ALICOM 99/20  |
| ALICOM 99/20 |
Conference on International Food Trade
|
Assuring Science Based Decisions - Determining the Appropriate Level of Protection: Threshold of Regulations/Implementation |
by |
Professor Arpad Somogyi, Directorate General Health and Consumer Protection, European Commission, Brussels, Belgium 1 |
1. The pre-eminent role of science in food-related regulatory decisions is undisputed. Science has been the basis for national and international food regulation for many years all over the world. With the increase of international trade in food during the second half of this century the need has arisen for a universally acceptable measure to ascertain both a high level of food safety and fair trading practices in international commerce with food. Science with its proverbial reputation of objectivity has been identified and increasingly implemented in international agreements among others in those regulating food trade. At its 21st Session the Codex Alimentarius Commission decided to adopt the "Statements of Principle Concerning the Role of Science in the Codex Decision-Making Process and the Extent to Which Other Factors are Taken into Account" (Codex Alimentarius Commission,1997). Also these statements, often referred to as the "Four Principles", clearly assign science a pivotal role while equally clearly emphasising the legitimacy of other factors in international food regulations. Likewise, the Treaty establishing the European Communities as recently amended by the Treaty of Amsterdam requests in Article 95 that the legislator take "as a base a high level of protection, taking account of any new development based on scientific facts" (Treaty of Amsterdam, 1997). In the United States of America the Committee to Ensure Safe Food from Production to Consumption jointly formed by the Institute of Medicine and the National Research Council came to the conclusion that among the characteristics of an effective food safety system the highest ranking attribute is that it "should be science based, with a strong emphasis on risk analysis, thus allowing the greatest priority in terms of resources and activity to be placed on the risks deemed to have the greatest potential impact" (Institute of Medicine, National Research Council, 1998). Numerous further examples could be cited which, in principle, all unequivocally confirm that science is the necessary, albeit, alone not sufficient basis of regulation. Before further pursuing our thoughts on the role of science in regulatory decision-making, we should pause for a moment and ask, what is actually science?
2. According to Merriam-Webster's Collegiate Dictionary (1998) science is defined as "the state of knowing: knowledge as distinguished from ignorance or misunderstanding". This definition does not discriminate between knowledge at various levels. Knowledge is hardly ever complete and never a static state. It is rather a dynamic concept, constantly in the process of development and refinement. Based on knowledge, hence science, that was prevailing in the last century, our contemporary life would be entirely unthinkable. It can confidently be predicted that the judgement of future generations about our present knowledge, which we are now so proud of, will likewise be not more complimentary. Consequently, regulation based on science must invariably be considered as a transitory stage reflecting current knowledge at a given point in time. Even this assertion is subject to interpretation. The history of science is full of contradictions, often of fierce competition of diametrically opposing views and ideas. The challenge to the knowledge of the day was always the most powerful propelling force for scientific progress. Therefore, it is often extremely difficult to determine what, in a given field at a given time, contemporary science is. Do the consolidated views of the majority or unorthodox new ideas of the minority, often of one single maverick, constitute "sound science"? Many great discoveries and scientific breakthroughs were born as bitterly contested ideas that initially were rejected by the mainstream scientific establishment or even condemned as heresies by others. On the other hand, probably many more interesting, plausible and ostensibly convincing ideas turned out later to be illusions, hoax or the products of outright fraud. Therefore, particularly if public health is at stake, it can easily become an awesome responsibility for decision-makers to opt for the opinion of either the majority or the minority. The BSE2 crisis is a tragic case in point: The late acceptance by the majority of well founded early predictive warning by the minority regarding the transmissibility of the disease from bovines to humans led to the belated implementation of appropriate regulatory measures.
3. Despite these imponderables, there is no reasonable alternative to science. It must, therefore, become and firmly remain an indispensable ingredient of all regulatory decisions. It should, however, be recognised that, as a rule, in order to be effective, regulatory decisions aimed at protecting the health of consumers often have to be made "here and now", before scientific controversies can be resolved and the verdict is in. It must, therefore, be clearly understood by all stakeholders what, in general and at a specified time, science can deliver and what it cannot. The life span of the scientific validity of any regulatory decision will always be a function of progress in the pertinent disciplines and, thus, can occasionally be extremely short. The scientific basis for a particular regulation that universally deemed rock solid today can, like sand, easily be washed away already by tomorrow.
