Xenobiotics and Food-Producing Animals: Metabolism and Residues (Acs Symposium Series)

258 Pages·1992·22.69 MB·English

by  D. H. Hutson

Xenobiotics and Food-
Producing Animals
In Xenobiotics and Food-Producing Animals; Hutson, D., et al.;
ACS Symposium Series; American Chemical Society: Washington, DC, 1992.

ACS SYMPOSIUM SERIES 503
Xenobiotics and Food-
Producing Animals
Metabolism and Residues
D. H. Hutson, EDITOR
Shell Research Limited
D. R. Hawkins, EDITOR
Huntingdon Research Centre
G. D. Paulson, EDITOR
U.S. Department of Agriculture
C. B. Struble, EDITOR
Hazleton Laboratories
Developed from a symposium sponsored
by the Division of Agrochemicals of the American Chemical Society
and the International Society for the Study of Xenobiotics
at the Fourth Chemical Congress of North America
(202nd National Meeting of the American Chemical Society),
New York, New York,
August 25-30, 1991
American Chemical Society, Washington, DC 1992
Library of Congress Cataloging-in-Publication Data
Xenobiotics and food-producing animals: metabolism and residues
D. H. Hutson . .. [et al.], editor.
p. cm.—(ACS symposium series, ISSN 0097-6156; 503)
"Developed from a symposium sponsored by the Division of
Agrochemicals of the American Chemical Society at the Fourth
Chemical Congress of Noroth America (202nd National Meeting of the
American Chemical Society), New York, New York, August 25-30,
1991."
Includes bibliographical references and indexes.
ISBN 0-8412-2472-2
1. Veterinary drugs—Congresses. 2. Xenobiotics—Metabolism-
Congresses. 3. Veterinary drugs—Metabolism—Congresses.
4. Veterinary physiology—Congresses. 5. Veterinary drug residues-
Congresses.
I. Hutson, D. H. (David Herd), 1935- . II. American Chemical
Society. Division of Agrochemicals. III. American Chemical Society.
Meeting (202nd: 1991: New York, N.Y.) IV. Series.
SF917.X46 1992
636.089'57—dc20 92-25718
CIP
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In Xenobiotics aWnda Fsohodin-Pgrtoodnu,c inDg. ACn.i m2a0l0s;3 H6u tson, D., et al.;
ACS Symposium Series; American Chemical Society: Washington, DC, 1992.
1992 Advisory Board
ACS Symposium Series
M. Joan Comstock, Series Editor
V. Dean Adams Bonnie Lawlor
Tennessee Technological Institute for Scientific Information
University
John L. Massingill
Mark Arnold Dow Chemical Company
University of Iowa
Robert McGorrin
David Baker Kraft General Foods
University of Tennessee
Julius J. Menn
Alexis T. Bell Plant Sciences Institute,
University of California—Berkeley U.S. Department of Agriculture
Arindam Bose Vincent Pecoraro
Pfizer Central Research University of Michigan
Robert F. Brady, Jr. Marshall Phillips
Naval Research Laboratory Delmont Laboratories
Margaret A. Cavanaugh A. Truman Schwartz
National Science Foundation Macalaster College
Dennis W. Hess John R. Shapley
Lehigh University University of Illinois
at Urbana-Champaign
Hiroshi Ito
IBM Almaden Research Center Stephen A. Szabo
Conoco Inc.
Madeleine M. Joullie
University of Pennsylvania Robert A. Weiss
University of Connecticut
Mary A. Kaiser
Ε. I. du Pont de Nemours and Peter Willett
Company University of Sheffield (England)
Gretchen S. Kohl
Dow-Corning Corporation
In Xenobiotics and Food-Producing Animals; Hutson, D., et al.;
ACS Symposium Series; American Chemical Society: Washington, DC, 1992.
Foreword
IHE ACS SYMPOSIUM SERIES was first published in 1974 to
provide a mechanism for publishing symposia quickly in book
form. The purpose of this series is to publish comprehensive
books developed from symposia, which are usually "snapshots
in time" of the current research being done on a topic, plus
some review material on the topic. For this reason, it is neces­
sary that the papers be published as quickly as possible.
Before a symposium-based book is put under contract, the
proposed table of contents is reviewed for appropriateness to
the topic and for comprehensiveness of the collection. Some
papers are excluded at this point, and others are added to
round out the scope of the volume. In addition, a draft of each
paper is peer-reviewed prior to final acceptance or rejection.
This anonymous review process is supervised by the
organizer(s) of the symposium, who become the editor(s) of the
book. The authors then revise their papers according the the
recommendations of both the reviewers and the editors,
prepare camera-ready copy, and submit the final papers to the
editors, who check that all necessary revisions have been made.
As a rule, only original research papers and original
review papers are included in the volumes. Verbatim reproduc­
tions of previously published papers are not accepted.
M. Joan Comstock
Series Editor
In Xenobiotics and Food-Producing Animals; Hutson, D., et al.;
ACS Symposium Series; American Chemical Society: Washington, DC, 1992.
Preface
GOOD ANIMAL HUSBANDRY IS CRITICAL in the conversion of plant-
derived feedstuff into animal protein for human consumption. Bioactive
chemicals play an important role in maintaining health, rapid growth rate,
and efficient feed conversion in animals used for food production. Con­
trol of disease by therapeutic and prophylactic use of veterinary pharma­
ceutical products has gained in importance as the numbers of animals
held in close proximity for confined rearing have steadily increased, thus
magnifying risk of animal-to-animal disease transmission. However,
improvements in the use of pharmaceutical products to control pests in
low-intensity animal production are also important. For example,
myasis-producing parasitic arthropods, such as the sheep blow fly (Lucila
cuprina) and disease-spreading blood-sucking flies, when uncontrolled
have devastating effects on the well-being of animals and on the econom­
