PK Gupta Series 10: TOXICOLOGY Question and Answer bank

INTRODUCTION

TOXICOLOGY Question and Answer bank is aimed to make the study of toxicology simple and understandable ----------------

Exercise 1

1.        Which one of the following statements regarding toxicology is true?

a. Modern toxic ology is concerned with the study of the adverse effects of chemicals on ancient forms of life.

b. Modern toxicology studies embrace principles from such disciplines as biochemistry, botany, chemistry, physiology, and physics.

c. Modern toxicology has its roots in the knowledge of plant and animal poisons, which predates recorded history and has been used to promote peace.

d. Modern toxicology studies the mechanisms by which inorganic chemicals produce advantageous as well as deleterious effects.

e. Modern toxicology is concerned with the study of chemicals in mammalian species.

2. Knowledge of the toxicology of poisonous agents was published earliest in the:

a. Ebers papyrus.

b. De Historia Plantarum.

c. De Materia Medica.

d. Lex Cornelia.

e. Treatise on Poisons and Their Antidotes.

3. Paracelsus, physician- alchemist, formulated many revolutionary reviews that remain integral to the structure of toxicology, pharmacology, and therapeutics today. He focused on the primary toxic agent as chemical entity and articulated the dose–response relation. Which one of the following statements is not attributable to Paracelsus?

a. Natural poisons are quick in their onset of actions.

b. Experimentation is essential in the examination of

responses to chemicals.

c. One should make distinction between the therapeutic and toxic properties of chemicals.

d. These properties are sometimes but not always indistinguishable except by dose.

e. One can ascertain a degree of specificity of chemicals and their therapeutic or toxic effects.

4. The art of toxicology requires years of experience to acquire, even though the knowledge base facts may be learned more quickly. Which modern toxicologist is credited with saying that “you can be toxicologist in two easy lesions, each of 10 years?”

a. Claude Bernard.

b. Rachel Carson.

c. Upton Sinclair.

d. Arnold Lehman.

e. Oswald Schmiedeberg.

5. Which of the following statements is correct?

a. Claude Bernard was a prolific scientist who trained over 120 students and published numerous contributions to the scientific literature.

b. Louis Lewin trained under Oswald Schmiedeberg

and published much of the early work on the toxicity

of narcotics, methanol, and chloroform.

c. An Introduction to the Study of Experimental Medicine was written by the Spanish physician Orfila.

d. Magendie used autopsy material and chemical analysis systematically as legal proof of poisoning.

e. Percival Potts was instrumental in demonstrating the chemical complexity of snake venoms.

Answers

1. b.

2. a.

3. a.

4. d.

5. b.

Exercise 2

1. Five identical experimental animals are treated with 1 mg of one of the following toxins. The animal treated with which toxin is most likely to die?

a. ethyl alcohol (LD50 = 10,000 mg/kg).

b. botulinum toxin (LD50 = 0.00001 mg/kg).

c. nicotine (LD50 = 1 mg/kg).

d. ferrous sulfate (LD50 = 1500 mg/kg).

e. picrotoxin (LD50 = 5 mg/kg).

2. Place the following mechanisms of toxin delivery in order from most effective to least effective—1: intravenous; 2: subcutaneous; 3: oral; 4: inhalation; 5: dermal.

a. 1, 5, 2, 4, 3.

b. 4, 1, 2, 3, 5.

c. 1, 4, 2, 3, 5.

d. 4, 2, 1, 5, 3.

e. 1, 4, 3, 2, 5.

3.A toxin with a half -life of 12 h is administered every 12 h. Which of the following is true?

a. The chemical is eliminated from the body before the next dose is administered.

b. The concentration of the chemical in the body will

slowly increase until the toxic concentration is attained.

c. A toxic level will not be reached, regardless of how many doses are administered.

d. Acute exposure to the chemical will produce immediate toxic effects.

e. The elimination rate of the toxin is much shorter than the dosing interval.

