In 2003, the United Nations published the Globally Harmonized System of Classification and Labelling of Chemicals (GHS), establishing a standardized framework for classifying chemical hazards and communicating hazard information through safety data sheets and labels. The GHS guidance document has subsequently been revised, for example, in 2019 as the 8th Revised Edition (UN, 2019). The objective of this guidance is to present a harmonized framework for communicating the physical, chemical, and toxicological human health and environmental hazards of chemicals to allow for safety precautions to be implemented during the use or transport of these chemicals or mixtures. The GHS framework consists of “building blocks” that comprise measurable endpoints (e.g., boiling point or acute toxicity) and hazard categories (including “not classified”) to which a chemical may be assigned. Hazard categories vary by endpoint and are often designated numerically, with Category 1 representing the greatest hazard. For many hazard endpoints, there is a high-end dose limit (i.e., effects observed above a certain dose are not classifiable).
The “building blocks” of the GHS framework are combinations of measurable endpoints and hazard categories to which a chemical may be assigned.
Although the objective of the GHS is to create a globally harmonized system, implementing countries are free to determine which of its building blocks to adopt and to make adaptations to the system’s classification criteria. As a consequence, some jurisdictions have not implemented the GHS at all or have only partially adopted the GHS hazard categories, which may result in different hazard classifications for the same chemical across different jurisdictions. Some jurisdictions have also adopted different editions of the GHS guidance as the basis of their regulations and classification systems. In addition, although the GHS guidance outlines the process and specifies the criteria for assigning hazard classifications, expert judgment must also be applied in this process. These factors have resulted in discordant hazard classifications for copper metal forms across jurisdictions, although this issue is certainly not unique to copper.
Copper and its forms
Copper is a naturally occurring element that is commonly found in the environment. Copper metal is widely used in industrial and commercial applications, because it has a number of key physical properties, including conductivity, malleability, and corrosion resistance (ECI, 2008). The two forms of copper metal discussed in the report are copper massive and copper powder. These two forms fall under Chemical Abstracts Service Registry Number (CAS) 7440-50-8.
Copper massive and copper powder fall under CAS# 7440-50-8.
Copper massive and powder are defined by their particle size and specific surface area (SSA; see Table 1.1 of the report). In line with Section A184.108.40.206 of the GHS guidance, a particle size cut-off of 1 mm distinguishes the two forms (UN, 2019). However, because it has been established that the environmental hazards of copper depend on the exposed surface area, this cut-off could also be expressed as SSA. A copper sphere (with a density of 8,960 kg/m3) of 1 mm diameter has an SSA of 0.67 mm2/mg, and this value can be used as an alternative, surface-area-based cut-off between copper powder and copper massive.
While “granulated copper” and “copper flakes (coated with aliphatic acid)” have been identified as active substances under the European Union Biocidal Products Regulation (European Parliament and Council of the European Union, 2012), these forms are not discussed separately in the report, because they would normally not be identified as separate forms of copper under the GHS (see, for example, GHS Section A220.127.116.11; UN, 2019). This website and the associated report also do not assess the hazards of other inorganic copper compounds, such as copper oxides and copper sulfates, although toxicological data from these forms are used for read-across in the WoE evaluations of copper massive and copper powder, when applicable. In addition, this assessment excludes nanoforms of copper.
The hazard classification process
Due to the number of chemical, physical, and toxicological endpoints considered under the GHS, multiple types of data (of varying complexity) need to be assessed to determine a hazard classification for a compound. Often, multiple datasets are available for a compound for a certain endpoint, and these datasets may be conflicting, inadequate, or inconsistent. The GHS guidance identifies tools such as WoE, read‑across, and expert judgment that can be applied when complex data interpretation is necessary (UN, 2019).
WoE evaluation is the process of evaluating one or more lines of evidence and integrating the results, considering the strengths and weaknesses of the evidence, to reach a justifiable conclusion. For each hazard endpoint, a WoE evaluation of the data (i.e., considering all available information characterizing a property or toxicological endpoint, including the quality and consistency of in silico, in vitro, in vivo, and human data) was conducted that considered data for the most relevant forms of copper.
Read‑across is when the toxicological properties of a well-studied (data-rich) chemical, called a surrogate or analog, are “read across” to a less-studied (data-poor) chemical. This approach was used to extrapolate from experimental data for more data-rich copper forms and compounds to reach hazard conclusions for copper massive and copper powder, when necessary.
Using a read-across approach, experimental data for copper forms and compounds were extrapolated to reach hazard conclusions for the forms of copper metal assessed in the report, when necessary.
Expert judgment was often also required for interpreting the various datasets available for the assessed copper compounds, based on prior experience with certain test methods, chemical classes, or quantitative analysis procedures.