Term
| 4 unique problems in dealing with toxicity of gaseous chemicals |
|
Definition
| tend to be colorless, odorless, and tasteless so exposures are hard to identify and detect :: Potency :: mixtures (additive? synergistic? etc) :: multiple routes of exposure (inhalation and per cutaneous) |
|
|
Term
| 7 classifications of gaseous chemicals |
|
Definition
| simple asphyxiants, those that decrease O2 carrying capacity, those that cause cellular anoxia, lung irritants, vesicants, sensory irritants, and miscellaneous |
|
|
Term
| how do simple asphyxiants work? target organs? |
|
Definition
| displace O2 and therefore create an O2 deficiency -- target organs: brain and heart (bc they're O2 dependent) |
|
|
Term
| ex of a simple asphyxiant |
|
Definition
| methane - swamp gas/natural gas - from decaying matter such as hog manure and nitrogen |
|
|
Term
| chemicals that reduce O2 carrying capacity |
|
Definition
| CO, aniline -- cause methemoglobinemia by oxidizing Fe2+ to Fe3+ (ferrous hemoglobin to ferric hemoglobin) -- tissues react the same as to simple asphyxiants |
|
|
Term
| cellular anoxia is caused by? |
|
Definition
|
|
Term
| 4 asphyxiants that affect the CNS |
|
Definition
| anesthetics, halogenated solvents, vapors, butane |
|
|
Term
| 2 gaseous chemicals that are lung irritants |
|
Definition
| chlorine and ammonia (mostly in farmers and meth producers) |
|
|
Term
| a gaseous chemical that causes burns and destruction of tissue both internally and externally.. and example of this |
|
Definition
|
|
Term
| a lacrimator is a ____. what does it irritate? |
|
Definition
| sensory irritant -- irritates eyes and lungs |
|
|
Term
|
Definition
| incomplete combustion -- produced CO instead of CO2 |
|
|
Term
| 2 mechanisms of CO action |
|
Definition
| outcompetes O2 and binds to hemoglobin, generating carboxyhemoglobin (HbCO) :: prevents release of O2 to tissues |
|
|
Term
| how does CO prevent the release of O2 from tissues? |
|
Definition
| Hb carries 4 O2, and each consecutive O2 is easier to release but with one CO bound, the other 3 O2 are hard to release |
|
|
Term
| death from CO can be due to what 3 things? |
|
Definition
| CNS effects that depress respiration, cardiovascular arrhythmias, and delayed neurological sequelae (DNS) |
|
|
Term
| Delayed neurological sequelae (DNS) from CO exposure |
|
Definition
| due to nerve damage, happens in about 25% of those exposed to severe CO :: Symptoms - amnesia, personality changes, neuritis (loss of senses) |
|
|
Term
| 2 methods of treatment for CO toxicity |
|
Definition
| 100% O2 supply, hyperbaric O2 chamber (100% of 2.5atm O2) |
|
|
Term
| Why is chronic CO toxicity hard to discern? |
|
Definition
| it never builds up in the blood because O2 fixes the problems ASAP, but it is thought that it could lead to neurosis |
|
|
Term
|
Definition
|
|
Term
| mechanism for CN toxicity |
|
Definition
| CN binds to Fe3+ in blood to make a complex via cyt oxidase. during oxidative phosphorylation, Fe3+ binds to the Cn and very quickly stops ATM production which interferes with the unitilization of O2 |
|
|
Term
|
Definition
| per cutaneous or inhalation - takes effect in 10-20s, death within minutes :: ingestion - effects in 20m (Jonestown cult suicides) |
|
|
Term
| signs and symptoms of CN poisoning |
|
Definition
| high dose - collapse and die due to CNS effects :: Low dose - headache, weakness, turn bright red due to blood retaining oxygen, liver turns blue |
|
|
Term
|
Definition
| must be done quickly - fresh air/stop exposure :: Eli Lilly CN antidote kit - give sodium nitrite to make MetHb in blood and then use Rhodanese in conjuction with sodiumthiosulfate to get rid of the MetHb |
|
|
Term
| ___ also acts by inhibiting mitochondrial respiration by inhibiting cyt oxidase, but it is not nearly as potent as CN |
|
Definition
|
|
Term
|
Definition
| inflammatory: eyes, lungs (bronchitis, dyspnea, edema), skin |
|
|
Term
| serious effects of H2S exposure |
|
Definition
| CNS effects: CNS depression, loss of consciousness, and death. Cardiac effects: alterations in the rhythm and contractility of the heart |
|
|
Term
| Where does H2S exposure often occur? |
|
Definition