4. The regulation of food reaches back to the beginning of human history. The parting twentieth century has witnessed an unprecedented upsurge of regulatory measures pertaining to food. Hence, food is today world-wide one of the most regulated commodities. Food regulation underwent since its beginnings profound changes. While early attempts to regulate food have primarily aimed at preventing and combating adulteration and fraud, current regulatory measures are centred around safety. As an extremely complex item, food safety can only be approached by a multitude of scientific disciplines. A multidisciplinary panoply of natural sciences (e.g., physics, chemistry, toxicology, hygiene, microbiology, engineering, and technology) laid the foundation of modern food regulation by national and international agencies all around the world. Particularly the use of increasingly sophisticated analytical, toxicological and microbiological methods in the evaluation of normal constituents and contaminants of food and of food additives as well as the advent of new concepts in risk analysis, including the precautionary principle (Belvèze, 1999), has made a decisive contribution in this respect. In recent years, especially with the establishment of the World Trade Organization (WTO), food safety has become the overbearing issue for international trade in commodities as well.
5. Food-related regulatory decisions have a direct relevance for each and every citizen of any community. Hence, the ever-increasing interest of the public in food safety issues is not surprising. Although, in general terms, it can be justifiably said that food is safer today than it ever has been, nevertheless, as shown by the results of a recent public opinion poll (Eurobarometer), the vast majority (68%) of consumers within the European Union (EU) is concerned about the safety of their food. Presumably, the perception of the public regarding food safety in other regions of the world is not profoundly different Particularly since reports, for example, on adulterated olive oil in Spain, the outbreak of BSE in the UK and its spread to other countries, the global emergence of Listeria monocytogenes and toxinogenic strains of Escherichia coli, contamination of feed by dioxins in Belgium affecting a gamut of food of animal origin sent shock waves around the world. In light of such dramatic cases in recent decades of foodborne infections and intoxications resulting in debilitating illness and fatalities, this heightened awareness and the preoccupation of the public with food safety is fully understandable.
6. As stated in the introductory paragraph, the reliance on science as the appropriate basis of regulatory decisions gained over the years universal acceptance. In the mid 50s, it was recognised that with the introduction of an increasing number of new additives to bestow on food desirable novel characteristics of quality, new questions as to the safety of these products arose. The toxicological evaluation of hitherto unfamiliar chemical molecules used in the burgeoning food technology of the post-war era became a formidable challenge to regulatory agencies and industry alike. Attempts to face this challenge often went beyond the ability and/or the capacity of individual national regulatory agencies. Moreover, it has become very soon evident that, in this uncharted territory, if national agencies ventured alone to tackle the task of the health evaluation of these new substances, a frequently disturbing heterogeneity of regulations ensued. To remedy this situation, international efforts led to the establishment of institutionalised mechanisms dealing with the safety evaluation of chemicals in food. Initially, following the Conference on Food Additives jointly organised in 1955 by the Food and Agriculture Organization of the United Nations (FAO) and the World Health Organization (WHO), the Joint FAO/WHO Expert Committee on Food Additives (JECFA) was inaugurated in 1956 (WHO 1987). In subsequent years, the scope of the categories of substances to be considered was widened to include normal constituents and contaminants of food as well as residues of pesticides and of veterinary drugs.
7. In Europe the Scientific Committee on Food (SCF) and its predecessor institutions have made invaluable contribution to the scientific base of regulatory decisions. Since its inception in 1974, the SCF has held to date nearly 120 plenary sessions. These along with countless meetings of its subsidiary working groups dealing with recurring problems in specific areas (e.g., food additives and contaminants, migrating chemicals from packaging materials, microbiology and hygiene, nutrition) or those set-up to resolve suddenly arising unexpected problems are the principle providers of food-related scientific advice for the European Commission (EC), the executive organ of the EU.
