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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
OCR for page 126
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.
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Representative terms from entire chapter:
inert ingredients