| it comes from decaying organic matter, so: farms, sewers, septic systems |
|
|
Term
| treatment for H2S toxicity |
|
Definition
| only for signs and symptoms -- occasionally with CN kit, but that's debated |
|
|
Term
| Origin and formation of sulfur dioxide |
|
Definition
| naturally occurs in coal. mixes with water to make sulfurous acid or sulfuric acid (acid rain) -- SEE NOTECARD |
|
|
Term
|
Definition
| conjunctivitis, bronchoconstriction (biggest problem) - decrease in flow rate due to increase in restriction. parasympathetic response - system shuts down when irritated. Measured by FEV1 |
|
|
Term
|
Definition
| chronic bronchitis - increase in goblet cells = hypersecretion of mucus and productive cough :: COPD - more into lung and lower resp tract |
|
|
Term
| How/where is NOx produced? |
|
Definition
| internal combustion engines, gas stoves main source of indoor air pollution |
|
|
Term
| What NOx is of most concern? |
|
Definition
|
|
Term
|
Definition
| affects lower resp tract because its not very water soluble -- most affects Type 1 cells in alveoli. Oxidant - affects O2 transfer across Type 1 cells and therefore interferes with O2 uptake |
|
|
Term
| type 1 and type 2 alveolar cells |
|
Definition
| type 1 - absorbs O2 :: Type 2 - makes surfactant |
|
|
Term
| 6 ways NO2 affects the respiratory system |
|
Definition
| Interferes with O2 uptake, causes fibrosis of the lung (which decreases O2 exchange), decreases surfactant production (lungs can collapse), emphysema (at high levels) - destroys alveolar architecture and therefore decreases the surface area of the lungs, decreased action of cilia, decrease in mobility and function of macrophages (without these working properly, the person is subject to resp infections) |
|
|
Term
| mechanism of ozone action |
|
Definition
| oxidant - like NO2 on steroids |
|
|
Term
|
Definition
| upper resp tract: trachea, bronchi, bronchioles :: Lower resp tract: type 1 alveolar cells, and cell damage via: lipid peroxidation (see notecard), proteins (see notecard), inflammation, and decreased cilia and macrophage function |
|
|
Term
| Basis of the term "pneumoconiosis" |
|
Definition
| pneumo = lung, coniosis = dust |
|
|
Term
| 4 mechanisms of particle deposition |
|
Definition
| impaction, interception, sedimentation, diffusion |
|
|
Term
|
Definition
| particles run straight into the wall in upper resp tract |
|
|
Term
|
Definition
| particles are too big to make the curve into another branch of the resp tract and run into the wall |
|
|
Term
|
Definition
| small particles follow gravity and eventually settle out |
|
|
Term
|
Definition
| brownian movement - like seeing dust in the sunlight - very small particles get breathed in and then back out |
|
|
Term
| the mucociliary escalator removes __% of particles that are inhaled. What does it do with them? |
|
Definition
| 90% - some are breathed back out, most are swallowed |
|
|
Term
|
Definition
| when small particles merge together into a big particle |
|
|
Term
| nanoparticles are defined as ___nm or less |
|
Definition
|
|
Term
| a tracheobronchial disease also known as "brown lung" |
|
Definition
|
|
Term
|
Definition
| endotoxins from gram negative bacteria that live on cotton bract and cause histamine release in humans |
|
|
Term
| Why is byssinosis also called "monday morning fever"? |
|
Definition
| cotton pickers would come in monday morning and get sick but body gets used to it throughout the week and stops showing symptoms |
|
|
Term
|
Definition
| coughing, dyspnea, wheezing, chronic bronchitis, decreased FEV1 |
|
|
Term
| where silica exposures usually occur |
|
Definition
| mining and stone cutting -- coal industry, abrasives industry, sand and cement production, sand blasting |
|
|
Term
| Fibrosis caused by silica |
|
Definition
| macrophages try to engulf silca but cannot dissolve it with lysosomal enzymes - so they just pick it up and then end up dropping it somewhere. then cytokines come along and coat it with collagen. the process is repeated several times until it creates an "onion skin" nodule |
|
|
Term
| How does fibrosis by silica adversely affect the body? |
|
Definition
