Implementing food-based dietary guidelines for - United Nations ...

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S28 Most of this discussion will draw on recent considerations of micronutrients [1, 2]. Additionally, there is a current international collaboration exploring systematic safety assessments of intakes of amino acids [3–5]. Toxicological risk analysis and assessment The values derived by the risk assessment are estimates of the quantity of a substance that can be ingested daily over a lifetime without appreciable risk to health and are termed health-based guidance values [6–9]. These include the acceptable daily intake (ADI) [6]) and the tolerable intake (TI), which may be weekly (TWI) or daily (TDI) [8]. The ADI is applied for estimates of safe exposure for food additives, i.e., for chemicals that are permitted to be used in foods, and the TDI relates to contaminants and pollutants. The US Environmental Protection Agency has replaced ADI and TDI with the term reference dose (RfD), which has been defined as an estimate of the daily exposure in the human population that is likely to be without an appreciable risk of deleterious effects during a lifetime. All these definitions are framed to avoid implying that they are absolutely “safe”; they are advisory (although they might subsequently be translated into regulations) and are the products of a systematic process of risk analysis, of which risk assessment is one element. Risk analysis is “a detailed examination, including risk assessment, risk evaluation and risk management alternatives, performed to understand the nature of unwanted, negative consequences to human life, health, property or the environment; an analytic process to provide information regarding undesirable events: the process of quantification of the probabilities and expected consequences of identified risks” [10]. The definitions used in the established process vary among the agencies involved, but with the maturation of the discipline and increased international and interagency harmonization, the definitions are very close and common wordings are emerging. In this process, the definition of a hazard is “the inherent property of a chemical to cause adverse effects depending upon the level of intake.” The modification of this to suit the needs of nutritional risk assessment (see above) is straightforward [1]. An adverse effect is “a change in morphology, physiology, growth, development or lifespan of an organism which results in impairment of functional capacity or impairment of capacity to compensate for additional stress or increase in susceptibility to the harmful effects of other environmental influences. Decisions on whether or not any effect is adverse require expert judgment” [7]. Again, this is little different from the definition derived for nutritional risk assessment. A risk is “the probability or likelihood that a hazard will actually cause harm to an individual or population group” In the model developed by the Food and Agriculture Organization/World Health Organization (FAO/WHO) and the Codex Alimentarius, Risk Analysis comprises three distinct steps: risk assessment, risk management, and risk communication. Although each is a distinct step, collectively they are intended to be a coherent and fluently progressive entity. This is a well-accepted model, because it provides a structure that ensures that any uncertainties, variabilities, or assumptions involved in the assessment can be identified, thereby enabling and encouraging a transparent explanation of the means by which these issues are compensated. Risk assessment P. J. Aggett In practice, the first step in risk analysis is that of “problem formulation,” i.e., setting the key purpose and objective of the exercise. Usually this is done by the risk managers and regulators who will be responsible for managing the risk of any particular exposure and communicating to the public about the risk and the strategy to manage it.. Often, but not necessarily always, problem formulation may involve consultation with those who have the task of assessing the hazards and any attendant risks. Once the problem has been set, the first phase in risk analysis, risk assessment, can start. Since this involves identifying and prioritizing hazards and the exposures at which they happen, this is the process that is most relevant for this paper. Risk assessment comprises four stages: hazard identification, hazard characterization (sometimes called dose–response assessment), exposure assessment, and risk characterization. Each is briefly described later, but in essence they involve first a full review of all relevant information and a qualitative identification and evaluation of all adverse effects associated with high exposures (hazard identification), followed by a quantitative estimation of risk for each adverse effect (hazard characterization). Assessment of dose–response often includes a modeling exercise to extrapolate from high to low levels of exposure. Hazard identification, as the determination of the relationship between the exposure to the chemical and one or more associated adverse effects, needs a full appraisal of information to characterize the absorption, systemic distribution, metabolism, and elimination (i.e., toxicokinetics) of the chemical and the toxic effects that the chemical, or its metabolites, may have at tissue and cellular functional levels (i.e., toxicodynamics). Both human and animal model data are used. Some of these are systematically acquired through specific studies (table 1), and this applies particularly to chemicals that are proposed as food additives. Other data may be acquired more opportunistically, such as from case studies and incident reports. This is more
