Copper dihydroxide

Acute Toxicity: dermal

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

Guideline:

EPA OPP 81-2 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Copper dihydroxide

EC Number:

243-815-9

EC Name:

Copper dihydroxide

Cas Number:

20427-59-2

Molecular formula:

CuH4O2

IUPAC Name:

copper(2+) dihydroxide

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 or test system 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 levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

3 200 mg/kg bw

Based on:

test mat.

95% CL:

2 712 - 3 776

Effect levels 2

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:

other: The clinical signs recorded included yellow fluid around the nose and mouth, and diarrhoea.

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.