| nodules physically obstruct air flow into alveoli and therefore create emphysema due to decreased surface area. also, blocks blood vessels and therefore blood flow -- system backs up and creates congestive heart failure of the right side. |
|
|
Term
| why does silicotuberculosis occur? |
|
Definition
| probably due to decrease macrophage function, which lessens the immune system and leads to TB |
|
|
Term
|
Definition
| bronchial - can only study in rats - IARC says quartz is an A1 carcinogen, ACGIH says A2 ... have to take into account whether person smokes or not |
|
|
Term
| chronic silicosis occurs in _-_ years |
|
Definition
|
|
Term
| chronic asbestosis occurs in __-__ years |
|
Definition
|
|
Term
| bronchogenic cancers caused by asbestos mainly effect ___ cells and are usually caused by what variety of asbestos? |
|
Definition
| epithelial cells -- chrysotile (serpentine) |
|
|
Term
| mechanism of action for bronchogenic cancer due to asbestos |
|
Definition
| may be due to reactive O2 species bc Fe growth factors increase cell replication and p53 is depressed which increases the cell cycle |
|
|
Term
| asbestos-induced mesothelioma is caused by what kind of fiber? latency period is usually ___ years. and it occurs in what area of the body? |
|
Definition
| amphibole -- 40-50yrs -- in pleural and abdominal cavities |
|
|
Term
| asbestos-induced bronchogenic cancer usually has a latency of __ years |
|
Definition
|
|
Term
| in terms of asbestosis and deposition of fibers in alveolar ducts and respiratory bronchioles, what kind of fibers are of most concern? |
|
Definition
| long, thin fibers (amphibole) |
|
|
Term
| how are asbestos bodies formed? and what are they aka? |
|
Definition
| amphibole fibers are coated with iron and proteins to form ferrugious bodies -- create a "ground-glass" appearance in the lungs |
|
|
Term
| in general, how does fibrosis work? |
|
Definition
| macrophages produce growth factors which cause fibroblasts to produce collagen and this creates nodules in the lungs |
|
|
Term
|
Definition
| transition metals, alkali earth metals, alkali metals, and metalloids |
|
|
Term
| a metal is an electro___ element with the tendency to ____ electrons in chemical reactions |
|
Definition
| electropositive, lose electrons |
|
|
Term
| heavy metals are aka. 7 heavy metals |
|
Definition
| transition metals -- Fe, Cu, Pd, Cd, Hg, Pb, Ag |
|
|
Term
| a metalloid resembles a metal in at least ___ amphoteric form and conducts electricity more/less easily than a true nonmetal. 4 metalloids. |
|
Definition
| one, more easily -- Si, As, Se, In |
|
|
Term
| 4 characteristics common to both metals and organic chemicals |
|
Definition
| structural mimcry to essential body consituents, covalent bonding, free radical formation, bioaccumulation |
|
|
Term
| 4 ways in which metals are different from organic chemicals |
|
Definition
| chemical forms of metals may change, but the basic unit is neither created nor destroyed :: catalytic function is in active centers :: metals are generally not metabolized and thus have a long life in the body :: metals persistently exist in the ecosystem |
|
|
Term
| Toxic metals are usually hard/soft acids/bases and therefore can form covalent bonds with hard/soft acids/bases |
|
Definition
| soft acids -- can form bonds with soft bases |
|
|
Term
| What functional group is the number 1 soft base to bind to heavy metals? |
|
Definition
|
|
Term
| metal toxicity increases/decreases as softness increases |
|
Definition
|
|
Term
| what are 6 properties of metals that make them so toxic? |
|
Definition
| readily lose electron in outer orbital :: electropositive :: soft acid :: catalytic function (transfer electrons and are reusable) :: retain their own identity (Hit and run in human body -- once it enters the body, there's nothing we can do about it) :: can form chelates with endogenous ligands such as proteins, amino acids, hormones, vitamins, etc |
|
|
Term
|
Definition
| a heterocyclic compound having a central metallic ion attached by covalent bonds to two or more nonmetallic atoms in the same molecule. |
|
|
Term
| final problem with Lead toxicity |
|
Definition
| blocks substrate and prevents heme synthesis |
|
|
Term
| final problem with arsenic toxicity |
