PVP: A Critical Review Of The Kinetics And Toxicology Of Polyvinylprrolidone (Povidone)

232 Pages·2018·12.499 MB·English

by  David S. Brown, Borzelleca, Joseph F., Robinson, Brian V., Schwartz, S. L., Sullivan, F. M

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PVP
A Critical Review of the Kinetics and
Toxicology of Polyvinylpyrrolidone (Povidone)
i •
Walter Reppe
(1892-1969)
PVP
A Critical Review of the Kinetics and
Toxicology of Polyvinylpyrrolidone (Povidone)
B. V. Robinson
F. M. Sullivan
Department of Pharmacology and Toxicology
United Medical and Dental Schools
Guy’s Hospital
University of London
London
J. F. Borzelleca
Department of Pharmacoiogy and Toxicology
Medical College of Virginia
Richmond, Virginia
S. L. Schwartz
Department of Pharmacology
Georgetown School of Medicine
Washington, D.C.
CRC Press
Taylor h Francis Group
Boca Raton London New York
CRC Press is an imprint of the
Taylor & Francis Croup, an informa business
Library of Congress Cataloging-in-Publication Data
PVP: a critical review of the kinetics and toxicology of polyvinylpyr­
rolidone (povidone)
Includes bibliographical references
1. Povidone—Pharmacokinetics. 2. Povidone—
Toxicology. I. Robinson, B.V. (Brian V.) [DNLM: 1. Povidone-
pharmacokinetics. 2. Povidone—toxicity. WH 450 P994]
RM666.P822P96 1990 615'.7 89-13515
ISBN 0-87371-288-9
COPYRIGHT © 1990 by LEWIS PUBLISHERS, INC.
ALL RIGHTS RESERVED
Neither this book nor any part may be reproduced or transmitted in
any form or by any means, electronic or mechanical, including photo­
copying, microfilming, and recording, or by any information storage
and retrieval system, without permission in writing from the publisher.
LEWIS PUBLISHERS, INC.
121 South Main Street, Chelsea, Michigan 48118
Preface
The new era of synthetic polymer chemistry opened by Wal­
ter Reppe in the 1930s led to the synthesis of polyvinyl­
pyrrolidone (PVP), which was patented in 1939. The physi­
cal, chemical, and physiological properties of this synthetic
polymer are the keys to its very widespread use in medicine,
pharmaceuticals, cosmetics, foods, printing inks, textiles,
and many more diverse applications.
In recent years, the general interest in reassessing the
safety of chemicals used in foods, drugs, and cosmetics has
led to the réévaluation and reaffirmation of the safety of PVP
by the Joint Expert Committee on Food Additives (JECFA) of
the World Health Organization (WHO). Along with others,
the authors of this book became involved in collecting and
reassessing the information, published and unpublished, on
the absorption, distribution, storage, and excretion of PVP
and in its toxicological evaluation. As 1989 is the 50th anni­
versary of the invention of PVP, it seemed appropriate to
assemble at this time both the published and the unpub­
lished data that have accumulated over the last 50 years, to
critically review it, and to assess the safety of PVP as judged
by present-day criteria.
In performing this task, extensive literature reviews were
carried out, covering the period from 1939 to 1989. The most
recent toxicological investigations have been carried out by
the two major world manufacturers of PVP, BASF Aktienge­
sellschaft in Ludwigshafen, Federal Republic of Germany,
and GAF Chemicals Corporation in Wayne, New Jersey,
Vi POLYVINYLPYRROLIDONE
USA, for submission to regulatory authorities and to WHO.
Most of this work is unpublished. We have been fortunate in
being given access to all of these data and so are able to
publish for the first time critiques of much of this invaluable
material. The very earliest use of PVP in medicine was dur­
ing World War 11 when a 3.5% solution of PVP was infused
into patients as a synthetic blood plasma volume expander.
This use recognized such valuable properties of PVP as
water solubility, viscosity, and osmotic activity and demon­
strated that the material appeared to be biologically inert and
safe. The toxicity of PVP, extensively studied in a variety of
species including humans and other primates, is of
extremely low order.
In Chapters 1 and 2 the reader is introduced to PVP, its
uses, and its synthesis and properties. We have been
assisted in the preparation of this material by both BASF and
GAF, who supplied the details of the determination of the
K-values of the different PVP polymers and the molecular
weight distributions of representative batches of these
polymers.
Chapter 3 is a discussion of movement of large molecules
across membranes and forms a basis for Chapter 4, which
discusses the absorption of PVP following various routes of
administration. The excretion and metabolism of PVP are
reviewed in Chapter 5, followed by a discussion on the dis­
tribution and storage of the material in Chapter 6. Chapter 7
reviews the storage of PVP in humans.
Chapter 8 presents a review of the functional conse­
quences of PVP uptake, with particular emphasis on the reti­
culoendothelial and immune systems. Chapter 9 is a broad
review of the toxicological studies performed on PVP, includ­
ing acute, subchronic, chronic, reproductive, mutagenicity,
and carcinogenicity studies. Each chapter ends with a sum­
mary of the main findings. In addition, there is a final, over­
all summary and conclusions.
We have also prepared an Appendix, listing the key stud­
ies, with references, on the absorption, renal elimination,
distribution, acute toxicity, subchronic toxicity, chronic toxic­
PREFACE vil
ity, teratogenicity, mutagenicity, and carcinogenicity of PVP.
The Appendix summarizes in list form the major toxico-
kinetic and toxicological studies that have been conducted
on PVP, giving the species used, the experimental methods
employed, the molecular weight of PVP or its K-value, the
observations made, and the source of the information.