4. Urushiol is the toxin found in poison ivy. It must first react and combine with proteins in the skin in order for the immune system to recognize and mount a response against it. Urushiol is an example of which of the following?

a. antigen.

b. auto-antibody.

c. superantigen.

d. hapten.

e. cytokine.

5. Toxic chemicals are most likely to be biotransformed in which of the following organs?

a. central nervous system.

b. heart.

c. lung.

d. pancreas.

e. liver.

6. When chemicals A and B are administered simultaneously, their combined effects are far greater than the sum of their effects when given alone. The chemical interaction between chemicals A and B can be described as which of the following?

a. potentiative.

b. additive.

c. antagonistic.

d. unctionally antagonistic.

e. synergistic.

7. With respect to dose–response relationships, which of the following is true?

a. Graded dose–response relationships are often

referred to as “all or nothing” responses.

b. Quantal dose–response relationships allow for the

analysis of a population’s response to varying dosage.

c. Quantal relationships characterize the response of an individual to varying dosages.

d. A quantal dose–response describes the response of an individual organism to varying doses of a chemical.

e. The dose–response always increases as the dosage is increased.

8. When considering the dose–response relationship or an essential substance:

a. there are rarely negative effects of ingesting too much.

b. the curve is the same or all people.

c. adverse responses increase in severity with increasing or decreasing dosages outside of the homeostatic range.

d. the relationship is linear.

e. deficiency will never cause more harm than over- ingestion.

9. The therapeutic index of a drug:

a. is the amount of a drug needed to cure an illness.

b. is lower in drugs that are relatively safer.

c. describes the potency of a chemical in eliciting a

desired response.

d. describes the ratio of the toxic dose to the therapeutic dose of a drug.

e. explains the change in response to a drug as the dose is increased.

10. Penicillin interferes with the formation of peptidoglycan cross-links in bacterial cell walls, thus weakening the cell wall and eventually causing osmotic death of the bacterium. Which of the following is true?

a. Treatment with penicillin is a good example of selective toxicity.

b. Penicillin interferes with human plasma membrane structure.

c. Penicillin is a good example of a drug with a low

therapeutic index.

d. Penicillin is also effective in treating viral infections.

e. Penicillin is completely harmless to humans

Answers

1. b.

2. c.

3. b.

4. d.

5. e.

6. e.

7. b.

8. c.

9. d.

10. a.                                                                         

Further Reading

Andrew Patkinson and Brian W. Ogilvie (2013) Biotransformation of Xenobiotics. In: Klaassen, C. D (Ed.) Casarett and Doull’s Toxicology: The Basic Science of Poisons, 8th ed (pp 185-366), McGraw-Hill New York 

Danny, D, Shen (2013) Toxicokinetics. In: Klaassen, C. D (Ed) Casarett and Doull’s Toxicology: The Basic Science of Poisons, 8th ed (pp 367-390) McGraw-Hill New York.

Deon van der Merwe, Ronette Gehring and Jennifer L. Buur (2017) Toxicokinetics In. Gupta R.C (Ed.) Veterinary Toxicology: Basic and Clinical Principles.3rd ed. Academic Press/Elsevier: Amsterdam (in press)

Gupta P.K (2010): Absorption, Distribution, & Excretion of Xenobiotics. In: Gupta, PK (Ed.) Modern Toxicology: Basis of Organ and Reproduction Toxicity, Vol. 1, 2nd reprint (pp 71-92) PharmaMed Press, Hyderabad, India.. 

Gupta P.K. (2014) Essential concept in toxicology. BSP India (chapter 7)

Gupta P.K. (2016) Fundamental of Toxicology: Essential concept and applications. Elsevier/BSP USA (Chapter 8)

Gupta P.K. (2016) Fundamental of Toxicology: Essential concept and applications. Elsevier/BSP USA (Chapter 9)

Curtis D. Klaassen, CD; Watkins III, JB (2015) Casarett & Doull’s Essentials of Toxicology. 3rd ed McGraw-Hill, USA pp 1-524.

Krishnamurti, C. R (2010): Biotransformation of Xenobiotics. In: Gupta, PK (Ed.) Modern Toxicology: Basis of Organ and Reproduction Toxicity, Vol. 1, 2nd reprint (pp 95-129). PharmaMed Press, Hyderabad, India.