|
Definition
| decreases acetyl CoA senthesis and decreases ATP production |
|
|
Term
| Which Chromium is toxic to purified enzymes and DNA but not to intact cells? |
|
Definition
|
|
Term
| Which Chromium is toxic to intact cells, but not to purified enzymes and DNA? How does it gain entry to the cell? |
|
Definition
| CrVI -- gains entry by using an anion that is usually a sulfate carrier |
|
|
Term
| inside cells, Cr__ is reduced to Cr__ |
|
Definition
|
|
Term
| How does Manganese toxicity occur? |
|
Definition
| Mn relaces Fe in the active center of IRP1 (iron regulatory protein-1) and thereby alters Fe metabolism and energy production |
|
|
Term
| Where is cadmium mostly stored? Where does it cause the most damage? |
|
Definition
| liver -- due to the induction of and binding to Metallothionine -- causes most damage to kidneys |
|
|
Term
| Why does cadmium bind to Metallothionein so well? |
|
Definition
| because it's a soft base and one MT can bind seven Cd |
|
|
Term
| how does Cd cause kidney damage? |
|
Definition
| Cd binds to MT in liver. the Cd-MT complex is transported to the proximal renal tubules. Once in the kidney, the MT releases free Cd and causes renal cell damage |
|
|
Term
| 2 metals that can be metabolized and how they are |
|
Definition
| As can be deactivated, Hg can be activated |
|
|
Term
| Metabolism of Mercury compounds results in bioactivation by creation of ____ |
|
Definition
|
|
Term
| Mechanism of mercury bioactivation |
|
Definition
| cysteine complex of MeHg enters brain using amino acid carrier. The hemolytic cleavage of the carbon-Hg bond produces methyl free radicals that initiate lipid peroxidation. MeHg-cysteine complexes mimic MT and inhibit protein synthesis in neuronal cells |
|
|
Term
| 3 mechanisms of free-radical induced cytotoxicity -- AKA oxidative stress |
|
Definition
| lipid peroxidation - membrane damage :: DNA oxidation - Strand breaks and creates mutations :: Protein oxidation - loss of enzyme activity and transport systems |
|
|
Term
| how does lead modulate gene expression in oligodendrocytes? |
|
Definition
| replaces Zn in the binding site |
|
|
Term
| mechanisms of metal-induced carcinogenesis |
|
Definition
| direct genotoxicity (DNA damage, altered infidelity of DNA synthesis, altered gene expression due to DNA binding), indirect genotoxicity (inhibition of DNA repair, generation of free radicals), Interactions with regulatory proteins (finger loop proteins), Immunotoxicity (immunosuppression) |
|
|
Term
| No clear carcinogenic mechanism has been defined for nay metal at present |
|
Definition
|
|
Term
| general mechanism for metal-induced carcinogenesis |
|
Definition
| Metal interferes wtih DNA crosslinks and generates a free radical, which damages the DNA |
|
|
Term
| 4 metals that are associated with alzheimer's disease |
|
Definition
| Mercury, Zinc, Copper, Aluminum |
|
|
Term
| What would you see on an MRI of a manganism patient? |
|
Definition
| white spots in the striatum where Mn accumulates |
|
|
Term
| what metal is associated with Parkinson's and Huntington's in the basal ganglia |
|
Definition
|
|
Term
| 3 main principles in treatment of metal poisoning |
|
Definition
| remove the person from the environment in which exposure occurred and clean up the environment, treat symptoms that may threaten the person's life, and treat with a metal-mobilizing drug (chelator, chelating agent, metal-complexing agent) to reduce body burden |
|
|
Term
| ____ provide electron-rich groups to form covalent bonds with metals in a coordinate ring strucutre |
|
Definition
|
|
Term
| how do chelating agents work? |
|
Definition
| form stable complexes between chelator and metals and prevent or reverse the binding of metals to cellular ligands. the formed complexes are more water soluble and more readily excreted from the body. |
|
|
Term
|
Definition
| british anti-lewisite : soft base given as a chelating agent after exposure to lewisite, an As-rich gas used in wars |
|
|
Term
| 2 chelating agents for Lead |
|
Definition
|
|
Term
| When would you use EDTA and when DMSA to treat lead intoxication? |
|
Definition
