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OCR for page 125
6 SUMMARY AND CONCLUSIONS A select universe of 65,725 listings of substances was created from lists of pesticides and registered inert ingredients of pesticide formulations, cosmetic ingredients, drugs and excipients in drug formulations, food additives, and chemicals in commerce as listed in the Inventory of the Toxic Substances Control Act. A sample of 675 substances chosen by a systematic stratified random process was selected from the 65,725 entries. A random subsample of 100 substances on which there was at least a prescribed minimum of toxicity information was then selected from the random sample. The subsample contained representatives of seven categories of substances: (1) 15 pesticides and inert ingredients of pesticide formulations, (2) 15 cosmetic ingredients, (3) 15 drugs and excipients in drug formulations, (4) 15 food additives, and 40 chemicals in commerce, which were divided into (5) 10 with 1977 production of at least 1 million pounds, (6) 10 with 1977 production of less than 1 million pounds, and (7) 20 whose 1977 production volume was unknown or inaccessible because of manufacturers' claims of confidentiality. The findings in this report apply to a total universe of approximately 53,500 unique substances, inasmuch as approximately 20% of the 65,725 listed substances were duplicates. A detailed dossier describing the adequacy of toxicity testing for conducting a health-hazard assessment was prepared for each of the 100 substances in the subsample. The analyses in this report are based on evaluations of testing adequacy for the subsample and information on the availability, nature, and extent of minimal toxicity information on the sample of 675 substances as prescribed by the Committee on Toxicity Data Elements. Of the seven categories, drugs and excipients in drug formulations have been tested most adequately. For about 18% of the substances in this category, sufficiently complete health-hazard assessments can be conducted that no further toxicity testing would be required. Chemicals in commerce, as enumerated in the Inventory of the Toxic Substances Control Act, have had least adequate testing. On no substance in the three production categories of chemicals in commerce examined by the committees is information sufficient to permit a complete health-hazard assessment. Partial assessments could be made for 10-37% of the substances in the select universe. Even though the subsample in each category was small, so that the confidence limits of these estimated mean percentages form a wide range, it is obvious that, overall, most of the substances have not been adequately tested. Adequacy of testing is, in large part, related to the intended use and regulatory history of a substance. Thus, pesticides and inert ingredients of pesticide formulations and drugs and excipients in drug formulations, which have the longest history of required testing, are the 125
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most fully tested substances. Substances that are ingested or otherwise applied to humans have in general been subjected to more testing than those to which there may be no intended or expected human exposure. Complete health-hazard assessments appear to require further testing of 82% of the drugs and excipients in drug formulations, 90% of the pesticides and inert ingredients of pesticide formulations, 95% of the food additives, 98% of the cosmetic ingredients, and essentially all the substances in the three production categories of chemicals in commerce. The committees concluded that lack of availability of information could not be used to judge adequacy of testing for the purposes of this report. me estimated percentages expressing the judgment that further testing is required exclude proprietary data, particularly on drugs, that were not available to the committees and would presumably not be available to any other independent body assessing the state of toxicity information. Toxicity tests, when conducted, have been of sufficiently high quality to obviate repetition or further testing. Approximately 80% of the acute-toxicity tests (based on the acute-toxicity test of highest quality for a given substance when more than one study was done) were judged not to need repetition by the committees. Only 33-50% of the chronic, long-term tests were considered not to need repetition. The test types that were done least frequently included those which are long, difficult, and complex. The committees did not evaluate or categorize the results of testing, such as the frequency of finding specific kinds of carcinogenicity, neurotoxicity, or genetic toxicity. Thus, no conclusions can be presented on the toxicity of the 100 substances examined in detail. Such categorization would require a different kind of review, as well as a sample of much more than 100 substances to determine reliable estimates of proportions of the select universe known to have specific health effects. Assessment of human health hazards requires information on the nature and extent of exposure, as well as on toxicity. For 36 of the 100 substances in the subsample, no data were available from which the committees could determine the extent of exposure, and, for 75 of the substances in the subsample, no information was available from which trends in exposure could be estimated. 126