8. In addition to numerous national agencies and advisory bodies to governments, JECFA and the Joint FAO/WHO Meetings on Pesticide Residues (JMPR) as well as several scientific committees of the EU made widely recognised contribution to the development of procedures for and performing the safety evaluation of chemical substances in food. Nevertheless, the success of the past should not make us complacent. Particularly not, as there was no shortage of justified criticism that occasionally has accompanied the work of these scientific institutions.
9. In preparation of legislative measures, the EC has always relied on scientific advice emanating from different sources. One of the most important of these sources was the system of scientific committees. In recent years with increasing complexity and sophistication of both science and legislation it became evident that the mechanisms of the past cannot satisfy the needs of the present and the future. Therefore, in the aftermath of the BSE crisis, the EC took in 1997 decisive steps to eschew deficiencies of the past and to introduce measures to further increase the integrity and the effectivity of its scientific advisory mechanisms. Based on their professional excellence and independence, 131 scientists of several disciplines have been selected among many hundreds of respondents to public calls for interest to become members in the scientific committees of the EC (Reichenbach, 1999). Eight scientific committees3 are devoted, among others, to issues of food safety, animal nutrition, animal health and welfare, plant protection, cosmetics, chemicals as well as medicinal products and medical devises, respectively. A multidisciplinary ninth group, the Scientific Steering Committee, in addition to dealing with specific issues mostly overlapping the area of mission of several scientific committees (e.g., BSE-related topics), exercises an overriding co-ordinating function. Appropriately, half of its 16 members are the chairpersons of the eight specialised scientific committees and the other half is singularly appointed to serve on the Scientific Steering Committee. Unlike JECFA and JMPR, which are operating with changing sets of members specifically selected for each individual session, in order to provide a desirable measure of continuity, the scientific committees of the EC are appointed for a period of three years at a time. About half a dozen of plenary meetings per year are held. During the first two years of their existence these scientific committees adopted more than 160 opinions on a plethora of questions posed to them by the EC. These opinions became immediately following their adoption - via the Internet - available to the public, just as the list of the members of the scientific committees, the agendas and the minutes of their meetings including minority opinions. Thus, in addition to the already mentioned attributes excellence and independence, transparency is equally an essential trait characterising the operation of the scientific committees of the EC.
10. On the way to international harmonisation of food regulations, the establishment of the WTO was a significant milestone (World Trade Organization, 1994). Particularly one of the constituting documents of the voluminous catalogue of rules, the "Agreement on the Application of Sanitary and Phytosanitary Measures (SPS Agreement)", gave important guidance concerning many aspects of scientific evaluation. Yet, the experience of nearly five years which have elapsed since the results of the Uruguay Round culminated in the foundation of WTO, and the SPS Agreement took effect, convincingly showed that considerable ambiguity still prevails. This became particularly obvious in the course of the dispute settlement procedures of WTO on "EC Measures Concerning Meat and Meat Products (Hormones)" (World Trade Organization, 1997). Characteristic for the intractable nature of that case was the substantial disagreement on pivotal points of the scientific evaluation and that key elements of reasoning put forward in the WTO Panel's Report have been overturned in the second instance by the Appellate Body (AB). The ruling by the AB provided further clarification and gave guidance regarding some critical aspects of that particular case bearing principal relevance for the future as well (World Trade Organization, 1999).
11. In particular, it is noteworthy that the AB reiterated that a protective measure taken by a member government has to be based on sound science or must be sufficiently warranted by a risk assessment. This risk assessment, on the other hand, does not necessarily have to be of quantitative nature. The AB ruled furthermore that signatory governments may base their measures on minority views from qualified and respectable sources. An entirely new aspect of the AB's ruling that risks arising from difficulties related to control and inspection can also be taken into account while considering the options in choosing appropriate measures.
12. These few examples illustrate that, although science is the solid basis but not the whole structure of an important piece of regulation devised to assure food safety and govern international trade in food. No matter how clear the scientific answer might be, which can only serve as the basis and guidance, the final decision taking into account all relevant aspects will always be the function of political instances. Therefore, to minimise the likelihood of conflicts in international trade, it is of utmost urgency to work at the international level steadfastly on the development of standards compatible with the regulatory philosophies of as many countries as possible.
