ALICOM 99/19  |
| ALICOM 99/19 |
Conference on International Food Trade
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Assuring Science-Based Decisions: Expert Advice and Risk Analysis - Validity of the Process and Dealing with Uncertainty |
by |
John L. Herrman and Nobumasa Nakashima,
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II. Expert advice at the international level
A. The importance of scientific advice to Codex
B. Joint FAO/WHO Expert Committee on Food Additives (JECFA)
C. Joint FAO/WHO Meeting on Pesticide Residues (JMPR)
D. Expert advice on risk assessment of microbiological hazards
1. All decisions on food safety should be based on sound scientific analysis. This requires characterization of the substance or biological organism, appropriate scientific investigations, and evaluation by an unbiased group of competent scientific experts. Final decisions on the establishment of standards or guidelines include decisions about the necessary level of protection of public health.
2. In recent years risk assessment, risk management, and risk communication have been formalized and incorporated into a process called risk analysis. Several FAO/WHO consultations have been held to lay out the principles and develop methods for risk analysis (1,2,3).
3. This paper emphasizes the increasing importance of independent scientific advice in the risk analysis process at national and international levels. The conclusions and recommendations emphasize initiatives that should be taken to strengthen the process to ensure that the needs of the Codex and governments are being met.
4. WHO and FAO have a long history of providing advice to Member States and the Codex Alimentarius Commission relating to the safety of chemicals in food. The Joint FAO/WHO Expert Committee on Food Additives (JECFA) has been meeting regularly since 1956 to evaluate food additives, contaminants, and residues of veterinary drugs in foods. Fifty-three meetings have been held to date, during which time more than 1300 food additives, approximately 25 contaminants and naturally occurring toxicants, and approximately 80 veterinary drugs have been evaluated. Based on the large number of food additives and contaminants identified by the Codex Committee on Food Additives and Contaminants (CCFAC) each year that require evaluation, JECFA will have a great deal of new work to do during the next few years.
5. The Joint Meeting of the FAO Panel of Experts on Pesticide Residues in Food and the Environment and the WHO Core Assessment Group, which comprises the Joint FAO/WHO Meeting on Pesticide Residues (JMPR), has been meeting yearly since 1963. Approximately 220 pesticides have been evaluated. Pesticides are being re-evaluated under a periodic review programme that is coordinated by the Codex Committee on Pesticide Residues (CCPR). Much work is yet to be done, and JMPR schedules are full through 2001 for toxicological evaluations and through 2002 for residue evaluations.
6. Microbiological agents have not until recently been the subject of systematic risk analysis by the Codex Alimentarius Commission. Foods have, however, been studied on a case-by-case basis when potential pathogens have been identified as being of concern to public health and international trade. Since the mid-1970s the Codex Committee on Food Hygiene (CCFH) has used a qualitative approach in identifying foodborne hazards, the recommendations of which have been in the form of Codes of Hygienic Practice, often supplemented by advisory microbiological specifications that are used to verify that the control processes described in the code have been carried out properly. Recently CCFH has recognized the need for independent scientific advice on foodborne microbiological hazards for assisting in risk management.
9. The first meetings of JECFA were held in response to a recommendation of a FAO/WHO Conference on Food Additives that was held in Geneva in 1955 (4) to consider means by which chemical additives in food could be properly assessed on an international scale. Among the recommendations made to the Directors-General of FAO and WHO was to convene one or more expert committees that would be concerned with the technical and administrative aspects of the problem of chemical additives in food.
10. A second Joint FAO/WHO Conference on Food Additives was held in Rome in 1963 (5) to (a) review the work of JECFA; (b) consider the future programme on food additives; and (c) discuss JECFA's relationship with, and contribution to, the newly-established Joint FAO/WHO Programme on Food Standards. The Conference reinforced the importance of this work and recommended that JECFA, which is a technical committee of specialists acting in their individual capacities, should serve as the advisory body to the Codex Alimentarius Commission on all scientific matters concerning food additives. JECFA works closely with CCFAC in this endeavour.
11. A third Joint FAO/WHO Conference on Food Additives and Contaminants met in Geneva in 1973 (6) to review the work carried out by JECFA during the period 1963-1973, to discuss the future work of JECFA, and to recommend priorities. The primary recommendation of this Conference was to expand JECFA's terms of reference to include the evaluation of food contaminants.
