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OCR for page 51
OPERATING POLICIES FOR IDENTIFICATION,
ACQUISITION, AND ORGANIZATION OF DATA
The available information on each of the 100 substances in the
subsample was collected and organized to facilitate assessment of the
quality and quantity of the toxicity data base. The algorithm for the
identification, acquisition, and organization of the data is summarized
schematically in Figure 2. This algorithm is the result of evolution and
refinement through a series of procedures, whose rationale and results
are described in Appendix M. The search pattern included several
computerized data bases and the resources of the NRC Toxicology
Information Center. Information was also sought from government and
industry files. During this search, the NRC personnel in charge of the
initial screening of data consistently tended to retain more information
than committee members eventually found to be relevant.
me Committee on Toxicity Data Elements formulated ground rules to:
· Ensure that documents selected were pertinent to the relevant data
base.
· Circumscribe precisely the limits of the data base to be used
(e.g., what was and what was not to be included).
· Encourage early resolution of difficult problems encountered by
the committee (e.g., the use of articles in foreign languages).
· Avoid unnecessary repetition of steps in data identification,
acquisition, and evaluation.
Operating policies were established regarding the use of
restricted-access or confidential information; toxicity information on
humans; data on physical and chemical characteristics, manufacturing
processes, production volumes, intended uses, and human exposures;
chemical review articles; articles in foreign languages; and information
on compounds structurally similar to those in the subsample. These
policies are discussed below.
RESTRICTED-ACCESS OR CONFIDENTIAL INFO~TION
Restricted-access or confidential information, which includes
proprietary or confidential business information supplied in the process
of chemical registration, is contained in the files of the Food and Drug
Administration (FDA) and the Environmental Protection Agency (EPA).
Because the committees wanted the search for information to be as complete
51
OCR for page 52
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OCR for page 53
as possible, they requested from these agencies the maximal
permissible access to restricted information related to the chemical
and physical characteristics, manufacturing processes, production
volumes, intended uses, environmental fate, human-exposure potentials,
and animal and human toxicity of substances in the subsample.
Confidential or restricted-access data were made available to the
committees under two conditions, and two operating policies were
adopted to suit these circumstances:
· Some confidential or restricted-access information was made
accessible only to specific committee members or staff of NRC. In
such cases, the information was evaluated by those persons according
to the prescribed procedure for all data evaluation but only the
results of the evaluation were presented to and
-~ _ =~ used by the Committee
on Toxicity Data Elements and its panels. The evaluated documents
remained confidential and unseen by other members of the committee.
m us, some confidential or restricted-access information was
incorporated into the evaluation process.
· The committee was aware that confidential or restricted-access
information was held in files that were not available for use in this
study. ~ ~ ~
the evaluation of a substance's data base. The committee's policy on
this matter reflected its general view that data not available for its
confidential review were presumably not available for legitimate
review by other interested parties; hence, in an operational sense,
such data no longer exist, although staff members of the government
agencies holding such information might have been able to use the data
for statutory purposes.
Under these circumstances, the data COULD not De considered In
INFORMATION ON TOXICITY IN HUMANS
To maintain consistency, all 100 substances in the subsample were
evaluated on the basis of animal toxicity data and human sensitization
and skin-penetration studies, when available. Other toxicity studies
in humans were not judged for the adequacy of their testing protocols,
because reference protocol guidelines do not exist for them.
Information contained in reports of these studies was, however,
considered in the final appraisal of a substance's toxicity-testing
needs. The side effects of drugs in humans were determined from
standard source books (see Appendix M); this procedure may have
excluded some preclinical and clinical data contained in inaccessible
FDA files.
CHEMI CAL AND PHYSI CAL CEIARACTERI ST ICS, bLANUFACTURI NG PROCESSES,
PRODUCTION VOLUMES, INTENDED USES, AND EXPOSURE OF HUMANS
Information on these subjects included all the data elements
listed in the "Physicochemical, Use, and Exposure Information" section
53
l
OCR for page 54
of Appendix L. Some elements were regarded by the committee as more
likely to exist or be readily obtainable than others and were
consequently pursued more aggressively. These were chemical
identification (structure, nomenclature, and defined purity), intended
use, production volume, chemical and physical data (e.g., state,
density, vapor pressure, water and organic solubilities, octanol:water
coefficient, and pH), and exposure potential in the various
intended-use, environmental, and occupational settings. This last
item included the probable routes of exposure and the manufacturing
system used (open or closed and with or without an exhaust control
mechanism and/or local ventilation). The various sources and
procedures used to obtain this information are described in Appendix M.
CHEMICAL REVIEW ARTICLES
In every instance, the Committee on Toxicity Data Elements used
primary-source literature in its evaluations. For substances with
large data bases (more than 250 computer citations), comprehensive
review articles were used as an aid to finding the primary-source
literature. Primary-source references cited in the reviews were
obtained; once those on the required test types (described later) for
a given substance had been identified, the data search was continued
only for the required test types that were still missing. The
committee recognizes that unrequited test types may not have been
found for substances with large data bases, but any such omissions
would not affect the committee's assessment of toxicity-testing needs.
ARTICLES IN FOREIGN LANGUAGES
English summaries or translated abstracts of articles in foreign
languages were examined to estimate their usefulness for the
committee's task. When it was appropriate, complete articles were
translated. Reasons for judgments concerning each abstract's
usefulness (or lack of it) were documented.
SUBSTANCES STRUCTURALLY SIMILAR TO THOSE IN THE SAMPLE
The use of surrogate chemicals (those with similar chemical
structures) was considered case by case. - ~ ~ ~
· . · . . . . ~
The policy established by
the committee required that surrogate information not be used until
all data on the substance in question had been completely evaluated.
At that point, specific information on surrogates could be used to
fill clearly defined voids where the data base was considered not to
be adequate for conducting a health-hazard assessment. Information on
surrogate substances was used on only two occasions.
54
Representative terms from entire chapter:
data elements