13. Inherent in the uncertainties of scientific evaluations, risk assessment, as its name implies, is not an accurate process of measuring but of approximation often based, instead of on established facts, on scientifically plausible hypotheses. In toxicological evaluations, the intrinsically complicated situation is further compounded by the fact that we have to extrapolate into the experimentally not amenable portion of the dose-response-curve. On the basis of studies, in which high doses (maximal tolerated doses; MTD) of the test substance are administered on relatively few animals, we are attempting to make predictions regarding safety for the global human population exposed to relatively low doses of the substances in question. In this endeavour - ultimately to determine safety - we are using models of extrapolation with increasing sophistication and often with increasing incompatibility. Consequently, they could lead to different results. Based on identical data derived from the same experiment, conclusions as to the level of safety might - depending upon the model used - lie orders of magnitude apart. The situation regarding the principles, procedures and the process of evaluation is in the fledgling exercise of microbiological risk assessment fraught with numerous additional difficulties. Understandably therefore, the results of risk assessment are, more often than not, subject to different interpretations (Tennant, 1997). This might be the principal reason why optimistic expectations as to the assured forging of consensus merely by enhanced implementation of science in the course of safety evaluation are so often frustrated.
14. Even in the clearly pure scientific exercise of risk assessment there are ample opportunities, indeed it is virtually unavoidable, to introduce elements of value judgement while planning, conducting and evaluating the process of scientific testing. Taking, for example, toxicological studies; the choice of the test animal species, the strain, the sex, the age of the animals, the route and the duration of the administration of the test substance, the length of the observation period, the choice of the test parameters to be evaluated and many other factors can profoundly influence, indeed, determine the outcome of the test. Guidelines on principles and procedures pertaining to test methods and means of evaluation (e.g. statistics and risk analysis) have made substantial progress, hence, rendered important contribution to increasing coherence at the international level during recent years. Yet, subjective judgement while attempting to cultivate scientific objectivity will always remain an inevitable fact of life (Somogyi et al., 1999).
15. Taken this state of affairs, it becomes clear that, at present, it is extremely difficult, if not entirely impossible, to arrive at an international consensus concerning a numerical value of the appropriate level of consumer health protection. General safety clauses in food legislation of most of the countries participating in Codex programmes and activities uniformly mandate that food must be wholesome and safe when consumed by humans. Despite this agreement in principle, philosophies and practices are far apart from each other. This does not necessarily imply that food safety must be in jeopardy in countries with deviating systems of evaluation. It merely demonstrates that food regulatory systems are the result of a long process of relatively independent efforts of nations with vastly different scientific, legal, economical, commercial and cultural tradition. It further demonstrates clearly that regulation is, and it rightly will always be, ultimately the domain of elected and/or appointed officials bearing, in addition to science, responsibility for a number of other aspects of life in their respective constituencies. Among these responsibilities setting the level of appropriate safety is one of the most important missions those officials have to undertake. To properly exercise this function on behalf and in the interest of the citizenry, naturally, they have to be guided most importantly by science. Conversely, science-based regulation should never be misunderstood to mean science converted, at its face value, into regulation. Accepting the heterogeneity of food regulation in the world as a fact of life, attempts must be made to narrow the currently prevailing gaps. Whenever failing to agree on international guidelines and standards, progress in this field might more likely be achieved by concentrating efforts on the mutual recognition rather than on the often elusive harmonisation of the respective regulatory systems. The upcoming round of negotiations within WTO could provide the appropriate forum for launching such an attempt.
16. In this context it is worthwhile to recall that the ground rules and methods to ascertain food safety have originally been devised and implemented more on empirical than on scientific basis. By elucidating the mechanisms of potential harm to human health, science has refined the process and gave an intellectually more satisfying explanation for what was already common practice. The invention of the legendary safety factor of 100 used in the course of the determination of the Acceptable daily intake (ADI) (cf. page 8) was at best an intelligent guess at the time, yet in retrospect it was one, which has proved over the years tremendously useful in contributing to food safety. The fact that for certain categories of toxic effects (e.g. teratogenicity), based on our improved insight into the mechanisms of action, the safety factor had to be modified, is an exception that rather confirms than refutes the rule.
