John W. Green, Timothy A. Springer, Henrik Holbech

Statistical Analysis of Ecotoxicity Studies (eBook, PDF)

• Format: PDF

Produktbeschreibung

A guide to the issues relevant to the design, analysis, and interpretation of toxicity studies that examine chemicals for use in the environment Statistical Analysis of Ecotoxicity Studies offers a guide to the design, analysis, and interpretation of a range of experiments that are used to assess the toxicity of chemicals. While the book highlights ecotoxicity studies, the methods presented are applicable to the broad range of toxicity studies. The text contains myriad datasets (from laboratory and field research) that clearly illustrate the book's topics. The datasets reveal the techniques, pitfalls, and precautions derived from these studies. The text includes information on recently developed methods for the analysis of severity scores and other ordered responses, as well as extensive power studies of competing tests and computer simulation studies of regression models that offer an understanding of the sensitivity (or lack thereof) of various methods and the quality of parameter estimates from regression models. The authors also discuss the regulatory process indicating how test guidelines are developed and review the statistical methodology in current or pending OECD and USEPA ecotoxicity guidelines. This important guide: * Offers the information needed for the design and analysis to a wide array of ecotoxicity experiments and to the development of international test guidelines used to assess the toxicity of chemicals * Contains a thorough examination of the statistical issues that arise in toxicity studies, especially ecotoxicity * Includes an introduction to toxicity experiments and statistical analysis basics * Includes programs in R and excel * Covers the analysis of continuous and Quantal data, analysis of data as well as Regulatory Issues * Presents additional topics (Mesocosm and Microplate experiments, mixtures of chemicals, benchmark dose models, and limit tests) as well as software Written for directors, scientists, regulators, and technicians, Statistical Analysis of Ecotoxicity Studies provides a sound understanding of the technical and practical issues in designing, analyzing, and interpreting toxicity studies to support or challenge chemicals for use in the environment.

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Produktdetails

• Verlag: John Wiley & Sons
• Seitenzahl: 416
• Erscheinungstermin: 4. Juli 2018
• Englisch
• ISBN-13: 9781119488828
• Artikelnr.: 53433687

Autorenporträt

JOHN W. GREEN, PHD, PHD is currently a Principal Consultant Biostatistics in DuPont Data Science and Informatics Group. Dr. Green is the lead DuPont statistician developing internal expertise and training in probabilistic risk assessment methods following guidance developed by EUFRAM and has been very active in OECD expert groups developing test guidelines and guidance documents. TIMOTHY A. SPRINGER, PHD has served as the statistician for Wildlife International, a leading contract ecotoxicology testing laboratory, for over 25 years. HENRIK HOLBECH, PHD is an Associate Professor in Ecotoxicology at the University of Southern Denmark.

