MT6314 ENVIRONMENTAL AND OCCUPATIONAL TOXICOLOGY Flashcards
Deals with the effects of chemicals in the workplace
Occupation toxicology
Major emphasis of occupational toxicology is to identify?
agents of concern
acute and chronic diseases
conditions for safe use
preventive measures
Can be called upon to treat the disease caused by chemicals
Occupational toxicologist
Occupational toxicologists may also?
carry out programs for surveillance
Regulatory limits for “safe” chemical exposure is promulgated by?
Occupational Safety and Health Administration (OSHA)
What are “safe” chemical exposure limits denoted as?
Permissible Exposure Limits (PELs)
Periodically prepare lists of their consensus versions of “safe” threshold limit values
American Conference of Governmental Industrial Hygienists
Environmental toxicology is now called?
Ecotoxicology
What does ecotoxicology deal with?
impact of chemicals (as pollutants in the environment)
toxic effects of chemical and physical agent on populations and communities of living organisms within defined ecosystems.
Ecotoxicology includes the study of?
transfer pathways of those agents & interactions with the environment
Concerned with the toxic effects on individual organisms
Traditional Toxicology
Air pollution is a main product of?
Industrialization, Technologic Development and
Urbanization
Environment mainly composes of?
Air, soil, water
Denote the daily intake of a chemical from food
Acceptable daily intake (ADI)
What air pollutant has the smallest permissible exposure limit value? and the biggest?
Smallest - ozone
Largest - 1,1,1-
trichloroethane
ability of chemical agent to cause injury/disease in a given situation or setting
Hazard
To assess hazards, one needs to have?
knowledge on the inherent toxicity of a substance
amounts to which individuals are liable to be exposed
Hazards are often based on?
Estimates rather than objective evaluation
expected frequency of the of the occurrence of an undesirable effect arising from exposure to a chemical or physical agent
Risk
Estimation of risk makes use of what data?
Dose-response data
Extrapolation from the observed relationships to the expected responses at doses occurring at exposure
Differs in different exposure situations
Route of entry
Major route of entry
Inhalation
Relatively minor route to transdermal
Oral ingestion
Primary prevention should be designated to reduce or eliminate?
Absorption by inhalation by topical contact
Routes of entry of atmospheric pollutants
inhalation and dermal
Water and soil pollutants route of entry
Inhalation, ingestion, and dermal
How much exposure notes chronic exposure?
Multiple exposures over a longer period of time
What exposures are usually chronic?
Air and water pollutants
Ranking of industrial routes of exposure?
Inhalation > Transdermal Route > Oral
An exposure to a toxic substance that is absorbed by the target human or animal results in?
a dose
single exposure or multiple exposure over a brief period of time
Acute exposure
single or multiple exposure over a longer period of time
Chronic Exposure
Hierarchy of controls?
Elimination > Substitution > Engineering controls > Administrative controls > PPE
Least and most effective control?
Least - PPE
Most - Elimination
Isolate people from the hazard
Engineering controls
Change the way people work
Administrative controls
Replace the hazard
Substitution
Physically remove the hazard
Elimination
Poorly degraded chemicals exhibit?
Persistence and can accumulate
Poorly degraded chemicals include?
Persistent organic pollutants (POPs), polychlorinated biphenyls, dioxins and furans
Responsible for the bioaccumulation of mercury compounds in higher marine mammals and fish higher in the food chain
Methyl mercury discharges
Tend to accumulate in body fat and cause endocrine disruption, neurological disorders, and carcinogenesis
Lipophilic substances: organochlorine pesticides
Intake of a contaminant by an organism exceeds the latter’s ability to metabolize or excrete the substance
Bioaccumulation
Contaminant concentration may be virtually undetectable in water, and may be magnified hundreds or thousands or times as the contaminant passes up the food chain
Biomagnification
Results from vapors, aerosols, smokes, particulates and individual chemicals
Air pollution
Associated with acute adverse effects among children, elderly and individuals with pre existing cardiac or respiratory disease
Sulfur dioxide and smoke from incomplete combustion of coal
Colorless, tasteless, odorless and non-
irritating gas
Carbon Monoxide (CO)
Carbon Monoxide (CO) is a byproduct of?
incomplete combustion
Mechanism of action in carbon monoxide?
