Exam 1

Question 1

The interaction of chemicals in toxicology includes all of the following except:

Answer 1

Subtractive

Question 2

Paracelsus was an expert in all of the following professions except:

Answer 2

Astrophysicist

Question 3

Which of the following is not considered a phase II biotransformation?

Answer 3

Epoxide hydration

Question 4

Toxicology may be defined as the study of:

Answer 4

The adverse effects of chemicals in living systems

Question 5

Toxicants may move across biological membranes by all of the following mechanisms except:

Answer 5

Aqueous hydrolysis

Question 6

Which of the following statements best characterizes synergism?

Answer 6

Synergism occurs if two chemicals with a similar action, when given together, produce an effect that is greater in magnitude than the sum of the effects when the chemicals are given individually

Question 7

Biotransformation reactions generally produce a product that is:

Answer 7

less lipid-soluble than the original chemical

Question 8

A toxicant’s distribution to a specific tissue does not:

Answer 8

Increase for xenobiotics that are bound to plasma proteins

Question 9

High-energy cofactors that are NOT involved in phase II reactions include:

Answer 9

Amino acids such as taurine and glycine

Question 10

Now that you know that all chemicals are toxic, which of the following corollary statements is false?

Answer 10

Exposure limits may be set for all chemicals that will instill confidence that we are safe from chemicals

Question 11

Toxicology testing in the 21st century will include in silico testing of chemicals. Advantages are numerous when compared with standard bioassasys, but some problems still need to be worked out. These problems include:

Answer 11

Predictive analyses, more informative, and efficient

Question 12

True or False. Pesticides are ubiquitous and present to the environment in a diversity of 900 ingredients composing 35,000 commercial products with billions of pounds being being released to the global environment annually.

Answer 12

True

Question 13

Which type of pesticide inhibits the acetylcholinesterase enzyme and with chronic exposure may result in neuropathy characterized by weakness or paralysis of the arms and legs?

Answer 13

Organophosphates

Question 14

Which of the following statements is false?
A. glucuronide conjugates are excreted readily by the kidneys
B. a lipid-soluble xenobiotic metabolite will sequester in fatty tissue
C. acidification of the urine may help trap acidic drugs in urine
D. for a weakly acidic drug (pKa+3) at equilibrium, the ratio of nonionized to ionized drug (HA/A-) equals 1 when the pH of the medium is 3

Answer 14

C. acidification of the urine may help trap acidic drugs in urine

Question 15

Induction of xenobiotic biotransformation by exposure to a toxicant will:

Answer 15

Result in increased amounts of enzymes in the ER

Question 16

Steps for liver ridding body of toxins

Answer 16

1. introduce oxygen (phase I)
2. create charge separated species (bioactivation)
3. Mechanisms try and force compounds to elimination
4. Tripeptide (GSH) sucks up reactive oxygen compounds (phase 2)
5. Result is R-O-Y, eliminated in feces

Question 17

What is risk assessment?

Answer 17

quantitative estimate of the potential effects on human health to illuminate the significance of exposure to chemicals in the environment

Question 18

What is a poison?

Answer 18

any agent capable of producing a deleterious response in a biological system

Question 19

What is the difference between a toxin and a toxicant?

Answer 19

toxin- produced by biological system (plants, fungi, animals, bacteria)

toxicant- produced or by-product of anthropogenic activity

Question 20

What are the three stages in the history of toxicology?

Answer 20

1. antiquity
2. Middle Ages
3. Age of Enlightenment

Question 21

Who developed a method for arsenic analysis?

Answer 21

Marsh, 1836

Question 22

Who developed a method for separating As and Hg?

Answer 22

Reinsh, 1841

Question 23

Who detected and identified phosphorus?

Answer 23

Stas-Otto, 1951

Question 24

What is the Delaney Cause (1958)?

Answer 24

any chemical found to be carcinogenic in lab animals or humans could not be added to the food supply

Question 25

What is regulatory toxicology?

Answer 25

determining whether a drug or chemical poses a low enough risk based on mechanistic and descriptive data

Question 26

What is mechanistic toxicology?

Answer 26

identifies and investigates cellular, biochemical, & molecular mechanisms by which chemicals exert their influence

Question 27

What is descriptive toxicology?

Answer 27

concerned with toxicity testing and evaluating the safety of certain substances

Question 28

What are the responsibilities of legislation?

Answer 28

1. protect human health and the env. from pesticides and waste disposal 2. conserve energy and natural resources 3. reduce generated waste, and ensure waste is managed in an environmentally sound manner

Question 29

How are toxic agents classified?

Answer 29

1. target organ (i.e. hematopoietic system) 2. use (i.e. pesticides) 3. source (i.e. toxin/toxicant) 4. effects (i.e. cancer/liver injury)

Question 30

What are some undesired effects of toxic agents?

Answer 30

1. allergic reactions/hypersensitivity 2. immediate vs. delayed toxicity 3. reversible vs. irreversible effects 4. local vs. systemic toxicity 5. interaction of chemicals 6. tolerance

Question 31

What is a hapten?

Answer 31

a molecule combines with an endogenous protein to cause an allergic reaction

Question 32

What are the four ways chemicals interact?

Answer 32

1. Additive (1+1=2) 2. Synergistic (1+1=>2) 3. Potentiation (0+1>1) 4. Antagonism (1+1

Question 33

What are the multiple mechanisms for antagonism?

Answer 33

1. functional 2. chemical 3. dispositional 4. receptor

Question 34

What are the major routes of chemical exposure?

