The detection and analyses of chemical compounds in foods at low levels (parts per billion–µg/kg range and lower) that are not regulated and for which no acceptable daily intake (ADI) or maximum residue limit (MRL) is established have substantially grown in importance. Technological advances in analytical chemistry make it possible to detect chemicals in food matrices at extremely low levels.

Simultaneously, setting scientific and policy standards that benchmark the benefits and risks of products intended to be consumed is of great consequence for industry, policymakers and consumers. Unfortunately, the safety of products consumed is more often than not defined as chemical product safety, meaning that the product consumed is regarded as “safe” when synthetic chemicals, such as antibiotics and pesticides and/or contaminants such as dioxins and PCBs, are absent or present only at very low levels.

Below, we will show that chemical product safety of foods is a misnomer partly related to the fact that many chemicals usually regarded as synthetic nevertheless can be natural. Moreover, toxicity of chemicals is related to ingested dose and the concomitant bioavailability rather than to mere presence as such. The latter, unfortunately, has taken center stage in many food safety policies because of analytical capabilities we will discuss as well.

Chemicals and Food
Nonregulated compounds that do not have an MRL or an ADI are, from a default regulatory point of view, not supposed to be present in food at any detectable level, yet are increasingly detected because of technological advances in analytical chemistry. The regulatory position to limit or ban the presence of these chemicals from foods is thus offset by greatly increased analytical capabilities we have seen in recent decades.

Indeed, we have entered the realm of atto- (parts per quintillion; 10-18) and zeptomoles (parts per sextillion; 10-21) of detectable analytes.[1] Basically, this means that the actual nonpresence of certain chemicals is shifting to ever lower exposure levels. Moreover, the chemical-analytical view screen has expanded as well: Smaller amounts of increasingly diverse chemicals can in fact be detected, whereby a regulatory impasse seems imminent. What will be the regulatory depth of chemical food safety? Overall, advances in “cleaner” consumable goods production are thus offset by increased detection capacities.

This development has raised quite a few questions:

1.    In current regulatory policies, is food safety equal to detectability (of compounds)?

2.    Is it possible to unequivocally assign sources—natural, synthetic, related to food processing, etc.—to detectable chemicals?

3.    What toxicological dose-response model is applicable to low-level exposures?

4.    What communication strategies should be developed for chemicals and foods, and the detectability of the former at (very) low levels?

We will look at issues 1, 2 and 4.

On Detectability
It still seems that current policies on chemical food safety revolve around detectability. The detection in 2001 of chloramphenicol (CAP), a broad-spectrum antibiotic, in shrimp imported into Europe from Asian countries was branded a food scandal and triggered the focus on CAP in foods since then. The initial European response was to close European borders to fish products, mainly shrimp, from these countries and make laboratories work overtime to analyze numerous batches of imported goods for the presence of this antibiotic. Some European countries went so far as to destroy food products containing CAP as public health was deemed to be at risk. This regulatory response spilled over to other major seafood-importing countries, including the U.S. Imported shrimp was found to contain between 1 and 10 ppb (µg/kg product) of CAP.[2]

The legislative background to the European response was found in Council Regulation 2377/90. This so-called MRL Regulation introduced community procedures to evaluate the safety of residues of pharmacologically active substances according to human food safety requirements.

Regulation 2377/90 contained an Annex IV listing of pharmacologically active substances for which no maximum toxicological levels (tolerable daily intake—TDI, also known as ADI) can be determined, either from lack of toxicological or pharmacological data, such as the absence of a definable NOAEL (no observed adverse effect level) or LOAEL (lowest observed adverse effect level), or because of genotoxic characteristics of the compound in question. These substances are consequently not allowed in the animal food-production chain. The presence of CAP in food products violates European law and purportedly is a threat to public health.[3]

Superseding Regulation 2377/90 with Regulation 470/2009[4] as the new regulatory standard for the establishment of residue limits of pharmacologically active substances in foodstuffs of animal origin did not fundamentally amend the regulatory situation spawning the CAP episode. Although this new regulation points to the “scientific and technical progress” by which the “presence of residues of veterinary medicinal products in foodstuffs” is detected “at ever lower levels,” it does not provide a fundamental solution, other than making the MRPL (minimum required performance limit), at whatever low concentration levels regulatory laboratories in the European Community (EC) could detect and confirm, an explicit level of concern. An MRPL is no more and no less than the concentration level that regulatory (reference) laboratories in the EC should at least be able to detect and confirm. EC regulatory laboratories are obliged to try to find residues of banned substances, like CAP, at the lowest technically attainable concentration. Thus, detectability still trumps toxicological relevance.

On Sources
Figure 1 shows a few examples of compounds found in foods as a natural component, a food processing residue or both that, in some instances, are rigorously regulated or might be part of the specific taste of some foods.

Semicarbazide (SEM), for instance, is regarded by the European Commission Directorate-General Health and Consumers as solely indicative of the illegal administration of nitrofurazone to live animals.[5] As of late, it has been shown that SEM is also found as a result of natural processes. Macrobrachium rosenbergii, cultivated under controlled conditions in the absence of nitrofurazone, was shown to have SEM present in the shell.[6] Wild-caught crustaceans that were tested by the research group were shown to have bound SEM in their shells at varying concentrations. The physiological source of SEM, now recognized as a natural metabolite in crustaceans, is not yet known. Similarly, CAP has been found as a natural component in plants used as animal feed and thereby transferred to animal tissue.[7, 8]

With respect to chemical food safety, regulation has been quite selective. Simply classifying certain compounds as synthetic and indicative of illegal use has created a naïve dichotomy between “natural” and “synthetic.” The biochemistry of animals (or plants) is immeasurably more intricate than the mere allocation of marker molecules for the ostensible legal control of certain pharmaceuticals implicitly or explicitly suggests. It is absurd that the complex biogeochemical reality is forced into a highly reductionist legal construct established to presumably protect the public against “toxic” chemicals of synthetic origin in food. It is not an exaggeration to state that most if not all molecules that can be identified as synthetic or man-made will have their natural counterparts.

