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Saturday, 24 March 2018

In Definitions , LD50 , Multiple choice questions , principles of toxicity , Question and Answers , toxicity , toxicology by Pawan Kumar Gupta // 11:30 // Leave a Comment

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.

Saturday, 17 March 2018

In classification of toxicants , Definitions , general toxicology , Question and Answers , Toxic agents , Toxicants , toxicity , toxicity rating , Toxicology Question bank by Pawan Kumar Gupta // 11:30 // Leave a Comment

Gupta's series 3:TOXICOLOGY Question and Answer bank

General Toxicology: Continued, FROM SERIES 2

Q. What are the sub-disciplines of toxicology?

Biochemical toxicology
Reproductive toxicology
Development toxicology
Teratology
Genetic toxicology
Clinical toxicology
Forensic toxicology
Analytical toxicology
Nutritional toxicology
Veterinary toxicology
Environmental toxicology
Occupational(Industrial) toxicology
Regulatory toxicology
Mechanistic toxicology
Aquatic toxicology
Ecotoxicology
Food toxicology
Formal toxicology
Descriptive toxicology

Q. Define occupational (Industrial) toxicology

Occupational (Industrial) toxicology is concerned with health effects from exposure to chemicals in the workplace. It deals with the clinical study of workers of industries and environment around him.

Q. Define regulatory toxicology:

It deals with administrative functions concerned with the development and interpretation of mandatory toxicology testing programs and controlling the use, distribution and availability of chemicals used commercially and therapeutically. For example, Food and Drug Administration (FDA) regulates drugs, cosmetics and food additives. Regulatory toxicology gathers and evaluates existing toxicological information to establish concentration-based standards of “safe” exposure. The standard is the level of a chemical that a person can be exposed to without any harmful health effects.

Q. Define food toxicology

It deals with natural contaminants, food and feed additives, and toxic and chemo-protective effects of compounds in food.

Explanation: Food Toxicology is involved in delivering a safe and edible supply of food to the consumer. During processing, a number of substances may be added to food to make it look, taste, or smell better. Fats, oils, sugars, starches and other substances may be added to change the texture and taste of food.

All of these additives are studied to determine if and at what amount, they may produce adverse effects. A second area of interest includes food allergies. Almost 30% of the American people have some food allergy. For example, many people have trouble digesting milk, and are lactose intolerant. In addition, toxic substances such as pesticides may be applied to a food crop in the field, while lead, arsenic, and cadmium are naturally present in soil and water, and may be absorbed by plants. Toxicologists must determine the acceptable daily intake level for those substances.

Q. Define formal toxicology

It deals with the formal toxicological studies which are pre-requisite for release of a new drugs/chemical e.g. calculation of LD₅₀and minimum toxic dose.

Q. Define descriptive toxicology

Descriptive Toxicology is concerned with gathering toxicological information from animal experimentation. These types of experiments are used to establish how much of a chemical would cause illness or death. The United States Environmental Protection Agency (EPA), the Occupational Safety and Health Administration (OSHA), and the Food and Drug Administration (FDA), use information from these studies to set regulatory exposure limits.

Q. Define mechanistic toxicology

Mechanistic Toxicology makes observations on how toxic substances cause their effects. The effects of exposure can depend on a number of factors, including the size of the molecule, the specific tissue type or cellular components affected, whether the substance is easily dissolved in water or fatty tissues, all of which are important when trying to determine the way a toxic substance causes harm, and whether effects seen in animals can be expected in humans.

Q. Define nutritional toxicology

Nutritional Toxicology is the study of toxicological aspects of food/feed stuffs and nutritional products/habits.

Q. Define toxicodynamics

It deals with the study of biochemical and physiological effects of toxicant and their mechanism of action.

Q. Define toxicokinetics

It deals with the study of absorption, distribution, metabolism and excretion of toxicants in the body.

Q. Define toxicovigilance

It deals with process of identification, investigation, and evaluation of various toxic effects in the community with a view of taking measures to reduce or control exposures involving the substances that produce these effects.

Q. Define toxinology

It deals with assessing the toxicity of substances of plant and animal origin and those produced by pathogenic bacteria/organism.

Q. Define toxicoepidemiology

It refers to the study of quantitative analysis of the toxicity incidences in organisms, factors affecting toxicity, species involved and the use of such knowledge in planning of prevention and control strategies.

1.1 Toxicity and Toxic Effects

Toxic or toxicity is relative terms commonly used in comparing one chemical with another.

Q. Define toxicity

It is a state of being poisonous or capacity to cause injury in living organisms.

Q. Define toxicosis

It is the condition or disease state that results from exposure to a toxicant. The term toxicosis is often used interchangeable with the term of poisoning or intoxication.