Inhaltsangabe

Preface ix Acknowledgments xi About the Companion Website xiii 1. An
Introduction to Toxicity Experiments 1 1.1 Nature and Purpose of Toxicity
Experiments 1 1.2 Regulatory Context for Toxicity Experiments 7 1.3
Experimental Design Basics 8 1.4 Hierarchy of Models for Simple Toxicity
Experiments 12 1.5 Biological vs. Statistical Significance 13 1.6
Historical Control Information 15 1.7 Sources of Variation and Uncertainty
15 1.8 Models with More Complex Structure 16 1.9 Multiple Tools to Meet a
Variety of Needs or Simple Approaches to Capture Broad Strokes? 16 2.
Statistical Analysis Basics 19 2.1 Introduction 19 2.2 NOEC/LOEC 19 2.3
Probability Distributions 24 2.4 Assessing Data for Meeting Model
Requirements 29 2.5 Bayesian Methodology 30 2.6 Visual Examination of Data
30 2.10 Time-to-Event Data 37 2.11 Experiments with Multiple Controls 38 3.
Analysis of Continuous Data: NOECs 47 3.1 Introduction 47 3.2 Pairwise
Tests 47 3.3 Preliminary Assessment of the Data to Select the Proper Method
of Analysis 53 3.4 Pairwise Tests When Data do not Meet Normality or
Variance Homogeneity Requirements 62 3.5 Trend Tests 67 3.6 Protocol for
NOEC Determination of Continuous Response 75 3.7 Inclusion of Random
Effects 75 3.8 Alternative Error Structures 76 3.9 Power Analyses of Models
77 Exercises 81 4. Analysis of Continuous Data: Regression 89 4.1
Introduction 89 4.2 Models in Common Use to Describe Ecotoxicity
Dose-Response Data 92 4.3 Model Fitting and Estimation of Parameters 95 4.4
Examples 104 4.5 Summary of Model Assessment Tools for Continuous Responses
112 Exercises 114 5. Analysis of Continuous Data with Additional Factors
123 5.1 Introduction 123 5.2 Analysis of Covariance 123 5.3 Experiments
with Multiple Factors 135 Exercises 41 6. Analysis of Quantal Data: NOECs
157 6.1 Introduction 157 6.2 Pairwise Tests 157 6.3 Model Assessment for
Quantal Data 160 6.4 Pairwise Models that Accommodate Overdispersion 162
6.5 Trend Tests for Quantal Response 165 6.6 Power Comparisons of Tests for
Quantal Responses 168 6.7 Zero-Inflated Binomial Responses 172 6.8
Survival- or Age-Adjusted Incidence Rates 175 Exercises 179 7. Analysis of
Quantal Data: Regression Models 181 7.1 Introduction 181 7.2 Probit Model
181 7.3 Weibull Model 188 7.4 Logistic Model 188 7.5 Abbott's Formula and
Normalization to the Control 190 7.6 Proportions Treated as Continuous
Responses 197 7.7 Comparison of Models 198 7.8 Including Time-Varying
Responses in Models 199 7.9 Up-and-Down Methods to Estimate LC50 204 7.10
Methods for ECx Estimation When there is Little or no Partial Mortality 206
Exercises 215 8. Analysis of Count Data: NOEC and Regression 219 8.1
Reproduction and Other Nonquantal Count Data 219 8.2 Transformations to
Continuous 219 8.3 GLMM and NLME Models 223 8.4 Analysis of Other Types of
Count Data 228 Exercises 237 9. Analysis of Ordinal Data 243 9.1
Introduction 243 9.2 Pathology Severity Scores 243 9.3 Developmental Stage
249 Exercises 255 10. Time-to-Event Data 259 10.1 Introduction 259 10.2
Kaplan-Meier Product-Limit Estimator 261 10.3 Cox Regression Proportional
Hazards Estimator 266 10.4 Survival Analysis of Grouped Data 268 Exercises
271 11. Regulatory Issues 275 11.1 Introduction 275 11.2 Regulatory Tests
275 11.3 Development of International Standardized Test Guidelines 276 11.4
Strategic Approach to International Chemicals Management (SAICM) 279 11.5
The United Nations Globally Harmonized System of Classification and
Labelling of Chemicals (GHS) 279 11.6 Statistical Methods in OECD
Ecotoxicity Test Guidelines 279 11.7 Regulatory Testing: Structures and
Approaches 279 11.8 Testing Strategies 287 11.9 Nonguideline Studies 291
12. Species Sensitivity Distributions 293 12.1 Introduction 293 12.2
Number, Choice, and Type of Species Endpoints to Include 294 12.3 Choice
and Evaluation of Distribution to Fit 294 12.4 Variability and Uncertainty
300 12.5 Incorporating Censored Data in an SSD 302 Exercises 307 13.
Studies with Greater Complexity 309 13.1 Introduction 309 13.2 Mesocosm and
Microcosm Experiments 310 13.3 Microplate Experiments 316 13.4
Errors-in-Variables Regression 321 13.5 Analysis of Mixtures of Chemicals
323 13.6 Benchmark Dose Models 326 13.7 Limit Tests 327 13.8 Minimum Safe
Dose and Maximum Unsafe Dose 329 13.9 Toxicokinetics and Toxicodynamics 331
Exercises 343 Appendix 1 Dataset 345 Appendix 2 Mathematical Framework 347
A2.3 Method of Maximum Likelihood 350 A2.4 Bayesian Methodology 352 A2.5
Analysis of Toxicity Experiments 354 A2.6 Newton's Optimization Method 358
Table A3.3 Linear and Quadratic Contrast A2.7 The Delta Method 359
Coefficients 366 A2.8 Variance Components 360 Table A3.4 Williams' Test
talpha ,k for alpha = 0.05 367 Appendix 3 Tables Table A3.1 Studentized
Maximum Distribution 364 Table A3.2 Studentized Maximum Modulus
Distribution 365 Table A3.3 Linear and Quadratic Contrast Coefficients 366
Table A3.4 Williams' Test talpha,k for alpha = 0.05 367 References 371
Author Index 385 Subject Index 389