Toxicology - Chapter 3/4 (Toxicant Classes)

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BIOG5140 (Toxicology) - NCCU
Dennis Jallah
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Anthropogenic examples of the 20th century Donora Episode of 1948 - killed 20 and sickened 7K in Donora, PA London Killer Smog (1952) - estimated 4K deaths above the normal daily count due to respiratory problems (i.e. bronchitis, pneumonia)
Carbon Monoxide Source - motor vehicle emissions, burning fossil fuels, and incomplete combustion Significance - Combines with hemoglobin to form carboxyhemoglobin (poisonous)
Particle Pollutants Dust Fumes Mist Smoke Aerosol
Natural Air Pollutants Volcano eruptions Forst Fires Dust storms Salt particle aerosol from ocean Hydrocarbons from trees Pollen and spores from plants
Anthropogenic Air Pollutants Combustion sources Exhaust emissions Industrial Processes Mining and drilling
Indoor Air Pollutants Combustion products from heating, cooking, pesticides, tobacco smoking
Which layer of the ozone is considered "bad" ozone? "Good" ozone? Bad - tropospheric ozone Good - stratospheric ozone
What are the six principal pollutants identified by US EPA? Carbon Monoxide Nitrogen Oxides Sulfur Oxides Ozone Particulate Matter Lead
T/F - Chlorofluorocarbons (CFCs) are the major contributors of damage to the stratospheric ozone layer True
Name some common toxicological features of metals Metal must cross membrane in order to exert toxicity lipid-soluble metals readily penetrate membranes e.g. methyl mercury protein bound metals absorbed via endocytosis e.g. cadmium-metallothionein metals can be absorbed via passive diffusion e.g. lead
Major metals associated with toxicity Lead, Mercury, Cadmium, Chromium and Arsenic
Define Water Pollution Any physical, biological, or chemical change in water quality that adversely affects living organisms or makes water unsuitable for desired uses
Define and give an example of Point Source pollution Discharge pollution from specific locations e.g. factories, power plants and drain pipes
Define and give an example of Nonpoint Source pollution Scattered or diffused with no specific location of discharge* e.g. agricultural fields, feedlots, golf courses, residential construction sites *Also includes atmospheric deposition (contaminants carried by air currents and precipitated into watersheds or directly onto surface waters)
Sulfur Oxides Sources - Coal and oil power plants Significance - Main component of acid deposition
Gaseous Air Pollutants CO H2S CH4 SO2 CO2 NO2 O3
Carbon Dioxide Sources - product of complete combustion Significance - may cause greenhouse effect
Nitric Oxide Sources - Automobile emissions, fossil fuel power plants Significance - pulmonary edema and impairment of lung function
Ozone (O3) Sources - Automobile emissions, photochemical smog Significance - Damage to vegetation, lung irritant
What are the two heavy metals of greatest health concern regarding drinking water exposure? Lead and arsenic
What are the two heavy metals of greatest health concern regarding food chain exposure? Cadmium (responsible for Itai-Itai disease) and mercury (most widespread in North America) Also, pesticides such as DDT (organochlorine compound)
Excess of these nutrients can lead to "algal blooms" or eutrophication Nitrates and phosphates
T/F - One potential adverse health effects of nitrate entering drinking water is anemia or blue baby disease? True
Two most important sources of toxic organic chemicals in water are: 1) improper disposal of industrial and household wastes 2) Runoff of pesticides from fields, roadsides, golf courses and lawns
Threshold limit values (TLVs) refer to airborne concentrations of substances and represent conditions under which repeated exposure causes no adverse effects
Threshold limit value-time-weighted average (TLV-TWA) concentration for a normal 8-hr workday or 40-hr workweek to which nearly all workers may be repeatedly exposed, day after day, without adverse effects.
Threshold limit value - short-term exposure limit (TLV-STEL) maximal concentration to which workers can be exposed fora period up to 15-min continuously without suffering from irritation, chronic or irreversible tissue change, or narcosis of sufficient degree that would increase accident proneness, impair self-rescue, or materially work efficiency, provided that no more than four excursions per day are permitted, with at least 60min between exposure periods, and provided that the daily TLV-TWA is not exceeded.
Threshold limit value-ceiling (TLV-C) the concentration that should not be exceeded even instantaneously
Biologic limit values (BLVs) represent limits of amounts of substances to which the worker may be exposed without hazard to health or well-being as determined by measuring the workers tissues, fluids, or exhaled breath.