Lois D Lehman-McKeeman (2013) Absorption distribution and excretion of toxicants. In: Klaassen CD (Ed) Casarett and Doull’s toxicology: The basic science of poisons, 8th ed (pp 153-184) (New York), McGraw-Hill,

Mats Ehrnebo (2010) Kinetic Analysis of . In: Gupta, PK (Ed.) Modern Toxicology: Basis of Organ and Reproduction Toxicity, Vol. 1, 2nd reprint (pp 130-151). PharmaMed Press, Hyderabad, India

Randy L. Rose, Hodgson E (2010) Chemical and Physiological Influences on Xenobiotic Metabolism. In: Hodgson, E.A (Ed) A Textbook of Modern Toxicology 4th edition (pp 163-201), John Wiley, New Jersey.

Randy L. Rose and Ernest Hodgson (2010) Metabolism of Toxicants. In: Hodgson, E.A (Ed) A Textbook of Modern Toxicology 4th ed (pp 111- 148), John Wiley, New Jersey.

Randy L. Rose and Patricia E. Levi (2010) Reactive Metabolites. In: Hodgson, E.A (Ed) A Textbook of Modern Toxicology 4th ed (pp 149-161), John Wiley, New Jersey.

Renwick AG (2008) Toxicokinetic. In: Hays AW (Ed) Principles and methods of toxicology. 5th ed (179-230). Boca Tato Taylor and Francis.

Timbrell JA (2009) Factors affecting toxic responses: disposition. In: Timbrell JA (Ed) Principles of biochemical toxicology. 4th ed. (35-74), Informa, New York:

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PK Gupta Series 7: Multiple Choice Questions and fill in blanks TOXICOLOGY Question and Answer bank.

Series 7: Multiple Choice Questions and fill in blanks

Multiple Choice Questions

Exercises

Q. 1. Examples of significant concentrations of a toxicant in a tissue that is not a target organ include all of the following except-----------.

a) lead in bone

b) DDT in adipose tissue

c) paraquat in lung

d) TCDD in adipose tissue

Q. 2. the ability of a chemical to cause acute skin and eye irritation is usually evaluated in a ------

a) rabbit

b) rat

c) mouse

d) dog

Q. 3.  before a potential pharmaceutical compound can be given to humans .-------.

a) an NDA must be filed with the FDA

b) an IND must be filled with the FDA

c) acute toxicity studies on 4 species must be conducted

d) a 2-year dog carcinogenicity study must be completed

Q. 4.  phase 1 clinical trials are conducted to determine all of the following except ---

a) pharmacokinetics

b) safety

c) rare adverse effects

d) preliminary efficacy

Q. 5. MTD stands for ------------------

a) minimum tolerated dose

b)maximum total dose

c) maximum tolerated dose

d) maximum threshold dose

Q. 6. the acute toxicity study in animals provides ------

a) an appropriate lethal dose

b) information on target organs

c) information on dose selection for long-term studies

d)all of the above

Q. 7. a subacute toxicity study in rats usually lasts ------.

a) 3 days

b)14 days

c) 3 months

d) 6 months

Q. 8. the period of organogenesis in rats is ---.

a) day 3-10

b) day 7-17

c)  day 12-25

d) day 17-56

Q. 9.  a dose of investigational drug that suppresses body weight gain slightly in a 90-day animal study is defined by some regulatory agencies to be-------.

a) LOAEL

b) NOAEL

c)MTD

d) reference dose

Q. 10. a subchronic animal study required by the FDA will usually include-----

a) two species (usually one rodent and one nonrodents)

b) both genders

c) at least three doses (low, intermediate, and high)

d) all of the above

Q.11 A dose of a compound A is toxic to animals in vivo. Another chemical B is not toxic when given at doses several orders of magnitude higher but when the two are given together the toxic response is greater than that of the given dose of A alone.

