataxia, subdued behaviour, diarrhoea, hunched and pale appearance, laboured or slow breathing, swollen abdomen, tail lesions, soiled coats with anal and perigenital staining, ocular discharge, dull/opaque eyes, vocalisation, hypothermia, alopecia and tremors. Most symptoms occurred between Day 2 and 7 though some effects persisted up to Day 15.
Body weight:
Surviving animals showed weight gain during the study.
Gross pathology:
No gross findings were recorded in surviving animals. The most notable necropsy finding in animals which died during the study was a green coloured, clear or dark liquid in the digestive tract. Foci, thickened mucosa and mucoid or liquid contents were also found in the caecum and one male treated at 2200 mg/kg bw had pale lungs.
Other findings:
None.

Any other information on results incl. tables

Table 1. Summary of Mortalities.

Dose
(mg/kg bw)

Males

Females

Mortality

Time of death

Mortality

Time of death

1000

2/5

Day 6 (2)

0/5

-

1400

4/5

Day 5 (2);
Day 6; Day 7

1/5

Day 6

1800

5/5

Day 3 (2); Day 5; Day 6; Day 7

3/5

Day 3 (2); Day 6

2200

5/5

Day 4 (2);
Day 5 (2); Day 6

3/5

Day 2; Day 3;
Day 7

Figures in parenthesis are the number which died on the day specified if more than one.

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral LD50 (calculated by probit analysis) of dicopper chloride trihydroxide to the rat was 1083 mg/kg bw for males (with 95% confidence limits of 239 to 1355 mg/kg bw), 1854 mg/kg bw for females (with 95% confidence limits of 1398 to 4909 mg/kg bw) and 1398 mg/kg bw for the sexes combined (with 95% confidence limits of 1018 to 1706 mg/kg bw).
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 acute oral toxicity study was conducted in accordance with the requirements of EU Guideline B.1 and OECD 401. Dicopper chloride trihydroxide was administered as a solution in carboxymethyl cellulose. Groups of five male and five female Sprague-Dawley rats weighing 127 to 204 g were used. The rats were housed in groups of five by sex, acclimatised, and fasted overnight prior to dosing. Food was returned four hours after dosing. Dose levels (based on a range-finding study) of 1000, 1400, 1800 and 2200 mg/kg bw were administered by single oral administration by gavage in 10 mL/kg on Day 1. Animals were observed frequently on the day of dosing and then once daily for the 14‑day post-dosing period. Animals were weighed prior to administration and after 7 days (on Day 8) and after 14 days (on Day 15) or at death. Decedents and animals surviving to 14 days were subject to gross necropsy.

There were two male mortalities but no female mortalities at 1000 mg/kg bw. At higher doses, the frequency of mortality increased and all males and three females died (or were killed in extremis) following 1800 and 2200 mg/kg bw. The deaths occurred between Day 2 and Day 7. There was a variety of clinical signs recorded including piloerection, nasal discharge, ataxia, subdued behaviour, diarrhoea, hunched and pale appearance, laboured or slow breathing, swollen abdomen, tail lesions, soiled coats with anal and perigenital staining, ocular discharge, dull/opaque eyes, vocalisation, hypothermia, alopecia and tremors. Most symptoms occurred between Day 2 and 7 though some effects persisted up to Day 15. Surviving animals showed weight gain during the study. No gross findings were recorded in surviving animals at necropsy.  The most notable necropsy finding in animals which died during the study was a green coloured, clear or dark liquid in the digestive tract. Foci, thickened mucosa and mucoid or liquid contents were also found in the caecum and one male treated at 2200 mg/kg bw had pale lungs.

The acute oral LD50 (calculated by probit analysis) of Dicopper chloride trihydroxide to the rat was 1083 mg/kg bw for males (with 95% confidence limits of 239 to 1355 mg/kg bw), 1854 mg/kg bw for females (with 95% confidence limits of 1398 to 4909 mg/kg bw) and 1398 mg/kg bw for the sexes combined (with 95% confidence limits of 1018 to 1706 mg/kg bw). On this basis, dicopper chloride trihydroxide is classified as Acute Tox. 4, H302: Harmful if swallowed.