Q 1 : A Small Dose of Toxicology Flashcards
Define Toxicology
Toxicology originally developed as the study of poisons and is now more formally described as the study of the adverse effects of chemical or physical agents on living organisms.
3 Basic Principles of toxicology
Dose/Response
hazard X exposure= Risk
Individual Sensitivity
What killed Socrates?
Hemlock(Alkaloid coniine)
What drug used for sedation in the early 1960’s(1962) pushed the FDA to require a trial before allowing new drugs to be used on a regular basis?
Thalidomide
Money lost or spent due to the consumption of alcohol or dug abuse, car accidents, lost work, etc…
276 Billion
Money lost to tobacco related illness or disease
65 Billion
Estimated Number of children with fetal alcohol syndrome
12,000
Pharmacology
Toxicology’s counterpart in medicine is pharmacology, the study of the beneficial and adverse effects of medicinal drugs.
Define Toxins and Toxicants
Hazardous naturally occurring agents produced by living organisms are called toxins, while hazardous manufactured agents are called toxicants.
What are the two most common physical agents?
Temperature and Noise
Toxicology no longer focuses on death but ____ and _____.
work performance, quality of life
What is the EPA and what is it responsible for?
The Environmental Protection Agency is responsible for regulating pesticides, industrial chemicals, hazardous waste, drinking water quality, air pollutants, and other environmental hazards.
When was toxicology created and by who?
The formal study of poisons (and thus toxicology) began 500 years ago during the Renaissance, a period of incredible change and challenge to traditional thought. Phillippus Aureolus (Figure 2.1) was born in Switzerland in 1493. He took the pseudonym of Theophrastus Bombastus von Hohenheim and still later invented the name PARACELSUS (1493-1541).
Individual Sensitivity to a hazardous agent is dependant on?
age, genetics, gender, current or prior illness, nutrition, and current or history of exposure to chemical agents.
What is a dose?
Is the amount of the material in relation to body weight.
Typically the amount of material is measured in grams or thousandths of a gram (milligrams, mg) and body weight is measured in kilograms (kg), equal to one thousand grams. The dose is the amount of material consumed divided by body weight, or mg/kg.
Oral dose = amount of material consumed (mg)/body weight (kg) Inhalation dose (mg/kg) = • Air concentration of agent (mg/ml) X volume of air inhaled per hour (ml/hr) X duration of exposure (hr)/body weight (kg
What is LD50?
The lethal dose for 50% of cases. Used to rank the toxicity of a substance.
what 2 things have an LD50 of 250?
Aspirin and DDT.
What has a LD50 of 1?
Nicotine
3 Parts of Exposure?
1) route of exposure, 2) frequency of exposure, and 3) duration of exposure.
3 Main routes of exposure?
1 Secondary Route?
1) skin (or dermal) exposure, 2) lung (inhalation) exposure, or 3) oral (gastrointestinal)
4. ) Injection
Duration is separated into 3 periods
1) acute exposure (usually just one or two exposures of short duration); 2) sub-chronic exposure (multiple exposures over many days or perhaps months); and 3) chronic exposure (long-term or even lifetime exposure).
After exposure if effects aren’t noticed in the short term then they are ______ affects.
Chronic
After exposure if effects are noticed in the short term then they are ______ affects.
accute
What body function aids in the detoxification of many toxins that enter the body?
What internal organ is the primary for detoxification?
What 2 Elements cannot be degraded by the liver?
- metabolism
- Liver
- Mercury and Lead
What is a chelator?
Chelators bind to metals so that they are more readily excreted in the urine. In the past, chelators were routinely prescribed to people with elevated blood lead levels in an effort to accelerate the excretion of lead in the urine. Unless the blood levels are excessively elevated, the current treatment is to determine the source of the lead exposure and take remedial action. The problem with chelators is that they are nonspecific and bind useful agents such as calcium.
What in the body does lead replace and therefore become stored?
Calcium
What are major factors in susceptibility?
Gender, age, Personal Health, and genetic variability.
Antagonistic Effect?
When two different chemicals are exposed to the same person and they have a reduced toxic affect in tandem then separately.
EX: Methanol and ethanol
Synergistic Effect?
When combined exposure of two chemicals has a more toxic affect then the sum of them separately.
EX: Tobacco Smoke and Asbestos
Risk assessment is separated into 4 sections?
1) hazard identification, 2) dose/response assessment, 3) exposure assessment, and 4) risk characterization.
