Chem 183 Lecture 3

Front 1

toxicology

Back 1

the study of the effects of chemicals on living organisms

Front 2

dioxins

Back 2

toxic compounds present in junk food meat

Front 3

acrylamide

Back 3

a carcinogen caused when break and buns are baked at high temperatures

Front 4

trihalomethanes

Back 4

compounds created when water is chlorinated that are carcinogenic

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bisphenol A

Back 5

a substance released by polycarbonate plastic water bottles that is an endocrine disruptor;

Front 6

parabens

Back 6

used to preserve antiperspirants; have been linked to breast tumors but this has been discredited

Front 7

plastic shower curtains

Back 7

release 108 chemicals in the air

Front 8

dibutyl phthalate

Back 8

compound used to make plastics softer and nail polish conform around the nail; it can reduce the distance between male rodent anus and genitals when exposed to the mother

Front 9

isocyanates

Back 9

can be released by polyurethane foam pillows

Front 10

nitrosamines

Back 10

a carcinogen that can contaminate balloons and condoms

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Accepted Daily Intake (ADI) of antimony

Back 11

6ppb; the water of a plastic water bottle contains 3ppb

Front 12

No Observed Adverse Effect Level (NOAEL)

Back 12

technique used to determine the ADI; it is the maximum amount of substance you can give an animal without observing adverse effects; this is done with rats; researchers start with a small dose and increase until an effect is noticed; the amount is then divided by 100(the safety factor) and that is the ADI

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downside to NOAEL

Back 13

it tests for acute toxicity in chemicals, not chronic

Front 14

"Three Tree Poison" (1595)

Back 14

a toxin used in hunting smaller animals in the jungles of South America (such as monkeys)--so called because the monkey hit with the poisoned arrow would jump between trees once, twice, but not make it to the third tree; it also existed in two tree and one tree forms

Front 15

Sir Walter Raleigh

Back 15

a British explorer who investigated the "three tree poison"; it turns out that the substance was Curare; it was isolated from the vine Chondodendron tomentosum using hot water

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Sir Charles Waterton

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a British physician who found that curare could cause muscle relaxation without causing death

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Claude Bernard (1844)

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a French physiologist who discovered that curare blocked nerve impulses that connected the central nervous system to muscles; thus at accurate doses it could cause paralysis; his observations caused it to be used during abdominal surgery to prevent muscle quivering

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tubocuranine

Back 18

the active ingredient of curare

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Dr. Harold Griffiths

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the first physician to use curare to relax the muscles of a patient undergoing an appendectomy (1942)--this was at what is now the Queen Elizabeth Hospital in Montreal

Front 20

execution lethal injection contents

Back 20

Step 1: sodium thiopentol (barbiturate)
Step 2: Pavulon/Pancuronium (derivative of curare that stops breathing)
Step 3: Potassium chloride (stops the heart)

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sulfanilamide

Back 21

compound that preceded penicillin as an antibiotic; it is used in the treatment of gonorrhoea and strep throat; it was introduced in the form of pills in Europe

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elixir

Back 22

a drug dissolved in alcohol; this was the tradition in the southern US because it was easier to give to children than tablets

Front 23

diethylene glycol

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a toxic substance that was used to make sulfanilamide elixirs because sulfanilamide was insoluble in alcohol;it was sweet tasting; it caused abdominal pain, vomiting, blinding, and 107 deaths; 260 were permanently disabled

Front 24

Harold Watkins

Back 24

the chief company chemist who came up with the idea of using diethylene glycol as a solvent for the drug, was blamed for its failure; he refused to believe it and took some himself, got really sick, and committed suicide

Front 25

Frances Kelsey

Back 25

a McGill graduate who discovered the connection between the deaths and the diethylene glycol; tested the substance on rats for toxicity; 234/240 gallons of the elixir were recalled

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Roosevelt

Back 26

signed the 1938 Food Drug and Cosmetic Act because of the extreme failure of elixir sulfanilamide

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threshold effect

Back 27

dosage below which no adverse effects of a toxic compound will be observed

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hormesis

Back 28

investigation of a substance at very low doses because they may behave differently at higher doses; here, a slightly larger dose can be less dangerous than a very small dose; an example of this is Vitamin A

Front 29

polar bear liver

Back 29

has lots of vitamin A

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DDT

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also exhibits a hormetic dose-response curve because small amounts of it rev up the immune system so it deals with toxic materials better

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risk

Back 31

=toxicity x exposure

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cyanide

Back 32

present in lima beans and apple seeds; the lethal dose is 10 000 micrograms

Front 33

Cassava

Back 33

a fruit consumed in Africa and the Caribbean that may release moderate amounts of cyanide upon ingestion; this happens when it is not prepared properly

