Q 1 : A Small Dose of Toxicology

Question 1

Define Toxicology

Answer 1

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.

Question 2

3 Basic Principles of toxicology

Answer 2

Dose/Response
hazard X exposure= Risk
Individual Sensitivity

Question 3

What killed Socrates?

Answer 3

Hemlock(Alkaloid coniine)

Question 4

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?

Answer 4

Thalidomide

Question 5

Money lost or spent due to the consumption of alcohol or dug abuse, car accidents, lost work, etc…

Answer 5

276 Billion

Question 6

Money lost to tobacco related illness or disease

Answer 6

65 Billion

Question 7

Estimated Number of children with fetal alcohol syndrome

Answer 7

12,000

Question 8

Pharmacology

Answer 8

Toxicology’s counterpart in medicine is pharmacology, the study of the beneficial and adverse effects of medicinal drugs.

Question 9

Define Toxins and Toxicants

Answer 9

Hazardous naturally occurring agents produced by living organisms are called toxins, while hazardous manufactured agents are called toxicants.

Question 10

What are the two most common physical agents?

Answer 10

Temperature and Noise

Question 11

Toxicology no longer focuses on death but ____ and _____.

Answer 11

work performance, quality of life

Question 12

What is the EPA and what is it responsible for?

Answer 12

The Environmental Protection Agency is responsible for regulating pesticides, industrial chemicals, hazardous waste, drinking water quality, air pollutants, and other environmental hazards.

Question 13

When was toxicology created and by who?

Answer 13

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).

Question 14

Individual Sensitivity to a hazardous agent is dependant on?

Answer 14

age, genetics, gender, current or prior illness, nutrition, and current or history of exposure to chemical agents.

Question 15

What is a dose?

Answer 15

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

Question 16

What is LD50?

Answer 16

The lethal dose for 50% of cases. Used to rank the toxicity of a substance.

Question 17

what 2 things have an LD50 of 250?

Answer 17

Aspirin and DDT.

Question 18

What has a LD50 of 1?

Answer 18

Nicotine

Question 19

3 Parts of Exposure?

Answer 19

1) route of exposure, 2) frequency of exposure, and 3) duration of exposure.

Question 20

3 Main routes of exposure?

1 Secondary Route?

Answer 20

1) skin (or dermal) exposure, 2) lung (inhalation) exposure, or 3) oral (gastrointestinal)
4. ) Injection

Question 21

Duration is separated into 3 periods

Answer 21

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).

Question 22

After exposure if effects aren’t noticed in the short term then they are ______ affects.

Answer 22

Chronic

Question 23

After exposure if effects are noticed in the short term then they are ______ affects.

Answer 23

accute

Question 24

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?

Answer 24

1. metabolism
2. Liver
3. Mercury and Lead

Question 25

What is a chelator?

Answer 25

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.

Question 26

What in the body does lead replace and therefore become stored?

Answer 26

Calcium

Question 27

What are major factors in susceptibility?

Answer 27

Gender, age, Personal Health, and genetic variability.

Question 28

Antagonistic Effect?

Answer 28

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

Question 29

Synergistic Effect?

Answer 29

When combined exposure of two chemicals has a more toxic affect then the sum of them separately.
EX: Tobacco Smoke and Asbestos

Question 30

Risk assessment is separated into 4 sections?

Answer 30

1) hazard identification, 2) dose/response assessment, 3) exposure assessment, and 4) risk characterization.

Question 31

Define Risk Management

Answer 31

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.

Question 32

Who is the father of Toxicology?

Answer 32

Paracelsus (1493-1541)

Question 33

Who is Shen Nung?

Answer 33

Shen Nung, the father of Chinese medicine (approximately 2695 BCE), who was noted for tasting 365 herbs and dying from a toxic overdose

Question 34

Mathieu J. B. Orfila (April 24, 1787 - March 12, 1853),

Answer 34

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.

