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 2017 as the 7th Revised Edition (UN, 2017). The objective of this guidance is to present a harmonized framework for communicating the physical, chemical, and toxicological hazards of chemicals for human health and the environment to allow for safety precautions to be implemented during the use or transport of chemical substances or mixtures. The GHS framework is comprised of “building blocks,” which are combinations of 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, such that effects observed above this dose are not classifiable.
The GHS framework is comprised of “building blocks,” which are combinations of measurable endpoints (e.g., boiling point or acute toxicity) and hazard categories (including “not classified”) 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 building blocks to adopt and to make adaptations to the classification criteria. As a consequence, there are jurisdictions that have not implemented the GHS or that have only partially adopted the GHS hazard categories. Another factor that may result in discordant hazard classifications is that jurisdictions have adopted different editions of the GHS guidance documents as the basis of their regulations and classification systems. In addition, although the GHS outlines the process and specifies the criteria for assigning hazards, expert judgment must also be applied. 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 three forms of copper metal discussed in the report are copper massive, copper powder, and copper flakes coated with aliphatic acid (hereafter, “coated copper flakes”). Copper massive and copper powder fall under Chemical Abstracts Service Registration Number (CAS#) 7440-50-8, while coated copper flakes have no CAS# assigned, according to the European Union’s Harmonized Classification, Labelling, and Packaging regulation.
Copper massive and copper powder fall under Chemical Abstracts Service Registration Number (CAS#) 7440-50-8, while coated copper flakes have no CAS# assigned, according to the European Union’s Harmonized Classification, Labelling, and Packaging regulation.
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 the GHS guidance, Section A18.104.22.168, a particle size cut-off of 1 mm distinguishes the two forms (UN, 2017). 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.
“Granulated copper” has been identified as active substance under the European Union Biocidal Products Regulation, but this form is not discussed separately here, because granulated copper would normally not be identified as a separate form of copper under GHS (see, for example, GHS Section A22.214.171.124; UN, 2017).
In contrast, coated copper flakes are comprised of copper metal flakes produced through a very specific process (e.g., ball-milling) and surrounded by aliphatic acids (e.g., stearic acid and zinc stearate) that prevent aggregation. Due to this, coated copper flakes have a very high reactive surface area compared to the other two forms of copper metal assessed in the report.
This website and associated report 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 weight-of-evidence (WoE) evaluations of copper massive, copper powder, and coated copper flakes, 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, 2017).
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.
Using a read-across approach, experimental data were extrapolated from copper forms and compounds to reach hazard conclusions for the forms of copper metal assessed in the report, when necessary.
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. Using a read-across approach, experimental data were extrapolated from copper forms and compounds 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.