- Email: [email protected]
50 Novel estimates of the exposure to flavouring substances
s16
Workshop W5. Safety evaluation of flavourings
programme a project on Food Safety in Europe (FOSIE): Risk Assessment of Chemicals in Food and Diet. One expert group within this project carried out a thorough and comprehensive investigation on the assessment of intake from the diet. In the case of chemicals in food this is based on three major aspects: (i) how to determine quantitatively the presence of a chemical in individual foods and diets including its fate during the processes within the food production chain; (ii) how to determine the consumption patterns of the individual foods containing the relevant chemicals and (iii) how to investigate both the likelihood of consumers eating large amounts of the given foods and of the relevant chemical being present in these foods at high levels. A critical review of the techniques used for the evaluation of these three aspects has been undertaken to determine those areas where the current approaches provide a solid basis for assessments and those areas where improvements are needed. In all three areas, the limitations of the approaches currently used lead to uncertainties, which can either cause an over- or underestimation of real intakes and thus risks. The expert group recommends using worst-case scenarios by applying conservative screening methods as a first step. In cases where these relatively crude tools predict a toxicologically significant exposure more sophisticated methods are needed to provide more accurate intake estimates.
W5 Safety evaluation of flavourings 49
THE SAFETY EVALUTATION OF FLAVOURS: CHALLENGES AND APPROACHES
Robert L. Smith. Biological Chemistry & Molecular Toxicology, Imperial College London, United Kingdom, SW7 2AZ There is nowadays general agreement that the conventional toxicological approaches are inappropriate for the safety evaluation of food flavour materials. The reasons for this are: (a) the large number of flavour substances in commercial use; massive resources would be needed should the evaluations be conducted using conventional procedures (b) the use-levels of many flavour substances amount to a few kg/year and there is inadequate economic base to support conventional assessment (c) human levels of exposure through the food are generally very low and self-limiting (d) there is a history of exposure to many naturally occurring flavour materials through food consumption (e) the majority of flavours belong to simple chemical classes devoid of ’structural alerts for toxicity’ although there are a few exceptions to this. With these facts in mind, several governmental (e.g. U.S.FDA, Europeans S.C.F. and JECFA) and non-governmental (FEMA Expert Panel) agencies have explored and developed non-traditional paradigms for the safety evaluation of food flavours. There is now a high degree of commonality in the various approaches but there are also some differences. These approaches take advantage of the fact that the majority of flavours belong to well-defined chemical groups where there exists a reasonable homology in terms of toxicity and metabolic fate. The goal of this symposium is to explore some of these differences and, in particular, to review the different ways at evaluating exposure and also to consider the applicability of some more recently derived concepts for assessing flavour safety. The key questions to be addressed are as follows: Assessment of exposure to flavours: What are the most appropriate methodologies; are there sub-groups of exposed people that require special attention? Thresholds and their utility: Are there robust thresholds for toxicity/carcinogenicity/saturation of metabolic pathways and metabolic switching and can these be used for safety assessment purposes? How can the safety of natural flavour complexes be evaluated: There are about 400 of these materials in current use as flavours; is there a need for a new paradigm for these materials?