12. At the Sixteenth Session of the Codex Alimentarius Commission in 1985 (7) the Codex Committee on Residues of Veterinary Drugs in Foods (CCRVDF) was established. At that time the Commission asked FAO and WHO to consider convening an appropriate expert body to provide independent scientific advice to the Committee. In response to this recommendation, FAO and WHO agreed that JECFA will serve as the scientific advisory body to CCRVDF.
13. A Joint FAO/WHO Conference on Food Standards, Chemicals in Food and Food Trade was held in Rome in 1991 to, inter alia, review the work of JECFA and to propose future areas of work. The Conference stressed the importance of the work of JECFA to both the Codex Alimentarius Commission and to Member States and recommended that the terms of reference of the Committee be expanded to include review of food products derived from contemporary biotechnology. Since that time JECFA has evaluated several enzyme preparations and other food additives produced by genetically modified microorganisms and recombinant bovine somatotropins.
14. The Secretariat announces its meetings well in advance and invites organizations and individuals to submit information on the substances to be considered and the Committee reviews the toxicological and related data that have been submitted as well as other information identified in literature reviews. The usual endpoint of evaluation is the acceptable daily intake (ADI), which is derived from the most relevant no-observed-effect level in an appropriate animal study with a safety factor, usually 100, applied to it to account for interspecies extrapolation and variation within human populations.
15. When considering food additives, specifications for their identity and purity are developed to ensure that the product in commerce is of appropriate quality and that it corresponds to the product that was tested for safety. The intakes of food additives and contaminants are also assessed. When evaluating veterinary drugs data relating to good practice in the use of veterinary drugs are reviewed and maximum residue limits (MRLs) in various edible animal tissues (muscle, liver, kidney, fat, milk, and/or eggs) are recommended, which provide assurance that the drug has been used properly and that intake of drug residues is unlikely to exceed the ADI.
16. JECFA establishes principles for the safety evaluation of substances that it evaluates at each meeting. A document was published in 1987 that updated and consolidated the principles for the safety assessment of food additives and contaminants (8). A document that consolidates the principles that have been established for the evaluation of residues of veterinary drugs in food will be available soon.
17. The first meeting of JMPR was convened on the basis of a recommendation of a Joint Meeting of the FAO Panel of Experts on the Use of Pesticides in Agriculture and the WHO Expert Committee on Pesticide Residues that was held in 1961 (9) to evaluate the "toxicological and other pertinent data . . . on those pesticides known to leave residues in food when used according to good agricultural practice". At the first two Meetings only the toxicological aspects of pesticides were considered, and since 1966 the Joint Meeting has also reviewed residue and analytical data, including data on their metabolism, fate in the environment, and use patterns, and for recommending MRLs for pesticides when used according to good agricultural practice. The toxicological endpoint is the ADI, which is established using the same general principles as for food additives.
18. Governments must be assured that the intake of residues of the pesticide will not exceed the ADI if the MRLs recommended by JMPR are adopted. A great deal of effort in recent years has gone into predicting the dietary intake of pesticide residues, the guidelines of which were revised in 1997 (10) "Regional" diets based on FAO food balance sheet data are used for estimating per capita consumption of raw and semi-processed agricultural commodities (11). Earlier predictions were based on a screen approach in that it was assumed in the first instance that the MRL represents the residue level (which is a vast overestimate of the average residue level). The estimates were then refined for those pesticides that did not pass the screen. The revised guidelines recommend a more refined approach from the beginning in that supervised trial median residue (STMR) levels are used when available. The STMR level is estimated as the median of the residue values (one from each trial) from supervised trials conducted according to maximum Good Agricultural Practice conditions.
19. The importance of estimations of acute toxicity for the acceptance of MRLs is recognized more now than in the past. JMPR establishes acute reference doses (acute RfDs) when considered appropriate, and beginning in 1998 this possibility is considered whenever a pesticide undergoes a full review(12). Methods for predicting the intake of pesticide residues to compare with the acute RfD are being developed, as recommended at a Joint FAO/WHO Consultation that was held in 1997(13) .
20. JMPR establishes principles for the toxicological evaluations of substances that it evaluates at each meeting. A document was published in 1990 that updated and consolidated the principles for the toxicological assessment of pesticide residues in food (14) An FAO manual on the submission and evaluation of pesticide residues data for the estimation of maximum residue levels in food and feed has also been published(15) .
