Reaction mass of copper oxide and manganese dioxide

Direct observations: clinical cases, poisoning incidents and other

Administrative data

Endpoint:

direct observations: clinical cases, poisoning incidents and other

Type of information:

experimental study

Remarks:

summary of various observations in humans after ingestion of copper compounds

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Data source

Reference

Reference Type:

review article or handbook

Title:

European Union Risk Assessment Report COPPER, COPPER II SULPHATE PENTAHYDRATE, COPPER(I)OXIDE, COPPER(II)OXIDE, DICOPPER CHLORIDE TRIHYDROXIDE CAS No: 7440-50-8, 7758-99-8, 1317-39-1, 1317–38–0, 1332-65-6 - VOLUNTARY RISK ASSESSMENT

Author:

European Copper Institute

Year:

2007

Bibliographic source:

https://echa.europa.eu/de/copper-voluntary-risk-assessment-reports

Materials and methods

Study type:

other: summary of various observations in humans after ingestion of copper compounds

Endpoint addressed:

acute toxicity: oral

Test material

Test material information

Constituent 1

Reference substance name:

Copper sulphate

EC Number:

231-847-6

EC Name:

Copper sulphate

Cas Number:

7758-98-7

Molecular formula:

CuSO4

IUPAC Name:

Copper sulphate

Test material form:

solid

Results and discussion

Any other information on results incl. tables

The most reliable studies for the determination of a NOAEL for adults are two well-controlled, internationally diverse volunteer studies in which copper (as copper sulphate) was administered as a single dose in drinking water (Arayaet al,2001; Arayaet al, 2003). Both studies reported a concentration-related increase in gastrointestinal symptoms associated with single oral exposure to copper in drinking water, the earliest and most frequently reported symptom being nausea. In both of these studies, the NOAEL for gastrointestinal symptoms in adults was a concentration of 4 mg/litre copper in drinking water (0.8 mg Cu); the LOAEL was 6 mg/litre copper in drinking water (1.2 mg Cu). These values were the same for a female study population or a male and female combined study population.

Ingestion of large amounts of copper sulphate, as in cases of self-poisoning, is associated with severe hepatotoxicity, nephrotoxicity and gastrointestinal effects, in several cases resulting in fatalities. Such reports of copper sulphate ingestion do not enable a NOAEL to be derived.

Effects generally observed include e.g. nausea, abdominal pain and vomiting.

With regard to inhalation exposure, although copper has been implicated in the aetiology of metal fume fever, a review of the available literature suggests there is insufficient evidence to support this claim (see also RAC- Opinion proposing harmonised classification and lebelling at EU Level of Copper (II) oxide; 2014).

Applicant's summary and conclusion

Conclusions:

The most reliable and relevant dose-response data for acute toxicity come from two well-controlled, oral exposure studies conducted in human volunteers (Araya et al, 2001; Araya et al, 2003). In both of these studies, a concentration-related increase in gastrointestinal symptoms was associated with single oral exposure to copper in drinking water. The NOAEL for gastrointestinal symptoms in adults was 4 mg Cu/litre drinking water (0.8 mg Cu) and the LOAEL was 6 mg/litre (1.2 mg Cu).