Front 34

Puffer fish (Fugu)

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a delicacy in Japan that contains tetrodotoxin; chefs must be properly trained in order to eviscerate it such that the poison is removed; eating it causes a tingling sensation to travel from the hands to the elbows; 1-2 die from poisoning a year;

Front 35

10 micrograms

Back 35

the lethal dose of tetrodotoxin

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botulin toxin

Back 36

comes from the bacteria Clostridium botulinum, an anaerobic bacterium first found in sausages (nitrites are now added to prevent their growth); lethal dose is 0.03 micrograms; can also be produced by the bacterium in garlic stored in oil; it is also used in medicine to prevent tremors and in Botox; can be used to ease migraine pain and treat chronic anal fissures

Front 37

difficulties in studying toxicology of substances

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type of exposure matters; biochemical individuality; acute vs. chronic effects; teratogenic effect; toxin recognition; animal models

Front 38

Nocebo effect

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people ho are told that a particular substance is dangerous will react negatively to it regardless of te real nature of it; e.g. aspartame

Front 39

Dr. Harvey W. Wiley

Back 39

the chief of the bureau of chemistry (of the US Department of Agriculture)--this department eventually became the FDA; was tasked with determining which substances were toxic in foods

Front 40

copper arsenate

Back 40

a toxin once used to color peas to make them more marketable for food companies

Front 41

"The Poison Squad" (1903)

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a dozen volunteers picked from workers at the department of agriculture; ate food prepared by renowned chef William R Carter, with a different food additive added to every meal (e.g. borax, salicylic acid, sodium benzoate, etc); volunteers were monitored

Front 42

Pure Food and Drug Act of 1906

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an Act that Wiley convinced the government to pass after his experiments with the Poison Squad; it was not originally very effective, then became more strict after the sulfanilamide scare

Front 43

Sodium benzoate

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Wiley found that this compound was in particularly dangerous doses in food; it is not found in much smaller doses

Front 44

Phase 1 enzymes

Back 44

first step of detoxification; these proteins increase the solubility of a toxic substance and provide a site of attachment on that molecule for a phase 2 enzyme; e.g. cytochrome P450

Front 45

Phase 2 enzyme

Back 45

proteins involved in the elimination of the now-soluble substance from the body

Front 46

benzopyrenes

Back 46

compounds formed when BBQing meat; they are composed of multiple aromatic rings, and are not chemically water soluble, nor particularly dangerous; when they are made more soluble by phase 1 enzymes, they become carcinogenic

Front 47

tea

Back 47

contains compounds that trick the body into making phase 1/2 enzymes; the extra enzymes help eliminate other toxins in the body

Front 48

glucuronyl transferase

Back 48

a phase 2 enzyme stimulated by tea; it attaches to glucuronic acid and rids it from the body

Front 49

sulforaphane

Back 49

a compound in broccoli that the body perceives to be toxic; stimulates enzyme generation

Front 50

garlic

Back 50

stimulates glutathione-s-transferase, which is an enzyme that attaches glutathione to toxins and to help remove them from the body

Front 51

St John's Wort

Back 51

a flower whose extract is used widely as a mild anti-depressant; sometimes referred to as nature's prozak; it induces the formation of cytochrome P450; in a case study a man taking it post-heart transplant rejected the heart because it was counteracting the cyclosporine

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drugs metabolized by cytochrome P450

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tetracycline, tamoxifen, MAO inhibitors, protease inhibitors, corticosteroids, antidepressants, anesthetics, contraceptives, anti-anxiety agents (Xanax), Dextrometorphan (a cough remedy)

Front 53

N-acetyl-p-benzoquinone imine

Back 53

a very reactive intermediate in the removal of tylenol from the body that can cause damage to the liver; it occurs when there is not enough glutathione and cytochrome p450 acts on tylenol instead of glutathione-s-transferase

Front 54

methionine

Back 54

a precursor to glutathione; it should be present in all acetaminophen tablets to help prevent liver damage but isn't ; glutathione is a tripeptide that cannot be consumed orally because it will be degraded in the stomach

Front 55

N-acetylcysteine

Back 55

a dietary supplement that can release cysteine into the bloodstream, which is necessary for glutathione synthesis; it can be taken to reduce the possibility of liver damage

Front 56

heme oxygenase

Back 56

breaks down heme into biliverdin, which is then further converted to bilirubin; glucuronic acid is then attached to bilirubin via glucuronyl transferase to make it more soluble so it can be excreted

Front 57

jaundice

Back 57

caused by insufficient glucuronyl transferase enzyme, which causes bilirubin accumulation under the skin; first sign of liver disease in adults