A famous example is the halogenated hydrocarbons, of which the chlorinated compounds are the most notorious. Chlorine is one of the most abundant elements in the world. It was widely believed that all chlorinated organic molecules are synthetic xenobiotic chemicals. However, it has become increasingly clear that organohalogens are ubiquitously produced in nature. Some of these compounds are produced in amounts that dwarf human production. The sum total of different organohalogens is staggering—more than 5,000 natural organic halogen compounds have been identified so far—and come from widely diverging sources.[9]

On Communication Strategies
Chemistry and its many spinoffs do not sit well with the public and policymakers. Chemophobia is known for a history too long to delve into here.[10] It is, however, important to remind ourselves and the public at large of the fact that access to sufficient food of adequate nutritional quality—that is, rich in micronutrients—is far more important for human health than protection from trace amounts of potentially harmful chemicals.[11]

It is quite obvious for people in developing countries that food security comes first, but this is also true for the poorer citizens in EU member states. Malnutrition is a common phenomenon, particularly with respect to vitamins and minerals. In the Netherlands, it is recognized that 25–40 percent of people admitted into hospitals are malnourished. The Dutch Malnutrition Steering Group is trying to interest other EU nations in tackling this problem.[12] Never- theless, the EU considers such aspects of food security to be primarily problems of developing nations.[13]

That the EU has shifted its own concerns in the second half of the 20th century from food security to food safety became very clear in the process that led to the establishment of the European Food Safety Authority. The original 1999 report regarding the never-established European Food and Public Health Authority clearly stated that this new institution should focus on food security as a human health marker next to safety issues.[14]

Overall, micronutrient malnutrition contributes substantially to the global burden of disease. The World Health Organization has noted, “More than 2 billion people in the world today suffer from micronutrient deficiencies caused largely by a dietary deficiency of vitamins and minerals. The public health importance of these deficiencies lies upon their magnitude and their health consequences, especially in pregnant women and young children, as they affect fetal and child growth, cognitive development and resistance to infection.”[15]

Therefore, if we are to educate on food and chemistry, the first approach might focus on the reality of malnutrition with respect to the essential chemicals of life. From there, the chemistry of food as a whole might be addressed and put into the context of the laboratory of the cook—aka the kitchen—and the consumption of many different chemicals that derive from the cooking process. Overall, it seems, context is everything when dealing with chemicals that make up our daily nutrition.

Jaap C. Hanekamp, Ph.D., is an associate professor at the University College Roosevelt, Middelburg, The Netherlands, and an adjunct professor at the University of Massachusetts, Amherst, in the department of environmental health sciences.

1. Pagnotti, V.S., N.D. Chubatyi and C.N. McEwen. 2011. Solvent assisted inlet ionization: An ultrasensitive new liquid introduction ionization method for mass spectrometry. Anal Chem 83:3981–3985.
2. Hanekamp, J.C., G. Frapporti and K. Olieman. 2003. Chloramphenicol, food safety and precautionary thinking in Europe. Environ Liability 6:209–221.
3. Commission regulation EU/37/2010 on pharmacologically active substances and their classification regarding maximum residue limits in foodstuffs of animal origin. 2010. Official Journal of the European Communities L15:1−72.
4. Regulation (EC) No 470/2009 of the European Parliament and of the Council of May 6, 2009, laying down community procedures for the establishment of residue limits of pharmacologically active substances in foodstuffs of animal origin, repealing Council Regulation (EEC) No 2377/90 and amending Directive 2001/82/EC of the European Parliament and of the Council and Regulation (EC) No 726/2004 of the European Parliament and of the Council. Official Journal of the European Union L152:11−22.
5. European Commission, Directorate-General Health and Consumers. 2003. Note to all chief veterinary officers. Subject: Semicarbazide in various foods.
6. Van Poucke, C. et al. 2011. Investigation into the possible natural occurence of semicarbazide in Macrobrachium rosenbergii prawns. J Agric Food Chem 59:2107–2112.
7. Berendsen, B. et al. 2010. Evidence of natural occurrence of the banned antibiotic chloramphenicol in herbs and grass. Anal Bioanal Chem 397:1955–1963.
8. Berendsen, B. et al. 2013. Occurrence of chloramphenicol in crops through natural production by bacteria in soil. J Agric Food Chem 61:4004–4010.
9. Gribble, G.W. 2010. Naturally occurring organohalogen compounds – A comprehensive update. Vienna: Springer-Verlag.
10. Hanekamp, J.C., S.W. Verstegen and G. Vera-Navas. 2005. The historical roots of precautionary thinking: The cultural ecological critique and ‘the limits to growth.’ J Risk Res 8(4):295–310.
11. Hanekamp, J.C. and A. Bast. 2007. Food supplements and European regulation within a precautionary context: A critique and implications for nutritional, toxicological and regulatory consistency. Crit Rev Food Sci Nutr 47:267–285.
14. James, P., F. Kemper and G. Pascal. 1999. A European Food and Public Health Authority. The future of scientific advice in the EU. Brussels: European Commission, Directorate-General Health and Consumers.
15. Lindsay Allen, L., B. Bruno de Benoist, O. Dary and R. Hurrell (eds.) 2006. Guidelines on food fortification with micronutrients. Geneva: World Health Organization.