The regulation of industry began in the late part of the Industrial Revolution with the creation of agencies like the Railways Department of the United Kingdom Board of Trade (later called Her Majesty's Railway Inspectorate) following the Railways Regulation Act of 1840. One of the foremost railway engineers of the time, Isambard Kingdom Brunel, strongly opposed this development on the fully rational grounds that railway engineers “understood very well how to look after the public safety, and putting a person over them must shackle them. They had not only more ability to find out what was necessary than any inspecting officer could have, but they had a greater desire to do it” [1]. Few others had the high principles of Brunel, however, and the inspectors were duly appointed.

The concept of regulation as an engineering device was very much in the air at the time. James Watt had introduced a regulator, or governor, for his steam engines to enable them to run at a constant speed [2]. The Alkali Act of 1863 created a formal regulatory agency, the Alkali Inspectorate (the first Alkali Inspector was Robert Angus Smith, the Scottish chemist who pioneered the study of air pollution and acid rain). The creation was reactive: the infant heavy chemical industry in north-west England, using notably the Leblanc process for making sodium carbonate (soda) from sodium chloride (salt) and calcium carbonate (chalk), released vast quantities of the highly corrosive hydrochloric acid into the atmosphere. Smith, believing that the best way to secure progressive improvements was to work with the industry rather than against it, established the consensual character of the Inspectorate, favoring compliance rather than enforcement, where negotiation and discussion predominated over formal, legal remedies [3].

Although the Alkali Inspectorate was highly successful—manufacturers complied with the need to eliminate emissions and found that the recovered hydrochloric acid was a highly profitable by-product—there is still controversy over whether regulatory agencies promote or depress the business they regulate. Whereas in the past industries have been well established by the time regulators have been appointed, in the intervening years the general public has become highly sensitized to the dangers of unprincipled and unregulated industry [4], and nanotechnology is now confronted by a barrage of regulation before the industry has really got under way.

In the past, new technological advances, such as new substances that had some obvious beneficial use, were often adopted enthusiastically almost immediately after their discovery, with very little consideration given to adverse effects on human health or the environment. As a clear result of the accumulation of examples of adverse effects, a much more cautious approach has begun to be adopted, with the safety of new substances having to be demonstrated before they are allowed to be traded.

Such caution has long been an accepted part of pharmaceutical medicine (regulation represents, indeed, a form of risk management). Indeed, it might be considered an obvious corollary of that ancient medical maxim “primum non nocere”, although the US Federal Food, Medicine & Cosmetic Act, which required new medicines be tested for toxicity before being put on the market, was only passed in 1938. Nowadays extremely stringent procedures are in force to ensure the safety of medicines (at least for the majority—taking due account of possible genetic variation in drug metabolism may be the next significant development in pharmaceutical safety), which apply equally to nanomedicine.

Apart from medicine, consideration of the safety of nanotechnology seems to have fallen under the umbrella of the chemical industry, perhaps because nanomaterials nowadays constitute the greatest volume of nanoproducts (ignoring nanoscale very large integrated circuits in computers), and many nanomaterials, especially nanoparticles, have traditionally been produced by chemists.

In the USA, chemicals are regulated by the Toxic Substances Control Act (TSCA) and the Occupational Health and Safety Act (OSHA). TSCA requires chemical manufacturers and importers to submit a pre-manufacture notification and risk assessment information to the Environmental Protection Agency (EPA). In principle these Acts could suffice to ensure the safe commercialization of nanomaterials. Nevertheless, the TSCA defines a chemical substance based solely on its “particular molecular identity”, and conventional chemistry does not distinguish between a regular chemical substance and that same substance in the form of nano-objects. For example, the same material safety data sheet (MSDS) for graphite (carbon) could be used for fullerenes, carbon nanotubes and graphene, in which carbon has sp² hybridization [5]. Graphite is a rather harmless substance, whereas carbon nanotubes may be highly toxic, especially if inhaled. To deal with this potential problem, the EPA has a “significant new uses rule” (SNUR), meaning that even if a nanomaterial is chemically the same as an already-registered bulk substance [6], it will need a fresh declaration.