17. Turning to the area of food hygiene, pasteurisation, one of the most widely used and extremely effective methods of protection against foodborne health hazards of microbial origin has likewise empirical roots. Pasteurisation was introduced around the turn of the century to inactivate in milk of Mycobacterium tuberculosis var. bovis, the causative agent of bovine tuberculosis prevalent in many areas of the world at that time. It has not only fulfilled its intended purpose but, in addition, prevented foodborne infections elicited by a number of other pathogenic microorganisms. By reducing the number of saprophytic bacteria, it extended the shelf life of milk as well. Interestingly, some of these latter microorganisms have not even been known at the time when pasteurisation became a standard method in food technology.
18. These remarks are not meant to question the value or discourage the use of scientifically based risk analysis in our attempt to determine the appropriate level of protection. They merely serve the purpose to call attention to the limits of our current possibilities in this branch of science. They might also help to explain why risk assessments based on the same data, but performed by different persons and/or institutions can lead to contradicting conclusions.
19. Yet, scientific risk assessment is at present the only way to provide an objective operational basis for regulatory decisions. Consequently, in Article 5 (1) of the SPS Agreement the central role of risk assessment in reaching sanitary or phytosanitary measures is explicit: "Members shall ensure that their sanitary or phytosanitary measures are based on an assessment, as appropriate, to the circumstances, of the risk to human, animal or plant life or health taking into account risk assessment techniques developed by relevant international organisations" (World Trade Organization, 1994). Attempts to develop such techniques have been undertaken by a joint FAO/WHO Expert Consultation on the "Application of Risk Analysis to Food Standards Issues" in 1995 (FAO/WHO 1995). Similar efforts by other international and supranational organisations are currently under way. The EC in its Consumer Policy Action Plan 1999-2001 clearly spells out its commitment to international collaboration in this field. It states: "Given that hazards to consumer health and safety are truly global, a purely EU approach will not be sufficient to promote consumer interests. A consensus at international level on the many aspects of risk analysis in the field of food and product safety is needed." (Commission of the European Communities, 1998) Risk assessment has become and is further becoming mandatory in a number of regulations in a steadily increasing number of countries. While the methods are characterised more and more by homogeneity, the philosophical approach and results remain still rather heterogeneous between individual nations.
20. There are basically two schools of thought to the approach of determining the appropriate level of protection. Although the general safety clause of food regulatory systems is, as already mentioned, quite similar world-wide, risk assessment, particularly for carcinogenic substances, reveals a dichotomy between the approaches in North America and in Europe. US regulatory measures are usually based on results obtained by applying special methods of quantitative risk assessment. Data gained in animal experiments are extrapolated to the so-called virtually safe dose (VSD) with the theoretically possible incidence in humans of the particular kind of toxicity of the test substance. The numerical value of the VSD is dependent both on the toxic potency of the substance under consideration and a predetermined incidence of disease (e.g. one additional case over the spontaneous rate in 106, in 105 or in 104) deemed acceptable in exposed individuals. On the other hand, the approach preferred by, for example, the SCF is a case-by-case evaluation based on the "weight of evidence" concept (Scientific Committee for Food, 1996). By this approach, animal experiments provide equally the base of departure, but the determination of the likely carcinogenic potency of substances for humans is done by full consideration of relevant comparative toxicokinetic, toxicodynamic and toxicological data.
21. Both these major systems have definite advantages and disadvantages. Regardless of the philosophical differences, through international co-operation, a great deal of harmonisation in methodologies leading to progressively increasing convergence of results could be achieved. Nevertheless differences, partially substantial differences, are still remaining. For example, crucial questions such as the mode and extent of the application of the precautionary principle as well as the definition of legitimate factors other than science in establishing international standards still await resolution. The very fact that despite intensive debates in various international fora over a number of years no agreement could be reached on these and several other critical issues, underlines the difficult nature of the subject. This is at the same time a gauge of the patience and perseverance required for settling fundamental questions in this complex area where science, politics and economical interests are so closely intertwined. The practical consequences of failure to come to grips with decisive issues is clearly demonstrated by past and current disagreements between partners in international trade persuading them to resort to the dispute settlement mechanisms of WTO.