21. Increasing international trade in food enhances the risks of transmission of infectious agents and underscores the need for assessing such risks to human health. At its Twenty-second Session, the Codex Alimentarius Commission (16) "requested FAO and WHO to convene an international expert advisory body similar to JECFA and JMPR on the microbiological aspects of food safety to address particularly microbiological risk assessments". In response to this recommendation, FAO and WHO convened an Expert Consultation on Risk Assessment of Microbiological Hazards in Food in Geneva, which was held from 15 to 19 March 1999. The Consultation was a first step toward providing expert scientific advice to FAO, WHO, Member States, and Codex relating to microbiological hazards in food.
22. The risk assessment process was originally developed for chemicals. Extending the practice to microbial pathogens1 poses significant difficulties. One difficulty relates to the fact that microbial pathogens can multiply as food moves from the farm to the table, making intake assessment very difficult. In addition, many data gaps exist, limiting the precision necessary for quantitative risk assessments. For example, little information is available to accurately estimate the relationship between the quantity of a biological agent and the frequency and magnitude of adverse human health effects, particularly for susceptible populations.
23. Methods being developed rely upon mathematical models to describe the introduction of pathogens into food, their replication in food over time, their destruction by heat treatment, their consumption in food, and subsequent illness. Both variability and uncertainty can be described by probability distributions. Control strategies can be modeled in the same way and the cost and benefit (in terms of illness prevented) can be compared.
24. Risk analysis is generally understood to consist of three components: risk assessment, risk management, and risk communication.
25. Risk assessment consists of four steps. These have been defined by the Codex on an interim basis as follows (17):
26. Codex defines risk management (17) as "the process, distinct from risk assessment, of weighing policy alternatives, in consultation with all interested parties, considering risk assessment and other factors relevant for the health protection of consumers and for the promotion of fair trade practices, and, if needed, selecting appropriate prevention and control options". The Consultation on Risk Management and Food Safety (2) identified four elements of risk management:
27. Risk communication is defined by the Codex (17) as "the interactive exchange of information and opinions throughout the risk analysis process concerning risk, risk-related factors and risk perceptions, among risk assessors, risk managers, consumers, industry, the academic community and other interested parties, including the explanation of risk assessment findings and the basis of risk management decisions".
28. Within the FAO/WHO/Codex system, scientific committees such as JECFA and JMPR assess risks, while Codex manages risks. All participants in the process are responsible for risk communication.
29. Risk assessments by scientific committees should be science-based, quantitative, explained clearly, and thoroughly documented. The risk assessment should identify any attendant uncertainties and their sources where appropriate, including deficiencies in available information. The risk assessment should also identify the potential risks to vulnerable populations (e.g. children, women of childbearing age, and the elderly).
30. The establishment of the ADI or other point estimates such as provisional tolerable daily or weekly intakes by scientific committees is generally considered to represent a safety assessment. Such safety assessments involve the first two steps of the risk assessment process, wherein the hazard has been identified and characterized through a dose-response assessment. There is considered to be no appreciable health risk so long as intake does not exceed the ADI over a long period of time.
31. All countries face the need to assess the risks of chemicals and biological agents in food, but few scientific institutions have the resources to undertake such assessments at the present time. Thus, many countries use the information developed by scientific committees such as JECFA and JMPR, both on the general aspects of risk assessment and on specific chemicals, in their regulatory programmes. In addition, institutions in countries that are active in risk assessment are seeking ways to share the work, and assessments performed by FAO and WHO scientific groups are of great value to these institutions. Work in the international arena to harmonize methods used for risk assessment increase confidence in the evaluations of other countries and organizations.
32. Toxicological evaluations are applicable globally. If sensitive population groups have been identified as being at particular risk by the scientific group, this should be taken into account at the national level. Because of varying national conditions, risk management decisions may vary considerably from one country to another. Malnutrition has sometimes been identified as a possible confounding factor, but unfortunately data relating to this factor are usually lacking.
33. Risk assessment policy may differ from one country to another, resulting in varying scientific conclusions. How mechanistic data are used or whether mathematical modeling rather than a safety factor approach is used are two examples of different risk assessment policies. In the project on Harmonization of approaches to the assessment of risk from exposure to chemicals coordinated by the International Programme on Chemical Safety (IPCS), it was realized early on that it is unrealistic to expect that everyone will use the same risk assessment policy. Instead, harmonization has been defined as an understanding of the methods and practices used by various countries and organizations so as to develop confidence in and acceptance of assessments that use different approaches. This requires scientific groups to thoroughly document the basis for their recommendations so that they can be adapted to differing local conditions and risk assessment policies.