A major issue with TSCA that weakens its ability to regulate nanoparticles is the exemption for “any food, food additive, drug, cosmetic, or device” [7]. This puts consumer applications in medicine and hygiene beyond the jurisdiction of the EPA. Instead, they fall under that of the Food and Drug Administration (FDA), which does require new drugs to be safety-tested (with nanoparticles being, however, considered to be the same as bulk materials made from the same substance), but most other items are merely subject to industry self-regulation. Furthermore, FDA testing only deals with the safety of the user; the contamination of waterways with pharmaceuticals, with possibly severely deleterious ecological consequences, falls outside its scope [8]. Another major issue with TSCA is that a chemical substance is defined in terms of its “particular molecular identity” [6,9]. Hence, most nanoparticles are not new substances according to this definition and nanofacturers do not need to notify the EPA about them. If the safety of bulk or micrometer-scale material has already been established by years of safe use, it may be difficult for the EPA to show a “more than theoretical basis” for ordering testing, as the law requires [10]. Hence there is, at present, little meaningful regulation of nanoparticles in the USA. The EPA does have the authority to regulate any existing chemical if it presents or will present “an unreasonable risk of injury to health or the environment” [11], which sounds like a guarantee of safety, but as is often the case with seemingly powerful overarching provisions, they are difficult to pin down to any concrete case in a court of law (this power does not appear to have been successfully used to regulate any existing substance for at least 25 years). There is, moreover, currently a trend to remove provisions that are seen as placing too onerous burden on industry, so it seems unlikely that they will be strengthened in the near future.

By far the most draconian régime is being promulgated in the European Union, despite the fact that nanotechnology has been designated by the European Commission as one of the key enabling technologies (KETs) considered to be the drivers for future economic development. The basic regulatory instrument is the Registration, Evaluation and Authorization of Chemicals (REACH) system. This was only proposed in 2003 and has still not yet been fully implemented. REACH transfers the burden of proof that a chemical is safe from public regulatory agencies to the industry producing it. The European Union also has a new Classification, Labelling and Packaging (CLP) regulation. REACH will incorporate the precautionary (or “White Queen” [12]) principle, which is a firm part of official European Union policy [13]. The principle is that if something is suspected of bearing a risk of causing harm to the public or to the environment, in the absence of clear scientific evidence that it is harmful, then the burden of proof that it is not harmful falls on those wishing to introduce that something. There are no official guidelines concerning the degree of suspicion that would trigger the application of the precautionary principle, hence any legislation based on it is essentially weak and potentially the object of endless litigation. Perhaps, however, in practice its application will turn out to be workably consensual—in accordance with the tradition established by Robert Angus Smith. The regulatory agencies have themselves made their task of achieving meaningful regulation more difficult by tolerating venality among their employees and members of oversight committees. This has undermined public confidence in their work [14].

The main problem with the regulatory régime in the European Union is the plethora of regulations, directives, recommendations, etc. potentially impinging on nanomaterials [15]. A small nanomaterials company will find merely keeping up with this enormous volume of paperwork an intolerable burden, yet failure to comply with some regulation possibly buried in one of the vast number of documents may lead to crippling litigation [16]. It is also unhelpful that some countries have introduced their own special regulations. The most notable is France, which introduced mandatory declaration of nanomaterials on 1 January 2013 [17]. This declaration is unlikely to be effective in tracing nanomaterials because it only obliges anyone producing more than 100 g of a nanomaterial—which corresponds to about 10²² 2 nm diameter silicon nanoparticles, for example—to file an annual return. A further problem is that the European Union has promulgated its own definition of a nanomaterial, which is different from that reached by ISO after several years of laborious consensus-seeking. Finally, there are grave doubts concerning the quality of the scientific advice provided to the European Commission. In common with most of the internal workings of the European Union the procedure whereby people (in this case, scientists) are appointed to advisory committees (such as the Scientific Committee on Emerging and Newly Identified Health Risks, SCENIHR) is opaque. Occasionally independent external experts are invited to comment on the reports of these committees and as a rule the comments are highly critical. It is not untypical for the Commission officials to agree with the criticism—but it is not considered to be appropriate for them to directly criticize the work of experts who have been officially appointed! As a net result, small companies (which are supposed to constitute the driving force for nano-innovation) get bogged down; only the largest companies have the resources to lobby the European Commission to ensure that their commercial interests are not damaged. Under this régime, any emergence of a competitive industry within the member states of the Union will be in spite of, not because of it; it is regrettable in the extreme that so much effort and energy has to be expended on artificially erected obstacles of this nature.

International activity is generally confined to guidelines and recommendations. Examples are the World Health Organization's “Guidelines on Nanomaterials and Workers Health”, the documents produced by the OECD's Working Party on Manufactured Nanomaterials, and the United Nations' Globally Harmonized System of Classification and Labelling of Chemicals.

