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Toxicity testing: Strategies to determine needs and priorities
Vol. 23, No. 11, pp. 101%1021, 1985 Printed in Great Britain
0278-6915/85 $3.00+0.00 Pergamon Press Ltd
Fd Chem. Toxic.
Review Section REVIEWS OF RECENT PUBLICATIONS Toxicity Testing: Strategies to Determine Needs and Priorities. Steering Committee on Identification of Toxic and Potentially Toxic Chemicals for Consideration by the National Toxicology Program. Whittenberger, J. L. (Chairman). National Academy Press, Washington, 1984. pp. xiii + 382. £25.85. ISBN 0-309-03433-7. The vast number of chemicals in the human environment and the limited resources available for testing their potential impact on public health require a priority-setting process for the selection of chemicals to be tested. The present volume represents an attempt by a large number of scientists---organized into committees and working under the auspices of the NIEHS, NRC and N A S - - t o identify the need for tests on substances to which humans are known or anticipated to be exposed, and to develop and validate criteria for setting testing priorities. The first part is entitled "Toxicity testing needs in the select universe" and describes how a 'select universe' of about 54,000 distinct substances of possible concern were reduced by random sampling to 675 substances representing seven major use categories. Detailed analysis on a subsample of 100 of these chemicals revealed--not surprisingly--that there were sufficient toxicity and exposure data for the complete health hazard assessment of only a small fraction. By extrapolation the same conclusion was drawn for the 'select universe'. It was concluded that drugs and pesticides have been the most comprehensively tested, followed by food additives and cosmetic ingredients, while--predictably--industrial chemicals take last place. The second part of the text describes an approach developed by the Committee on Priority Mechanisms for setting priorities for toxicity testing--their goal, a system to "yield the most information about the overall hazards of chemicals". The Committee decided that the art of toxicity testing is still expanding too rapidly to come down firmly in favour of any definite scheme and therefore it has presented only an approach for designing an appropriate system "that can keep pace with advances in the field". However, it is admitted that the possible design is "sketchy and incapable of immediate implementation". The system would assess concern about exposure, toxicity and social considerations. Factors such as the number of people exposed, the degree and frequency of exposure, the probability and severity of toxic responses at that exposure level and the costs of adverse effects and treatment to society or to the individual would be important. In such a scheme, cigarette smoke would probably rate highly whereas vinyl chloride, for example, would rate as low. As an
example of the Committee's approach, bisphenol A is escorted through an illustrative scheme. In another chapter, the operation of an illustrative system is described in detail and suitable sources of exposure and toxicity data are suggested. This chapter also contains useful tables for checking the predictive accuracy of various short-term mutagenicity tests and of their combinations. The future development, implementation and refinement of the system are discussed in the following chapter. In general the text is clear and well presented. Mathematical approaches to some of the aspects of toxicity testing priorities (a model of the prioritysetting process, estimation of the social costs of misdassifying a chemical's hazard) are included among the appendices. On this side of the Atlantic, phrases such as "probabilistic thinking" and "valueof-information analysis" induce the occasional shudder. Some of the conceptual sections are hard-going at times but, like many novels, there are good bits to be found on re-reading. It should be remembered that none of the available priority-setting schemes is a panacea for the problems of health evaluation. They are based on data that have been previously generated and on existing technologies; both of these will grow and change. Therefore flexibility, which the approach outlined in the present volume caters for, is a crucial feature of any priority-setting system if it is to survive the slings and arrows of toxicological fortune. The bottom line must be, however, that no priority-setting system can solve the basic problem of insufficient data.
Safety Testing of New Drugs. Laboratory Predictions and Clinical Performance. Edited by D. R. Laurence, A. E. M. McLean & M. Weatherall. Academic Press, London, 1984. pp. v i i i + 174. £19.00. ISBN 0-12-438350-5. The publicity occurring when marketed drugs cause severe adverse reactions, in spite of extensive safety tests in animals, has created the impression that these lack predictive value and has resulted in a proliferation of preclinical requirements to be fulfilled before a new drug can be marketed. The editors of "Safety Testing of New Drugs" argue that the routine nature of current tests carried out to satisfy regulatory authorities precludes true scientific studies, and that the confidential nature of the data further restricts their contribution to scientific knowledge. They state that, "The regulations are now seen in many quarters to have become excessive, to the extent of hampering the introduction of valuable
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0278-6915/85 $3.00+0.00 Pergamon Press Ltd
Fd Chem. Toxic.
