TOXICOLOGICAL ASSESSMENT OF NEW FOODS A. Spicer
TOXICOLOGICAL ASSESSMENT OF NEW FOODS A. SPICER* D.Sc. F.R.I.C. Park Farm, Robertsbridge, Sussex
The introduction of novel foods, in particular novel proteins, must be preceded by an evaluation of their safety, nutritional standard and acceptability, regardless of the origin of the material. If this statement appears to be broad and comprehensive, it is deliberately meant to be so. National regulatory agencies, such as the Food Standard and Food Additive Committees of the UK, or the Food and Drug Administration of the USA, or international advisory bodies such as the Food and Agriculture Organization (FAO), the World Health Organization (WHO) or the Protein Advisory Group of FAO and WHO, have, over a number of years, in many publications, stressed the need for, and in some cases given fairly precise details of, the pre-clinical investigations required. They are strict and extensive as far as foods for human consumption are concerned, and only moderately less extensive if the materials are destined for incorporation into animal feed. Many of the foods that form a part of the diet of civilized man were introduced only recently, as human history goes (Oser, 1970). Local availability, palatability, and more-or-less empirical recognition of their nutritive value and safety were the principal determinants of the acceptability of new food items. A major consequence of the application of the scientific method in our time has been the experimental approach to the discovery and development of such foods, and to their evaluation from the standpoint of current concepts of nutrition, safety and acceptability. Primitive trial-and-error methods were capable of eliminating as potential foods only those plant or animal products that were acutely, i.e., recognizably, toxic. In contrast, modem procedures for safety evaluation must provide "...convincing evidence to establish with reasonable certainty that no harm will result from the intended use of the food additive ..." (Oser, 1968) that may be consumed over an entire lifetime. The progress of nutrition as a scientific discipline enabled us to conduct chronic toxicity trials on selected animals under laboratory conditions over their entire life-spans. The most recent proposals for safety evaluation involved the use of human subjects as well as animals, thus specifying man as an experimental test subject rather than an empirical one. A prerequisite to the appraisal of the safety of a dietary constituent is full information as to its origin and identity. Regardless of whether it is old or new, natural or artificial, the source and composition of the food item must be known in order to plan experimental diets and procedures properly. In any well-designed test, anticipation of the nature and
TOXIC CHEMICALS IN FOODS Natural 1 Normal components of natural food products 2 Natural contaminants of natural food products a Microbiological origin: toxins b Non-microbiological origin: toxicants (e.g. mercury, selenium) consumed In feeds by animals used as food sources Man-Made 3 Agricultural chemicals (e.g. pesticides, fertilizers) 4 Food additives 5 Chemicals derived from food packaging materials 6 Chemicals produced In processing of foods (e.g. by heat, ionizing radiation) 7 Inadvertent or accidental contaminants a Food preparation accidents or mistakes b Contamination from food utensils c Environmental pollution d Contamination during storage or transport
On a world-wide basis, substances in categories 1 and 2a have produced greater known injury to man than have those in the other categories. Category 4 has also made a substantial, though lesser, contribution to the total incidence of foodborne illness. On the other hand, categories 3 and 6 are not known to have been responsible for adverse effects on human health when such materials have been used in accordance with good agricultural and manufacturing practice. So long as our diet contains a reasonable diversity of foods and no excessively large amount of any specific food, then it is unlikely that any single chemical will be consumed in a toxic amount. It is important to bear in mind that the toxicities of many of the different chemicals present in our diet may not be additive. The human organism can readily tolerate small amounts of many different chemical substances taken simultaneously, even though any one of them might not be tolerated in a somewhat larger amount. We often find in the daily newspapers, and even in scientific journals, strong antagonism expressed against processed foods. Yet technology has been largely responsible for protecting man against the potential hazards of the natural chemical composition or contamination of his foods. Heating or other processing methods remove toxic components such as cyanogenetic glycosides, and some of the goitrogens. Refrigeration, running, packaging, and other preservation measures suppress contamination by microbial toxins and chemical changes in foods that might generate toxic materials.