Referring back to Brunel's criticism of regulation, by far the most effective solution to ensuring the safe worldwide deployment of nanomaterials would be to let the industry regulate itself. This can very easily be accomplished through the medium of a commercial exchange (Section 13.4). Due diligence, including site visits, is applied to all companies wishing to become members of an exchange, ensuring that only reputable firms are allowed to do so. All trade is in materials that comply with published standard specifications, and every trade benefits from downstream audit sequencing (DAS), also known as “track-and-trace”: each individual trade has a unique number that is passed from producer to consumer and is entirely compatible with CLP. Ensuring that all nanomaterials are exchange-traded makes the new French reporting system completely redundant, and is far more effective since every trade is essentially logged when it occurs, rather than consolidated into an annual return, and there is no minimum quantity above which the obligation to report is automatically triggered.

Unlike conventional materials, it is often extremely difficult to trace nano-objects once they are incorporated into a product, let alone once they are released into the environment. For example, silver nanoparticles are now incorporated into several textile products, such as wound dressings and socks, as a bactericide. If the textile is laundered many of the particles escape into the waste water and could end up widely dispersed in the environment. The difficulty of tracing nano-objects is above all due to their minute size and their fugitive nature (which is a consequence of their minute size). Regulations may forbid the release of silver nanoparticles into the environment (because of the risk of destroying bacteria essential for a healthy ecosystem), but how is such a regulation to be enforced if the nanoparticles cannot be detected? Silver would at least be an unusual element to find in most soils, but iron nanoparticles, which are also finding an increasing number of applications, are likely to closely resemble the natural components of many soils. Possibly in the future the discipline of “nanoforensics” will be developed [18].

Risk is the product of hazard and exposure (cf. Section 20.1). Certain nano-objects may be very hazardous if they are inhaled (and suitable precautions must be taken during their manufacture). But once they are incorporated into another product, the probability of exposure may become negligible. An example is the use of carbon nanotubes in composite materials. The nanotubes are dispersed in a polymer matrix. For most structural applications, the nanotubes will never be released and hence the overall risk is negligible. Nevertheless, the composite is a nanomaterial according to the standard vocabulary developed by ISO (and according to the official definition of the European Union), and may, therefore, be subject to very restrictive conditions of use according to present or proposed regulations.

Although in some countries (such as the UK) the government is required to carry out assessments (impact assessment, IA, or regulatory impact assessment, RIA) of the likely costs, benefits, and adverse effects of any legislation it implements [19], little assessment appears to have been done at EU level, which is the main locus for the regulation of nanotechnology within Europe. The present situation appears to be rather fluid, and stakeholders would be well advised to energetically investigate exactly what is happening that potentially impacts on their activities, and allocate resources for defending their interests.

There is a long history of the purveyors of foods and drugs paying scant attention to the safety of consumers [20]. Even if the upstream manufacturers of nano-objects responsibly and effectively self-regulate themselves using such systems as DAS, that does not guarantee that the downstream manufacturer (i.e., the end-user prior to release of the product to the public) will act similarly. In fact, presently there are no proper regulations for using nanotechnology in the food and health-food sectors. The nano-industry is so much more complex than the chemical and pharmaceutical industries that it actually requires its own regulatory agency, if there is to be any meaningful and effective regulation at all, rather than relying on existing and possibly slightly modified provisions applicable to chemicals and drugs. This is well illustrated by the problem of defining workplace exposure limits. A separate limit needs to be established for every substance available as a nano-object, for every size, shape, and kind of surface treatment, because all these characteristics affect the physiological action. Furthermore, composite nano-objects are becoming more widespread, with an almost infinite range of variety, and each particular composition may have a unique physiological effect.

In order to prevent such a regulatory régime from becoming so onerous that the industry would be stifled, it is essential to properly assess the reasonableness of any proposed regulatory measure. Since the purpose of such measures is to increase the safety of the public, they can be objectively assessed according to the Judgment (J)-value approach outlined in Section 14.11.

There has lately been a great increase in regulatory activity (in the sense of drawing up new regulatory proposals) and it must now constitute a major source of employment of nanotechnologists. Possibly there is some kind of dynamic cyclic quasi-equilibration process operating here (cf. Lotka–Volterra): if the number of regulators significantly exceeds the numbers of inventors of new nanoproducts and of those devising ways to produce them commercially, the need for regulators will decline and innovation will once again increase.

The consumer can always fall back on caveat emptor to protect himself or herself, but the environment has to rely on its innate resources operating reactively. Here it is as well to keep in mind the immense resources of the microbial world, and the fact that its interests may not always be aligned with those of humankind. Nevertheless, the efforts of regulators to protect the environment are well-meaning and doubtless essential for protecting the survival of higher life forms. Furthermore, some kind of regulatory framework, including intelligible standards and downstream audit sequencing, is essential for being able to stably insure nanoproducts in transit and in use, and are needed for any meaningful litigation to be able to take place in the case of civil disputes.