## 2.2.3. Industrial Chemicals

Authors: Steven Droge

Reviewer: Michael McLachlan

Learning objectives:

You should be able to

- discuss a history perspective on key chemical legislations around the world
- look up registration dossiers yourself to obtain relevant ecotoxicological information
- realize that complete dossiers are most urgent for high production tonnage substances and the most hazardous substances
- understand why for some groups of chemicals already specific regulations were in place apart from common industrial substances.

Keywords: Chemical industry, tonnage, hazardous chemicals, REACH, regulation

Introduction

The chemical industry produces a wide variety of chemicals that find use in industrial process and as ingredients in day-to-day products for consumers. Instead of chemicals, ‘substances’ may be a more carefully worded description as it also includes complex mixtures, polymers and nanoparticles. Many substances are produced by globally distributed companies in very high volumes, ranging for example from 100 - 10,000 tonnes (1 tonne = 1000 kg) per year. Worldwide, governments have tried to control and assess chemical safety, as nicely summarized on the ChemHAT website. Australia for example, has the Industrial Chemicals (Notification and Assessment) Act 1989 (2013 version). Just like elsewhere in the world, in the European Union (EU) a variety of regulatory institutes at all levels of government used to perform safety assessments regarding the use of substances in products, and how these are emitted into waste streams. This changed dramatically in 2007.

On June 1st, 2007 (Figure 1), a new EU regulation went into force called REACH (official legislation documents C 1907/2006; about REACH; EU info on REACH). This law reversed the role of governments in chemical safety assessment, because it placed the burden of proof on companies that manufacture a chemical, import a chemical into the EU, or apply chemicals in their products. Within REACH companies must identify and manage the risks linked to the chemicals they manufacture and market in the EU. REACH stands for Registration, Evaluation, Authorisation and Restriction of Chemicals. China soon followed with the analogous “China REACH” in 2010, and then came South Korea in 2015 with “K-REACH”. The main focus in this module is on EU-REACH as the leading and well documented example. Other legislation regulating industrial chemicals can often be easily found online, e.g. via the ChemHAT link above.

Figure 1. Scheme for the registration phase of the REACH regulation for existing industrial chemicals of different tonnage bands and hazardous potential, as well as newly developed chemicals (“Non phase-in”) for the EU market. CMRs = chemicals that are proven carcinogenic, mutagenic or toxic to reproduction. R50/R53 labels indicate “Very toxic to aquatic organisms”/ “May cause long-term adverse effects in the aquatic environment”. Source: http://www.cirs-reach.com/REACH/REACH_Registration_Deadlines.html (with permission).

In REACH, each chemical is registered only once. Accordingly, companies must work together to prepare one dossier that demonstrates to the European Chemical Agency (ECHA) how chemicals can be safely used, and they must communicate the risk management measures to the users. ECHA, or any Member State, authorizes the dossiers, and can start a “restriction procedure” when they are concerned that a certain substance poses an unacceptable risk to human health or the environment. If the risks cannot be managed, authorities can restrict the use of substances in different ways. In the long run, the most hazardous substances should be substituted with less dangerous ones.

So which chemicals have been registered in the past decade (2008-2018) in REACH?

In principle, REACH applies to all chemical ‘substances’ in the EU zone. This includes metals, such as “iron” and “chromium”, organic chemicals such as “methanol” and “fatty acids” and “ethyl-4-(8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)piperidine-1-carboxylate (see Box 1)”, and (nano)particles like “zink oxide” and “silicon dioxide”, and polymers. Discover for example the registration dossier link in Box 1.

Box 1. Examples from the REACH dossiers The REACH registration data base can be searched via LINK. Accept the disclaimer, and you are ready to search for chemicals based on name, CAS number, substance data, or use and exposure data. Search for example for the name “ethyl 4-(8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)piperidine-1-carboxylate” and you find the link to the dossier of this substance with CAS 79794-75-5 as compiled by the registrant. This complex chemical name is better known as the antihistamine drug Loratadine, but this name does not show up in the dossier search! Click on the name to get basic information on the compound. The hazard classification reads: “Warning! According to the classification provided by companies to ECHA in REACH registrations this substance is very toxic to aquatic life, is very toxic to aquatic life with long lasting effects, is suspected of causing cancer, causes serious eye irritation, is suspected of causing genetic defects, causes skin irritation, may cause an allergic skin reaction and may cause respiratory irritation.” This compound is “PBT” labeled based on limited available data (classifying as a combination of Persistent / Bioaccumulative / Toxic). However, the section [About this substance] reads: “for industrial use resulting in the manufacture of another substance (use of intermediates).” As an intermediate in a restricted process, many parts of the dossier did not have to be completed for REACH. As a medicinal product Loratadine is strictly regulated elsewhere. Scroll down to the REACH link for the registration dossier (.../21649) to find out more the different entries for this chemical. If we do a search for [“ Bisphenol ”], we get a long list of optional chemicals, for example Bisphenol A (CAS 80-05-7) but also for example Bisphenol S if you scroll down further (CAS 80-09-1). If we look at the dossier of the first Bisphenol A entry, with tonnage “100 000 - 1 000 000 tonnes per annum”, you can find a long list of REACH information packages besides the dossier, as this chemical is hotly debated. The dossier for Bisphenol A was evaluated in 2013, and also this is available (look for the pdf in the Dossier evaluation status). In this compliance check, the registrant is requested to submit additional rat and mouse toxicity data, along with statements of reasons. There is for example also a link to the [Restriction list (annex XVII)], which leads to a pdf called 66.pdf, which states an adopted restriction for this chemical within the REACH framework and the previous legislation, Directive 76/769/EEC: “Shall not be placed on the market in thermal paper in a concentration equal to or greater than 0,02 % by weight after 2 January 2020”. Find your own chemical of interest to discover more on the transparancy of the chemical information on which risk assessment is based.