Combines tightly but reversibly with o2 binding sites in hemoglobin 220x more than oxygen
Affinity of CO with Hb product is?
Carboxyhemoglobin (cannot transport oxygen)
The formation of COHb is a result of what effect?
Bohr effect
What organs are most affected with COHb?
Brain, heart, kidneys
Has teratogenic potential, easily absorbed through the lungs
CO
CO exposure may be?
Chronic or acute
CO is usually seen in?
gas stoves; generators gasoline-powered equipment; automobile exhaust and tobacco smoke
Clinical effects of CO?
Hypoxia developing from psychomotor impairment, headache and tightness in the temporal area, confusion and loss of visual acuity, tachycardia, tachypnea, syncope, and coma and deep coma, convulsions, shock and respiratory failure
40% COHb exposure may lead to?
collapse and syncope
Clinical effects are aggravated by?
- Heavy labor
- High Altitude
- High Ambient Temperature
- Cardiorespiratory disease
- Smoking exposure
CO intoxication is usually thought of as a form of what kind of toxicity?
Acute
T or F: The developing fetus is quite susceptible to the effects of CO exposure
T
Treatment for CO?
Remove from source
Maintain respiration (O2 is specific antagonist for CO)
What kind of therapy can be done as treatment for CO?
Hypothermic therapy
What persists for a long time after treatment of CO?
Neuropsychological and motor dysfunction
Colorless irritant gas generated primarily by the combustion of sulfur-containing fossil fuel
Sulfur Dioxide (SO2)
Principal source of urban SO2 is?
burning of coal, domestic heating, high-sulfur transportation and coal-fired power plants
At room temperature, the solubility of SO2 is approximately?
200g SO2/L of water
SO2 is a severe irritant to?
eyes, mucous membranes, respiratory tract and skin
T or F: Because of SO2’s high solubility, when it comes in contact with moist membranes, it becomes sulfurous acid
T
Inhalation of SO2 causes?
bronchioconstriction and bronchorrhea
Clinical outcome of 90% of inhalation of SO2 in the upper Respiratory tract?
Acute Irritant Asthma
When severe acute SO2 exposure has occurred, what may be observed?
Delayed onset pulmonary edema
Treatment for SO2 is?
supportive, non-specific
Brownish irritant gas associated with fires and formed from fresh silage
Nitrogen Oxides (NO2)
Exposure of farmers to Nitrogen Oxides (NO2) in the silo can lead to what illness?
Silo-filler’s disease, a severe and potentially lethal form of acute respiratory distress syndrome (ARDS)
The most common source of human exposure to NO2 comes from?
automobile and truck traffic emissions
Relatively insoluble deep lung irritant
Nitrogen Oxides (NO2)
Nitrogen Oxides (NO2) is capable of producing what illnesses from its mechanism of action?
pulmonary edema and ARDS
Inhalation of Nitrogen Oxides (NO2) damages what?
lung infrastructure that produces the surfactant necessary to allow smooth and low-effort lung alveolar expansion
After respiratory insult from NO2, what can patient develop?
non-irritant asthma or twitchy airway
What events cause permanent restrictive respiratory disease?
Damage to the type 1 and 2 alveolar cells, that impairs the type 1’s ability to replenish, causing progressive fibrosis
Acute or Chronic exposure to NO2: Irritation of eyes and nose, cough, mucoid or frothy sputum production
Acute
Acute or Chronic exposure to NO2: dyspnea and chest pain; Pulmonary edema, fibrotic destruction of terminal bronchioles
Acute
Acute or Chronic exposure to NO2: Emphysematous changes
Chronic
Bluish irritant gas naturally found in the earth’s atmosphere
Ozone (O3) and Other Oxides
At high altitudes, Ozone (O3) and Other Oxides is an important absorbent of? How about on ground levels?
UV light - high altitudes
Pollutant - ground levels
Ozone (O3) and Other Oxides are primarily produced from?
