Toxicity Testing Strategies to Determine Needs and Priorities (1984) / Chapter Skim
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5. RESULTS
5. RESULTS
Pages 81-124
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From page 81... ...
In each instance, the origin of the information is stated to aid the reader in understanding the nature and implications of the data. The Committee on Sampling Strategies and the Committee on Toxicity Data Elements recognize that their estimates of testing need may be less than the reference protocol guidelines call for, even though some tests may have been done not at all or not in compliance with the guidelines.
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From page 82... ...
Inert ingredients of pesticide formulations and excipients of drug formulations were included in the select universe, because the Committee on Toxicity Data Elements desired to include to the fullest extent in the select universe the substances that were of possible interest to NTP because of their potential for human exposure. Of the 50 pesticides and inert ingredients of pesticide formulations in the sample, 37 were on the list of active pesticides, 11 were on the list of inert ingredients, and 2 were on both lists; of the 15 in the subsample, 12 were on the list of active pesticides, 2 were on the list of inert ingredients, and 1 was on both.
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From page 83... ...
The tests most frequently encountered for each category of substances in the sample of 675 during the search for prescribed minimal toxicity information are presented in Table 7. The data in these tables include the best estimates of the Committee on Sampling Strategies and the Committee on Toxicity Data Elements with upper and lower 90% confidence limits.
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From page 84... ...
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From page 85... ...
Of the substances examined in this category, about 39% were found to meet the requirements adopted by the Committee on Toxicity Data Elements for minimal toxicity information. In contrast, only about 20% of the compounds in the three categories of chemicals in commerce were found to meet the requirements for minimal toxicity information, although these requirements were much less strict than those adopted for drugs and excipients in drug formulations.
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From page 88... ...
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From page 91... ...
the highest rating, for a test protocol performed according to current reference protocol Guidelines adopted by the committee. · A, an adequate rating for a protocol that did not strictly follow current reference protocol guidelines, but was nevertheless deemed adequate for conducting a health-hazard assessment.
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From page 93... ...
~r ~ ~ ~ ~ 0 ~n a, ~o ~ ~ ~ 0 oo ~l cr ~ ~ ~ CD 0 r~ ~ ~ ~D ~O O ~ ~ O ~ O u' ~ a, ~ 0 ~ O a~ c ~u~ ~ ~ ~ ~o ~ ~ ~ ~ ~ o ~o ~ o u~ ~ , 1 ~u ~ ~c JJ ·~.
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From page 95... ...
For some types (e.g., acute oral administration in rodents, acute dermal application, acute eye irritation and corrosivity, guinea pig skin sensitization, and subchronic dermal application for 90 d) , the majority of tests were deemed not to require repetition.
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From page 96... ...
The committee used this information to assess which deficiencies were most prevalent, which ones could be overridden, and which ones caused studies to be of little or no value for conducting a health-hazard assessment. Some of the more common minor deviations from reference protocol guidelines that nevertheless resulted in a rating of adequate included the use of too few animals per dosage group, the use of only one sex, the use of too few or improper dosages, and the absence of various kinds of observations (e.g., clinical chemistry or histopathology)
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From page 97... ...
Among the 18 tests deemed by the Committee on Toxicity Data Elements to be required for pesticides and inert ingredients of pesticide formulations (see Appendix F) , the proportion of substances with tests performed inadequately and needing repetition (IR + C)
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From page 98... ...
Substances Having Test Typea at Least One Test Proportion with Ratings Evaluated of G A, or IN,b % Acute: Acute oral in rodents 63 74-83-90 Acute dermal 30 76-87-95 Acute dermal irritation 37 70-81-91 and corrosivity Acute eye irritation 33 63-76-88 and corrosivity Chronic: Multigeneration reproduction 12 12-33-61 in rodents Carcinogenicity in rodents 23 34-52-70 Chronic toxicity 29 23-38-50 Combined carcinogenic~ty 8 20-50-80 and chronic toxicity in rodents a These tests were selected for illustrative purposes.
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From page 99... ...
To some extent, these differences may reflect the spectrum of individual tests that the Committee on Toxicity Data Elements prescribed as necessary to meet its criteria for adequacy of information in each category. The relative comparisons in Table 19 are based on estimates for the select universe based on the sample of 675 substances and the subsample of 100 substances.
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From page 101... ...
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From page 102... ...
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From page 103... ...
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From page 106... ...
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From page 107... ...
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From page 109... ...
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From page 111... ...
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From page 118... ...
No Toxicity Information Available FIGURE 2 Ability to conduct health-hazard assessment of substances in seven categories of select universe.
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From page 119... ...
Results of this analysis indicate not only the percentage of substances in each of the seven categories that have sufficient testing of adequate quality to conduct a health-hazard assessment, but also the percentage that would require additional testing according to the standards adopted by the Committee on Toxicity Data Elements if an assessment were to be performed. It should be remembered that the requirement for minimal toxicity information (see Chapter 2)
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From page 120... ...
INTERPRETATION AND ANALYSIS OF PHYSICOCHEMICAL AND EXPOSURE DATA The committees attempted to relate the quantity and quality of toxicity testing to several factors that seem to be logical determinants of testing, such as breadth of known exposure, expected trends in exposure, physicochemical properties and chemical fate of the substances, and strength of evidence of toxicity in humans, including the severity of reported chronic human toxicity. In audition, the committees sought information on occupational and environmental exposure and attempted to relate this information to the extent and quality of toxicity testing.
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From page 121... ...
Chemical-reactivity data were most available for the pesticides and inert ingredients of pesticide formulations (73%) , drugs and excipients in drug formulations (6711, food additives (47~)
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From page 122... ...
to o an A u In u]
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From page 123... ...
. Data elements concerning use, production processes and volumes, chemical bioavailability, and exposure related to the workplace, the general environment, and intended use are necessary to assess the relation between exposure potential and overall health hazard.
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From page 124... ...
For example, the intensity of occupational exposure is strongly influenced by the choice of process and control equipment, and the intensity of environmental exposure is strongly influenced by the selection of waste-disposal technique, chemical reactivity, and degree of biodegradability. In view of the great importance of exposure data and indexes of hazard assessment and the nearly complete absence of such data, the committees recommend that planning begin for the development of much more 'I than now exist for exposure The committees recognize that this will require a substantial effort and allocation of resources.
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