Update Project Chapter 3: Analytics and Specifications Draft May 2008 1 PRINCIPLES AND METHODS FOR THE RISK ASSESSMENT OF CHEMICALS IN FOOD 2 3 CHAPTER 3. CHEMICAL CHARACTERIZATION, ANALYTICAL 4 METHODS AND THE DEVELOPMENT OF SPECIFICATIONS FOR 5 HAZARD IDENTIFICATION AND CHARACTERIZATION AND RISK 6 MANAGEMENT 7 8 3.1 INTRODUCTION.................................................................................................................................................1 9 3.2 CONSIDERATIONS FOR LABORATORIES ............................................................................................................2 10 3.2.1 Guidance from Codex Alimentarius Commission (CAC/GL 27 - 1997)................................................2 11 3.2.2 Best practices in analytical measurement ..............................................................................................2 12 3.3 CONSIDERATIONS FOR SELECTION OF VALIDATED ANALYTICAL METHODS ....................................................3 13 3.3.1 General considerations ...........................................................................................................................3 14 3.3.2 Multilaboratory method trials and collaborative studies ......................................................................3 15 3.3.3 Routine regulatory methods....................................................................................................................4 16 3.3.4 Validation of methods in a single laboratory (the criteria approach)...................................................4 17 3.3.5 Method validation process......................................................................................................................6 18 3.4 DEVELOPMENT OF ANALYTICAL METHODS......................................................................................................6 19 3.4.1 Defining the analytical measurement requirements (fitness for purpose).............................................6 20 3.4.2 Analytical performance characteristics..................................................................................................6 21 3.5 GENERAL CONSIDERATIONS FOR USE OF ANALYTICAL METHODS IN A REGULATORY PROGRAMME FOR 22 FOODS.....................................................................................................................................................................7 23 3.6 FOOD ADDITIVES—SPECIFICATIONS ................................................................................................................7 24 3.6.1 General considerations ...........................................................................................................................7 25 3.6.2 Formulation of specifications and information requirements ............................................................... 9 26 3.6.3 Stability and fate of additives in food ...................................................................................................10 27 3.6.4 Methods of analysis...............................................................................................................................10 28 3.7 PESTICIDES—SPECIFICATIONS .......................................................................................................................11 29 3.7.1 General considerations .........................................................................................................................11 30 3.7.2 Identity and purity .................................................................................................................................13 31 3.7.3 Stability..................................................................................................................................................14 32 3.7.4 Physical and chemical properties.........................................................................................................14 33 3.7.5 Analytical methods ................................................................................................................................14 34 3.7.6 Analytical problems and challenges.....................................................................................................16 35 3.8 VETERINARY DRUG RESIDUES........................................................................................................................17 36 3.8.2 Analytical methods ................................................................................................................................17 37 3.8.3 Analytical problems and challenges.....................................................................................................18 38 3.9 CONTAMINANTS .............................................................................................................................................18 39 3.9.1 Sampling plans ......................................................................................................................................19 40 3.9.2 Analytical methods ................................................................................................................................20 41 3.9.3 Reactions and fate of contaminants in food..........................................................................................20 42 3.10 SUBSTANCES CONSUMED IN LARGE AMOUNTS ............................................................................................21 43 3.11 REFERENCES ................................................................................................................................................21 44 45 3.1 Introduction 46 Chemical characterization plays a critical role in risk assessment. Risk characterization brings 47 together the results of hazard characterization with the estimated human exposure, and these 48 should be based on data for the same chemical entity or a more complex material that has 49 been properly characterized and quantified. The report of the WHO Scientific Group on 50 Procedures for Investigating Intentional and Unintentional Food Additives indicated in 1967 51 that “adequate specifications for identity and purity should be available before toxicological 52 work is initiated. Toxicologists and regulatory bodies need assurance that the material [to be] 53 tested corresponds to that to be used in practice” (WHO, 1967). 54 Analytical methods have to be fit for purpose with respect to defining 1) the nature 55 and chemical purity of the material investigated during in vitro and in vivo hazard 1 Update Project Chapter 3: Analytics and Specifications Draft May 2008 1 identification and characterization studies and 2) the concentrations of the chemical in foods 2 in relation to regulatory limits or exposure surveys. 3 The dietary exposure (intake) of any chemical depends on the concentrations present 4 in foods and the amounts of the relevant foods consumed. For residues of pesticides and 5 veterinary drugs, the concentrations used for exposure estimates are the MRLs and maximum 6 limits (MLs) established by the JMPR and JECFA, respectively. The derivation of MRLs is 7 discussed in chapter 8. For food additives, the exposure assessment and risk characterization 8 are based on the proposed use levels for an additive in different foods. Risk characterization 9 of contaminants differs from that for other types of chemical, because there is not an 10 approved, accepted or proposed concentration in food and the exposure estimate has to use 11 actual analytical data rather than a recommended maximum limit. Methods of exposure 12 assessment are described in chapter 6. 13 Analytical requirements of the JECFA and the JMPR for food additives, pesticides, 14 veterinary drug residues, contaminants and substances consumed in large amounts are given 15 in sections 3.6, 3.7, 3.8, 3.9 and 3.10, respectively. 16 17 3.2 Considerations for laboratories 18 3.2.1 Guidance from Codex Alimentarius Commission (CAC/GL 27 - 1997) 19 The CAC has provided guidance for laboratories involved in the import/export testing of 20 foods (FAO/WHO, 1997a). This includes the recommendations that such laboratories should: 21 22 • use internal quality control procedures that comply with the Harmonized Guidelines for 23 Internal Quality Control in Analytical Chemistry Laboratories (Thompson and Wood, 24 1995); 25 • participate in proficiency testing schemes designed and conducted in accordance with the 26 International Harmonized Protocol for Proficiency Testing of (Chemical) Analytical 27 Laboratories (Thompson and Wood, 1993); 28 • become accredited according to International Organization for Standardization 29 (ISO)/International Electrotechnical Commission (IEC) Guide 25 on general requirements 30 for the competence of calibration and testing laboratories and its subsequent replacement 31 (ISO/IEC-17025, 2005); and 32 • whenever available, use methods that have been validated according to the principles laid 33 down by the CAC. 34 35 3.2.2 Best practices in analytical measurement 36 The OECD established Principles of Good Laboratory Practice (GLP) in 1978 under the 37 Special Programme on the Control of Chemicals. The Principles were formally recommended 38 for use in Member countries by the OECD Council in 1981. They were developed primarily 39 in relation to the performance of toxicology (safety) studies, but the principles related to 40 facilities, personnel, methods, data recording and quality assurance are equally applicable to 41 analytical methods. The Principles were