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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:
1988

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EPA OPP 81-1 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Copper hydroxide.
- Lot/batch No.: Not stated.
- Content of copper and content of copper hydroxide: Not stated.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
The rats were housed in groups of up to five by sex, acclimatised, and fasted overnight prior to dosing. Food was returned four hours after dosing.
Body weights at study initiation were approximately 150 to 250 grams.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: deionised water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 90%
- Amount of vehicle (if gavage): 10 ml/kg
Doses:
0 (vehicle only; three rats/sex), 708, 1000, 1100 (females only), 1202, 1300 (males only) and 1413 mg/kg bw.
No. of animals per sex per dose:
Groups of 5 or 10 males and five female.
Control animals:
yes
Details on study design:
Animals were observed several times 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:
1 280 mg/kg bw
Based on:
test mat.
95% CL:
1 123 - 1 459
Sex:
female
Dose descriptor:
LD50
Effect level:
1 180 mg/kg bw
Based on:
test mat.
95% CL:
1 054 - 1 322
Mortality:
There were no mortalities at 708 mg/kg bw. At 1000 mg/kg bw and above mortalities occurred and the frequency of mortality increased at higher doses up to 100% mortality at 1413 mg/kg bw. The majority of deaths occurred in the first week after dosing. Refer to Table 1.
Clinical signs:
The clinical signs recorded including dehydration, diarrhoea, scruffy coats and red staining around the snout.
Body weight:
Most surviving animals showed weight gain during the study though some lost weight in the first week after treatment.
Gross pathology:
Findings in surviving animals and those which died during the study included mottled lungs, presence of test material in the digestive tract, pale, mottled liver, discoloured adrenals and haemorrhaging in the digestive tract.
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

0

0/3

-

0/3

-

708

0/5

-

0/5

-

1000

1/5

Day 9

1/5

Day 6

1100

-

-

3/5

Day 2 (3)

1202

3/10

Day 2 (3)

2/5

Day 2; Day 7

1300

4/5

Day 2 (3); Day 9

-

-

1413

5/5

Day 1 (4); Day 7

5/5

Day 2 (4); Day 6

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 Litchfield-Wilcoxon analysis) of copper hydroxide to the rat was 1280 mg/kg bw for males (with 95% confidence limits of 1123 to 1459 mg/kg bw) and 1180 mg/kg bw for females (with 95% confidence limits of 1054 to 1322 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 US EPA Guideline 81-2 without significant deviation. Copper dihydroxide was administered diluted in deionised water to groups of 5 or 10 male and five female Sprague-Dawley rats weighing approximately 150 to 250 g. The rats were housed in groups of up to five by sex, acclimatised, and fasted overnight prior to dosing. Food was returned four hours after dosing. Dose levels of 0 (vehicle only; three rats/sex), 708, 1000, 1100 (females only), 1202, 1300 (males only) and 1413 mg/kg bw were administered by single oral administration via a metal cannula in 10 ml/kg on Day 1. Animals were observed several times 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 no mortalities at 708 mg/kg bw. At 1000 mg/kg bw and above mortalities occurred and the frequency of mortality increased at higher doses up to 100% mortality at 1413 mg/kg bw. The majority of deaths occurred in the first week after dosing. The clinical signs recorded including dehydration, diarrhoea, scruffy coats and red staining around the snout. Most surviving animals showed weight gain during the study though some lost weight in the first week after treatment. Necropsy findings in surviving animals and those which died during the study included mottled lungs, presence of test material in the digestive tract, pale, mottled liver, discoloured adrenals and haemorrhaging in the digestive tract. 

 

The acute oral LD50 of copper hydroxide to the rat was 1280 mg/kg bw for males (with 95% confidence limits of 1123 to 1459 mg/kg bw) and 1180 mg/kg bw for females (with 95% confidence limits of 1054 to 1322 mg/kg bw). On this basis, copper dihydroxide is classified as Acute Tox. 4, H302: Harmful if swallowed.