United States
Environmental Protection
Agency
Environmental Monitoring
Systems Laboratory
Las Vegas, NV 89193-3478
Research and Development
EPA/600/S8-91/043 June 1992
& EPA Project Summary
Protein Adducts for Exposure
Monitoring: A Computerized
Database (Software and User's
Manual)
F. C. Schnell and Charles H. Nauman
This user's manual contains direc-
tions for installing and using the Com-
puterized Protein Adducts Database
(CPAD). Most of this documentation is
also available on-screen in the form of
CPAD's "Readme" files and program
prompts. CPAD, a user-friendly, menu-
driven, stand-alone DBASE™ applica-
tion provides an efficient means of up-
dating and disseminating information
on protein adducts relating to their use
as dosimeters of exposure to environ-
mental contaminants, especially geno-
toxic and carcinogenic compounds. The
structure of the database as well as its
initial contents were derived primarily
from the document, "Protein Adduct-
Forming Chemicals for Exposure Moni-
toring: Chemicals for Further Study,"
EPA/600/4-89/035.:
Software for executing CPAD accom-
panies the User's Manual on a single
high-density 3.5" diskette. The diskette
contains (1) two versions of CPAD that
run with DBASE™ III PLUS and
DBASE™ IV, version 1.1, respectively,
(2) the DBRUN™ files needed to run
CPAD as a stand-alone DBASE™ III
PLUS application, (3) a copy of the
User's Manual (a WORDPERFECT™ 5.0
document file), which may be viewed
on-screen or printed out, and (4) the
source code and unlinked object code
files used to develop CPAD's main pro-
gram. The latter files are not required
to run CPAD and are included only for
the Information of users who may be
interested in the program's design.
This Project Summary was developed
by EPA's Environmental Monitoring
Systems Laboratory, Las Vegas, NV, to
announce key findings of the research
project that is fully documented in a
separate report of the same title (see
Project Report ordering information at
back).
Information
The U.S. Environmental Protection
Agency (EPA) generated an initiative to
develop, refine, and apply appropriate
biomarkers for use in conjunction with en-
vironmental monitoring data to provide
better estimates of exposure and risk to
individuals and populations. Among the
biomarkers under study are macromolecu-
lar adducts formed in vivo by reactive
environmental chemicals or their
metabolities.
A report entitled "Protein Adduct-Form-
ing Chemicals for Exposure Monitoring:
Literature Summary and Recommenda-
tions, EPA/600/4-90/007, summarized the
literature regarding adducts formed by
xenobiotics with proteins, particularly he-
moglobin and serum albumin, and exam-
ined the feasibility of their use as dosim-
eters of exposure. Twenty-two chemicals
were recommended for further study and
ranked according to their potential use in
exposure monitoring by protein adduct-
based methods. These prioritized chemi-
cals were then examined in greater detail
in a report entitled "Protein Adduct-Form-
ing Chemicals for Exposure Monitoring:
Chemicals Selected for Further Study,"
EPA/600/4-89/035.
Due to rapid developments in the field
of molecular dosimetry, information in the
project report (EPA/600/4-89/035), as well
as the prioritized chemicals list, could pos-
sibly require frequent amendents and up-
^§g> Printed on Recycled Paper
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dates in the future. To facilitate that pro-
cess, the Computerized Protein Adducts
Database (CPAD) was developed. The
structure of the database as well as its
initial contents were derived primarily from
the aforementioned project report. The
database includes entries on the following
topics: manufacture and use, sources and
levels of exposure, known health effects,
metabolism (detoxification and activation),
host factors, reactive metabolities, adduct
characterization, rates of adduct forma-
tion (i.e., second-order rate constants),
background adduct levels, dose-response
relationships, and methods of adduct de-
tection.
Procedure
CPAD is intended to run on an IBM-
compatible PC with hard disk under DOS.
It can be run from a 3.5" drive, but this is
not recommended, as program execution
is slowed down considerably.
The DBASE™ III PLUS Version
This version of CPAD may be used with
or without DBASE™ 111 PLUS. If your com-
puter has DBASE™ 111 PLUS installed,
only the files in the CPAD.DB3 Directory
of the 3.5" CPAD diskette need to be
copied to a separate subdirectory on your
hard drive (e.g., c:\CPAD). These files will
require approximately 270 K of memory. If
your computer does not have DBASE™ III
PLUS installed, then the three DBRUN
files provided must also be copied into the
CPAD directory on your hard disk. The
resulting stand-alone version of CPAD re-
quires a total of 605 K.
