List of Contributors | p. IX |
Preface | p. XI |
The Practical Applicability of Toxicokinetic Models in the Risk Assessment of Chemicals | p. 1 |
Introduction | p. 1 |
Underlying Principles of Toxicokinetic Models | p. 1 |
Lack of Data | p. 2 |
Use of Structure-Activity Relationships (SARs) | p. 2 |
Standard Tests versus Compound-Specific studies | p. 3 |
Application of Toxicokinetic Data in Hazard Identification | p. 4 |
References | p. 5 |
Physiologically Based Pharmacokinetic Modeling of the Glycol Ether, 2-Butoxethanol, and Its Application in Human Health Risk Assessments and Exposure Guidelines | p. 7 |
Introduction | p. 7 |
Exposure Guidelines Using Traditional Approaches | p. 10 |
Rationale for the Development of a PBPK Model for BE | p. 13 |
Development of a Rat and Human PBPK model for BE and BAA | p. 15 |
Use of PBPK model in Risk Assessments | p. 27 |
Conclusions | p. 35 |
Acknowledgments | p. 36 |
References | p. 36 |
Application of Pharmacokinetic Modelling to Biological Monitoring | p. 41 |
Introduction | p. 41 |
Biological Monitoring | p. 42 |
Description of the Pharmacokinetic Models used | p. 43 |
Case Studies | p. 45 |
Tetrahydrofuranet | p. 45 |
Formic Acid after Methyl Formate or Methanol Exposure | p. 48 |
Comments and Conclusion | p. 50 |
References | p. 52 |
Dermal Absorption from Pesticide Residues Data Analysis | p. 55 |
Introduction | p. 55 |
Background | p. 56 |
The Zendzian Protocol | p. 60 |
Results and discussion | p. 61 |
Conclusions | p. 76 |
References | p. 78 |
Inter-Species Pharmacokinetic Comparison of Organic Acid Herbicides. Is the Dog a Relevant Species for Evaluation of Human Health Risk? | p. 79 |
Background | p. 80 |
Toxicology Background | p. 81 |
Hypothesis | p. 82 |
Approach | p. 83 |
How are organic acids cleared in the kidney of dogs and excreted in the urine? | p. 89 |
Are renal functional changes a toxicological response or a physiological adaptation associated with the excretion of organic acids? | p. 93 |
What potential mechanism(s) may be responsible for the reduced elimination of organic acids in the dog? | p. 97 |
Is the dog toxicity data obtained with either triclopyr or 2,4-D of any relevance for the extrapolation of human health risk? | p. 99 |
Regulatory Outcomes | p. 100 |
Utility of Comparative Pharmacokinetics | p. 103 |
Summary & Conclusions | p. 104 |
References | p. 104 |
Modeling the Uptake and Disposition of Hydrophobic Organic Chemicals in Fish Using a Physiologically Based Approach | p. 109 |
Development of PBTK Models for Fish | p. 109 |
Branchial Efflux of Organic Chemicals | p. 111 |
Erickson-McKim Gill Models | p. 111 |
Empirical Relationship Between Log PBW and Log KOW | p. 112 |
Chemical Distribution between Blood and Tissues | p. 115 |
Equilibrium Tissue:Blood Partitioning | p. 115 |
Flow vs. Diffusion Limitations | p. 116 |
PBTK Models for Fish | p. 117 |
TCDD Model | p. 117 |
TCB Model | p. 122 |
Discussion | p. 128 |
References | p. 131 |
Chair's Introduction to the Second Symposium Day | p. 135 |
Introduction | p. 135 |
Cancer risk assessment of azo dyes and aromatic amines from garment and footwear (Speijers et al, 1996; Zeilmaker et al. 1999) | p. 136 |
Calculation of human toxicity thresholds for TCDD (Zeilmaker and Van Eijkeren, 1998) | p. 137 |
PBPK simulated adduct formation as a result of benzopyrene administration (Zeilmaker et al, 1997-1999) | p. 137 |
Model for estimating lipophilic contaminants in cattle (Freijer et al, 1999) | p. 138 |
Last, but certainly not at least, the modelling of consumer exposure (Van Veen et al, 1994-now) | p. 138 |
Can Biologically Based Models of Carcinogenesis Be Used for Risk Assessment? Potentials and Limitations of Carcinogenesis Models | p. 141 |
Introduction | p. 141 |
Models of carcinogenesis | p. 142 |
Quantitative risk assessment with multistage models | p. 147 |
Summary | p. 151 |
References | p. 151 |
The Prediction of Systemic Toxicity by Integrating the Results of Biokinetic Models and Biologically Based in Vitro Test Methods | p. 155 |
Introduction | p. 156 |
Integration of kinetic and dynamic data to estimate systemic toxicity | p. 160 |
Biokinetic modelling | p. 163 |
In vitro and other non-animal studies for obtaining compound-specific parameters for the use in PB-BK models | p. 164 |
Toxicity test batteries: in vitro approaches | p. 168 |
Results of the ECITTS project | p. 169 |
Discussion | p. 177 |
Kinetics | p. 177 |
Dynamics | p. 182 |
Conclusions from the ECITTS study | p. 185 |
A generic scheme for evaluating chemical toxicity | p. 185 |
Concluding remarks | p. 188 |
References | p. 189 |
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