Reaction mass of copper oxide and manganese dioxide

Additional toxicological data

Administrative data

Endpoint:

additional toxicological information

Type of information:

other: general mechanistic explanation

Adequacy of study:

other information

Data source

Reference

Reference 1

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

Reference 2

Reference Type:

review article or handbook

Title:

Copper and its inorganic compounds - MAK Value Documentation

Author:

Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area of the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation).

Year:

2014

Bibliographic source:

http://onlinelibrary.wiley.com/doi/10.1002/3527600418.mb744050e5715/pdf

Reference 3

Reference Type:

other: biocidal products assessment report

Title:

Biocidal products Assessment Report - Copper (II) oxide (Inclusion of active substances in Annex I or IA to Directive 98/8/EC)

Author:

BPC, Biocidal Products Committee (French competent authority)

Year:

2011

Bibliographic source:

ECHA, European Chemicals Agency. - http://dissemination.echa.europa.eu/Biocides/ActiveSubstances/0017-08/0017-08_Assessment_Report.pdf

Materials and methods

Type of study / information:

Overall general mechanistic considerations

Test material

Test material information

Constituent 1

Reference substance name:

Copper

EC Number:

231-159-6

EC Name:

Copper

Cas Number:

7440-50-8

Molecular formula:

Cu+2

IUPAC Name:

copper(2+)

Test material form:

solid

Results and discussion

Any other information on results incl. tables

Free ionic copper is considered the toxic agent e.g. for local effects in the nose after inhalation exposure or for systemic effects which are dependent on ROS generation (genotoxicity).

Free ionic copper was considered active and the bioavailability from other compounds is less than from copper sulphate. Because copper is an essential element, the concentration of copper in the body is strictly and efficiently regulated. The essentiality of copper arises from its incorporation into a large number of proteins and this can be considered as having two components. Firstly,copper has the ability to cycle between stable oxidised Cu(II) and unstable reduced Cu(I) and is used by several cuproenzymes participating in fundamental redox reactions (e.g. cytochrome oxidase, Cu/Zn superoxide dismutase, dopamine-β-hydroxylase, lysyl oxidase and ceruloplasmin). Secondly, as an essential structural component of many macromolecules, a large number of enzymes and other proteins are dependent on copper for their normal activity

Copper is highly toxic if protective mechanisms are bypassed (i.v., i.p. dosing).

The main daily dietary intake of copper in adults ranges between 1.5 and 3.0 mg. Most human diets naturally contain between 1 and 2 mg/person/day of copper, with some containing up to 4 mg/person/day.

Copper is regulated by homeostatic mechanism. Homeostasis can be described as the maintenance of a constant internal environment in response to changes in internal and external environments.

Homeostatic maintenance requires the tightly coordinated control of copper uptake, distribution and efflux in cells and the organism as a whole. The ability of the body to control the uptake and excretion

of copper makes this an important factor in considering the exposure and effects of essential elements like copper.

Major control mechanism is gastrointestinal absorption and biliary excretion into faeces. Liver has an important role in the maintenance of the copper homeostasis. The failure to maintain homeostasis may lead to adverse effects resulting either from deficiency or excess.

Copper is involved in the reactions and functions of many enzymes, including angiogenesis, neurohormone release, oxygen transport and regulation of genetic expression. In this scope, copper compounds can be considered as a precursor, releasing cupric ion, which is the actual active substance. This explains that, while several endpoints were documented by studies directly performed with

other copper salts than the copper (II) oxide which is contained in hopcalite (mainly copper sulphate).

In mammalian toxicity, it is also considered that the most toxic moiety of any copper salt is the Cu2 + ion. This can be shown through the comparison of the most soluble salt (copper sulphate) with other

relatively insoluble copper salts, where the solubility, bioavailability and hence toxicity of these salts can vary – with copper sulphate representing the worst-case scenario. When the acute oral toxicity of

this salt is compared with either copper oxide or copper carbonate, the data indicate that copper sulphate is more toxic and thus more bioavailable. Therefore all the properties described for

copper will also be applicable to copper (II) oxide.

This has also been confirmed in comparative bioavailability studies where copper sulphate was shown to be more or equally bioavailable in relation to the copper carbonate in poultry and swine.

Moreover, as presented in the table attached the Copper sulphate is more toxic than the other copper compounds, and then using studies performed with copper sulphate could be considered as a worst-case.

Applicant's summary and conclusion

Conclusions:

Free ionic copper is considered to be the toxic agent. The bioavailability from other compounds is less than from copper sulphate, thus using studies performed with copper sulphate could be considered as a worst-case. Because copper is an essential element, the concentration of copper in the body is strictly and efficiently regulated (homeostasis). Copper is highly toxic if protective mechanisms are bypassed (i.v., i.p. dosing).