'Formerly Director of Retearch, Rinks Hovis McDougall Retearcb limited.
High Wyconibo, T^icUpghMmtftiift
220
Br. Med. Bull. 1975
Downloaded from https://academic.oup.com/bmb/article-abstract/31/3/220/365022 by University of Winnipeg user on 22 January 2019
degree of effects that might be observed in the laboratory animals is essential for deciding which tests and criteria are to be employed. This can only come from a knowledge of the raw materials, the processes and sanitary conditions of manufacture and the chemical structure and impurities in the substance under test. Nature has introduced more toxic substances into food than has man. Mostly by trial and error, man has in the past discovered how to avoid, minimize or eliminate them, and has probably become adapted to traces of ubiquitous toxicants. The following table indicates the origin of potentially harmful chemical substances occurring in foods eaten as they are grown, or entering foods as the result of man's effort to process food (Institute of Food Technologists' Expert Panel on Food Safety and Nutrition, 1975):
TOXICOLOGICAL ASSESSMENT OF NEW FOODS A. Spicer in soya protein concentrates and isolates (the most commonly used soya products for textured foods today), there is little or no concern to be felt. Microbial Protein The most extensive testing programme, nutritional as well as toxicological, is reserved for the one really new food product resulting from prodigious scientific effort over the last 10-15 years, namely microbial protein, classified now under the name of SCP (single-cell protein). A number of diverse carbon substrates—long-chain n-alkanes, methane, methanol and ethanol—as well as carbohydrates, are converted by microbial action in continuous fermentation processes, to an edible biomass containing 45-75 % protein, depending on the type of micro-organism employed. The various substrates and different processes may present impurities or residues, though not necessarily in quantities large enough to interfere with the nutritional value or palatability of the food or feed, but, nevertheless, sufficient to make the product unsafe. The whole armamentarium of chemists and microbiologists is therefore brought to bear in appraising this food source for potentially toxic or pathogenic contaminants. A five-to-six year testing programme, undertaken by all those companies with a commitment for SCP production, involves the most comprehensive nutritional and toxicological investigation ever devoted to a food or drug. Animal species employed arc rats, mice, chickens, guinea-pigs, primates and pigs—and often, to represent the neonatal animal, calves are chosen. Oral dosing of mice and rats with extracts from the microbial protein is undertaken to simulate acute toxicity testing and to investigate the characteristics of sub-fractions. Guineapigs are used to determine if extracts promote skin reaction. Then specific pathogen-free rats and mice form the basis of life-cycle experiments, in which histopathological examination of 20-25 target tissues is made in the search for treatmentrelated effects. The Protein Advisory Group (1972) details the procedure for anyone wishing to acquaint himself with the effort and time required to assure the reasonable safety in use of products becoming available, in time to assist in the prevention of large-scale nutritional deficiencies of an evergrowing world population.