ics of food production.
Thus, an array of bioactive compounds, often derived directly from
the pharmaceutical and crop protection industries, are used: antibacteri-
als, anticoccidials, miticides, nematicides, parasiticides (for control of both
internal and external parasites), and insecticides. In addition, other speci­
alty chemicals, such as growth-regulating, estrous-synchronizing, and
nutrient-repartitioning agents, are in use and are being considered for use
in animal production.
In the United States, crop protection agents used in food production
are regulated by the Environmental Protection Agency, and the use of
veterinary products is closely regulated by the Food and Drug Administra­
tion. Clear differences exist between the problems associated with the
administration of veterinary products and the exposure of animals to crop
protection agents. The use of veterinary products involves their deliber­
ate and controlled application for benefit. Studies conducted in the
development phase of a veterinary product address, in addition to the tox­
icology, the fate of the chemical in the test species. Withdrawal periods
are set so that residues in edible tissues are at or below an acceptable
concentration.
In contrast, the exposure of animals to crop protection agents is
adventitious and usually via feedstuff. Animal studies on crop protection
agents are designed to determine if residue transfer (from feed to animal
product) occurs at an acceptably low level. However, there is much in
common between studies on veterinary products and crop protection
xi
In Xenobiotics and Food-Producing Animals; Hutson, D., et al.;
ACS Symposium Series; American Chemical Society: Washington, DC, 1992.
agents. Some of the agents (e.g., insecticides) are common. The species
exposed to these agents are also common (ruminants, swine, poultry, and
fish). Of paramount importance, the terminal residues to which humans
are exposed via food consumption present similar toxicological issues.
Most of this book concerns the metabolism of veterinary products, as
opposed to crop protection agents, because the former grouping covers a
wider range of bioactivities. The content will, however, be of interest to
those working with both types of agents. Specifically, a substantial
amount of information about general methods for studying the fate of
xenobiotics in species grown for human consumption is available.
Increased attention is being paid to the fate of veterinary drugs in the
environment, a major concern for crop protection agents for 30 years.
Turning this situation around, environmental scientists concerned with
the fate of other (e.g., industrial) chemicals should gain understanding of
the capacity of food-producing animals to metabolize and eliminate chem­
icals. This knowledge is important as a basis for judgments about poten­
tial risk in the event of a major chemical contamination.
We acknowledge the support of the International Society for the
Study of Xenobiotics and the American Chemical Society's Division of
Agrochemicals. We thank the authors for their efforts and we are grate­
ful for the help provided by the ACS Books Department.
D. H. HUTSON
Shell Research Limited
Kent, England
G. D. PAULSON
U.S. Department of Agriculture
Fargo, ND 58105-5674
D. R. HAWKINS
Huntingdon Research Centre
Cambridgeshire, England
C. B. STRUBLE
Hazleton Laboratories
Madison, WI 53707
April 6, 1992
xii
In Xenobiotics and Food-Producing Animals; Hutson, D., et al.;
ACS Symposium Series; American Chemical Society: Washington, DC, 1992.
Chapter 1
Uses and Regulation of Veterinary Drugs
Introduction
Κ. N. Woodward
Veterinary Medicines Directorate, Woodham Lane, New Haw, Addlestone,
Surrey KT15 3NB, United Kingdom
There are a variety of veterinary drugs available and at
the disposal of the veterinarian and the safety of these
to the consumer must be assured in most countries of the
world before marketing authorizations can be granted. A
large body of pharmacological, toxicological and
residues data is generated and assessed so that the
toxicological profile of the drug can be established and
a maximum residue limit elaborated. This, along with
the residues depletion profile, allows a withdrawal
period to be defined so that the consumer is protected
from exceeding the acceptable daily intake for the drug
in question. Worker safety is also of paramount
importance when assessing a drug and its formulations
prior to marketing authorisation. Veterinary medicines
take many forms and a few of the more important groups
are described in this article.
The range of veterinary medicines now available reflects both the
diseases they are intended to combat and the range of species they
are intended to treat. In addition, there are a number of drugs
available for so-called zootechnical treatment (eg the use of
steroid hormones in synchronization of oestrus) as opposed to
disease treatment or prophylaxis. These aspects will be briefly
discussed in this article, but a certain amount of liberty has
been taken with the title so that the word "use" is interpreted in
its widest sense to include a description of what occurs before
"use" is allowed! Consequently, a large part of this work will
deal with the general requirements of marketing authorization; the
regulatory requirements that are applied before a veterinary
medicine may be marketed.
UB&U of Veterinary Medicines
Veterinary medicines, like their human counterparts come in many
forms (1). Some would be instantly recognizable as tablets, pills
0097-6156/92/0503-00002$06.00/0
© 1992 American Chemical Society
In Xenobiotics and Food-Producing Animals; Hutson, D., et al.;
ACS Symposium Series; American Chemical Society: Washington, DC, 1992.