Answer 34

1. ingestion 2. inhalation 3. dermal 4. parenteral routes

Question 35

What is slope indicative of in a dose-response relationship?

Answer 35

half life

Question 36

What does time to toxicity depend on?

Answer 36

1. frequency of administration 2. dose level 3. time to recover between doses

Question 37

What is a quantal dose-response relationship?

Answer 37

1. "all or non" | 2. at any dose, any individual in the population either does or does not responsd

Question 38

What is hormesis?

Answer 38

xenobiotics may cause stimulatory effects at low dose but adverse effects at high doses

Question 39

Where do ED, TD, and LD lie on a dose-response graph by comparison?

Answer 39

ED- left shifted TD- center LD- right shifted

Question 40

What is potency?

Answer 40

the range of doses over which a chemical produces increasing responses

Question 41

What is allometry?

Answer 41

the study of the relationship between body weight and physiology

Question 42

What is NOAEL?

Answer 42

no observable adverse effect level

Question 43

What are the major functions of the liver?

Answer 43

1. maintain metabolic homeostasis | 2. bile formation

Question 44

Where does bioreactivation (R-O-Y)?

Answer 44

hepatocytes

Question 45

What are the three zones of the acinus, or functional hepatic unit?

Answer 45

1. closest to the entry of blood 2. intermediate 3. abuts the terminal hepatic vein

Question 46

What cells act as macrophages in the liver?

Answer 46

Kupffer cells

Question 47

What happens when the liver dysfunctions due to toxins?

Answer 47

1. high secretios of metabolites 2. inhibition of bilirubin uptake 3. inhibition of clotting factor secretion

Question 48

What are some types of injuries of the liver due to toxic chemicals?

Answer 48

1. fatty liver 2. cell death 3. canalicular cholestasis 4. bile duct damage 5. sinusoidal disorders 6. fibrosis and cirrhosis 7. tumors

Question 49

What do activated Kupffer cells secrete?

Answer 49

cytotoxins (ROS and RNS)

Question 50

What are phase I reactions?

Answer 50

hydrolysis reduction oxidation

Question 51

What are phase II reactions?

Answer 51

conjugation

Question 52

What components in phase II reactions can cause organ damage?

Answer 52

charge separated species

Question 53

What are the steps in benzo(a)pyrene activation?

Answer 53

1. receptor (AhR) bind to BAP to form complex 2. ARNT pulls complex into nucleus 3. Complex sits on a promoter 4. Complex initiates expression of CYP450

Question 54

What leads to suppression of hematopoiesis in bone marrow?

Answer 54

CYP450 activation of benzene

Question 55

What is the goal of toxicology?

Answer 55

1. hazard identification 2. dose-response assessment 3. exposure assessment 4. risk characterization

Question 56

What are the three most commonly used forms of asbestos used commercially?

Answer 56

Chrysotile Amosite Crocidolite

Question 57

What diseases do fleas carry?

Answer 57

Plague | Murine typhus

Question 58

What diseases do lice carry?

Answer 58

Typhus | Relapsing fever

Question 59

What diseases do sand flies carry?

Answer 59

Pappataci fever Three-day fever Sandfly fever Phlebovirus

Question 60

What diseases can mice carry?

Answer 60

Rat-bite fever Weil's disease Hantavirus pulmonary syndrome

Question 61

What molecules do organophosphates and carbamates inactivate?

Answer 61

acetylcholinesterase

Question 62

What are the manifestations of developmental toxicology?

Answer 62

1. structural malformations 2. growth retardation 3. functional impairment 4. death of the organism

Question 63

What are some human developmental toxicants?

Answer 63

Radiation Infection Maternal trauma and metabolic imbalances Drugs/chemicals

Question 64

What is the threshold phenomenon in developmental tox?

Answer 64

That a maternal dosage below which an adverse response is not elicited because some repair or defense system is able to combat exposure

Question 65

What maternal factors affect fetal development?

Answer 65

``` Genetics Disease Nutrition Stress Placental toxicity Maternal toxicity ```

Question 66

What is the Barker Hypothesis (Susceptibility Exposure Paradigm)?

Answer 66

the effects of early childhood exposure may not be apparent until later in life

Question 67

What does ADME stand for?

Answer 67

Absorption Distribution Metabolism Excretion

Question 68

What is step one of the mechanisms of toxicology?

Answer 68

Delivery from the site of exposure to the targe

Question 69

What are the two possible outcomes of step one of the mechanisms of tox?

Answer 69

Absorption | Pre-systemic elimination

Question 70

What path does a first-path effect take?

Answer 70

``` Drug Digestive system Portal circulation Liver Extensively metabolized ```

Question 71

Where does reabsorption of chemicals take place?

Answer 71

kidney | GI tract

Question 72

What is involved with the toxification of numerous chemicals?

Answer 72

formation of electrophiles

Question 73

What are there no efficient elimination mechanisms for?

Answer 73

nonvolatile, highly lipophilic chemicals

Question 74

What does phase II metabolism eliminate to prevent its biotransformation?

Answer 74

the ultimate toxicant

Question 75

What is the second step of the mechanisms of tox?

Answer 75

reaction of the ultimate toxicant with target molecule

Question 76

What is the third step of the mechanisms of tox?

Answer 76

cellular dysfunction and resultant toxicities

Question 77

What is step 4 of the mechanisms of tox?

Answer 77

repair or dysrepair

Question 78

What happens when repair fails in the mechanisms of tox?

Answer 78

Tissue necrosis Fibrosis Carcinogenesis