Registration Dossier

Toxicological information

Acute Toxicity: dermal

Currently viewing:

Administrative data

Endpoint:
acute toxicity: dermal
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 81-2 (Acute Dermal 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.
- Composition of test material, percentage of components: Not stated.
- Lot/batch No.: Not stated.

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
The rabbits were housed individually and acclimatised prior to dosing. Body weights were approximately 2 kg.

Administration / exposure

Type of coverage:
other: non-occlusive
Vehicle:
water
Remarks:
test material was moistened with deionised water prior to application.
Details on dermal exposure:
Doses were applied to an area of intact shaven skin (equivalent to approximately 10% of the body area) on each rabbit on Day 1. Males only were treated at 2700 mg/kg bw. The test substance was held in place with surgical gauze and surgical tape and the entire trunk of the animal was wrapped in a non-occlusive dressing. After 24 hours, the dressing was removed and residual test substance gently rinsed off with water.
Duration of exposure:
24 hours.
Doses:
Dose levels were 2000, 2300 and 2700 mg/kg bw.
No. of animals per sex per dose:
Groups of five or 10 males and five females.
Control animals:
no
Details on study design:
Animals were observed frequently for treatment-related clinical signs on the treatment day and then 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). 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:
3 200 mg/kg bw
Based on:
test mat.
95% CL:
2 712 - 3 776
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There was one male mortality at 2000 mg/kg bw and two male mortalities at 2300 mg/kg bw. The deaths occurred on Day 2 and Day 13. There were no female mortalities at 2000 mg/kg bw and no male mortalities at 2700 mg/kg bw. Refer to Table 1.
Clinical signs:
The clinical signs recorded included yellow fluid around the nose and mouth, and diarrhoea.
Body weight:
Females and most surviving males treated at 2000 mg/kg bw gained weight during the study. Males treated at 2300 or 2700 mg/kg bw gained little weight or lost weight during the study.
Gross pathology:
No abnormalities were recorded in males treated at 2700 mg/kg bw. Findings in surviving animals and those which died following treatment at lower doses included mottled lungs, pale kidneys, pale red mottled liver, foam/gas filled intestines, green mucoid material around the anus and red mottled adrenals.
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

2000

1/10

Day 3

0/5

-

2300

2/5

Day 2; Day 13

-

-

2700

0/5

-

-

-

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute dermal LD50 (calculated by Litchfield-Wilcoxon analysis) of copper hydroxide to the rabbit was 3200 mg/kg bw for males (with 95% confidence limits of 2712 to 3776 mg/kg bw) and greater than 2000 mg/kg bw for females.
Classification according to Directive 67/548/EEC: Not classified.
Classification according to CLP/GHS: Not classified.
Executive summary:

A GLP-compliant acute dermal toxicity study was conducted in accordance with US EPA 81-2 without deviation. Copper dihydroxide was moistened with deionised water prior to application. Groups of five or 10 male and five female New Zealand white rabbits weighing approximately 2 kg were used. The rabbits were housed individually and acclimatised prior to dosing. Dose levels of 2000, 2300 and 2700 mg/kg bw were applied to an area of intact shaven skin (equivalent to approximately 10% of the body area) on each rabbit on Day 1. Males only were treated at 2700 mg/kg bw. The test substance was held in place with surgical gauze and surgical tape and the entire trunk of the animal was wrapped in a non-occlusive dressing. After 24 hours, the dressing was removed and residual test substance gently rinsed off with water. Animals were observed frequently for treatment-related clinical signs on the treatment day and then 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). Decedents and animals surviving to 14 days were subject to gross necropsy.

 

There was one male mortality at 2000 mg/kg bw and two male mortalities at 2300 mg/kg bw. The deaths occurred on Day 2 and Day 13. There were no female mortalities at 2000 mg/kg bw and no male mortalities at 2700 mg/kg bw. The clinical signs recorded included yellow fluid around the nose and mouth, and diarrhoea. Females and most surviving males treated at 2000 mg/kg bw gained weight during the study. Males treated at 2300 or 2700 mg/kg bw gained little weight or lost weight during the study. No abnormalities were recorded at necropsy in males treated at 2700 mg/kg bw. Findings in surviving animals and those which died following treatment at lower doses included mottled lungs, pale kidneys, pale red mottled liver, foam/gas filled intestines, green mucoid material around the anus and red mottled adrenals.

 

The acute dermal LD50 of copper dihydroxide to the rabbit was 3200 mg/kg bw for males (with 95% confidence limits of 2712 to 3776 mg/kg bw) and greater than 2000 mg/kg bw for females. Copper dihydroxide is not classified.