Review Section REVIEWS OF RECENT PUBLICATIONS Toxicity Testing: Strategies to Determine Needs and Priorities. Steering Committee on Identification of Toxic and Potentially Toxic Chemicals for Consideration by the National Toxicology Program. Whittenberger, J. L. (Chairman). National Academy Press, Washington, 1984. pp. xiii + 382. £25.85. ISBN 0-309-03433-7. The vast number of chemicals in the human environment and the limited resources available for testing their potential impact on public health require a priority-setting process for the selection of chemicals to be tested. The present volume represents an attempt by a large number of scientists---organized into committees and working under the auspices of the NIEHS, NRC and N A S - - t o identify the need for tests on substances to which humans are known or anticipated to be exposed, and to develop and validate criteria for setting testing priorities. The first part is entitled "Toxicity testing needs in the select universe" and describes how a 'select universe' of about 54,000 distinct substances of possible concern were reduced by random sampling to 675 substances representing seven major use categories. Detailed analysis on a subsample of 100 of these chemicals revealed--not surprisingly--that there were sufficient toxicity and exposure data for the complete health hazard assessment of only a small fraction. By extrapolation the same conclusion was drawn for the 'select universe'. It was concluded that drugs and pesticides have been the most comprehensively tested, followed by food additives and cosmetic ingredients, while--predictably--industrial chemicals take last place. The second part of the text describes an approach developed by the Committee on Priority Mechanisms for setting priorities for toxicity testing--their goal, a system to "yield the most information about the overall hazards of chemicals". The Committee decided that the art of toxicity testing is still expanding too rapidly to come down firmly in favour of any definite scheme and therefore it has presented only an approach for designing an appropriate system "that can keep pace with advances in the field". However, it is admitted that the possible design is "sketchy and incapable of immediate implementation". The system would assess concern about exposure, toxicity and social considerations. Factors such as the number of people exposed, the degree and frequency of exposure, the probability and severity of toxic responses at that exposure level and the costs of adverse effects and treatment to society or to the individual would be important. In such a scheme, cigarette smoke would probably rate highly whereas vinyl chloride, for example, would rate as low. As an
example of the Committee's approach, bisphenol A is escorted through an illustrative scheme. In another chapter, the operation of an illustrative system is described in detail and suitable sources of exposure and toxicity data are suggested. This chapter also contains useful tables for checking the predictive accuracy of various short-term mutagenicity tests and of their combinations. The future development, implementation and refinement of the system are discussed in the following chapter. In general the text is clear and well presented. Mathematical approaches to some of the aspects of toxicity testing priorities (a model of the prioritysetting process, estimation of the social costs of misdassifying a chemical's hazard) are included among the appendices. On this side of the Atlantic, phrases such as "probabilistic thinking" and "valueof-information analysis" induce the occasional shudder. Some of the conceptual sections are hard-going at times but, like many novels, there are good bits to be found on re-reading. It should be remembered that none of the available priority-setting schemes is a panacea for the problems of health evaluation. They are based on data that have been previously generated and on existing technologies; both of these will grow and change. Therefore flexibility, which the approach outlined in the present volume caters for, is a crucial feature of any priority-setting system if it is to survive the slings and arrows of toxicological fortune. The bottom line must be, however, that no priority-setting system can solve the basic problem of insufficient data.
Safety Testing of New Drugs. Laboratory Predictions and Clinical Performance. Edited by D. R. Laurence, A. E. M. McLean & M. Weatherall. Academic Press, London, 1984. pp. v i i i + 174. £19.00. ISBN 0-12-438350-5. The publicity occurring when marketed drugs cause severe adverse reactions, in spite of extensive safety tests in animals, has created the impression that these lack predictive value and has resulted in a proliferation of preclinical requirements to be fulfilled before a new drug can be marketed. The editors of "Safety Testing of New Drugs" argue that the routine nature of current tests carried out to satisfy regulatory authorities precludes true scientific studies, and that the confidential nature of the data further restricts their contribution to scientific knowledge. They state that, "The regulations are now seen in many quarters to have become excessive, to the extent of hampering the introduction of valuable
1019