Define Risk Management
Risk management is the political or social process of deciding how the benefits balance the associated risks. Risk management is also concerned with how the public perceives risk and how we judge and perform our own risk assessments. An example of risk management was the decision to remove lead from gasoline. After a great deal of research it was demonstrated that low levels of lead exposure are harmful to the developing nervous system. It was then determined that the benefits of removing lead from gasoline were greater than the costs. A program was developed to gradually phase out lead from gasoline, design new engines not requiring lead, and replace old cars.
Who is the father of Toxicology?
Paracelsus (1493-1541)
Who is Shen Nung?
Shen Nung, the father of Chinese medicine (approximately 2695 BCE), who was noted for tasting 365 herbs and dying from a toxic overdose
Mathieu J. B. Orfila (April 24, 1787 - March 12, 1853),
a French toxicologist and chemist, is credited with founding the modern science of toxicology, in part through analytical work in forensic toxicology related to the poison of the day, arsenic.
rotenone
Effective at killing fish
Limited toxicity to man
Roots of specific plants are pulverized into water
All gill breathing animals are paralyzed or killed
Absorbed over gills
Not effectively absorbed in gut
Fish are safe to eat
is rotenone poisonous to humans, why or why not
can only affect gills, not the digestive tract
what is rotenone now used for
fish sampling (counting),- they can be revived if taken out of the rotenone fast enough, can remove invasive species,-fishering managing technique
when was the earliest recorded instance of poisoning
in athen- poisoned water in 590BC - hellebore
what is hellebore
poisonous plant wiped out ppl of kirha
what happened in 129 BC by general aquillius
killed both civilians and combatants- hellbore
what is scythicon
arrow drug created by scythians of central asia concoction of putrified caucasion vipers, dung and blood- scratch of this is lethal- gangrene, tetanus
what happened in 65 BC with the bees anf the roman army
unusual poison unusual poison created by bees was wielded against the Roman army of Pompey by Mithradates of Pontus (northern Turkey)
The enemy placed wild honeycombs along Pompey’s route. The starving soldiers feasted on on the honey.
Reeling and babbling, they collapsed en masse, wracked by diarrhea and vomiting.
The enemy slaughtered over a 1,000 men paralyzed by a naturally occurring neurotoxin (grayanotoxin) in Rhododendron nectar
why were the bees poisonous to the roman army
the bees ate rhododendron nectar
why were the fires from the persian army poisonous
They added bitumen (petroleum) and sulphur, to produce a cloud of asphyxiating sulphur dioxide
what was said in the myth of hercules and hydra and why
toxic weapons often have unintended consequences, because, A well-preserved skeleton, in Persian chain mail, reveals that the man who ignited the fire succumbed to the fumes before he could escape.
what did earyl toxicologists focus on
killing ppl, strived for undetectable poisons, few texts one was by shen nung 2695BC
who is paracelusus
the father of modern toxicology 1493 1541
who said “All things are poison and nothing (is) without poison; only the dose makes that a thing is no poison.(
paracelusus
what was devonshire colic
ppl in devon were getting lead poisoning (stomach pain, death)- The precise cause was not discovered until the 1760s when Dr George Baker put forward the hypothesis that poisoning fromleadin cider was to blame.
He observed that the symptoms of the colic were similar to those of lead poisoning.
Lead was used in the cider making process as a component of cider presses and as lead shotused to clean them.
He also conducted chemical tests to demonstrate the presence of lead in Devon apple juice.- - regected by the cider company
what is fowlers solution
1% solution of potassium arsonic, prescribed in the United States until the late 1950s for a range of ailments including malaria, chorea, and syphilis.
In 2001 the U.S.Food and Drug Administration(FDA) approved a drug ofarsenic trioxideto treatacute promyelocytic leukaemia - interest in arsenic has returned
what is the arsenic act?
was passed in the UK in 1851
Arsenic compounds were widely used as pigments and in agricultural products such as sheep dressings
The Act was introduced to address increasing public concern over accidental and deliberate arsenic poisonings.
The Act required those selling such products to maintain a written, signed record of those to whom it was sold, including the quantity and its stated purpose.
The maximum penalty for breaching the Act, or providing false information, was £20 ($25,000 in 2010
what was an example in the past of regulated controled substances
the arsenic art
what was the prohibition in the usa
banned all alcohol production
what is the substance found in alcohol
`ethanol- not methanol that one causes blindness
what does methanol do
caus blindness, brain damage
what is ddt
as aninsecticideby Swiss scientistPaul Hermann Muller
DDT helped 1 billion people live malaria-free for 30 years after its discovery, saving millions of lives.