The Soya Bean The soya bean, its defatted flour, its 70 % protein concentrate, and its protein isolate, are classified as novel food items, though in fermented form—as misoh or tempeh— they were an ancient corner-stone of nutrition in South-East Asia. It is only through the considerable advances in technology that soya beans have re-emerged as one of the best sources of food to help in combating serious food and protein shortages in the world today. One is justified in drawing attention to the diverse biological and physiological eflFects of soya beans and soya protein products. Although toxicity, or toxic factors, are terms frequently used to refer to the antinutritional properties of raw soya products, such designations are unwarranted (Rackis, 1974). Proper heat treatment exerts a beneficial effect on the whole soya bean and the products that derive from it. It inactivates the trypsin inhibitor present and other heat-labile undesirable factors and converts raw refractory proteins to forms more readily digested. Depending on the right combination of temperature, duration of heating and moisture (dry heat has no effect), even the pancreatic hypertrophic factor and haemagglutinins can be eliminated. Flatulence is another problem referred to in the ingestion of soya products. There are many causes for the formation of gastrointestinal gas, which may lead to nausea, cramps, diarrhoea, pain and social discomfort. Flatus produced in human beings by the fermentation of dietary carbohydrates in the lower intestines is, as an incident, unpredictable. The gas-producing factor resides mainly in the low-molecularweight carbohydrate fractions, such as raffinose and stachyose. Since only small amounts of these oligosaccharides are present
REFERENCES
Institute of Food Technologists' Expert Panel on Food Safety and Nutrition (1975) /. Food Set. 40, 215-222 Miller, J. A. (1973) In: Committee on Food Protection. Toxicants occurring naturally in foods, 2nd ed., pp. 508-549 (Food and Nutrition Board, National Research Council). National Academy of Sciences, Washington, D.C. Oser, B. L. (1968) In: Mateles, R. L & Tannenbaum, S. R., ed. Single cell protein, pp. 153-162. The M.T.T. Press, Cambridge, Mass., & London
221 Vol. 31 No. 3
Oser, B. L. (1970) In: Bender, A. E., Kihlberg, R., Lofqvist, B. & Munck, L., cd. Evaluation of novel protein products, pp. 267275 (Proceedings of the International Biological Programme, Stockholm, 11-13 September 1968). Pergamon Press, Oxford Protein Advisory Group (1972) Systems guideline no. 6, revised ed. Food and Agriculture Organization, Rome Rackis, J. J. (1974) /. Am. Oil Chem. Soc. 51,161A-174A
Downloaded from https://academic.oup.com/bmb/article-abstract/31/3/220/365022 by University of Winnipeg user on 22 January 2019
The Newer Foods About the newer or really new foods, Miller (1973) said that we are being exposed to a great number of substances not encountered by our ancestors, to which we therefore have not been specifically adapted by natural selection. One can answer by stating that man is not yet fully adapted to the natural chemical components of his daily food. More than one hundred hereditary diseases are now known, but there is no reason to believe that there are more such diseases now than there were when man's environment was wholly natural.
TOXICOLOGICAL ASSESSMENT OF NEW FOODS A. SPICER* D.Sc. F.R.I.C. Park Farm, Robertsbridge, Sussex
The introduction of novel foods, in particular novel proteins, must be preceded by an evaluation of their safety, nutritional standard and acceptability, regardless of the origin of the material. If this statement appears to be broad and comprehensive, it is deliberately meant to be so. National regulatory agencies, such as the Food Standard and Food Additive Committees of the UK, or the Food and Drug Administration of the USA, or international advisory bodies such as the Food and Agriculture Organization (FAO), the World Health Organization (WHO) or the Protein Advisory Group of FAO and WHO, have, over a number of years, in many publications, stressed the need for, and in some cases given fairly precise details of, the pre-clinical investigations required. They are strict and extensive as far as foods for human consumption are concerned, and only moderately less extensive if the materials are destined for incorporation into animal feed. Many of the foods that form a part of the diet of civilized man were introduced only recently, as human history goes (Oser, 1970). Local availability, palatability, and more-or-less empirical recognition of their nutritive value and safety were the principal determinants of the acceptability of new food items. A major consequence of the application of the scientific method in our time has been the experimental approach to the discovery and development of such foods, and to their evaluation from the standpoint of current concepts of nutrition, safety and acceptability. Primitive trial-and-error methods were capable of eliminating as potential foods only those plant or animal products that were acutely, i.e., recognizably, toxic. In contrast, modem procedures for safety evaluation must provide "...convincing evidence to establish with reasonable certainty that no harm will result from the intended use of the food additive ..." (Oser, 1968) that may be consumed over an entire lifetime. The progress of nutrition as a scientific discipline enabled us to conduct chronic toxicity trials on selected animals under laboratory conditions over their entire life-spans. The most recent proposals for safety evaluation involved the use of human subjects as well as animals, thus specifying man as an experimental test subject rather than an empirical one. A prerequisite to the appraisal of the safety of a dietary constituent is full information as to its origin and identity. Regardless of whether it is old or new, natural or artificial, the source and composition of the food item must be known in order to plan experimental diets and procedures properly. In any well-designed test, anticipation of the nature and