22. Threshold as the lowest point of the dose-response-curve is a well-established notion in pharmacology and toxicology. In the course of the safety evaluation of a large variety of chemical substances, among them food additives and chemical contaminants in food, the determination of the threshold of toxicity in animal studies is a decisive step. It lies between the no observed adverse effect level (NOEAL) and the lowest observed adverse effect level (LOAEL). Using the NOAEL, or exceptionally the LOAEL, together with a safety factor to account for differences between test animals and humans regarding the toxicity of the substance, a number of fundamental parameters used in the practical determination of safety can, according to internationally established procedures, be calculated. Most important among these parameters are the acceptable daily intake (ADI), the tolerable daily intake (TDI) or the provisional tolerable weekly intake (PTWI) (WHO, 1987; Somogyi et al., 1999).
23. The basis for the idea of the, what we consider today, threshold of regulation (TR) and the threshold of toxicological concern (TTC) has been put forward by Frawley in 1967. Ever since, numerous authors in countless publications refined the idea and in 1995 the United States Food and Drug Administration (FDA) introduced it into regulatory decision-making (FDA 1995, Cheesman and Machuga, 1997).
24. The essence of this concept is to establish a concentration and to determine an intake level which, across the boundaries of numerous chemical classes, could be tolerated in food without the necessity to test beforehand and to individually consider in the course of the customary case-by-case evaluation. This concept was devised, and is being currently applied by FDA for contaminants migrating from packaging materials into food. Following the evaluation of a substantial toxicological database, it was concluded that no adverse health affects in humans could reasonably be expected if dietary concentration of components of food contact materials remain below 0.5 ppb (1.5 g/person/day or 0.03 g/kg/bw/day).
25. The main argument for promoting this idea and for developing this concept was the goal, in face of a high number of chemical substances in current use waiting to be evaluated, to alleviate the load both for regulatory agencies and industry to deal with trivial exposure of no toxicological concern to consumers. This is in line both with the established legal concept de minimis non curat lex and the world-wide limited capacity for toxicological testing.
26. As mentioned above, the concept of threshold has long been used in the toxicological evaluation of natural constituents and contaminants of food, of food additives as well as of residues of pesticides and veterinary drugs in food. It is the experimentally established basis for calculating the amount of these chemical substances that are judged, by scientific inference, to be safe if consumed by humans via food.
27. The principal axiom of the recently introduced TR is that, even in the absence of toxicological data, a safe threshold level of intake in food for a variety of structurally and toxicologically unrelated compounds can be established below which no regulation is necessary and, consequently, required. This assertion is theoretically fully compatible with the thesis introduced in the sixteenth century by Paracelsus, the founding father of toxicology. According to him the dose alone makes a substance poisonous (i.e., toxic) clearly implying that below a certain level all toxicants are innocuous.
28. In practice, however, it is much more difficult to approach this question than in general theoretical terms. At least, as far as genotoxic carcinogens are concerned the validity of this paradigm remains to be proven. The pertinent regulation enacted by the FDA is limited to the application of this procedure to migrants from food contact materials into food and to carcinogenic endpoints. Earlier the concentration of these chemicals in food was either slightly above the limit of detection (barely detectable) or below it (practical "zero"). Consequently, it was not an issue in food safety. However, in the ensuing years as a consequence of rapid development and emergence of increasingly sensitive analytical methods, the concentration of hitherto undetectable migrating chemicals, although generally declining, could be accurately measured resulting in numerical values often with several digits. Therefore, the safety evaluation of this sort of contaminants could not be ignored anymore. Indeed, it became a problem of increasing importance and complexity. In addition, also as a result of the availability of new highly sensitive analytical methods, other contaminants at extremely low concentration could be detected. Several of these substances have been adequately tested before for other reasons than food safety, while for a number of migrants no such data were available. Therefore, the question arose whether all these substances, although consumed in minuscule amounts, should undergo traditional testing. The database for the former gave a good opportunity to investigate whether the assumption that a level of no toxicological concern could be found. Using these data, and extending the studies to other databases, numerous statistical analyses have been performed on the results of toxicological testing. They led to the conclusion that, apart from a few exceptions, the parameters established for the TR, as referred to above, are applicable for other groups of substances that are present in food at very low concentration. In fact, this principle and method were recently used in the evaluation of flavouring substances by the JECFA (Munro et al. 1999a, b).