However, some groups of chemicals are (partly) exempt from REACH because they are covered by other legislation in the EU:

- Active substances used in plant protection products (Section 2.3.1) and biocidal products (Section 2.3.2) are considered as already having been registered and assessed by institutes separate from ECHA. Biocides such as disinfectants and pest control products are per definition hazardous chemicals, but they are also very useful in many ways. The very strict and elaborate biocide laws aim to verify that the potential risk of harm associated with the intended emission scenarios is in balance with expected benefits.
- Food and feedstuff additives (Section 2.3.9) have different legislation and authorisation laws to demonstrate (following a scientific evaluation) that the additive has no harmful effects on human and animal health or on the environment ( developed since 1988, schematic graph, Regulation (EC) No 1331/2008)
- Medicinal products (Sections 2.3.3 and 2.3.4) have different legislation and authorisation laws to guarantee high standards of quality and safety of medicinal products, while promoting the good functioning of the internal market with measures that encourage innovation and competiveness (starting with Directive 65/65 in 1965, an overview since, a pdf of the 2001 EU legislation 2001/83/EC)
- “Waste” is not part of the REACH domain, but a product recovered from waste is not.

A detailed overview of European chemical safety guidelines related to chemicals with different application types is presented in Figure 2.

Figure 2. Scheme of societal sectors, their chemical uses, the dedicated policy frameworks for registration and authorization, and pathways to the aqueous environment direct or via industrial- or household effluent treatment plants (circle symbols). Redrawn from Van Wezel et al. (2017) by Evelin Karsten-Meessen.

Following pre-registration of the 145,297 chemicals most likely to require regulation, REACH came into force in 2008 in a stepwise process with different deadlines for different groups of chemicals. The first dossiers were to be completed by 2010 for the highest produced volume chemicals (>1000 tonnes/y) and the most hazardous chemicals (CMRs >1 tonne/y, and chemicals with known very high aquatic toxicity >100 tonnes/y). These groups potentially pose the greatest risk because of either their high emissions or their inherent toxicity. In 2013, registration dossiers for chemicals with a lower tonnage (100-1000 tonnes/y) were to be completed. By May 31 2018, all chemicals with a quantity of 1-100 tonnes/y chemicals on the EU market should have been registered. New chemicals will all be subject to the REACH procedures.

In 2018, 21.787 substances had been registered under REACH. A total of 14.262 companies were involved. In comparison, 15.500 substances were registered in 2016 (i.e., 6287 chemicals were added in the two following years). In 2018, 48% of all substance registrations had been done in Germany. For 24% of the registered substances a dossier was already available prior to REACH, 70% are “old chemicals” for which no registration had been done before REACH was initiated, and only 6% are newly developed substances that needed to be registered before manufacture or import could start.

There are multiple benefits of REACH regulation of industrial chemicals. Most data on chemicals entered in the registration process is publically available, creating transparency and improving customer awareness. If registered chemicals are classified as Substance of Very High Concern (SVHC) based on the chemical information in these dossiers and after agreement from research panels, alternatives that passed the same regulation can be suggested instead.

The necessity to add data on potential toxicity for so many chemicals has been combined with a strong focus on, and further development of, animal friendly testing methods. Read-across from related chemicals, weight of evidence approaches, and calculations based on chemical structures (QSAR) allow much experimental testing to be circumvented. In vitro studies are also used, but a 2017 REACH document (REACH alternatives to animal testing 2017, which followed up 2011 and 2014 reports) reports that 5.795 in vitro studies were used overall to determine endpoints for REACH, compared to 9,287 in vivo studies (ratio of 0.6). Clearly, many new animal tests have been performed under REACH to complete the dossiers on industrial chemicals. Prenatal developmental and repeated dose toxicity testing as well as extended one generation reproductive toxicity studies remain difficult to circumvent without animal use. However, the safe use of industrial chemicals must be ensured and demonstrated.

References:

Van Wezel, A.P., Ter Laak, T.L., Fischer, A., Bäuerlein, P.S., Munthee, J., Posthuma, L. (2017). Mitigation options for chemicals of emerging concern in surface waters; operationalising solutions-focused risk assessment . Environmental Science: Water Research 3, 403–414.