TOXIC CHEMICALS IN FOODS Natural 1 Normal components of natural food products 2 Natural contaminants of natural food products a Microbiological origin: toxins b Non-microbiological origin: toxicants (e.g. mercury, selenium) consumed In feeds by animals used as food sources Man-Made 3 Agricultural chemicals (e.g. pesticides, fertilizers) 4 Food additives 5 Chemicals derived from food packaging materials 6 Chemicals produced In processing of foods (e.g. by heat, ionizing radiation) 7 Inadvertent or accidental contaminants a Food preparation accidents or mistakes b Contamination from food utensils c Environmental pollution d Contamination during storage or transport
On a world-wide basis, substances in categories 1 and 2a have produced greater known injury to man than have those in the other categories. Category 4 has also made a substantial, though lesser, contribution to the total incidence of foodborne illness. On the other hand, categories 3 and 6 are not known to have been responsible for adverse effects on human health when such materials have been used in accordance with good agricultural and manufacturing practice. So long as our diet contains a reasonable diversity of foods and no excessively large amount of any specific food, then it is unlikely that any single chemical will be consumed in a toxic amount. It is important to bear in mind that the toxicities of many of the different chemicals present in our diet may not be additive. The human organism can readily tolerate small amounts of many different chemical substances taken simultaneously, even though any one of them might not be tolerated in a somewhat larger amount. We often find in the daily newspapers, and even in scientific journals, strong antagonism expressed against processed foods. Yet technology has been largely responsible for protecting man against the potential hazards of the natural chemical composition or contamination of his foods. Heating or other processing methods remove toxic components such as cyanogenetic glycosides, and some of the goitrogens. Refrigeration, running, packaging, and other preservation measures suppress contamination by microbial toxins and chemical changes in foods that might generate toxic materials.
'Formerly Director of Retearch, Rinks Hovis McDougall Retearcb limited.
High Wyconibo, T^icUpghMmtftiift
220
Br. Med. Bull. 1975
Downloaded from https://academic.oup.com/bmb/article-abstract/31/3/220/365022 by University of Winnipeg user on 22 January 2019
degree of effects that might be observed in the laboratory animals is essential for deciding which tests and criteria are to be employed. This can only come from a knowledge of the raw materials, the processes and sanitary conditions of manufacture and the chemical structure and impurities in the substance under test. Nature has introduced more toxic substances into food than has man. Mostly by trial and error, man has in the past discovered how to avoid, minimize or eliminate them, and has probably become adapted to traces of ubiquitous toxicants. The following table indicates the origin of potentially harmful chemical substances occurring in foods eaten as they are grown, or entering foods as the result of man's effort to process food (Institute of Food Technologists' Expert Panel on Food Safety and Nutrition, 1975):
TOXICOLOGICAL ASSESSMENT OF NEW FOODS A. Spicer in soya protein concentrates and isolates (the most commonly used soya products for textured foods today), there is little or no concern to be felt. Microbial Protein The most extensive testing programme, nutritional as well as toxicological, is reserved for the one really new food product resulting from prodigious scientific effort over the last 10-15 years, namely microbial protein, classified now under the name of SCP (single-cell protein). A number of diverse carbon substrates—long-chain n-alkanes, methane, methanol and ethanol—as well as carbohydrates, are converted by microbial action in continuous fermentation processes, to an edible biomass containing 45-75 % protein, depending on the type of micro-organism employed. The various substrates and different processes may present impurities or residues, though not necessarily in quantities large enough to interfere with the nutritional value or palatability of the food or feed, but, nevertheless, sufficient to make the product unsafe. The whole armamentarium of chemists and microbiologists is therefore brought to bear in appraising this food source for potentially toxic or pathogenic contaminants. A five-to-six year testing programme, undertaken by all those companies with a commitment for SCP production, involves the most comprehensive nutritional and toxicological investigation ever devoted to a food or drug. Animal species employed arc rats, mice, chickens, guinea-pigs, primates and pigs—and often, to represent the neonatal animal, calves are chosen. Oral dosing of mice and rats with extracts from the microbial protein is undertaken to simulate acute toxicity testing and to investigate the characteristics of sub-fractions. Guineapigs are used to determine if extracts promote skin reaction. Then specific pathogen-free rats and mice form the basis of life-cycle experiments, in which histopathological examination of 20-25 target tissues is made in the search for treatmentrelated effects. The Protein Advisory Group (1972) details the procedure for anyone wishing to acquaint himself with the effort and time required to assure the reasonable safety in use of products becoming available, in time to assist in the prevention of large-scale nutritional deficiencies of an evergrowing world population.
