Module 2: Hazardous Substances and What Makes a Chemical Toxic

Important Terms:

  1. Hazard: Any physical, chemical, or biological agent that has the capacity to cause physical damages or harm to the health of living organisms

  2. Hazardous Material: Any chemical substance or agent that poses a potential health hazard

  3. Toxic Substance: Chemical substances that have the potential to harm the health of living organisms

  4. Pollutant: Any chemicals that produces or has the potential to produce actual environmental harm

  5. Contaminant: Any chemical not naturally found in our environment (does not imply a hazard)

  6. Bioaccumulation: The accumulation of substances in an organism at a faster rate than they can be excreted

  7. Bioconcentration: The accumulation of substances in an organism at a higher concentration than the surrounding environment

  8. Biomagnification: Accumulating increased concentrations of substances that are resulting from consumption of lower trophic level organisms that contain these substances

  9. Carcinogen: Any substance that is involved in the development of cancer

  10. Mutagen: a chemical or substance that causes harm or changes to genetic material

  11. Teratogen: Any chemical or substance that disrupts normal development of an embryo or fetus

  12. Neurotoxicity: Refers to a chemicals ability to disrupt normal nerve function whether in the central or peripheral nervous system

  13. Nephrotoxicity: Refers to a substances ability to disrupt normal kidney function

  14. Hepatotoxicity: Refers to a substances ability to disrupt normal liver function

  15. Oxidative Stress/Damage: Refers to damage as a result of the reactive oxygen species

Physical Properties of Chemical that may influence their Toxicity

  • Water Solubility: the maximum amount of substance that can be dissolved in a known volume of water

  • Acid Dissociation Constant: (pKa): The strength of an acidic substance in solution. Expressed as the pH where the acidic groups of substance dissociate

  • Molecular Weight: the mass of a single molecule/ substance

  • Octanol-Water Partitioning Coefficient (Kow): Ratio of the amount a substance that dissolves in a hydrophobic phase (octanol) and a hydrophilic phase (water)

    • Ratio indicates how readily any chemical dissolves in a fatty or oily medium compared with water

    • higher the number, the more lipophilic it is and is an indicator of bioaccumulation as these chemicals are usually absorbed quickly through the skin and enter into the blood

  • Flash Point: The temperature at which a substance gives off enough vapor in the air to form an ignitable mixture.

    • Lower the flash point, the greater the risk for explosion and fire

Toxicity and the Factors that Modify Toxic Responses

  • All chemicals have the potential to produce toxicity

  • Toxicity: the adverse effect of some normal aspect of normal biology that is causally linked to exposure to a chemicals agent

    • enzyme inhibition, induction, or activity

    • cytoxicity

    • inflammation (local or systemic)

    • covalent binding (ie electrophilic metabolites to DNA)

    • Receptor interaction

    • necrosis (tissue death)

    • lethal synthesis

    • oxidative injury lipid peroxidation ( free radical oxidation of fatty acids = cell injury or death)

    • induction of apoptosis

    • immune mediated hypersensitive reactions

    • immunosuppression

    • neoplasia (formation of tumors)

    • mutagenesis

Examples:

  1. Botulinum toxin binding to nerve terminal to block the release of a neurotransmitter

  2. Dioxin in lab tests showed as endocrine disrupters due to its mimicry to the estrogen hormone thus disrupting the fetus early on in the pregnancy

Factors that modify toxicity

  • age

    • decreased organ function for the elderly

    • decreased bio transforming ability prolonged retention times

  • gender

  • disease

    • suppressed immune function

  • lifestyle and diet

    • modifiable risk behaviors

  • genetics

Toxicogenomic: the study of the elucidation of gene expression in response to toxicants. It combines toxicology with genetic and molecular profiling technologies such as transcriptomics, proteomics, and metabolomics

  • this helps to predict toxicity or genetic susceptibility to chemical exposures