CLINICAL TOXICOLOGY Principles and Mechanisms
BERRNIP3DJHLL7XHVGD\2FWREHU$0
CLINICAL T...
119 downloads
1280 Views
4MB Size
Report
This content was uploaded by our users and we assume good faith they have the permission to share this book. If you own the copyright to this book and it is wrongfully on our website, we offer a simple DMCA procedure to remove your content from our site. Start by pressing the button below!
Report copyright / DMCA form
CLINICAL TOXICOLOGY Principles and Mechanisms
BERRNIP3DJHLL7XHVGD\2FWREHU$0
CLINICAL TOXICOLOGY Principles and Mechanisms
FR ANK A. BARILE
CRC PR E S S Boca Raton London New York Washington, D.C.
This edition published in the Taylor & Francis e-Library, 2005. “To purchase your own copy of this or any of Taylor & Francis or Routledge’s collection of thousands of eBooks please go to www.eBookstore.tandf.co.uk.”
Library of Congress Cataloging-in-Publication Data Barile, Frank A. Clinical toxicology: principles and mechanisms/ Frank A. Barile. p. cm. Includes bibliographical references and index. ISBN 0-8493-1582-4 1. Clinical toxicology. [DNLM: 1. Toxicology—standards. 2. Pharmacology, Clinical—standards. 3. Toxicity Tests—standards. 4. Toxicology—classification. QV 600 B252c 2003] I. Title. RA1218.5.B37 2003 615.9—dc22 2003055716
This book contains information obtained from authentic and highly regarded sources. Reprinted material is quoted with permission, and sources are indicated. A wide variety of references are listed. Reasonable efforts have been made to publish reliable data and information, but the author and the publisher cannot assume responsibility for the validity of all materials or for the consequences of their use. Neither this book nor any part may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, microfilming, and recording, or by any information storage or retrieval system, without prior permission in writing from the publisher. The consent of CRC Press LLC does not extend to copying for general distribution, for promotion, for creating new works, or for resale. Specific permission must be obtained in writing from CRC Press LLC for such copying. Direct all inquiries to CRC Press LLC, 2000 N.W. Corporate Blvd., Boca Raton, Florida 33431. Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation, without intent to infringe.
Visit the CRC Press Web site at www.crcpress.com © 2004 by CRC Press LLC No claim to original U.S. Government works International Standard Book Number 0-8493-1582-4 Library of Congress Card Number 2003055716 ISBN 0-203-49326-5 Master e-book ISBN
ISBN 0-203-58701-4 (Adobe eReader Format)
BERRNIP3DJHY7XHVGD\2FWREHU$0
Dedication 7RWKHPHPRU\RI)UDQN%DULOH6U
BERRNIP3DJHYL7XHVGD\2FWREHU$0
BERRNIP3DJHYLL7XHVGD\2FWREHU$0
Preface ,QWKHODVW\HDUVWKHVFLHQFHRIFOLQLFDOWR[LFRORJ\KDVHYROYHGIURPDQDSSOLHG VFLHQFHSURJUHVVLQJLQWKHVKDGRZVRIPRUHKLJKO\GHÀQHGDUHDVRIWR[LFRORJ\WR LWV RZQ UHFRJQL]HG GLVFLSOLQH 0XFK OLNH WKH GHYHORSPHQW RI RWKHU À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ÁRRGHGWKHVWUHHWVDWXQSUHF HGHQWHGUDWHV$PHULFDQVRIDOODJHVHWKQLFEDFNJURXQGVDQGVRFLRHFRQRPLFVWDWXV ZHUH LQXQGDWHG ZLWK WKH VXGGHQ DFFHVVLELOLW\ RI FKHPLFDOV WKDW FRXOG DOWHU PLQG PRRGEHKDYLRUDQGSHUFHSWLRQ/DUJHDQGFXPEHUVRPHJRYHUQPHQWFDPSDLJQVWR WKZDUW WKH LQÁ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´%DVHPHQWµGHULYDWLYHVRISDUHQWLOOLFLWGUXJVUHOHDVHGPRUHSRWHQWDQDORJVRQWR WKHVWUHHWV$JHQWVVXFKDV3&3DQG´HFVWDV\µSURGXFHGWR[LFV\QGURPHVWKDWZHUH QRWLPPHGLDWHO\DSSDUHQWDIWHULQJHVWLRQ7KHFDUGLRYDVFXODUWR[LFLW\DQGSV\FKR ORJLFDOGHUDQJHPHQWDVVRFLDWHGZLWKWKHVHQHZHUFRPSRXQGVDUHWRGDWHGLIÀFXOW WRPDQDJH 7KHVDQGWKHWULDORIIRRWEDOOVWDU2-6LPSVRQGLGPRUHIRUWKHVFLHQFHV RIIRUHQVLFDQGFOLQLFDOWR[LFRORJ\WKDQDQ\RWKHUHYHQWWRGDWH7KHH[SODQDWLRQRI WKHDQDO\WLFDOPHWKRGVRI'1$LVRODWLRQDQGLGHQWLÀFDWLRQDQGWKHGHSLFWLRQRIWKH ODGGHUOLNHSDWWHUQVRI'1$SURÀOHVDSSHDUHGRQHYHU\WHOHYLVLRQQHZVFKDQQHOIRU PRQWKV)RUDEULHIWLPHUHSRUWLQJRQWKHWHFKQLTXHVRIIRUHQVLFDQGFOLQLFDOWR[L FRORJ\ ZDV VR FRPPRQ WKDW LW ZDV QRW QHFHVVDU\ WR GHÀQH WKH WHUPV ´'1$µ RU ´JHQHWLFPDWHULDOµLQWKHQDWLRQDOPHGLDUHSRUWV
BERRNIP3DJHYLLL7XHVGD\2FWREHU$0
7KHSULQFLSOHVRIFOLQLFDOWR[LFRORJ\GRQRWGLIIHUVLJQLÀFDQWO\IURPRWKHUWR[ LFRORJ\GLVFLSOLQHV&RQVHTXHQWO\PDQ\RIWKHWRSLFVGLVFXVVHGLQWKLVWH[WLQFOXGH WKRVHFRPPRQO\EURDFKHGLQJHQHUDOWR[LFRORJ\WH[WVQDPHO\PHFKDQLVPRIWR[ LFLW\PHGLFLQDOFKHPLVWU\DQGWR[LFRNLQHWLFV7RSLFVVXFKDV VLJQVDQGV\PSWRPV DQGFOLQLFDOPDQDJHPHQWRIDFXWHWR[LFLW\DUHXQLTXHWRWKHGLVFLSOLQH+RZHYHULW LV LPSRUWDQW WR QRWH WKDW WKLV ERRN LV QRW DQ HPHUJHQF\ UHIHUHQFH WH[W $V VXFK GHWDLOHG WKHUDSHXWLF PDQDJHPHQW SURWRFROV DUH QRW LQFOXGHG 6SHFLÀ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ÀFD WLRQ RI WKH GUXJ RU FKHPLFDO LQ ERG\ Á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
BERRNIP3DJHL[7XHVGD\2FWREHU$0
The Author )UDQN$ %DULOH 3K' LV DVVRFLDWH SURIHVVRU LQ WKH 7R[LFRORJ\ 'LYLVLRQ RI WKH 'HSDUWPHQW RI 3KDUPDFHXWLFDO 6FLHQFHV DW 6W -RKQ·V 8QLYHUVLW\ &ROOHJH RI 3KDU PDF\DQG$OOLHG+HDOWK3URIHVVLRQV-DPDLFD1HZ