34. Intake assessments performed at the international level provide a barometer of the magnitude of likely intake, which is useful for governments in deciding whether proposed international standards are acceptable. However, if the margin between intake and levels that may present a safety problem is small, governments need to characterize the risk based on their own consumption patterns and residue levels in food, taking into account people who consume high amounts of products that contain the substance.
35. Predictions of the intake of pesticide residues by JMPR are based on Codex MRLs (or those being considered as Codex MRLs), and the range of commodities may not be the same as at the national level. Thus, if a detailed intake assessment is considered necessary, commodities registered at the national level should be used as the basis for the assessment.
36. Pesticide use varies from one area to another because of varying climatic and pest conditions. JMPR evaluates field trial data from around the world, which represent a much wider range of conditions than will be found when national or regional data are evaluated. Thus, the MRLs recommended by JMPR are often higher than those in national regulations. This should not automatically be seen as representing a safety problem, because MRLs are not based on safety data. In most cases intake will be well below the ADI when the higher MRL is accepted, but this can only be determined by assessing the intake.
37. Risk management should be functionally separate from risk assessment. However, risk assessors and risk managers should communicate with one another in an iterative process to ensure that the questions asked by the risk managers are understood and addressed. This is difficult in practice within the Codex system because of the long period of time between meetings of Codex and scientific committees. Thus, it is extremely important that Codex committees explain their priorities and requests for evaluation very clearly to the secretariats of the scientific committees the first time around.
38. The Consultation on Risk Management and Food Safety (2) identified several risk assessment policies that JECFA and JMPR use at specific decision points in their work:
39. The report goes on to say:
In carrying out their work the experts in JECFA and JMPR continually need to select and utilise various scientific assumptions. This is necessary because there are inevitable gaps in the science of risk assessment that need to be filled with default assumptions in order to be able to conduct a risk assessment. These assumptions also need to be constantly re-evaluated to keep them up-to-date with scientific developments. Each of these represent scientific value judgements ("risk assessment policy"), and the assumptions embodied in them can significantly influence the outcome of the risk assessment. Each also represents a choice among a number of plausible alternatives.
40. The Consultation recommended that "the Codex Alimentarius Commission should make explicit the role of CCFAC, CCRVDF, and CCPR in providing clear and unequivocal risk assessment policy guidance to JECFA and JMPR. This should include acknowledgement of the continuing need for risk assessment choices by JECFA and JMPR, but provide guidelines for value judgements and policy choices which may need to be applied in the risk assessment process."
41. The relevant Codex committees and JECFA and JMPR have considered this recommendation. A confounding issue that the scientific committees have identified in their discussions is that, although most of their priorities come from the Codex, requests for evaluations also come from Member States and FAO and WHO. Inconsistencies would result if risk assessment policy were to be set by all of these organizations.
42. Scientists generally regard the size of the safety factor to be a scientific decision and jealously guard it as their prerogative. The imposition of a rigid safety factor for teratogenicity or the protection of infants and children, for example, does not permit the use of scientific judgement based on the available data. An implicit risk assessment policy that has been in effect for many years in the Codex system for food additives, pesticide residues, and residues of veterinary drugs is that ADIs should be established that represent no appreciable health risk. The scientific committee decides on the appropriate safety factor to accomplish this goal.
43. The evaluation of contaminants, naturally occurring toxicants, and microbiological agents presents different problems. JECFA has traditionally established tolerable daily or weekly intakes for contaminants, and when the margin between the tolerable intake and toxic effects is narrow has recommended that levels be kept as low as reasonably achievable (ALARA). Safety factors have often been quite small, because the Committee recognizes that elimination of the contaminant from the food supply may entail loss of a major nutritious food item.
44. This approach has been criticized as mixing risk assessment and risk management, and it has been argued that a better approach is to identify risks at various levels of intake so that the risk manager can decide on the appropriate level of protection that can reasonably be achieved within the population based on risk-risk and risk-benefit considerations. JECFA used this approach when evaluating aflatoxins at its forty-ninth meeting (18) wherein potencies were estimated in individuals who carry hepatitis B virus and those who do not. Population risks based on intake data available at the meeting and hypothetical standards were calculated. These population risks are presented as examples, and when deciding on a standard the risk manager should use consumption and contamination patterns and incidence of hepatitis B in his country, in conjunction with the potency estimates of JECFA.