1. Assessment of exposure to flavouring agents and natural flavour mixtures 50
NOVEL ESTIMATES OF THE EXPOSURE TO FLAVOURING SUBSTANCES
P. Cadby. Department of Product Safety and Regulatory Affairs, Firmenich SA, Geneva, Switzerland There are thousands of flavouring substances and hundreds of ways of consuming them. It is consequently impossible to carry out detailed analysis of the consumption patterns of each one, so as a result, it is necessary to find more practical and conservative methods for assessing exposure. Two studies have compared the suitability of one method: the Maximised Survey-derived Daily Intake (MSDI). In one of these studies, the MSDI-estimated intakes of 9 flavouring substances and one spice oleoresin were compared with detailed dietary intakes calculated over a 14 day period using frequency of eating, portion sizes, levels of the flavouring substance and probability of presence in a particularly food item. In a second study, the MSDI-estimated intakes of 12 flavouring substances were compared with intakes calculated using a stochastic model. This model used real levels in over 40,000 flavour formulae used in 31 different categories of food for which the intakes of males in the 16–24 year age group had been surveyed. In both of these studies, the ability of the MSDI to accurately but conservatively estimate upper percentile intakes was demonstrated. This stochastic method offers an opportunity to test whether the MSDI can also be used to estimate the intakes of the volatile constituents that are common to a number of different botanically-derived flavouring materials and food ingredients. 51
SAFETY EVALUATION OF NATURAL FLAVOUR COMPLEXES
V.J. Feron 1 , T.B. Adams 2 , S. Cohen 3 , J. Doull 4 , J.I. Goodman 5 , R.L. Hall 6 , L.J. Marnett 7 , I.C. Munro 8 , P.S. Portoghese 9 , R.L. Smith 10 , W.J. Waddell 11 , B.M. Wagner 12 . 1 TNO Nutrition and Food Research, Zeist, The Netherlands, 2 Scientific Secretary of the FEMA Panel Flavor & Extract Manufacturers Association, Washington, DC, USA, 3 Nebraska Medical Center, University of Nebraska, Omaha, NB, USA, 4 Dept. of Pharmacology and Toxicology, University of Kansas Medical Center, Kansas City, KS, USA, 5 Dept. of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, USA, 6 Towson, MD, USA, 7 Dept. of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, USA,8 CanTox Health Sciences International, Mississauga, ON, Canada, 9 Dept. of Medicinal Chemistry, University of Minnesota, Minneapolis, MN, USA, 10 Div. of Biomedical Sciences, Section of Molecular Toxicology, Imperial College School of Medicine, South Kensington, London, UK, 11 Dept. of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY, USA, 12 New York University School of Medicine, New York, B.M. Wagner Associates, Milburn, NJ, USA Natural flavour complexes (NFCs) are chemical mixtures obtained by applying physical separation methods to botanical sources such as pulp, peel, vegetables and spices. Many of the approximately 300 NFCs have a food origin. To date no scheme that allows the safety evaluation of NFCs has been developed by any agency, governmental or non-governmental. In this presentation, such a scheme, “The Naturals Paradigm”, will be discussed. The scheme is intended only for the safety evaluation of NFCs derived from higher plants to be used as flavouring substances for food and beverages. The scheme begins with a review of data on the history of dietary use of the NFC, and describes its chemical composition to ensure that the commercial product conforms to the composition limits that define the product. Next the paradigm assigns each known constituent to one of three structural classes of toxic potential, each class with its own exposure threshold of toxicological concern. Moreover, each constituent is assigned to one of some 30 congeneric groups. In subsequent steps, for each congeneric group
Workshop W5. Safety evaluation of flavourings
programme a project on Food Safety in Europe (FOSIE): Risk Assessment of Chemicals in Food and Diet. One expert group within this project carried out a thorough and comprehensive investigation on the assessment of intake from the diet. In the case of chemicals in food this is based on three major aspects: (i) how to determine quantitatively the presence of a chemical in individual foods and diets including its fate during the processes within the food production chain; (ii) how to determine the consumption patterns of the individual foods containing the relevant chemicals and (iii) how to investigate both the likelihood of consumers eating large amounts of the given foods and of the relevant chemical being present in these foods at high levels. A critical review of the techniques used for the evaluation of these three aspects has been undertaken to determine those areas where the current approaches provide a solid basis for assessments and those areas where improvements are needed. In all three areas, the limitations of the approaches currently used lead to uncertainties, which can either cause an over- or underestimation of real intakes and thus risks. The expert group recommends using worst-case scenarios by applying conservative screening methods as a first step. In cases where these relatively crude tools predict a toxicologically significant exposure more sophisticated methods are needed to provide more accurate intake estimates.
W5 Safety evaluation of flavourings 49
THE SAFETY EVALUTATION OF FLAVOURS: CHALLENGES AND APPROACHES
Robert L. Smith. Biological Chemistry & Molecular Toxicology, Imperial College London, United Kingdom, SW7 2AZ There is nowadays general agreement that the conventional toxicological approaches are inappropriate for the safety evaluation of food flavour materials. The reasons for this are: (a) the large number of flavour substances in commercial use; massive resources would be needed should the evaluations be conducted using conventional procedures (b) the use-levels of many flavour substances amount to a few kg/year and there is inadequate economic base to support conventional assessment (c) human levels of exposure through the food are generally very low and self-limiting (d) there is a history of exposure to many naturally occurring flavour materials through food consumption (e) the majority of flavours belong to simple chemical classes devoid of ’structural alerts for toxicity’ although there are a few exceptions to this. With these facts in mind, several governmental (e.g. U.S.FDA, Europeans S.C.F. and JECFA) and non-governmental (FEMA Expert Panel) agencies have explored and developed non-traditional paradigms for the safety evaluation of food flavours. There is now a high degree of commonality in the various approaches but there are also some differences. These approaches take advantage of the fact that the majority of flavours belong to well-defined chemical groups where there exists a reasonable homology in terms of toxicity and metabolic fate. The goal of this symposium is to explore some of these differences and, in particular, to review the different ways at evaluating exposure and also to consider the applicability of some more recently derived concepts for assessing flavour safety. The key questions to be addressed are as follows: Assessment of exposure to flavours: What are the most appropriate methodologies; are there sub-groups of exposed people that require special attention? Thresholds and their utility: Are there robust thresholds for toxicity/carcinogenicity/saturation of metabolic pathways and metabolic switching and can these be used for safety assessment purposes? How can the safety of natural flavour complexes be evaluated: There are about 400 of these materials in current use as flavours; is there a need for a new paradigm for these materials?