Immediately dangerous to life or health (IDLH) conditions pose a threat of sever exposure to contaminants that are likely to have adverse cumulative or delayed effects on health
T/F - Metals interacting with enzymes may induce toxic action via either inhibition or activation True
Carcinogenic metals Known: arsenic, nickel, and certain chromium compounds Probable: beryllium, cadmium, cisplatin
What organ is most susceptible to metal toxicity Kidney, main excretory organ, is particularly susceptible to cadmium and mercury. Note: water solubility increases nephrotoxicity
Metals can act directly on sex organs Acute cadmium exposure can produce testicular injury Lead accumulation in the testes is associated with testicular degeneration, inhibition of spermatogenesis, and Leydig cell atrophy
How does acute metal exposure differ from chronic metal exposure? Acute metal exposure causes irritations and inflammation of the respiratory tract Chronic exposure leads to fibrosis or carcinogenesis
What is the name of the metal binding protein responsible for regulating the intracellular bioavailability of cadmium, copper, mercury, silver, and zinc Metallothionein (MT)
What are the main targets of lead toxicity? Hematopoietic and nervous system
Organic mercury primarily affects the _____ system. nervous system Note: Elemental mercury absorbed by the respiratory system and permeates the BBB, effecting the nervous system
Cadmium inhibits what organelle function? Lysosomes Note: Very slowly excreted from the body. Long-term exposure damages the kidney. Transported via MT
What two forms of chromium are of biological significance? Trivalent (Cr^+3) and hexavalent (Cr^+6)
T/F - High levels of arsenic may result in gangrene of the lower extremities or cancer of the skin? True
What is used to reverse or prevent metal toxicity? Chelating agents - formation of metal ion complex in which the metal ion is associated with an electron donor ligand
How does a "general" use pesticide differ from a "restricted" use pesticide Restricted - generally causing undesirable effects on the environment, applicator, or workers. Can only be purchased by state licensed individuals General - causes no unreasonable, adverse effects when used according to the label. Can be purchased and applied by anyone.
Chlorinated hydrocarbons are _____ and cause acute effects by interfering with the transmission of _____ Neurotoxicants; nerve impulses
Published by Rachel Carson in Silent Spring, this pesticide was identified as a neurotoxicant that interferes with the transmission of nerve impulses DDT Note: insecticide
How do organophosphorus (OP) insecticides exert their toxicity? Via inhibition of acetylcholinesterase Note: principle site of action is the PNS
Carbamates share a similar mode of action to OPs, inhibiting acetylcholinesterase. What is a notable difference between carbamates and OP insecticides? Carbamates are more rapidly reversed than OP compounds
Pyrethroid Insecticides Affect nerve membranes by modifying the sodium and potassium channels, resulting in depolarization of the membranes.
Herbicides The most widely used class of pesticides e.g. TCDD aka Agent Orange
Fungicides Relatively nontoxic Note: Hydrolyze to produce known carcinogens such as ethylenethiourea (ETU)
Examples of food additives and containinants Antioxidants, fungistatic agents, emulsifiers, stabilizers, humectants, dyes, vitamins, amino acids, inorganics, chelating agents
Microbial toxins toxic substances produced by microorganisms that are of high molecular weight and have antigenic properties e.g. Clostridium tetani (tetanus), C. botulinum (botulinum) Note: toxic compounds produced by bacteria that do not fit these criteria are referred to as poisons
Mycotoxins Ergot alkaloids consist of three groups: ergotamine, dihydroergotamine, and ergonovine. Affect the nervous system and induce vasoconstriction Aflatoxins undergo hepatic metabolism to form reactive epoxide intermediate
Algal toxins Represent the array chemicals derived from cyanobacteria, dinoflagellates, and diatoms
Plant toxins (phytotoxins) Common drugs of abuse (e.g. cocaine, caffeine, nicotine) and components of food (e.g. safrole found in black pepper)
Animal toxins Actively Venomous - injecting poisons through specially adapted strings or mouthparts Passively Venomous - inadvertent ingestion
Solvents Common classes: Aliphatic hydrocarbons, halogenated aliphatic hydrocarbons, aliphatic alcohols, glycols and glycol ethers, and aromatic hydrocarbons
Drugs of abuse either have no medicinal function or are taken at dose levels higher than would be required for therapy
Combustion products polycyclic aromatic hydrocarbons (PAHs) are the most widely studied for aspects of chemical carcinogenesis
Cosmetics Little risk of systemic poisoning. Most common deleterious effects are allergic reactions and contact dermatitis.
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