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Statistics and experimental design for toxicologists PDF

389 Pages·2018·14.992 MB·English
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Statistics And Experimental Design For Toxicologists Statistics and Experimental Design For Toxicologists Shayne C. Gad G.D. Searle and Company Skokie, Illinois and Carrol S. Weil C.S. Weil, Inc. Pittsburgh, Pennsylvania TELBoFcaO RaRtonD Lo nPdoRn ENeSwS Y ork CRC Press is an imprint of the Taylor &C Faralndciws Gerolulp, , aNn ewinf oJrmears beusyin ess First published 1988 by CRC Press Taylor & Francis Group 6000 Broken Sound Parkway NW, Suite 300 Boca Raton, FL 33487-2742 Reissued 2018 by CRC Press © 1988 by The Telford Press, Inc. CRC Press is an imprint of Taylor & Francis Group, an Informa business No claim to original U.S. Government works This book contains information obtained from authentic and highly regarded sources. Reasonable efforts have been made to publish reliable data and information, but the author and publisher cannot assume responsibility for the validity of all materials or the consequences of their use. The authors and publishers have attempted to trace the copyright holders of all material reproduced in this publication and apologize to copyright holders if permission to publish in this form has not been obtained. If any copyright material has not been acknowledged please write and let us know so we may rectify in any future reprint. Except as permitted under U.S. Copyright Law, no part of this book may be reprinted, reproduced, transmitted, or utilized in any form by any electronic, mechanical, or other means, now known or hereafter invented, including photocopying, microfilming, and recording, or in any information storage or retrieval system, without written permission from the publishers. Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation without intent to infringe. Library of Congress Cataloging-in-Publication Data Statistics and Experimental Design for Toxicologists 1. Toxicology—Statistical methods. 2. Toxicology, Experimental—Statistical methods. I. Gad, Shayne, C., 1948 — II. Weil, Carrol S. RA1199.4.S73S73 1986 615.9’0072 86—1953 ISBN 0-936923-17-2 ISBN 0-936923-18-0 A Library of Congress record exists under LC control number: 93012834 Publisher’s Note The publisher has gone to great lengths to ensure the quality of this reprint but points out that some imperfections in the original copies may be apparent. Disclaimer The publisher has made every effort to trace copyright holders and welcomes correspondence from those they have been unable to contact. ISBN 13: 978-1-315-89315-0 (hbk) ISBN 13: 978-1-351-07225-0 (ebk) Visit the Taylor & Francis Web site at http://www.taylorandfrancis.com and the CRC Press Web site at http://www.crcpress.com DEDICATION To my beloved Suzann, who made me real again and brought me back to the World. SCG CONTENTS ACKNOWLEDGEMENTS PREFACE I. INTRODUCTION ........................................................... I Philosophy and General Principles/Overview II. BASIC PRINCIPLES ....................................................... 5 Types of Data/Functions of Statistics/Descriptive Statistics/Sampling/Outliers and Rounding/ Decision Trees for Methods Ill. EXPERIMENTAL DESIGN .......................................... 2I Objectives/General Principles/Approaches for Toxicology/Logistical and Planning Tools/ Necessary Sample Sizes IV. COMPUTATIONAL DEVICES .................................... 30 Calculators/Microcomputers and Software/ Statistical Libraries V. METHODS FOR DATA PREPARATION AND EXPLORATION .................................................. 40 Randomization/Bartlett's Test/Scattergram/ Exploratory Data Analysis VI. HYPOTHESISTESTING: CATEGORICAL AND RANKED DATA ...................... 53 Fisher's Exact Test/R X C Chi Square/Wilcoxon Rank-Sum Test/Distribution-Free Multiple Comparisons/Mann-Whitney U Test!Kmskal-Wallis Non parametric Analysis of Variance VII. HYPOTHESIS TESTING: UNIVARIATE .................. 70 Student's t-Test/Cochran's t- Test/F-Test/Analysis of Variance/Post-Hoc Tests/Duncan's Multiple Range/ Scheffe's Multiple Comparisons/Dunnett's/ William's t- Test/ Analysis of Covariance VIII. MODELING ................................................................... 93 - Linear Regression/Probit!Log Plots/Moving Averages/Correlation Coefficient/Nonlinear Regression/Kendall's Rank Correlation/Trend Analysis vii II. METHODS FOR THE REDUCTION OF DIMENSIONALITY .................................................... 111 Classification/Construction of Tables/ Statistical Graphics/Multidimensional and Nonmetric Scaling/Cluster Analysis/Fourier Analysis/Life Tables X. MULTIVARIATE METHODS .................................... 130 Multivariate Distribution and Population Parameters/Data Preparation/MANOVN Factor Analysis/Multi pie Regression/Discriminant Analysis/Canonical Correlation Analysis/ Principal Components/Correspondence Analysis/Biplot Analysis XI. DATAANALYSISAPPLICATIONS IN TOXICOLOGY ....................................................... 147 LD50 and LC50/Body and Organ Weights/ Clinical Chemistry/Hematology/Histopathology/ Reproduction/Teratology/Dominant Lethal/Diet and Chamber Analysis/ Aerosol Statistics/Mutagenesis/ Behavioral Toxicology XII. CARCINOGENESIS AND RISK ASSESSMENT ...... 176 Analysis of Carcinogenicity Bioassay/Low Dose Extrapolation XIII. STRUCTURE ACTIVITY RELATIONSHIPS .......... 244 XIV. AREAS OF CONTROVERSY ..................................... 253 One or Two Sided Comparisons/Unbalanced Study Designs/Computerized Statistical Packages APPENDICES: 1. Tables: A. Logarithms ............................................ 256 B. Probit Transform Values ....................... 261 C. Chi Square ............................................. 266 D. H Values ................................................ 268 E. Mann-Whitney U Values ....................... 270 F. t-Test Critical Values ............................... 2 7 6 G. F Distribution (.05, .01, .001) ................ 2 7 7 H. Z scores for Normal Distribution ......... 283 I. Table for Calculation of Median Effective Dose by Moving Average ........ 285 J. Critical Values For The Wilcox Rank Sum Test ................................................. 323 2. Definition of Terms ....................................... 331 3. Greek Alphabet, Abbreviations and Symbols .......................................................... 334 INDEX viii ACKNOWLEDGEMENTS There are a number of people without whom this book would either never have been completed or would be much less than it is. Lorie Abraham and Nancy Bruce spent many hours struggling with translating handwritten pages into the final polished manuscript-a feat of typing, given the use of unfamiliar specialized symbols, which was certainly beyond the scope of any job requirement. And Gary Roy and Ann Smith provided exacting proofreading of the manuscript without which the final product would not be nearly as lucid as it is. We wish to thank these fine people for their support. ix

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