Setting upper levels for nutrient risk assessment TABLE 1. Current tests and endpoints used in toxicology a Study type Endpoints measured 30-day study Clinical signs, mortality Body weight, body weight gain, organ weights Food consumption, water consumption Hematology and clinical chemistry Urinalysis Macroscopic/microscopic histopathology 90-day study Clinical signs, mortality Body weight, body weight gain, organ weights Food consumption, water consumption Hematology and clinical chemistry Urinalysis Macroscopic/microscopic histopathology 2-yr/lifetime study Clinical signs, mortality Body weight, weight gain, organ weights Food consumption, water consumption Hematology and clinical chemistry Urinalysis Macroscopic/microscopic histopathology Developmental toxicology Reproductive toxicology(multigenerational study) often the case for contaminants and pollutants. As a principle, wherever possible, data from human experimental or observational and epidemiologic studies are preferred. Commonly in toxicology the critical “adverse effect” refers to an unambiguously demonstrable adverse event, rather than a phenomenon that might be regarded as adaptive [8]. This selection is part of the hazard characterization, but in practice there would be some iteration between this and the preceding hazard identification. The regulatory assessment of applications by producers to add a chemical to a food requires an extensive database. This would be expected to include toxicokinetic information from studies in animals and Dams Clinical signs, mortality Body weight, body weight gain Food and water consumption Macroscopic/microscopic histopathology Fetal data Numbers of corpora lutea and implantations Numbers of viable fetuses and resorptions Sex ratio, fetal and litter weights Skeletal and visceral examination Parental Clinical signs, mortality Body weight, body weight gain Fertility Macroscopic pathology Histopathology of reproductive organs Litter/pup data Litter size, numbers of live and dead pups Pup sex Pup weight, pup organ weights Pup macroscopic/microscopic pathology a. In addition to these toxicologic studies, studies of absorption, distribution, metabolism, and excretion are usually undertaken. Furthermore, tests of mutagenicity are carried out both in vitro and in vivo. S29 perhaps in humans, and acute, short-term, repeateddose studies in two animal species. These are listed in table 1. Occasionally, but not usually for food additives, tests relevant to skin sensitivity and allergenicity may be required. Information from metabolic and toxicokinetic studies can help determine whether adverse effects are caused by the parent compound or by its metabolites, and also provide information that would characterize interspecies and interindividual differences in toxicokinetics and toxicodynamics and susceptibility to adverse effects. It is customary to assess the quality of all published data and to consider their “totality” and coherence. Data that have been peer reviewed and produced in
Page 1 and 2: Contents International harmonizatio
Page 3 and 4: Executive summary Harmonization of
Page 5 and 6: Executive summary [11]. These are l
Page 7 and 8: Executive summary and converted to
Page 9 and 10: Executive summary very rapidly and
Page 11 and 12: Executive summary References Concep
Page 13 and 14: Introduction Janet C. King and Cutb
Page 15 and 16: Introduction References 1. King JC,
Page 17 and 18: Terminology and framework for nutri
Page 27: Nutrient risk assessment: Setting u
Page 31 and 32: Setting upper levels for nutrient r
Page 39 and 40: Establishing nutrient intake values
Page 51 and 52: Methods for using nutrient intake v
Page 53 and 54: Using nutrient intake values to ass
Page 61 and 62: Determining life-stage groups and e
Page 63 and 64: Life-stage groups and nutrient inta
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Diet- and host-related factors in n
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Human nutrition and genetic variati
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Application of nutrient intake valu
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Trade, development, and regulatory
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Beyond recommendations: Implementin
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Dietary guidelines and nutrient int
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International Dietary Harmonization
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