In 1948 Muller received the Nobel Prize for discovering the insecticidal qualities of DDT and its use in controlling vector borne diseases such as malaria and yellow fever
what is the consequence of ddt
it softened birds shells, it was banned in 1972 after the book silent spring by rachel carson was released in 1962
when was ddt banned
1972
wwhat was thalidomide used for
popular as a sedative and tranquilizer chemically similar to barbiturates with relatively low adult toxicity
After it’s introduction there was a huge increase in birth defects
Many women who took as little as 1 dose gave birth to babies with serious birth defects
what did the epidemic of thalidomide teach the world
that many toxic substances have chemical structures that give them the ability to penetrate the placenta.
why was thalidomide thought to be acceptable
we did not know the Sensitivity of the fetus compared to the adult
what is happening now with thalidomide in research
become a potential agent for the treatment of hematologic malignancies (cancers of blood) and some solid tumors.
Thalidomide in combination with dexamethasone is approved for use in multiple myeloma.Current data show promising results for hepatocellular carcinoma, prostate, neuroendocrine, and ovarian cancers
what drug do we combine with dexamethasone
thalidomide
when was the first modern text of toxicolgy book
1975 caserett & doull’s the basic science of poisons
what agent that if you have a dose of 0.00001 50% of ppl will die
botox
Puffer Fish?
About 100 species of puffer fish use the powerful tetrodotoxin to discourage consumption by predators. Tetrodotoxin is found in all organs of the fish but is highest in the liver, skin, and intestine. The origins of the toxin are not clear, but one possibility is that the fish come in contact with bacteria that produce tetrodotoxin. Puffer fish may also have elevated levels of saxitoxin, a neurotoxin responsible for paralytic shellfish poisoning. Saxitoxin is produced by dinoflagellates (algae) and most often contaminates mussels, clams, and scallops. Both saxitoxin and tetrodotoxin are heat stable so cooking does not reduce toxicity
Experienced chefs make meals using puffer fish as a delicacy which giver the consumer mild tingly feeling.
Tetrodotoxin?
Pufferfish: Tetrodotoxin causes paralysis by affecting the sodium ion transport in both the central and peripheral nervous systems. A low dose of tetrodotoxin produces tingling sensations and numbness around the mouth, fingers, and toes. Higher doses produce nausea, vomiting, respiratory failure, difficulty walking, extensive paralysis, and death. As little as 1 to 4 mg of the toxin can kill an adult.
Tetrodotoxin is heat stable but water soluble, so careful preparation is necessary to limit neurological effects.
Saxitoxin?
Puffer Fish: Saxitoxin has a very different chemical structure than tetrodotoxin but has similar effects on transport of cellular sodium and produces similar neurological effects. Saxitoxin is less toxic that tetrodotoxin
Jimson Weed?
Jimson weed, part of the belladonna family of plants, is a common weed in North America. The easy availability of Jimson weed and its ability to alter the nervous system leads to youth experimenting with the plant. Unfortunately, the consequences, especially when combined with other drugs, can be very serious and even lead to death
Part of the larger family of Plants called Nightshade
Nightshade?
The deadly nightshade plant (Atropa belladonna) was used in the Roman Empire and during the Middle Ages both as a cure and a poison
In addition to atropine, this family of plants contains scopolamine and other belladonna alkaloids. They act by inhibiting the actions of acetylcholine at central and peripheral nerves. Besides dilation of the pupils, exposure to the belladonna alkaloids stops salivation, causing a dry mouth, difficulty swallowing, and an irregular heart rate. A larger dose causes central nervous system effects such as hallucinations, loss of memory, and confusion
Worlds most dangerous mushrooms?
“Death cap” or “death angel”- Amatoxin
Amatoxin
Often it is difficult to associate symptoms with eating the mushrooms because there is a 10-12 hour delay before symptoms become apparent
The initial symptoms are nausea, vomiting, diarrhea, and an irregular heart rate. Ultimately the toxin, amatoxin, damages liver cells causing liver and kidney failure and possibly death
Animal toxins divided into two subsections?
- Venoms
2. Poisons
Venoms?
Venoms are offensive, used in the quest for food. Snakes produce toxins that can immobilize or kill prey for food. The venom of spiders paralyzes insects to allow the spider to feed on the victim’s body fluids. While the venoms may also be used defensively, their primary purpose is to aid in the quest for food. Most venom is delivered from the mouth, but there are exceptions, like the scorpion that uses its tail.
Poisons?
Poisons are primarily defensive, designed as protection against predators. Poisons are often sprayed or delivered with a stinger to penetrate the skin. Some fishes have poisons in their spines. Toxins can also be on the skin or be part of the meat of the animal, thus making them poisonous to touch or eat. Some poisonous animals develop very colorful markings to advertise their undesirable qualities
Black Widow Spider
black widow spider, but there are many similar species found around the world in temperate or tropical climates. It has a number of common names depending on the region of the world and
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ranges in color from brown to gray to black. The black widow species is shiny black and on the belly of the females is a red hourglass. Both the male and females are venomous, but only the female has fangs large enough to penetrate human skin. The venom of this species is made up of large proteins thought to affect the transmission of calcium ions of nervous system cells. The initial sting of the bite is followed by muscle cramps, sweating, and possibly decreased blood pressure. There is no adequate treatment but the bite is seldom fatal.
