PUBH 114 CH06

  1. define toxicology

       1. the study of the effects of chemicals on the human body

             1. types of toxins

                   1. toxin

                         1. natural          2. toxicant

                         1. synthetically made             2. how do toxicants affect the body

                               1. toxicants have the potential to harm bodily organs and processes either at the site of exposure or beyond             3. example: BPA             4. how to classify toxicants

                               1. use 3 categories

                                     1. what is the chemical class                   2. what is the source of exposure                   3. what is the target organ                2. toxicants, mutagens, and carcinogens

                                     1. classified as disrupting DNA

                                           1. how can chemicals disrupt DNA?

                                                 1. must be “bioactivated” or taken in by the body and was transformed to become toxic metabolites                   2. progression of chemical carcinogens

                                           1. initiation

                                                 1. change of genes from exposure                      2. promotion

                                                 1. time passes and the changed cells grow in numbers                         2. effects of DNA change can be reversed                      3. progression

                                                 1. increases in the size of tumor and mutations                         2. invasive                      4. metastasis

                                                 1. spread of changed cells from the original site to other parts of the body via the bloodstream    2. Paracelsus:

             1. “the dose makes the poison”

                   1. this statement does not apply to toxins that can have damaging results with low doses    3. toxicity

             1. poisons

                   1. causes illness/ death at low doses

                         1. adult low doses

                               1. 3/4 tsp             2. toddler low dose

                               1. 1/8 tsp          2. acute toxicity

                         1. when a one-time high dosage causes harm
         3. chronic toxicity

                         1. exposure to a low dosage over time and how the chemical affects a human’s health             2. use to measure chronic toxicity

                               1. the dose-response curve

                                     1. as the dose increases (the x-axis) the effects increase (the y-axis)                   2. the only time there is no change in the effects is before the threshold                   3. there is a maximum effect range                2. dose-response relationship

                                     1. looks at the relationship between the dosage amount and the maximal therapeutic effect versus the toxic effects                   2. can be used when determining if a drug is relevant to prescribe when comparing therapeutic effects and toxic effects       2. endocrine disruptors

                   1. potential sources

                         1. metals             2. industrial chemicals             3. natural and synthetic hormones             4. drugs             5. pesticides             6. personal hygiene products          2. the effects of EDC

                         1. can change the epigenetics of a mother and pass it down to the fetus and create unexplainable effects such as obesity, change in metabolism, neurological disorders, and cancer.          3. an example of EDC

                         1. PAHs

                               1. created from natural products such as coal and crude oil                2. produced when the sources are burned such as wood.                3. PAHs can bind to particles in the air changing elements                4. burned meat contains PAHs                5. mothballs (naphthalene)                6. cigarettes                7. impact of concerns:

                                     1. carcinogenesis                   2. reproductive and immune disorders    4. levels of toxicity

             1. population       2. body       3. organ       4. the functional unit (ex: Leydig cells)       5. cellular       6. organelle       7. molecule    5. toxicokinetics

             1. the movement of toxins from the environment to the molecule       2. the steps

                   1. absorption to the body

                         1. dependent on solubility

                               1. hydrophilic are excreted through urine                2. hydrophobic needs extra steps to break down the chemical                3. follows diffusion          2. distribution of chemicals in the body          3. metabolism of chemicals so the body can eliminate them

                         1. biotransformation of the chemicals occurs in the liver

                               1. the liver is high in p450s                2. although toxicants are found to be broken down in the liver, all cells have the capacity to break down xenobiotics                3. biotransformation occurs to increase solubility and easy excretion             2. 4 categories to metabolize

                               1. oxidation                2. reduction                3. hydrolysis                4. conjunction

                                     1. adding a polar molecule                5. why do individuals react differently to certain chemicals?

                                     1. genetic polymorphism and the available enzymes          4. excretion is the route of removal from the body

                         1. the major route of excretion is through the kidneys             2. liver and bile can be used to break down chemicals             3. gases and vapors are excreted through the lungs when absorbed through the skin or ingested             4. basic fat-loving chemicals are excreted through breast milk

  1. examples of toxins

       1. BPA

             1. an endocrine-disrupting class because it can act like a hormone in the human biology

                   1. the effect includes

                         1. reproduction             2. regulation of the immune system             3. cancer             4. metabolism       2. found in plastics and metal can liners

                   1. can be found in waterways       3. what is normal plastic usage?       4. how can BPA be exposed to human biology?

                   1. ingestion          2. inhalation          3. skin/eye contact          4. maternofetal transmission       5. what biological systems can BPA exposure affect?

                   1. the thyroid gland          2. adipose tissue          3. liver          4. heart          5. female/ male reproductive systems       6. which recycling labels are safe from BPA

                   1. 1, 2, 4, 5       7. what does it mean to be BPA free

                   1. the company of the product used the label as marketing and may not have had any BPA in the beginning          2. there is an unknown effect on BPA substitutes

  1. how to test and regulate toxins

       1. acute

             1. LD50 (the dosage that kills 50% of the exposed population in 14 days) may be a crude measurement

                   1. the end goal is the same          2. can be used to compare all different types of compounds          3. used to identify lethal chemicals to regulate    2. chronic

             1. NOAEL

                   1. no observed adverse effect level

                         1. uses a dose response curve to see what is the highest dose that can be given without harmful effects             2. used to regulate

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