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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:
OECD Guideline 401 (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.
- Storage condition of test material: The test substance was stored at ambient temperature in a dark place.

Test animals

Species:
rat
Strain:
other: Crl.: (WI) BR - Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga, 8741 Sulzfeld, Sandhofer Weg 7.
- Age at study initiation: Not stated.
- Weight at study initiation: Males 247 - 289 g. Females 188 - 228 g.
- Fasting period before study: 16 hours.
- Housing: During acclimation groups of 5 animals were kept in Makrolon Type III cages. During the experiment single animals were kept in Makrolon Type II cages.
- Diet: ad libitum.
- Water: ad libitum.
- Acclimation period: Not less than 7 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C +/- 2°C.
- Humidity (%): 50 - 85%.
- Photoperiod (hrs dark / hrs light): 12 hrs light/ 12 hrs dark.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: deionised water.
Details on oral exposure:
VEHICLE
- Concentration in vehicle: The test substance was used as a 20% solution in deionised water.

MAXIMUM DOSE VOLUME APPLIED: Not stated.
Doses:
250, 500, 1000, 1500 mg/kg, based on a range-finding study.
No. of animals per sex per dose:
5 males and 5 females per dose.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing: 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, after 7 days (on day 8), after 14 days (on day 15) or at death.
- Necropsy of survivors performed: Yes. Animals were examined for macroscopic organ changes in the cranial cavity, thoracic cavity and abdominal cavity.
- Other examinations performed: Mortalities, clinical signs, body weights.
Statistics:
Calculation of the oral LD50 with Probit Analysis according to Finney.

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
878 mg/kg bw
Based on:
test mat.
95% CL:
582 - 3 025
Sex:
female
Dose descriptor:
LD50
Effect level:
657 mg/kg bw
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
763 mg/kg bw
Based on:
test mat.
95% CL:
527 - 1 272
Mortality:
There was one female mortality at 250 mg/kg bw. At higher doses, the frequency of mortality increased and four males and all females died at 1500 mg/kg bw. The majority of deaths occurred on day 1. Refer to Table 1.
Clinical signs:
There was a variety of clinical signs recorded including apathy, slight tremors, spasms or cramps, impaired co-ordination, reduced reflex reaction, cyanosis and pallor of the mucosa, reduced respiratory rate and reduced body temperature. The symptoms appeared approximately 20 minutes after administration and persisted in some surviving animals until day 4.
Body weight:
All surviving animals showed expected weight gain during the study. Refer to Table 2.
Gross pathology:
No gross findings were recorded in surviving animals. In animals that died during the study residues in the digestive tract and reddening or haemorrhage of the digestive tract mucosa were recorded.
Other findings:
None reported.

Any other information on results incl. tables

Table 1: Summary of mortalities following acute oral administration of copper hydroxide to rats

Dose

(mg/kg bw)

Males

Females

Mortality

Time of death

Mortality

Time of death

250

0/5

--

1/5

day 2

500

1/5

Day 1

2/5

Day 1 (2)

1000

3/5

Day 1 (2); Day 2

1/5

Day 1

1500

4/5

Day 1 (4)

5/5

Day 1 (5)

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

Table 2: Summary of body weights following acute oral administration of copper hydroxide to rats

Dose

(mg/kg bw)

Mean weight start (g)

n

Mean weight 7 days (g)

Mean weight end (g)

n

250

231.9

10

267.7

299.4

9

500

246.2

10

276.9

309.3

7

1000

234.7

10

253.6

287.4

5

1500

228.5

10

278.0

297.0

1

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 copper dihydroxide to the rat was 878 mg/kg bw for males (95% confidence limits 582 - 3025 mg/kg bw), 657 mg/kg bw for females and 763 mg/kg bw for the sexes combined (95% confidence limits 527 - 1272 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 carried out in rats according to OECD Guideline 410 without deviation. Copper dihydroxide was administered in deionised water by oral gavage to groups of 5 male and 5 female rats at doses of 250, 500, 1000 and 1500 mg/kg bw. 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 treatment and after 7 days (Day 8) and 14 days (Day 15). All animals were subjected to necropsy.

Adverse findings included one female mortality at 250 mg/kg bw. At higher doses, the frequency of mortality increased and four males and all females died at 1500 mg/kg bw. The majority of deaths occurred on day 1. Clinical signs related to treatment included apathy, tremors, spasms/cramps, impaired co-ordination, reduced reflex reaction, cyanosis and mucosal pallor, reduced respiratory rate and body temperature. Symptoms appeared about 20 minutes after dosing and persisted in some animals until day 4. Bodyweight gain in surviving animals was as expected. There were no gross necropsy findings in surviving animals. Those which died during the study showed reddening and haemorrhage of digestive tract mucosa.

The acute oral LD50 of copper hydroxide was determined to be 878 mg/kg bw for males (95% confidence limits 582 - 3025 mg/kg bw), 657 mg/kg bw for females and 763 mg/kg bw for the sexes combined (95% confidence limites 527 - 1272 mg/kg bw). Copper dihydroxide is classified as Acute Tox. 4, H302: Harmful if swallowed.