| EDTA can cross BBB and therefore reach Pb in brain. DMSA can excrete more Pb through urine and is safer to use in general |
|
|
Term
| 3 chelating agents for mercury intoxication |
|
Definition
|
|
Term
| what is the #1 chelating agent for mercury intoxication and why? |
|
Definition
| DMPS - eas of administration and low side effect profile |
|
|
Term
| 3 chelating agents for arsenic intoxication |
|
Definition
|
|
Term
| what is the #1 chelating agent for As intoxication and why? |
|
Definition
| BAL - can penetrate into CNS |
|
|
Term
| Pros and cons of DMPA as a chelating agent for Cd Intoxication |
|
Definition
| can remove Cd from MT and excrete it through urine... but is very toxic itself |
|
|
Term
| 3 chelating agents for Mn intoxication |
|
Definition
|
|
Term
| what chelating agent for Mn is not yet approved in the US but seems to be the most effective at eliminating symptoms of toxicity? |
|
Definition
|
|
Term
| conventional vs unconventional pesticides |
|
Definition
| conventional are what you normally think of on crops and around houses, unconventional are those used for wood perservation, chlorine in pools, biocides, etc |
|
|
Term
| what is the largest user of pesticides? |
|
Definition
|
|
Term
| most commonly used pesticide |
|
Definition
| glyphosate (herbicide) -- 85-90M lbs/year... used bc they were able to genetically engineer crops so that they have a glyphosate-metabolizing gene so weeds die and plants flourish |
|
|
Term
| most commonly used pesticide by homeowners |
|
Definition
|
|
Term
| how does lead modulate gene expression in oligodendrocytes? |
|
Definition
| replaces Zn in the binding site |
|
|
Term
| ___million lbs/year of conventional pesticides are used in the US |
|
Definition
|
|
Term
| what kind of pesticides are used most and why? |
|
Definition
| herbicides - bc plants require more pesticide to kill them |
|
|
Term
|
Definition
| some fungi produce aflatoxins, some cause crops to fail, some prevent preservation due to mold/mildew growth |
|
|
Term
| most important use of bactericides |
|
Definition
| hospitals to prevent staph |
|
|
Term
| US EPA regulation principles for pesticide use |
|
Definition
| benefits must outweigh the cost, use must minimize adverse economic impact, health and safety of the public must be protected |
|
|
Term
| 3 parts of risk assessment of pesticides |
|
Definition
| hazard identification, dose response assessment, and exposure assessment |
|
|
Term
| minimum time between application of a pesticide and when people are allowed to enter the application site without protective equipment |
|
Definition
|
|
Term
| what is the minimum reentry interval? when would it need to be longer? |
|
Definition
| until the spray is dry -- longer for more toxic pesticides... until the residue has time to dissipate |
|
|
Term
| maximum allowable residue at the time of harvest |
|
Definition
|
|
Term
| any pesticide with a density greater than __ is considered a problem. why? |
|
Definition
| 1 -- because it is more dense than water and can therefore travel down through it and contaminate groundwater |
|
|
Term
| 6 insecticide target sites |
|
Definition
| neurotoxins, insect midgut, hormone analogs, respiratory poisons, chitin synthesis |
|
|
Term
| environmental fate is measured by what 6 things? |
|
Definition
| hydrolysis, photodegradation in water, soil, and air, metabolism in soils (aerobic/anaerobic and aquatic/terrestrial), leaching, absorption/desorption in soils, laboratory and field volatility and dissipation study |
|
|
Term
| the rules for pesticide use are contained in a legal document called the ____. |
|
Definition
|
|
Term
| ___ are proteins that create ion channels or pores in cell membranes |
|
Definition
|
|
Term
| most toxic class of insecticides to humans |
|
Definition
| acetylcholinesterase inhibitors -- carbamates and organophosphates |
|
|
Term
|
Definition
| they are substrates for AChE but metabolism is much slower than ACh, so the ACh remains in the synapse for a longer time and disrupts neural signaling which causes prolonged muscle contraction |
|
|
Term
|
Definition
| they competitively inhibit ACh and Carbamylate the AChE rather than the normal acetylation |
|
|
Term
| regeneration vs. aging of AChE after phosphorylation by OPs |