a) antagonism

b) synergism

c) additivity

d) potentiation

e) none of the above

Q.12 Which information may be gained from an acute toxicity study

a) no effect level

b) LD₅₀ 

c) therapeutic index

d) target organ

e) all of the above

Q.13The therapeutic index is usually defined as

a) TD₅₀ / LD₅₀ 

b) ED₅₀ / LD₅₀ 

c) LD₅₀   / ED₅₀

d) ED₅₀  / TD₅₀

e) LD₅₀   / ED₅₀

Q.14 1000 ppm is equivalent to 1%

a) True

b) False

Answers

1. c;      2. a;      3. b ;     4.c ;      5.c ;      6.d ;      7.b ;     8.b ;      9.c ;      10. d; 11. d; 12. e; 13. c ; 14. b.

Fill in blanks

Q. 1. The branch of science which deals with the harmful effects of physical and chemical agents of human and animal life is ------------------------------------

Q. 2. In the term toxicology, the word ‘toxicon’ (Greek) means --------------------

Q. 3. The branch of toxicology, which deals with diagnosis, treatment and management of toxic substances, is known as -----------------------------------

Q. 4. The development and interpretation of mandatory toxicology testing programs is addressed by -------------------------------------------

Q. 5 Investigating and controlling the toxic effects of various substances on the community is dealt by ----------------------.

Q. 6. The study of toxicity produced by subsances of plant, animal and microbial origin is termed as -------------

Q. 7. A foreign chemical substance, which is not normally produced in the body or forms a part of the food, is known as --------------------.

Q. 8. The source of adverse effect/ damage is known as ----------------------

Q. 9. The likelyhood/probability of adverse effect upon exposure to a hazard is known as --------------------.

Q. 10. The statement, “all substances are poisons; the dose differentiates poison from a remedy” is associate with -------------------------.

Answers

1.TOXICOLOGY; 2. POISON; 3.CLINICA L TOXICOLOGY; 4. REGULATORY TOX COLOGY; 5 TOXICOVIGILANCE; 6. TOXINOLOGY; 7. XENOIOTIC; 8 HAZARD. (eg: Water containing Fluoride; Here fluoride is the hazard and fluorosis is the adverse effect. Hazard is independent of dose or exposure i.e., it is present whether someone drinks the water or not).

9. RISK. (eg: While drinking water containing fluoride, the chances of getting fluorosis is called risk. Risk can range from 0 to 100% depending on dose and exposure i.e., one should be exposed to a hazard to calculate the risk); 10. PARACELSUS

Exercises

Q. 1 The scientist referred to as ‘Father of Toxicology’ is ------------------------

Q. 2.  DDT (Dichlorodiphenytrichloro ethane) which is used to control malaria and typus was discovered by ----------------------------

Q. 3. The person who is known as ‘Father of Nerve Agents’ is ------------------------------

Q. 4. The author of the book ‘Silent Spring’ in which the detrimental effect of DDT and other pesticides on environment –particularly on birds was document is -------------------------. 

Q. 5. Bhopal gas tragedy, which is considered to be the world’s worst industrial disaster, was caused due to the leakage of------------------------------------ from Union Carbide fertilizer company.

Q. 6. Use of thalidomide in pregnant women for treating women for treating morning sickness led to -------------------------condition in the infants.

Q. 7. If the action of one substance opposes or neutralizes the effect of another substance, the relationship is referred to as -------------------------..

Q. 8. Rodents are preferred for oral toxicity testing as they lack ------------------ reflex.

Q. 9. Maximum acceptable/ permitted amount of a drug present in feed and foods is known as ----------------------------------------------------------------------.

Q. 10. The highest dose of a compound, which produces adverse effects but no mortality is called -----------------------------------------------------------------------.

Answers

1. M.J.B. Orfila; 2. Pau Muller; 3 GERHARD SCHRADER; 4. RACHEL CARSON;5. METHYL-ISOCYANATE (MIC); 6. PHOCOMELIA; ;7. ANTAGONISM (All antidotes have antagonistic relationship with their respective toxicants) have antagonistic relationship with the irrespective toxicants); 8. VOMITION; 9 MAXIMUM RESIDUE LEVEL (MRL). (For pesticides – MAXIMUM RESIDUE LIMIT); 10 MAXIMUM TOLERATED DOSE {(MTD),  MTD is also referred to as LD0 (Zero) as it will cause adverse effects but no mortality)}.