Burning of fossil fuel
Nitrogen oxides are emitted from?
power plants, motor vehicles and other sources of high heat compounds
Ozone can be generated in the workplace by?
high-voltage electrical equipment and air and water purification systems
Irritant of mucous membranes and is involved with mild exposure that produces upper respiratory tract infection
Ozone (O3) and Other Oxides
Severe exposure to Ozone (O3) and Other Oxides can cause?
deep lung irritation
O3 toxicity may result from the formation of?
Reactive free radicals
Acute or Chronic exposure to O3: Irritation and dryness to throat, changes to visual acuity
Acute
Acute or Chronic exposure to O3: substernal pain and dyspnea, ARDS
Acute
Acute or Chronic exposure to O3: Chronic Bronchitis, Bronchiolitis, Empyshema
Chronic
Solvents include?
- Halogenated Aliphatic Hydrocarbons
- Aromatic Hydrocarbons
HAHs include?
Carbon tetrachloride, trichloroethylene, chloroform, tetrachloroethylene and 1,1,1-trichloroethane
Most HAHs are classified as?
known or probable human carcinogens
HAH that causes severe damage in the ozone
Freon, a fluorinated aliphatic
HAHs cause what clinical effects?
CNS depression, kidney injury, liver injury, cardiotoxicity, arrythmia
“reasonably anticipated to be a human carcinogen”
Trichloroethylene and tetrachloroethylene
Chronic Exposure in the Workplace can cause?
Impaired memory, peripheral neuropathy
Aromatic Hydrocarbons include?
- Benzene
- Toluene
- Xylene
Known for its solvent properties as an intermediate in the synthesis of other chemicals
Benzene
Important component of gasoline that may be found in premium gasolines at concentrations of about 1.5%
Benzene
Acute or Chronic exposure to benzene: CNS Depression, Nausea, Euphoria, Locomotor Problems and Coma
Acute
Acute or Chronic exposure to benzene: Vertigo, Drowsiness and Headache
Acute
Acute or Chronic exposure to benzene: Bone Marrow Injury
Chronic
Targets of benzene or its metabolites?
Pluripotent Bone Marrow Stem Cells
Benzene was also known to be a?
Potent Clastogen - acts by chromosomal breakage
IARC considers Benzene as class what of human carcinogen?
1
Methylbenzene that does not contain myelotoxic properties of benzene, or association with leukemia
Toluene
What class carcinogen is toulene?
3
Effects of Toluene?
CNS depressant, skin and eye irritant, fetotoxic
Toluene is associated with?
rapid loss of consciousness, severe fatigue, ataxia
Dimethylbenzene that has been substituted for benzene in many solvent degreasing operations
Xylene
Colorless, sweet-smelling agent that is not associate with leukemia
Xylene
Effects of xylene?
CNS depressant, skin irritant
Kinds of pesticides?
- Organochlorine Pesticides
- Organophosphorus Pesticides
- Carbamate Pesticides
- Botanical Pesticides
Organochlorine Pesticides kinds?
DDT (chlorphenothane) and analogs,
Benzenehexachlorides
Cyclodienes
Toxaphenes
The 4 classes of organochloride pesticides are what kind of compounds?
Aryl, carbocyclic, heterocyclic compounds containing chlorine substituents
Aryl, carbocyclic, heterocyclic compounds containing chlorine substituents can be absorbed in the body through?
Skin, inhalation and ingestion
Organochloride pesticides were known to disrupt what system in humans and animals?
Endocrine
DDT continues to have restricted use in for?
domestic mosquito elimination in malaria infested regions of Africa
Compounds seen in DDT and analogs?
Dichlorodiphenyltrichloroethane (DDT)
Methoxychlor
Tetrachlorodiphenylethane (TDE)
Compounds in benzene hexachlorides?
Benzene hexachloride (BHC; hexachlorocyclohexane)
Lindane
Compounds in cyclodienes?
Aldrin
Chlordane
Dieldrin
Heptachlor
Compounds in Toxaphenes?
Toxaphene (camphechlor)
Largest acceptable daily intake?
Methoxychlor (DDT)
Organochloride pesticides interfere with the activation of?
sodium channels in excitable membranes and cause rapid repetitive firing in most neurons
inhibits calcium ion transport
Major effect of organochloride pesticides?
