Principles+Lec+3+2013

7 useful applications ddt ld50 differences between

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Unformatted text preview: umans have 1% dermal appendages, other mammals have higher DA’s Rabbit 12 Monkey 6 Human 3.7 • Useful applications - DDT LD50 differences between insects and mammals humans and low (pesticide use) high value forabsorb much morefor insects do insects then humans - Species differences affect testing levels (2,4-D) (consideration for regulatory toxicology) 2. Gastrointestinal Tract: “Oral Route” Structure vs. Function: Absorption of nutrients Characteristics Favoring absorption: a. Single cell lipoidal membrane short distance to cover therefore more absorption to diffuse b. Large surface area (villi-microvilli) more areamore absorption therefore c. High blood and lymph flow d. Variable pH (3 - 8 )* (range of organic acids) a weak acid/base may eventually get to a part where its absorption is favoured based on pH e. Many specialized transport proteins (not diffusion dependant) have the ability to pump in different compounds that can’t normally get in Organization of the GI System Long length: Absorption can occur from the mouth to the colon Variable pH: 2 in stomach, 6 in SI, 8 in Colon GI tract is long, so there is a long residency time for something to be absorbed thought this tract Intestinal Mucosa Gastrointestinal Tract Structure goes to liver, filters and changes stuff then blood goes to circulatory system pH 3 Surface area pH 8 Villi of Gastrointestinal Tract Large surface area Blood / lymph close • Mucosa has villi and microvilli (600x increase in SA • Diffusion mediated transport increases • Blood supply keeps gradient in order • Transporter proteins for numerous xenobiotic expressed on brush border Transporter Proteins dont memorize names of transporters • Specific Proteins bring in large water soluble molecules know these ones • Protein families like Organic Anion Transporters (OAT) or Organic Cation Transporter (OCT) transport molecules with similar physical or chemical properties • Competition for limited sites huge surface area through GI tract, helps with competition, so more absorption can occur • Balance between in and out determines final blood concentration...
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This document was uploaded on 04/07/2014.

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