Q. Define toxic effects

These are undesirable effects produced by a toxicant/drug which are detrimental to either survival or normal functioning of the individual.

Q. Define side effects

These are undesirable effects which result from the normal pharmacological actions of drugs. These results may not be detrimental or harmful to the individual.

Q. Define selective toxicity

It is the toxicity produced by a chemical to one kind of living matter without harming another form of life even though the two exist in intimate contact.

Q. Define plant toxins?

Different portions of a plant may contain different concentrations of chemicals. Some chemicals made by plants can be lethal. For example, taxon, used in chemotherapy to kill cancer cells, is produced by a species of the yew plant.

Q. Define animal toxins?

Animal toxins can result from venomous or poisonous animal releases. Venomous animals are usually defined as those that are capable of producing a poison in a highly developed gland or group of cells, and can deliver that toxin through biting or stinging. Poisonous animals are generally regarded as those whose tissues, either in part or in their whole, are toxic. For example, venomous animals, such as snakes, spiders, etc., and poisonous animals, such as puffer fish, or oysters, which may be toxic to some individuals when contaminated with vibrio vulnificus.

1.1 Toxicity in Relation to Frequency and Duration of Exposure

The exposure of experimental animals to chemicals can be divided into four categories: acute toxicity and repeated exposure (sub-acute, sub-chronic, and chronic).

Q. Define acute toxicity

Acute exposure is defined as exposure to a chemical for less than 24 hr. The exposure usually refers to a single administration, repeated exposures may be given within a 24 hr period for some slightly toxic or practically nontoxic chemicals. Acute exposure by inhalation refers to continuous exposure for less than 24 hr, most frequently for 4 hr.

Q. Define repeated exposure

Repeated exposure is divided into three categories:

sub-acute ii) sub-chronic, and iii) chronic.

Sub-acute exposure to a chemical is for 1 month or less, sub-chronic for 1 to 3 months, and chronic for more than 3 months (usually this refers to studies with at least 1 year of repeated dosing).

Explanation: Acute or repeated exposure can be by any route, but most often they occur by the oral route, with the chemical added directly to the diet. In human exposure situations, the frequency and duration of exposure are usually not as clearly defined as in controlled animal studies. However, almost same terms are used to describe general exposure situations. Thus, workplace or environmental exposures may be described as acute (occurring from a single incident or episode), sub-chronic (occurring repeatedly over several weeks or months), or chronic (occurring repeatedly for many months or years).

1.2 Toxicity in Relation to Time of Development and Duration of Induced Effects

Q. Define transient or reversible or temporary toxicity

It is the toxicity or harmful effect that remains for short duration of time. e.g., narcosis produced organic solvents.

Q. Define persistent or permanent or irreversible toxicity

It is the toxicity or harmful effects that persists throughout life span of the individual and are of permanent nature, e.g. scarring of skin produced by corrosives.

Q. Define immediate toxicity

It is the toxicity that develops shortly after a single exposure to a toxicant e.g. cyanide poisoning.

Q. Define delayed toxicity

It is the toxicity or harmful effect which has delayed onset of action, e.g. peripheral neuropathy produced by some organophosphorus insecticides and radiation sickness.

Q. Define cumulative toxicity

It is progressive toxicity or harmful effect produced by summation of incremental injury resulting from successive exposures, e.g. liver fibrosis produced by ethanol.

Accumulative effects: occurs two ways...

a) accumulation of toxin: exposure to heavy metals (lead, mercury) that have long half-lives result in disease due to metal accumulation.

b) accumulation of effect: low level exposure to organophosphate pesticides depresses acetylcholine esterase to a point where symptoms occur.

1.3 Other Terms Used in Toxicology

Q. Define cheminformatics?

Cheminformatics (also known as chemoinformatics, chemioinformatics and chemical informatics): Cheminformatics is the use of computer and informational techniques applied to a range of problems in the field of chemistry. These in silico techniques are used in, for example, pharmaceutical companies in the process of drug discovery.

Q. Define end point study record?

Endpoint study record or IUCLID (International Uniform Chemical Information Data base) format of the technical dossier is used to report study summaries and robust study summaries of the information derived for the specific endpoint according to the REACH Regulation.

Q. Define end point of study design?

Endpoint: an observable or measurable inherent property/data point of a chemical substance. For example, a physical-chemical property like vapor pressure or degradability or a biological effect that a given substance has on human health or the environment, e.g. carcinogenicity, irritation, aquatic toxicity.

Q. Define in vitro test?

In vitro test: literally stands for “in glass” or “in tube”, refers to the test taking place outside of the body of an organism, usually involving isolated organs, tissues, cells, or biochemical systems.

Q. Define in vivo test?

In vivo test: a test conducted within a living organism.