|
Definition
| regeneration - a molecule of water forms an intermediate with the phosphorylated AChE and the phosphate is removed by the OH group :: aging - when water forms an intermediate with the phosphorylated AChE, it leaves with an alkyl group rather than breaking the phosphate-serine bond. the AChE is irreversibly inhibited and must be replaced by synthesis of a new enzyme. |
|
|
Term
| how is OP exposure measured? |
|
Definition
| through blood esterase levels -- bc OPs affect all esterases in the body, not just AChE |
|
|
Term
| treatment of poisoning by cholinesterase inhibitors |
|
Definition
| ACH receptor (AChR) inhibitors such as atropine |
|
|
Term
| how can OP poisoning be treated to limit the amount of damage due to AChE aging? |
|
Definition
| pralidoximes such as 2-PAM facilitate AChE regeneration |
|
|
Term
| When should Pralidoximes be administered? |
|
Definition
| ONLY to OP poisoning, NEVER carbamate bc it exacerbates acute symptoms. Also, only after convulsions have been controlled by atropine. |
|
|
Term
| why is it important to rapidly distinguish between OP and Carbamate poisoning? |
|
Definition
| bc OP needs to be treated with 2-PAM and carbamate must NOT be treated with 2-PAM, but the 2-PAM administration for OP must be done within the first 6-8h after poisoning. ... best way to do this is to bring in the container of the pesticide used |
|
|
Term
|
Definition
| poisoning symptoms occur before a toxic dose is acquired. often self-warning agents are added to the pesticide (to produce an odor or something) that lets a person know they're being exposed before they are in danger |
|
|
Term
| why is parathion particularly dangerous? |
|
Definition
| it is an OP that is converted by P450 in the liver to the more toxic paraoxon, because of this there is a 8-10h delay between exposure and symptoms. so by the time symptoms start to appear, the victim is probably in bed and the problem has already progressed beyond repair |
|
|
Term
| 3 reasons that parathion poisoning is delayed |
|
Definition
| the time required for parathion to reach the blood, the time required for activation to the the more toxic paraoxon in the liver, and time required for transport to active sites at neuromuscular junctions |
|
|
Term
| neurodegenerative disease caused by some OPs |
|
Definition
| OPIDN - Organophosphorous Induced Delayed Neurotoxicity |
|
|
Term
| OPIDN is the result of inhibition of the enzyme ____, which is responsible for ____. Inhibition of this enzyme ultimately leads to ____. |
|
Definition
| NTE - neuropathy target esterase... responsible for metabolizing membrane lipids... inhibition leads to loss of nerve myelination |
|
|
Term
| why are OPs tested on chickens? |
|
Definition
| bc they're most sensitive to OPIDN so if a chicken doesn't get OPIDN from a chemical, a human won't either |
|
|
Term
| what kind of herbicide affects both plants and animals? |
|
Definition
| mitochondrial respiratory inhibitors |
|
|
Term
|
Definition
| herbicide that contains substantial quantities of dioxin -- used a lot in vietnam war |
|
|
Term
| __ and ___ are the most toxic herbicides to humans |
|
Definition
|
|
Term
| why is paraquat so deadly? |
|
Definition
| accumulates in alveolar cells of the lungs and hydrogen peroxide is produced and destroys cell membranes. there is no therapy to treat this process and it tends to cycle through quickly. patient eventually suffocates. |
|
|
Term
| why are fungicides problematic? |
|
Definition
| it is difficult to kill eukaryotic fungal cells without adverse effects on eukaryotic cells of non-target animals |
|
|
Term
| test used to initially screen for carcinogenicity in pesticides |
|
Definition
|
|
Term
| coumarins such as warfarin and inandiones are common _____ |
|
Definition
|
|
Term
|
Definition
| animal control poison that is a glycine agonist |
|
|
Term
| the use of ____ revolutionized pesticides in the 1940s to make them less toxic to humans and more toxic to pests |
|
Definition
|
|
Term
| why are Na channel inhibitors better at colder temps? |
|
Definition
| because they work by clogging the channels and the channels are tighter at colder temps |
|
|