29. In an extensive treatise Kroes et al. (1999) presented a comprehensive review of the pertinent literature and explored the possibility of expanding the scope of potential applicability of the TTC concept to a wider range of chemicals based on an increased number of toxicological endpoints. FDA's TR was limited, as already stated, to migrants of food contact materials, and the toxicological properties considered focused on non-genotoxic carcinogens. Kroes et al. investigated the question as to whether other, perhaps more sensitive toxicological parameters rather than carcinogenicity could become the limiting factor in the use of this approach. In particular, they have included a number of non-cancer endpoints, such as neurotoxicity, developmental neurotoxicity, immunotoxicity, and developmental toxicity. Analysing data derived from far broader databases than have been evaluated by earlier investigators, they have arrived at the conclusion "that none of the specific non-cancer endpoints evaluated in the present study was more sensitive than cancer and, that a TTC of 1.5 µg/person/day based on the cancer endpoint provides an adequate margin of safety."
30. The TTC is an intellectually stimulating concept with a potential for far reaching practical applicability. Despite convincing arguments supported by several thorough studies on large databases, the time for its universal use in safety evaluation of all sorts of chemical substances and practically for all purposes does not appear to have arrived yet. Rather this concept should be submitted to further rigorous scrutiny and extensive peer-review. It should remain the subject of an intensive scientific debate preferably in the framework of an international meeting with the participation of outstanding experts representing the widest possible spectrum of views in this field. Among the topics to be discussed, particularly the question should be addressed as to whether concentrations of chemicals capable of triggering physiologically discernible actions (e.g., perception of scent in fragrances or taste in flavourings) are beyond any doubt devoid of toxicological effects. In the meantime the TTC approach could well be considered as an appropriate method for setting priorities for further toxicological testing and/or evaluation of substances in question.
31. The great significance of science in regulatory decisions - not only in those related to food - is now universally recognised. The quality of scientific advice is therefore of paramount interest in any process of decision making. With the aim in mind to enhance the level and integrity of the scientific constituent of regulation many institutions underwent recent organisational changes, others are to follow. The recognition is likewise universal that science is only one, although a decisive factor of decision making. New concepts and methods in risk analysis including the precautionary principle gave during the past decade new impetus to rapid development in several areas of the evaluation of food safety. For a number of reasons discussed in this paper, the subject of food safety has, in recent years, occupied centre stage in the scientific, political and public arena.
32. Despite great progress, unresolved questions and misunderstandings hamper international efforts to mutually recognise and/or harmonise heterogeneous food regulatory systems. The failure to settle critical issues in the area of the evaluation food safety has repeatedly led in the past to controversies and caused disturbances in international trade in food. The upcoming round of negotiations within WTO should be used to clarify and, preferably, resolve a number of outstanding problems. In particular there is an urgent need to revisit the "Four Principles" referred to in the introduction. After the long-time debate on this subject, progress must now finally be made in the application of the precautionary principle and in defining the nature and role of other legitimate factors than science in decision making process. It should however be remembered that, even provided the optimal outcome of the negotiations, a blueprint for a watertight system running with flawless reliability cannot reasonably be expected to emerge. Rather, inherent in the nature of science and of commerce, the need for a well functioning dispute settlement mechanism characterised by a high level of competence, fairness and transparency will unabatedly remain. Nevertheless, progress achieved with realistic expectations in resolving the questions identified in this paper would lead to the much awaited contribution of the WTO negotiations to the enhancement of health protection of consumers as well as free and fair trade in food all over the world.
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1 This paper expresses the views merely of the author and does not necessarily reflect the opinion of the European Commission.
2 Bovine Spongiform Encephalopathy (mad cow disease)
3 Scientific Committee on Food (SCF); - Scientific Committee on Animal Nutrition (SCAN); Scientific Committee on Animal Health and Animal Welfare (SCAHAW); Scientific Committee on Veterinary Measures relating to Public Health (SCVPH); Scientific Committee on Plants (SCP); Scientific Committee on Cosmetic Products and Non-Food Products (SCCNFP); Scientific Committee on Medicinal Products and Medical Devices (SCMPMD); Scientific Committee on Toxicity, Ecotoxicity and Environment (SCTEE)