1. Assessment of exposure to flavouring agents and natural flavour mixtures 50
NOVEL ESTIMATES OF THE EXPOSURE TO FLAVOURING SUBSTANCES
P. Cadby. Department of Product Safety and Regulatory Affairs, Firmenich SA, Geneva, Switzerland There are thousands of flavouring substances and hundreds of ways of consuming them. It is consequently impossible to carry out detailed analysis of the consumption patterns of each one, so as a result, it is necessary to find more practical and conservative methods for assessing exposure. Two studies have compared the suitability of one method: the Maximised Survey-derived Daily Intake (MSDI). In one of these studies, the MSDI-estimated intakes of 9 flavouring substances and one spice oleoresin were compared with detailed dietary intakes calculated over a 14 day period using frequency of eating, portion sizes, levels of the flavouring substance and probability of presence in a particularly food item. In a second study, the MSDI-estimated intakes of 12 flavouring substances were compared with intakes calculated using a stochastic model. This model used real levels in over 40,000 flavour formulae used in 31 different categories of food for which the intakes of males in the 16–24 year age group had been surveyed. In both of these studies, the ability of the MSDI to accurately but conservatively estimate upper percentile intakes was demonstrated. This stochastic method offers an opportunity to test whether the MSDI can also be used to estimate the intakes of the volatile constituents that are common to a number of different botanically-derived flavouring materials and food ingredients. 51
SAFETY EVALUATION OF NATURAL FLAVOUR COMPLEXES
V.J. Feron 1 , T.B. Adams 2 , S. Cohen 3 , J. Doull 4 , J.I. Goodman 5 , R.L. Hall 6 , L.J. Marnett 7 , I.C. Munro 8 , P.S. Portoghese 9 , R.L. Smith 10 , W.J. Waddell 11 , B.M. Wagner 12 . 1 TNO Nutrition and Food Research, Zeist, The Netherlands, 2 Scientific Secretary of the FEMA Panel Flavor & Extract Manufacturers Association, Washington, DC, USA, 3 Nebraska Medical Center, University of Nebraska, Omaha, NB, USA, 4 Dept. of Pharmacology and Toxicology, University of Kansas Medical Center, Kansas City, KS, USA, 5 Dept. of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, USA, 6 Towson, MD, USA, 7 Dept. of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, USA,8 CanTox Health Sciences International, Mississauga, ON, Canada, 9 Dept. of Medicinal Chemistry, University of Minnesota, Minneapolis, MN, USA, 10 Div. of Biomedical Sciences, Section of Molecular Toxicology, Imperial College School of Medicine, South Kensington, London, UK, 11 Dept. of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY, USA, 12 New York University School of Medicine, New York, B.M. Wagner Associates, Milburn, NJ, USA Natural flavour complexes (NFCs) are chemical mixtures obtained by applying physical separation methods to botanical sources such as pulp, peel, vegetables and spices. Many of the approximately 300 NFCs have a food origin. To date no scheme that allows the safety evaluation of NFCs has been developed by any agency, governmental or non-governmental. In this presentation, such a scheme, “The Naturals Paradigm”, will be discussed. The scheme is intended only for the safety evaluation of NFCs derived from higher plants to be used as flavouring substances for food and beverages. The scheme begins with a review of data on the history of dietary use of the NFC, and describes its chemical composition to ensure that the commercial product conforms to the composition limits that define the product. Next the paradigm assigns each known constituent to one of three structural classes of toxic potential, each class with its own exposure threshold of toxicological concern. Moreover, each constituent is assigned to one of some 30 congeneric groups. In subsequent steps, for each congeneric group