The most common venomous snakebites in N.A is from?
vipers. This class of snakes has the most advanced venom delivery system. The venom is quickly injected through hinged tubular fangs that can be folded into the snake’s mouth. The pit vipers, such as rattlesnakes, have a head sensor located between their nostril and eyes, which is thought to guide the strike even in the dark. The venom from vipers is a very complex enzyme-based substance that quickly causes localized swelling and tissue destruction (necrosis). The protein-based venom causes an allergic-type reaction leading to hemorrhage of body fluids, decreased blood pressure, shock, fluid in the lungs, and death.
Shellfish?
Shellfish such as mussels, clams, oysters, and scallops are not naturally toxic but can become so after feeding on plankton contaminated with a toxin. When visible, the blooming of the plankton (dinoflagellate) is called red tide and can cause significant death among marine animals. There are several types of toxins, mostly affecting the nervous system.
Newest toxin found in Plankton => shellfish?
The newest, domoic acid, first appeared in 1987 off Prince Edward Island in Canada. This neurotoxin caused confusion and memory loss, particularly in the elderly. Several elderly people died following seizures and coma. Domoic acid is
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heat stable, so cooking does not affect the toxin. Government agencies now monitor for contaminants of shellfish and move quickly to restrict harvesting. The domoic acid incident clearly indicates the importance of ongoing monitoring of the food supply.
Best method of protection for a plant?
One of the best methods of protection for a plant is to make skin contact painful. This is done through either an allergic antibody-mediated response or through direct-acting chemicals. For an allergic-type response it is not the first contact that produces the reaction but rather the next contact. For example, poison ivy produces a class of chemicals called urushiol that cause a widely variable allergic response in about 70% of people exposed. Although not a direct protection for the plant, pollen of ragweed, mugwort, or grasses cause an allergic response in many people.
urushiol?
Poison Ivy compound
Dieffenbachia or “dumb cane”
a common houseplant, produces a juice that is released when a stem is broken or chewed and causes a painful, rapid swelling and inflammation of the tongue and mouth. The symptoms can take several days to resolve and are caused by oxalate crystals coated with an irritating protein. Stinging nettle (Urtica) releases histamine, acetylcholine, and serotonin from fine tubes with bulbs at the end that break off on the skin, causing an intense burning or stinging sensation.
Ways Plants can protect themselves?
- Skin Irritant
- Gastrointestinal irritation
- Cardiovascular
- Liver
- Reproductive System
Effects on the Gastrointestinal System
For the plant, another good way to stop consumption by an animal is to make the animal sick to the stomach. This approach is used by a number of plants, but the mechanism of action varies. The first approach is direct irritation of the stomach lining
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to induce nausea and vomiting. The induction of mild vomiting is medically useful in some situations. The “sacred bark” of the California buckthorn produces cascara that is used as a purgative to induce mild vomiting.
Effects on the Cardiovascular System
The medically important drug digitalis was derived from foxglove (Digitalis purpurea). At medically useful doses, digitalis slows and stabilizes the heart rate, but at high dose it produces an irregular heart rate and decreased blood pressure.
The Greeks first reported “mad honey poisoning” almost 2500 years ago, and honey poisoning still affects people around the world, when bees gather nectar from
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rhododendrons and take it back to their hives. The cardiovascular effects are caused by grayanotoxin, which is produced in the leaves and nectar of rhododendrons and are concentrated in the honey by the bees. Goats and sheep are also affected when they consume the leaves of rhododendron or some lily plants
grayanotoxin
found on the leaves of rhododendrons
Effects on the Liver
Fungi produce two of the most potent toxins affecting the liver. The “death cap” and “death angel” mushrooms from the Amanita family kill several people every year when mistakenly consumed. There are also a number of fungi and molds that grow on nuts or grain. High humidity and poor storage conditions encourage the growth of a fungus on nuts that produces aflatoxin, a very potent toxin that causes liver cancer. People with prior liver disease such as hepatitis are particularly susceptible
Effects on the Reproductive System
Reproductive and developmental toxins are primarily a concern for livestock. A high rate of fetal malformations in sheep offspring occurs following grazing on Veratrum californicum that grows in the mountains of North America. Plants that induce abortion, such as bitter melon seeds, have a long history of use of in humans.