Question 35

rotenone

Answer 35

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

Question 36

is rotenone poisonous to humans, why or why not

Answer 36

can only affect gills, not the digestive tract

Question 37

what is rotenone now used for

Answer 37

fish sampling (counting),- they can be revived if taken out of the rotenone fast enough, can remove invasive species,-fishering managing technique

Question 38

when was the earliest recorded instance of poisoning

Answer 38

in athen- poisoned water in 590BC - hellebore

Question 39

what is hellebore

Answer 39

poisonous plant wiped out ppl of kirha

Question 40

what happened in 129 BC by general aquillius

Answer 40

killed both civilians and combatants- hellbore

Question 41

what is scythicon

Answer 41

arrow drug created by scythians of central asia concoction of putrified caucasion vipers, dung and blood- scratch of this is lethal- gangrene, tetanus

Question 42

what happened in 65 BC with the bees anf the roman army

Answer 42

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

Question 43

why were the bees poisonous to the roman army

Answer 43

the bees ate rhododendron nectar

Question 44

why were the fires from the persian army poisonous

Answer 44

They added bitumen (petroleum) and sulphur, to produce a cloud of asphyxiating sulphur dioxide

Question 45

what was said in the myth of hercules and hydra and why

Answer 45

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.

Question 46

what did earyl toxicologists focus on

Answer 46

killing ppl, strived for undetectable poisons, few texts one was by shen nung 2695BC

Question 47

who is paracelusus

Answer 47

the father of modern toxicology 1493 1541

Question 48

who said “All things are poison and nothing (is) without poison; only the dose makes that a thing is no poison.(

Answer 48

paracelusus

Question 49

what was devonshire colic

Answer 49

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

Question 50

what is fowlers solution

Answer 50

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

Question 51

what is the arsenic act?

Answer 51

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

Question 52

what was an example in the past of regulated controled substances

Answer 52

the arsenic art

Question 53

what was the prohibition in the usa

Answer 53

banned all alcohol production

Question 54

what is the substance found in alcohol

Answer 54

`ethanol- not methanol that one causes blindness

Question 55

what does methanol do

Answer 55

caus blindness, brain damage

Question 56

what is ddt

Answer 56

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

Question 57

what is the consequence of ddt

Answer 57

it softened birds shells, it was banned in 1972 after the book silent spring by rachel carson was released in 1962

Question 58

when was ddt banned

Answer 58

1972

Question 59

wwhat was thalidomide used for

Answer 59

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

Question 60

what did the epidemic of thalidomide teach the world

Answer 60

that many toxic substances have chemical structures that give them the ability to penetrate the placenta.

Question 61

why was thalidomide thought to be acceptable

Answer 61

we did not know the Sensitivity of the fetus compared to the adult

Question 62

what is happening now with thalidomide in research

Answer 62

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

Question 63

what drug do we combine with dexamethasone

Answer 63

thalidomide

Question 64

when was the first modern text of toxicolgy book

Answer 64

1975 caserett & doull’s the basic science of poisons

Question 65

what agent that if you have a dose of 0.00001 50% of ppl will die

Answer 65

botox

Question 66

Puffer Fish?

Answer 66

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.

Question 67

Tetrodotoxin?

Answer 67

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.

Question 68

Saxitoxin?

Answer 68

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

Question 69

Jimson Weed?

Answer 69

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

Question 70

Nightshade?

Answer 70

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

Question 71

Worlds most dangerous mushrooms?

Answer 71

“Death cap” or “death angel”- Amatoxin

Question 72

Amatoxin

Answer 72

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

Question 73

Animal toxins divided into two subsections?

Answer 73

1. Venoms

2. Poisons

Question 74

Venoms?

Answer 74

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.

Question 75

Poisons?

Answer 75

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

Question 76

Black Widow Spider

Answer 76

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.

Question 77

The most common venomous snakebites in N.A is from?

Answer 77

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.

Question 78

Shellfish?

Answer 78

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.

Question 79

Newest toxin found in Plankton => shellfish?

Answer 79

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
194
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.

Question 80

Best method of protection for a plant?

Answer 80

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.

Question 81

urushiol?

Answer 81

Poison Ivy compound

Question 82

Dieffenbachia or “dumb cane”

Answer 82

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.

Question 83

Ways Plants can protect themselves?

Answer 83

1. Skin Irritant
2. Gastrointestinal irritation
3. Cardiovascular
4. Liver
5. Reproductive System

Question 84

Effects on the Gastrointestinal System

Answer 84

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.

Question 85

Effects on the Cardiovascular System

Answer 85

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
198
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

Question 86

grayanotoxin

Answer 86

found on the leaves of rhododendrons

Question 87

Effects on the Liver

Answer 87

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

Question 88

Effects on the Reproductive System

Answer 88

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.