The DBASE™ IV (1.1) Version
For the benefit of those who have
DBASE™ IV, version 1.1, installed on their
computers, a compatible version of CPAD
is included on the CPAD diskette. To in-
stall this version of CPAD, simply copy all
the files from the CPAD.411 directory of
the CPAD diskette to a separate directory
on your hard drive (e.g., c:\CPAD). You
will need only about 325 KB of disk space
for the DBASE™ IV version. A stand-alone
(Runtime) DBASE™ IV, 1.1 version of
CPAD is not included, because it would
require a million bytes more than the stand-
alone DBASE™ III PLUS version.
Operation
Getting Started
To run either version of CPAD, simply
enter "START" from within the subdirectory
that contains the CPAD files (and the three
DBRUN files, in the stand-alone version).
Alternatively, the compatible version of
CPAD may be run from within DBASE™
III PLUS or DBASE™ IV by entering "DO
PADDUCTS" or "DO MAINMENU," respec-
tively, at the dot prompt, provided that (1)
DBASE™ is loaded from within your CPAD
directory, thereby making it the default
directory, and (2) the DBASE™ directory
is in your PATH statement.
Searching the Database
The main menu of CPAD is a scrolling,
alphabetical list of chemicals for which
records exist in CPAD. When a chemical
is selected, the main menu closes and the
field-selection menu opens. The user may
choose one of three options: (1) view only
those fields containing information on the
selected chemical, (2) view only those
fields containing information on the pro-
tein adducts formed by the chemical, or
(3) browse through all the data fields on
the selected chemical. Chemical Data
Fields include CAS Number, Synonyms,
Volume and Method of Manufacture, Ma-
jor Uses, Sources and Levels of Expo-
sure, Health Effects, Metabolism, and Host
Factors. Protein Constant Adduct Data
Fields include Reactive Metabolites, Ad-
ducts Formed, (second order) Rate Con-
stant (of formation), Background Levels
(of adducts), Dose-Response Data, Meth-
ods of Detection, and References. After
selecting 1 or 2 above, the user may se-
lect to view individual data screens or
browse through all data screens (i.e.,
Chemical or Protein Adduct) in sequence.
Modifying the Database
Existing data on a selected chemical
may be edited/updated at the appropriate
data screen by entering Edit Mode. The
Delete Menu works the same way the
Main Menu does, except that the entire
record for the selected chemical is de-
leted if the user's intent to do so is con-
firmed at the prompt. The Add Menu al-
lows the user to add new records (i.e.,
chemicals and CAS numbers, only). A
Duplicate Entry Protection Feature keys
on CAS number rather than chemical
name. Any new chemical names added at
the Add Menu will subsequently appear in
the alphabetical listing at the Main Menu.
All other data for new records is keyed in
at the individual data display screens in
input mode, after selecting the new chemi-
cal at the Main Menu.
Software Availability
The Computerized Protein Adducts Da-
tabase (CPAD) can be obtained by send-
ing a single, formatted, high-density (1.44
MB), 3.5" diskette to the following ad-
dress:
Dr. Charles H. Nauman
USEPA, EMSL, MC-EAD
P.O. Box 93478
Las Vegas, NV 89193-3478
The CPAD Software, the accompany-
ing User's Manual, and the protein ad-
ducts project reports (EPA/600/4-90/007
and EPA/600/4-89/035) were written by
Dr. Frank C. Schnell. He may be con-
tacted at the following address:
Lockheed Engineering and Sciences
Company
1050 E. Flamingo Road
Las Vegas, NV 89119
•U.S. Government Printing Office: 1992— 648-080/60018
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Frank C. Schnellis with Lockheed Engineering and Sciences Co., Las Vegas, NV
89119. The EPA author, Charles H. Nauman (also the EPA Project Officer, see
below), is with Environmental Monitoring Systems Laboratory, Las Vegas, NV
89193-3478.
The complete report, entitled "Protein Adducts for Exposure Monitoring: A Comput-
erized Database: (Software and User's Manual)," (Order No. PB92-501873/AS;
Cost: $90.00; subject to change) will be available only from:
National Technical Information Service
5285 Port Royal Road
Springfield, VA 22161
Telephone: 703-487-4650
The EPA Project Officer can be contacted at:
Environmental Monitoring Systems Laboratory
U.S. Environmental Protection Agency
Las Vegas, NV 89193-3478
United States
Environmental Protection
Agency
Center for Environmental
Research Information
Cincinnati, OH 45268
BULK RATE
POSTAGE & FEES PAID
EPA
PERMIT No. G-35
Official Business
Penalty for Private Use $300
EPA/600/S8-91/043
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