The Soya Bean The soya bean, its defatted flour, its 70 % protein concentrate, and its protein isolate, are classified as novel food items, though in fermented form—as misoh or tempeh— they were an ancient corner-stone of nutrition in South-East Asia. It is only through the considerable advances in technology that soya beans have re-emerged as one of the best sources of food to help in combating serious food and protein shortages in the world today. One is justified in drawing attention to the diverse biological and physiological eflFects of soya beans and soya protein products. Although toxicity, or toxic factors, are terms frequently used to refer to the antinutritional properties of raw soya products, such designations are unwarranted (Rackis, 1974). Proper heat treatment exerts a beneficial effect on the whole soya bean and the products that derive from it. It inactivates the trypsin inhibitor present and other heat-labile undesirable factors and converts raw refractory proteins to forms more readily digested. Depending on the right combination of temperature, duration of heating and moisture (dry heat has no effect), even the pancreatic hypertrophic factor and haemagglutinins can be eliminated. Flatulence is another problem referred to in the ingestion of soya products. There are many causes for the formation of gastrointestinal gas, which may lead to nausea, cramps, diarrhoea, pain and social discomfort. Flatus produced in human beings by the fermentation of dietary carbohydrates in the lower intestines is, as an incident, unpredictable. The gas-producing factor resides mainly in the low-molecularweight carbohydrate fractions, such as raffinose and stachyose. Since only small amounts of these oligosaccharides are present
REFERENCES
Institute of Food Technologists' Expert Panel on Food Safety and Nutrition (1975) /. Food Set. 40, 215-222 Miller, J. A. (1973) In: Committee on Food Protection. Toxicants occurring naturally in foods, 2nd ed., pp. 508-549 (Food and Nutrition Board, National Research Council). National Academy of Sciences, Washington, D.C. Oser, B. L. (1968) In: Mateles, R. L & Tannenbaum, S. R., ed. Single cell protein, pp. 153-162. The M.T.T. Press, Cambridge, Mass., & London
221 Vol. 31 No. 3
Oser, B. L. (1970) In: Bender, A. E., Kihlberg, R., Lofqvist, B. & Munck, L., cd. Evaluation of novel protein products, pp. 267275 (Proceedings of the International Biological Programme, Stockholm, 11-13 September 1968). Pergamon Press, Oxford Protein Advisory Group (1972) Systems guideline no. 6, revised ed. Food and Agriculture Organization, Rome Rackis, J. J. (1974) /. Am. Oil Chem. Soc. 51,161A-174A
Downloaded from https://academic.oup.com/bmb/article-abstract/31/3/220/365022 by University of Winnipeg user on 22 January 2019
The Newer Foods About the newer or really new foods, Miller (1973) said that we are being exposed to a great number of substances not encountered by our ancestors, to which we therefore have not been specifically adapted by natural selection. One can answer by stating that man is not yet fully adapted to the natural chemical components of his daily food. More than one hundred hereditary diseases are now known, but there is no reason to believe that there are more such diseases now than there were when man's environment was wholly natural.