45. Estimating risk at various levels of intake is an inexact science and is very difficult in practice. In most cases it relies upon the use of mathematical models and the use of epidemiology data are necessary to avoid extrapolation from low-doses, which carries with it the inherent problem of the conclusions being highly dependent upon the model that is used. Nonetheless, JECFA intends to use this approach to the extent possible in the future.
46. Both uncertainty and variability confound the risk assessment process. Variability represents heterogeneity within biological systems and populations, while uncertainty represents a lack of precise knowledge.
47. Uncertainty and variability arise at all steps of the risk assessment process (1):
48. An important step in the risk assessment process is the characterization of uncertainties. In the ideal situation, a three-tiered uncertainty analysis is performed:
49. While it is recognized that quantitative estimates of uncertainty that are generated by such analyses are of great value to risk managers, the state of the art based upon information that is currently available permits only a qualitative uncertainty analysis for most agents. All sources of uncertainty and variability that have been identified and their likely impact on the characterization of risk should be clearly presented by the risk assessors.
50. Expert scientific advice on chemical and microbiological agents in food is essential to the development of sound food standards. Considering the increasing importance of Codex standards and the recognition that health should be the primary consideration in risk management decisions (2), it is essential that food standards be based on credible risk assessments performed by competent independent scientists.
51. The safety assessments by JECFA and JMPR of traditional food additives, veterinary drugs, and pesticides have generally been accepted and the recommendations have been adopted by the Codex. However, the evaluations of substances involved in trade disputes and modern biotechnological processes, such as hormones used in beef production and recombinant bovine somatotropins, have not been so widely accepted. The problems lie not so much with the interpretation of the data as with the conservatisms that should be used, with some governments calling for use of the "precautionary principle", which has not been defined by Codex. Even if governments do not agree with the recommendations of JECFA or JMPR, they should be able to make use of their evaluations so long as the bases for the conclusions are clearly explained.
52. Because risk managers need information on risks of contaminants and naturally occurring toxicants at various levels of intake rather than point estimates, JECFA is changing the way that it evaluates such substances. This is a resource-intensive activity and requires a clear indication from the risk manager, either CCFAC or a Member State, as to the questions that should be answered.
Recommendation 1: Codex committees, when referring chemical or biological agents to scientific committees for assessment, should clearly indicate what they want. Particularly for controversial agents, guidance should be provided to the scientific committee on the risk assessment policy that should be applied. Scientific committees have the responsibility to explain clearly the basis for their assessments.
53. The credibility of the risk analysis process depends upon the independence and competency of the experts that provide scientific advice. At the present time members are required to inform the secretariat of any potential conflicts of interest. While FAO and WHO have full confidence in the experts that have been serving on JECFA and JMPR, measures must be taken to ensure that users of the evaluations share this confidence.
54. The base of scientific experts available to FAO and WHO should be expanded. A problem for the Secretariat is that it is very difficult to identify experts to serve on scientific committees, despite several attempts in recent years to expand the roster. Help is needed from FAO and WHO Member States to do so. The fact that scientific group meetings are conducted in English limits the range of experts that can participate. However, due to the high cost and difficulty communicating intricate scientific nuances through interpretation, simultaneous interpretation is impractical
Recommendation 2: FAO and WHO be encouraged, with the help of Member States, to expand the range of experts who serve on scientific committees and to consider tightening their conflict of interest requirements.
55. Resources for JECFA and JMPR are very tight, and with the need for expert advice on microbiological hazards and the increasing complexity of the evaluations, the problem is likely to worsen. Most of the funds that WHO uses for these activities are from extrabudgetary sources that may not continue in the future.
Recommendation 3: Member States should find a means to increase resources to FAO and WHO for risk assessments of chemical and microbiological agents in food.
56. Human resources are needed in addition to financial resources for the conduct of risk assessments. Members of FAO and WHO scientific committees are selected on the basis of their specialized knowledge on the particular subject for which they are selected. They serve in their personal capacities, and not as representatives of their governments. Other than a return ticket and a per diem allowance for their expenses at the meeting, there is no payment to them or their employer (usually a government agency) for their working time at the meeting or for the preparatory work that they perform, which usually is extensive, prior to the meeting.
57. When the government agency provides time for this work, the expertise and working time of the experts are, in effect, national contributions to FAO and WHO. Unfortunately, in many cases working time is not provided, which requires that the scientist use his personal time for the preparatory work.
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1) Including risks arising from the presence of bacterial, viral, protozoal, fungal organisms, or their metabolites in food.