Exercise

Q.1. If the period of exposure of a toxicant is more than 3 months, the type of study is termed as ---------------------.

Q. 2. The type of toxicity which results due to progressive accumulation of a toxicant in the body is known as ------------------------------.

Q. 3. The amount of toxicant in food and water, which can be consumed daily over a life time without any significant health risk, is called as ------------------------------------------.

Q. 4 Unlawful or criminal killing of animals through administration of poisonsis known as -----------------------

Q. 5. Unintentional addition of toxicants and contaminants in feed  and water is known as ----------------------.

Q. 6. Man -made sources of toxicants are referred to as ------------------------ sources.

Q. 7. Genetically determined abnormal reactivity of an individual to a chemical is known as----------------------------..

Q. 8. Failure to elicit a response to an ordinary dose of a substance due prior usage is known as --------------------------.

Q. 9. The beneficial effects of toxic substances at low doses are known as-----------------.

Q. 10. In the event of irreparable injury, the cell undergoes a process of programmed cell death known as ----------------------------.

Q. 11 A substance is classified as extremely toxic if the lethal dose (LD) is LESS THAN ------------- and as practically non-toxic if the LD is ------------.

Q. 12. The ability of a substance to induce cancer is known as ------------------.    

Answers

1. CHRONIC TOXICITY; 2. CUMULATIVE TOXICITY(Several toxicants such as heavy metals, alcohol, DDT etc cause cumulative toxicity.); 3. ACCEPTABLE DAILY INTAKE (ADI); 4. MALICIOUS POISONING; 5. ACCIDENTAL POISONING; 6. ANTHROPOGENIC; 7. IDIOCYNCARY; 8. TOLERANCE(Tolerance is generally caused due to the induction of metabolizing enzymes in liver. However, in case of chronic alcoholism, pseudo-tolerance is observed, due to thickened GIT mucosa, which reduces absorption);

9. HORMESIS; 10. APOPTOSIS(Apoptosis is also involved in number of physiological process such as embryogenesis, ageing, cancer prevention etc); 11. 1mg/kg, 5 to 15 g/kg(It should be remembered that more the LD of a compound, less is its toxicity); 12. CARCINOGENESIS

FURTHER READING

Gupta PK (2018) Illustrative Toxicology with Question bank. 1st Edition. Elsevier, USA

Gupta PK (2016) Fundamentals of Toxicology: Essential concepts and applications. 1st Edition. ISBN-9780128054260, pp 438, BSP/Elsevier, USA

The Merck Veterinary Manual (2016). Chapter “Herbicide Poisoning” by PK GUPTA 11^th edition, Merck & Co. Inc Whitehouse Station, NJ, USA  2969-99

The Merck Veterinary Manual (2016). Chapter “Pentachlorophenol Poisoning” by PK GUPTA 11^th edition, Merck & Co. Inc Whitehouse Station, NJ, USA  pp 3052-53

Gupta PK (2016) Essential Concepts in Toxicology. Published by PharmaMed Press (A unit of BSP Books Pvt. Ltd), Hyderabad, India pp 362.

Gupta PK (2010) Modern Toxicology, Basis of organ and reproduction toxicity. Vol 1. Published by Pharma  Med Press (A unit of BSP Books Pvt. Ltd). Hyderabad, India pp 1-460.

Gupta PK (2010) Modern Toxicology, Adverse effects of xenobiotics. Vol 2, Published by PharmaMed Press (A unit of BSP Books Pvt. Ltd). Hyderabad, India pp 1-460.

Gupta PK (2010) Modern Toxicology, Immuno and clinicsal toxicology Vol 3. Published by PharmaMed Press (A unit of BSP Books Pvt. Ltd). Hyderabad, India pp 1-340.

                                                                                                                     To be cont'd

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