1. Reading Casarett and Doull Chapters 5 and 7 Timbrell, Chapter 3 EXPOSURE: Absorption, Distribution, Elimination. Or, how do chemicals (and microbes) get into, around and out of our bodies

2. Routes of Exposure Airborne – inhalation –Respiratory tract, nose-lungs Foodborne – ingestion –Gastrointestinal tract Skin Contact - transdermal Waterborne Injection –Wounds, needlesticks

4. The plasma membrane Lipid bilayer Polar Non-polar (Lipid) Protein Av. Width 7.5 nm (75 Å) Sugar Glycolipid Glycoprotein

6. Mechanisms of uptake Passive diffusion Filtration Carrier-mediated transport –Facilitated diffusion –Active transport Engulphment –Pinocytosis –Phagocytosis

7. Uptake Higher concentration Lower concentration Diffusion Filtration Pore Lipid bilayer Carrier Facilitated diffusion Active transport

8. Engulfment

9. Engulphment

10. Microbes Host cell receptors – glycolipids, glycoproteins or proteoglycans Microbial pili, fimbriae, adhesins – lectins, hemagglutinin

11. Factors influencing route and rate of uptake Properties of the chemical –Size and shape –Similarity to “endogenous” molecules –Solubility Hydrophilicity/hydrophobicity Lipophilicity/lipophobicity Partition coefficient: K ow –Log 10 of [octanol]/[water] –Charge Ionization state

12. For an acid: HAH + + A - –Henderson-Hasselbach equation: pH = pK ’ + Log 10 [A - ]/[HA] For a base: BH + B + H + –Henderson-Hasselbach equation: –pH = pK ’ + Log 10 [B]/[BH + ]

13. Properties of the membrane/tissue/organ –Presence/absence of pores –Presence/absence of carrier molecules –Thickness –Lipid content Factors influencing route and rate of uptake Carrier

14. Skin

15. Surface area approximately 2 m 2 Multilayered –Epidermis Stratum corneum Living epidermis –Dermis Blood circulation

16. Respiratory Tract

17. Respiratory tract Surface area approximately 50 to 100 m 2

19. Gastrointestinal tract Surface area approximately 600 m 2

21. Intestinal wall - villi

22. Cross-section of villus

23. Placenta

25. Distribution Factors affecting tissue localization Plasma proteins Barriers to distribution –Blood-brain barrier –Blood-nervous system barrier Factors that facilitate distribution –Sinusoids –Trans-membrane carriers

26. Location (In)ability to detoxify/clear infection Specific susceptibility – receptors, metabolic characteristics

27. Excretion Routes of elimination –Urine –Bile –Feces –Exhaled air –Sweat –Tears –Milk –Leaves

28. The Kidney

30. Lung again

32. Excretion Routes of elimination –Urine –Bile –Feces –Exhaled air –Sweat –Tears –Milk –Leaves