Front 58

blue "Bili" lights

Back 58

lights built into incubators/blankets that are used to prevent jaundice in babies; these lights change the shape of the bilirubin molecule to make it more soluble; they are available for home use today

Front 59

Seldane

Back 59

one of the first non-sedating anti-histamine drugs available for the public; when it is ingested, the body perceives it as foreign and pursues its elimination; the phase 1 enzyme changes it to its soluble and metabolically active form, which is also quite toxic; now removed from the market

Front 60

ketoconazole

Back 60

an antifungal drug that cross reacts with the phase 1 enzyme that affects Seldane; prevents the formation of metabolically active Seldane; causes accumulation of regular Seldane which causes heart attacks

Front 61

Allegra

Back 61

the metabolically active form of Seldane (with no risks of heart attacks)is now used

Front 62

antihypertensive drugs

Back 62

drugs that reduce blood pressure

Front 63

felodipine

Back 63

a common antihypertensive drug; it is also metabolized by cytochrome P450

Front 64

grapefruit juice

Back 64

inhibits the formation of cytochrome P450

Front 65

Furanocoumarins

Back 65

compounds found in grapefruit juice that are responsible for its ability to inhibit the formation of cytochrome P450

Front 66

erythromycin

Back 66

a very effective antibiotic which is also metabolized by cytochrome enzymes; has the ability to induce irregular heartbeats if taken with other drugs affecting the cytochrome P450 pathway

Front 67

monoamineoxidase inhibitors (MAOIs)

Back 67

drugs often used to treat depression; inhibit MAO which is a detoxicating enzyme, thus inhibiting the breakdown of norepinephrine, serotonin, and dopamine; can't be taken with large amounts of tyramine

Front 68

tyramine

Back 68

a compound found in aged cheese, red wine, and salami; it increases blood pressure; it is also broken down by MAO; in the presence of MAOIs it can cause blood pressure to increase too much and cause stroke

Front 69

1,4-dichlorobenzene

Back 69

substance that is used in mothballs and air fresheners; has been linked to causing respiratory problems

Front 70

dioxin

Back 70

most toxic man-made chemical; it is a byproduct of some industrial processes; tetrachlorodibenzodioxin is the most toxic one (TCDD); four chlorines are needed for toxicity; byproduct of pulp bleaching to paper and white paper coffee filters

Front 71

Charles Darwin

Back 71

a naturalist that studied plants; he realized that plants growth was governed by plant hormones

Front 72

auxin

Back 72

the first plant hormone extracted; chemical name is indole-3-acetic acid; adding it to plants makes them grow too fast (without the necessary nutrients) leading to their death

Front 73

auxin analogs

Back 73

2,4-D and 2,4,5-T; chemicals that make very good weed killers; the weeds grow too fast and die, but do not affect grass; they were the original herbicides;

Front 74

Agent Orange

Back 74

a mixture of 2,4-D and 2,4,5-T that was used to defoliate trees during the Vietnam War; this was known as Operation Ranch Hand; turns out the 2,4,5-T was contaminated with TCDD, making it a potent carcinogen

Front 75

2,4,5-T

Back 75

an auxin analog that was shown to create birth defects in mice because of TCDD contamination; it cannot be made without contamination; it also caused chloracne

Front 76

lethal dose 50

Back 76

dose of a chemical required to kill 50% of the animals that it is being tested on

Front 77

polyvinyl chloride

Back 77

a plastic, that when incinerated, releases small amounts of TCDD

Front 78

Seveso

Back 78

a small town in Italy that had a chemical spill in 1976; men exposed to the dioxins seem to have had more female babies on average

Front 79

Viktor Yuschenko

Back 79

former president of Ukraine; had an attempt made on his life; dioxin was put in his food; he was discovered with chloracne but survived

Front 80

Jean-Dominic

Back 80

a young boy with lymphoma whose parents started anti-pesticide activism in Quebec 15 years ago; he is now cured and grown up and stil lobbying for a ban on the use of pesticides

Front 81

Love Canal

Back 81

the name of a community near Niagara Falls, New York; which was shut down due to a chemical company dumping chemicals, including dioxins, near the town

Front 82

fluoride

Back 82

a chemical used in rat poison, is now used in our waters for tooth enamel health; in Kingston, New York, the nocebo effect came about when people assumed they had started adding the chemical to the water but they hadn't yet

Front 83

diethylstilbestrol (DES)

Back 83

a synthetic hormone that was used to prevent miscarriage in women; recommended regimen started in the 7th week of pregnancy; 1/1000 women gave birth to daughters with a higher risk of clear cell adenocarcinoma