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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: Already evaluated by the Competent Authorities for Biocides and Existing Substances Regulations.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990

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:
Copper(II) carbonate--copper(II) hydroxide (1:1)
EC Number:
235-113-6
EC Name:
Copper(II) carbonate--copper(II) hydroxide (1:1)
Cas Number:
12069-69-1
Molecular formula:
CuCO3.Cu(OH)2
IUPAC Name:
copper(II) carbonate, basic
Details on test material:
Batch number - not reported
Description - powder
Purity - not reported
Stability - Stable at room temperature

Test animals

Species:
rat
Strain:
other: Crl.: (WI) BR - Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
Source - Firma Charles River Wiga, Germany
Weight at study initiation - Males weighed 220-314 g and females weighed 181-262 g.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: Carboxymethylcellulose
Details on oral exposure:
Concentration in vehicle - 10, 15 and 20%
Total volume applied - 1.8 – 3.1 ml
Doses:
Following a preliminary range finding test with a dose of 2000 mg/kg the final doses were 1000, 1500 and 2000 mg/kg.
No. of animals per sex per dose:
5 male and 5 female
Control animals:
no
Details on study design:
Clinical observations were recorded after 10 minutes, 1, 2, 6, 24 hours and once daily thereafter up to Day 14 following test substance
administration. The bodyweights of test organisms were recorded immediately before treatment (Day 0) and surviving animals reweighed on Day 7
and Day 14 (termination).

Animals found dead or killed in extremis were immediately necropsied. The surviving animals were sacrificed after 14 days and gross pathological
examinations performed.
Statistics:
The LD50 values were carried out by probit analysis.

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
ca. 1 434 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD50
Effect level:
ca. 1 291 mg/kg bw
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 1 385 mg/kg bw
Based on:
test mat.
Mortality:
See Table 1.
Clinical signs:
Severe clinical symptoms related to CNS-symptoms, coordination, reflexes and automatic functions were observed with dose related intensity up to 9 days post administration. For further details, refer to Table 1.


Body weight:
Weight gains were reduced in surviving animals. In the 1500 and 2000 mg/kg dose groups some weight losses were observed. For further details,
refer to Table 1.
Gross pathology:
Gross pathological examination at 14 days post administration revealed no test article dependent findings in any of the dose groups. Those
macroscopic changes observed were attributable to the sacrificing procedure or to minor variations which often occur spontaneously in rats of this
strain and age.

In contrast, severe macroscopic changes of the gastro-intestinal tract were observed in all mid and high dose animals killed in extremis or died
spontaneously. The findings are considered to be test article-related. For further details refer to Table 1
Other findings:
None.

Any other information on results incl. tables

Table 1.    Summary of Findings for Acute Oral Toxicity

Dose mg/kg

Number of dead /
number of investigated

Time of death (range)

Observations

1000 males

0/5

-

Clinical observations included reduced activity, general reactions, body tone and skin turgor. Additional signs were piloerection, diarrhoea, paleness in skin/mucous membrane and test organisms adopted a squatting position.

One animal was killed in extremis and pathological investigations determined residues of the test article in the stomach and green discolouration of the intestine.

After 14 days observation period, pathological findings included a white cover on the mucous membrane of the stomach in one male and one female, foamy yellow contents in the intestine, swollen liver and spleen, pale kidneys and hydrometra in the genital system of one female.

1000 females

2/5

Day 7

1500 males

4/5

Day 2 – Day 8

Clinical observations included reduced activity and general reactions. Additional signs were pilorection, diarrhoea, paleness in skin/mucous membrane and test organisms adopted a squatting position.

Pathological findings of animals killed in extremis prior to test termination included marbled lung, green discoloured and swollen mucous membrane of the stomach.

After 14 days, pathological findings included swollen mucous membranes in the stomach and intestine of one male and two females. One organism had an enlarged and darkened spleen.

1500 females

3/5

3 hours – Day 6

2000 males

4/5

Day 3 – Day 9

Clinical observations included reduced activity, general reactions, body tone and skin turgor. Additional signs were pilorection, diarrhoea, paleness in skin/mucous membrane and test organisms adopted a squatting position.

Pathological findings in animals killed in extremis included swollen mucous membranes, green discoloration and mucous membrane and corrosion in the stomach of 3 males and 3 females. Four males and three females had hyperaemic and green discolouration of the intestine. Other findings were reduced and discoloured spleen and abnormal coloured kidney.

After 14 days two individuals had enlarged and dark discoloured spleen. Other pathological findings included a marbled liver and lung, enlarged and dark coloured spleen, marbled and discoloured kidney and inflated and green coloured intestine.

2000 females

3/5

4 hours – Day 7

LD50value

Male – 1434 mg/kg Female – 1291 mg/kg Males and Females – 1385 mg/kg

   

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The resulting LD50 values were 1434, 1291 and 1385 mg/kg for males, females and both sexes combined respectively. Based on these results and according to EU directive 83/467/EEC copper carbonate should be classified as 'Harmful if Swallowed’ under Commission Directive 93/21/EC)
Executive summary:

Materials and Methods

The aim of this study was to determine the acute oral toxicity of copper carbonate to male and female rats. The test concentrations were 1000, 1500 and 2000 mg/kg bw. During a 14-day post exposure period the test animals were assessed for clinical observations, bodyweight change and mortality. At the end of the study all animals were sacrificed and subject to pathological examination.

 

The study was conducted according to GLP and the following guidelines;

OECD Guidelines, No. 401. Acute Oral Toxicity (February 24, 1987).

EEC Directive 84/449/EEC. (September 19, 1984).

Results and Discussions

Severe clinical symptoms were observed up to 9 days post administration. There were reduced weight gains in all test animals. Gross pathological examinations at 14 days revealed no test article dependant findings in any of the dose groups. However, all mid and high dose animals killed in extremis or died spontaneously revealed characteristic gastro-intestinal alterations, which were considered to be test article related.

 

The resulting LD50 values were 1434, 1291 and 1385 mg/kg for males, females and both sexes combined respectively. Based on these results and according to EU directive 83/467/EEC copper carbonate should be classified as 'Harmful if Swallowed’ under Commission Directive 93/21/EC)