Copper dichloride

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP guideline study (OECD)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Copper chloride

EC Number:

231-842-9

EC Name:

Copper chloride

Cas Number:

7758-89-6

Molecular formula:

ClCu

IUPAC Name:

copper (I) chloride

Details on test material:

- Name of test material: Copper monochloride
- Molecular formula: CuCl
- Molecular weight: 98.999
- Smiles notation: [Cu]Cl
- InChl: 1S/ClH.Cu/h1H;/q;+1/p-1
- Analytical purity: 97%
- Source: Simga-Aldrich corporation
- Lot/batch No: Lot No. 17119BO

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Group mean bodyweight at study initiation: 255.3 g for males; 216.6 - 225 g for females

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

other: The test substance was wetted with a saline lotion

Details on dermal exposure:

TEST SITE:
- Area of exposure: dorsal part.
- % coverage: approximately 10% of the total body surface area.
- Type of wrap if used: porous gauze dressing covered from a non-irritating tape for 24 hours.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): residual test substance was removed using a saline solution.
- Time after start of exposure: 24 hours.

TEST MATERIAL
- For solids, paste formed: yes.

Duration of exposure:

24 h

Doses:

2000 mg/kg bw for males: 2000, 1500, 1000, 500 mg/kg bw for females

No. of animals per sex per dose:

5 (In total: 5 males; 25 females)

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Cages of rats were checked at least once a day for any mortality. Animals were individually observed hourly during the first 4 hours after dosing with special attention, and daily for a total of 14 days. The nature and severity of the clinical signs and time were recorded at each observation. The body weight of each rat was recorded on day 1 (prior to dosing), day 8 and day 15 (prior to necropsy). Individual body weight changes were calculated.
- Necropsy: All animals were killed on day 15 by carbon dioxide asphyxiation and subjected to a gross necropsy. All gross pathological changes were recorded for each animal. Microscopic examination was not conducted because evidence of gross pathological changes was not showed.

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

1 224 mg/kg bw

95% CL:

1 032 - 1 453

Mortality:

Males showed no death but females showed 4 deaths in 2000 mg/kg bw, 4 deaths in 1500 mg/kg bw, and 1 death in 1000 mg/kg bw, respectively.

Clinical signs:

other: It was observed that there was hardness of the skin, an exudation from the hardness site, formation of scar/falling off of scar, and reddish change in application sites. These findings were considered to be related to application of test substance. Red

Gross pathology:

In macroscopic examination of application sites, the males showed hardness of skin and subcutaneous necrosis and hemorrhage. At test conclusion, a crust was observed at the application sites in necropsied rats. These findings were severe at the higher dose concentration. There appeared to be an inflammatory response at the application site with toxicity. Internally, no abnormality was observed in any animal. One female from the 1500 mg/kg bwgroup had enlarged kidney, adrenal gland and spleen, whereas lungs were smaller. This was considered not to be related to the test substance (it was a lesion in the rodent).

Any other information on results incl. tables

Justification for read-across from copper chloride to copper dichloride:

Acute toxicity, irritation and sensitisation data for copper dichloride have been read across from the closely analogous substance copper chloride. These substances are chemically similar; copper dichloride contains only cupric copper and ionic chlorine, whereas copper chloride contains cuprous copper and ionic chlorine. Available data on (cuprous) dicopper oxide and (cupric) copper oxide show that cuprous copper is inherently more acutely toxic and irritant than the cupric form (neither compound is a skin sensitiser). The results of an acute oral toxicity test available in the public literature (Singh and Junnarkar, 1991) confirm that this principle can also be applied to the cuprous and cupric chlorides. On this basis, and in order to minimise animal testing, a worst-case approach has been adopted in which data generated using copper choride has been directly read across to copper dichloride.

Applicant's summary and conclusion

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LD50 of the test item in males and females respectively was >2000 mg/kg bw and 1224 mg/kg bw.
Classification according to Directive 67/548/EEC: Harmful (Xn). R21, Harmful in contact with skin.
Classification according to CLP/GHS: Acute Tox. 4, H312: Harmful in contact with skin.

Executive summary:

The test item administered to rats by the dermal route was found to cause skin inflammation and injury. Dermal absorption was found to cause symptoms of systemic toxicity. Female rats appeared to be more susceptible than males, based on mortality and clinical signs.