CNS stimulation
Most postulated mechanism in organochloride pesticides?
Endocrine pathway disruption
Tremor is the first manifestation in?
DDT
Considered as persistent chemicals
organochloride pesticides
Used against large variety of pests
Organophosphorus Pesticides
Organophosphorus Pesticides are useful when in direct contact with insects or when used as?
plant systemics
Agent of translocated within the plant and exerts its effects on insects that feed on the plants
plant systemics
Organophosphorus Pesticides are based on warfare chemicals such as?
sarin, soman and tabun (often called G compounds)
Examples of Organophosphorus compounds that are less toxic than the military grade compounds?
Parathion, malathion, azinphos
Organophosphates are absorbed into the body through?
skin, respiratory, GI
Mechanism of action of Organophosphorus Pesticides?
inhibition of acetylcholinesterase through phosphorylation of the esteratic state
Organophosphorus Pesticides causes what clinical effects?
M-U-D-D-L-E-S: miosis, urination, diarrhea, diaphoresis, lacrimation, excitation of the central nervous system, and salivation
If Organophosphorus Pesticides toxicity is not reversed, patients will develop?
neuromuscular transmission failure – cardiorespiratory failure, weakness of respiratory muscles and death
What treatments are available for the toxicity of organophosphates?
physostigmine, pralidoximine
Organophosphorus pesticides with the highest acceptable daily intake?
Trichlorfon and Dimethoate
Some organophosphate agents are capable of?
phosphorylating the neuropathy target esterase which results in progressive demyelination of the longest nerves
In humans, progressive chronic axonal neurotoxicity has been observed with?
triorthocresyl phosphate (TOCP)
T or F: Organophosphorus pesticides are persistent
F, break down in the environment due to photolysis and hydrolysis
Inhibit acetylcholinesterase by carbamoylation of the esteratic site
Carbamate pesticides
Binding site of carbamate pesticides are (weak/strong)
Weak
Carbamate or organophosphate: Aldicarb
Carbamate
Carbamate or organophosphate: Azinphos-methyl
Organophosphate
Carbamate or organophosphate: Dimetilan
Carbamate
Pesticides derived from natural resources include?
nicotine, rotenone, pyrethrum
Nicotine reacts with?
acetylcholine receptor of the post synaptic membrane resulting in its depolarization
Pyrethrum consists of 6 known insecticidal esters which are?
pyrethrin 1, 2, cinerin 1, 2, jasmolin 1, 2
Causes reactive airways dysfunction syndrome and anaphylaxis
Pyrethrum
Herbicides include?
Chlorophenoxy herbicides
Glyphosate
Bipyridyl herbicides
Used for the destruction of weeds with low acute human toxicity
Chlorophenoxy herbicides
Dichlorophenoxy and related herbicides have been found to contain and generate?
NMDA
Principal ingredient in Roundup and most widely used in herbicides in the world
Glyphosate
May damage crops and plants even if used as directed since it is non-selective; skin and eye irritant which can cause esophageal erosion
Glyphosate
Most important agent of bipyridyl herbicides?
Paraquat
Bipyridyl herbicides mechanism of action involves?
Single-electron reduction of the herbicide to free radical species
Environmental Pollutants consist of?
- Polychlorinated and Polybrominated Biphenyls
- Perfluorinated Compounds
- Endocrine Disruptors
- Asbestos
Highly halogenated biphenyl compounds which are used for insulation, fire retardancy
Polychlorinated Biphenyls
Mass production resulted in enormous environmental problems; very toxic and now banned for use
Polychlorinated Biphenyls
Used as dielectric and heat transfer fluids, lubricating oils, plasticizers, wax extenders and flame retardants
Polychlorinated Biphenyls
Major source of PCB Residues in humans
Food
AKA dioxins, group of halogenated congeners where tetrachlorodibenzodioxin has been studied carefully
polychlorinated dibenzo-p-dioxins (PCDDs)
Coolant materials in air-conditioning systems, oxygen-carrying materials in clinical studies, heat-stain-, and stick-resistant coatings for cookware, fabrics and other materials
Perfluorinated Compounds (PFCs)
Had deleterious effect in the ozone layer of the atmosphere
Perfluorinated Compounds (PFCs)
Human exposure to Perfluorinated Compounds (PFCs) mainly takes place through?
