Toxicology of Methanol

JOHN J. CLARY is President of Bio Risk, a toxicology consulting firm. Previously, he worked for two U.S. government research laboratories, managed the toxicology groups of DuPont and Hoechst Celanese, and served as Director of Toxicology for Dow Corning and Celanese. Dr. Clary has authored sixty-five articles.

• Preface xiii Contributors xv1 Methanol Production and Markets: Past, Present, and Future 1Gregory A. DolanReferences 92 Methanol: Fate and Transport in the Environment 11Rula A. Deeb, Todd L. Anderson, Michael C. Kavanaugh, and Lauren A. Kell2.1 Introduction 112.2 Partitioning of Methanol in the Environment 162.3 Fate and Transport of Methanol in the Environment 222.4 Methanol Additives 372.5 Conclusions 40References 403 Human Toxicity 47John J. Clary3.1 Introduction 473.2 Exposure 483.3 Metabolism in Humans 503.4 History of Human Toxicity 543.5 Controlled Human Studies 603.6 In Utero Exposure 623.7 Repeat Inhalation Exposure 633.8 Management of Methanol Poisoning 643.9 Conclusions 66References 674 General Animal and Aquatic Toxicity 73John J. Clary4.1 Introduction 734.2 Acute Toxicity 744.3 Irritation 864.4 Sensitization 874.5 Repeat Exposure—Inhalation 874.6 Repeat Exposure—Oral 944.7 Repeat Exposure—Dermal 964.8 Aquatic Toxicity 964.9 Conclusion 99References 1005 Developmental and Reproductive Toxicology of Methanol 107John M. Rogers, Jeffrey S. Gift, and Stanley Barone, Jr.5.1 Introduction 1075.2 Reproductive Toxicity 1085.3 Developmental Toxicity 1105.4 Conclusions 136Disclaimer 139References 1396 Exploring Differences Between PBPK Models of Methanol Disposition in Mice and Humans: Important Lessons Learned 145Thomas B. Starr6.1 Background 1456.2 Are Humans More or Less Sensitive than Mice to the Toxic Effects of Methanol? 1486.3 Are the Two Models’ Predictions of Human Blood Methanol Concentrations at Steady State Consistent with Each Other? 1536.4 Are the Values of Key Human Metabolism Parameters Consistent with Those in the Published Scientific Literature? 1556.5 Shouldn’t the Possibility of Systematic Bias be Considered Carefully During the Model Fitting and Parameter Estimation Process? 1606.6 Is “Visual Optimization” an Adequate Technique for Estimating PBPK Model Parameters? 1616.7 When Human Data are Available, Shouldn’t they be Utilized in Making an Objective Comparison of Model-Specific Predictions? 1636.8 Summary of Lessons Learned 164References 1657 Oxidative Stress and Species Differences in the Metabolism, Developmental Toxicity, and Carcinogenic Potential of Methanol and Ethanol 169Peter G. Wells, Gordon P. McCallum, Lutfiya Miller, Michelle Siu, and J. Nicole Sweeting7.1 Introduction 1697.2 Species Differences in Methanol Metabolism 1797.3 Species and Strain Differences in Methanol Toxicity 1917.4 Oxidative Stress 2137.5 Conclusions 237Acknowledgment 238References 2388 Methanol and Cancer 255John J. Clary8.1 Introduction 2558.2 Rodent Bioassay 2568.3 Possible Mechanisms 2708.4 Human Cancer Data 2768.5 Conclusion 276References 277Index 283