Inhalation and ingestion
Human half life of perfluorooctanoic acid is estimated to be?
3 Years
T or F: PFCs are only a endocrine disruptor
F, chemical and endocrine
PFCs have a long term effect on?
Reproductive function
Cellular proliferation
Cellular homeostatic mechanisms
What is caused by pyrolysis of PFOA?
Polymer fume fever (acute pulmonary disorder)
PFCs is associated with proliferation of _______; _______,________,______ and __________
proliferation of breast cancer cells; renal, ovarian, prostate and Non-Hodgkin’s lymphoma
PFCs are associated with what abnormalities?
cholesterol and uric acid abnormalities
Mimic, enhance or inhibit a hormonal action with estrogen-like or antiandrogenic effects; some affect thyroid functions
Endocrine Disruptors
Endocrine disruptors include?
phytoestrogens (plant derived), mycoestrogens, industrial chemicals, persistent organochlorine
agents (DDT), PCBs and brominated flame retardants
Increasing concerns in endocrine disruptors due to?
bioaccumulation, toxicity and increasing contamination in the environment
Large family of cyclic peptides, alkaloids, and lipopolysaccharides
Cytotoxins
Cytotoxins are a product of?
blue-green algae widely distributed in lakes and salt water
Low or high concentrations of cytotoxins: GI, neurologic, hepatic dysfunction
Low
Low or high concentrations of cytotoxins: poisoning and respiratory failure
High
Widely used in industry for over 100 years but causes progressive fibrotic lung diseases, lung cancer, mesothelioma
Asbestos
What increases the incidence of asbestos-caused lung cancer in synergistic fashion?
Cigarette smoking and exposure to radon daughters
All forms of asbestos cause?
Mesothelioma of the pleura or peritoneum at very low doses
T or F: Mechanism of asbestos causing cancer is well-defined
F, not well-defined
Metals consist of?
- Beryllium
- Cadmium
- Nanomaterials
anticipated to be human carcinogens: Manganese, uranium, cobalt
Light alkaline metal used in ceramics and alloys; computers; dental equipment; devices that requires hardening like missile ceramic nose cones and heat shield tiles in space vehicles
Beryllium
What class carcinogen is beryllium?
1
Route of entry of beryllium?
Inhalation
What does inhalation of beryllium cause?
Acute Beryllium Disease and Chronic Beryllium Disease characterized by progressive pulmonary fibrosis
Acute or Chronic Beryllium Disease: granulomatous pulmonary fibrosis
Chronic
Transition metal found in nickel batteries, pigments, low-melting point eutectic materials; in solder; in television phospors; and in plating operations; semiconductors and plastics
Cadmium
Route of entry of cadmium?
Inhalation and ingestion
When metals which have been plated with cadmium or welded with it are vaporized by the heat of cutting implements, the fine dust and fumes produce?
Cadmium fume fever
What level carcinogen is cadmium?
1
Chronic cadmium exposure may lead to?
progressive pulmonary fibrosis, renal failure
Nanomaterials are any material, natural or manufactured, bearing a size of at least one dimension that lies between?
1-100nm
Examples of nano materials?
Gold, silver, cadmium, ceramic, aluminum oxide
nanowears, carbon, silicon, and germanium
nanotubes, zinc oxide nanocrystal, gold nanowafers, and copper oxide nanocubes
Toxicology profile is fairly novel
Nanomaterials
Route of entry of nano materials?
Inhalation, oral, dermal, parenteral
T or F: Nanomaterial toxicity may be both similar and different from the larger, bulk materials
T
Nanomaterials can cross and penetrate what?
Can cross cellular membranes, penetrate nuclear material and genetic information
Demonstrated to produce kidney toxicity in humans
Silica
Toxic to human liver cells, hepatocellular damage
Zinc oxide
Cytotoxic in human lung cells
Multiwalled carbon nanotubes
Used in sunscreens, cosmetics, pharmaceuticals and products toxic to the lungs
Titanium dioxide