Q. Define in silico test?

In silico: In silico (a phrase coined as an analogy to the familiar phrases in vivo and in vitro), is an expression used to denote “performed on computer or via computer simulation.” Means scientific experiments or research conducted or produced by means of computer modeling or computer simulation.

Q. Define IUCLID flag?

IUCLID flag: an option used in the IUCLID software to indicate submitted data type (e.g. experimental data) or their use for regulatory purposes (e.g. confidentiality).

Q. Define prediction model?

Prediction model is a theoretical formula, algorithm or program used to convert the experimental results obtained by using a test method into a prediction of the toxic property/effect of the chemical substance.

Q. Define QSARs and SARs?

QSARs and SARs: theoretical models that can be used to predict in a quantitative or qualitative manner the physic-chemical biological (e.g. (eco)toxicological) and environmental fate properties of compounds from knowledge of their chemical structure. A SAR is a qualitative relationship that relates a (sub) structure to the presence or absence of a property or activity of interest. A QSAR is a mathematical model relating one or more quantitative parameters, which are derived from the chemical structure, to a quantitative measure of a property or activity.

Q. Define test or assay, validation test and validation.

Test (or assay): an experimental system set up to obtain information on the intrinsic properties or adverse effects of a chemical substance.

Validated test: a test for which its performance characteristics, advantages, and limitations has been adequately determined for a specific purpose.

Validation: the process by which the reliability and relevance of a test method are evaluated for the purpose of supporting a specific use.

Q. Define vertebrate animal?

Animals that belongs to subphylum Vertebrata, chordates with backbones and spinal columns is known as Vertebrate animal.

Q. Define accidental poisoning

Accidental poisoning may occur when human beings or animals take toxicant accidentally or is added unintentionally in food or through in its feed, fodder or drinking water. Such toxicants come from either natural sources or manmade sources. The natural sources include ingestion of toxic plants, biting or stinging by poisonous reptiles, ingestion of food contaminated with toxins, contaminated water with minerals, etc. Man made sources include therapeutic agents, household products and agrochemicals, etc.

Q. Define malicious poisoning

It is the unlawful or criminal killing of human beings or animals by administering certain toxic/poisonous agents. Incidence of such poisonings is more prevalent in human beings and less in animals.

1.4 Classification of Toxic Agents

Toxic agents are classified in number of ways depending on the interests and needs of the classifier. There is no single classification applicable for the entire spectrum of toxic agents and hence combinations of classification systems based on several factors may provide the best rating system. Classification of poisons may take into account both the chemical and biological properties of the agent, however, exposure characteristics are also useful in toxicology.

Q. Classify toxic agents

In toxicology, compounds are classified various ways, by one or more of the following classes:

Use e.g, pesticides (atrazine), solvents (benzene), food additives (nutrasweet), metals, war gases,

Effects e.g. carcinogen (benzo-a-pyrene), mutagen (methylnitrosamine), hepatotoxicant (CHCl₃) …….

Physical state such as oxidant (ozone), gas (CO₂), dust (Fe₂O₃), liquid (H₂O) .........

Chemistry such as: aromatic amine(aniline), halogenated hydrocarbon (methylene chloride) and so on.

Sources of toxicants e.g. plant or animal or natural and so on.

Mechanism of action: cholinesterase inhibitor (malathion), methemoglobin producer (nitrite).... ….

Q. Classification based on sources of toxicants

i) plant toxins,

ii) animal toxicants,

iii) mineral toxicants,

iv) synthetic toxicants

v) physical or mechanical agents

Q. Classification based on physical state of toxicants

i) gaseous toxicants

ii) liquid toxicants

iii) solid toxicants

iv) dust toxicants,

Q. Classification based on target organ or system

i) neurotoxicants

ii) hepatotoxicants

iii) nephrotoxicants

iv) pulmotoxicants

v) hematotoxicants

vi) dermatotoxicants

vii) development and reproductive toxicants

Q. Classification based chemical nature/structure of toxicants

i) metals

ii) non-metals

iii) acids and alkalis

iv) organic toxicants (carbon compounds other than oxides of carbon, the carbonates, and metallic carbides and cyanides),

Q. Classification based on analytical behavior of toxicants

i) volatile toxicants

ii) extractive toxicants

iii) metals and metalloids

Q. Classification based on type of toxicity

i) acute

b) subacute

c) chronic

Q. Classification based on toxic effects

i) carcinogens

ii) mutagens

iii) teratogens

iv) clastogens

Q. Classification based on their uses

i) insecticides

ii) fungicides

iii) herbicides

iv) rodenticides

v) food additives, etc

Q. Classification based on symptoms produced

i) corrosive poisons

ii) irritant poisons

iii) systemic poisons

iv) miscellaneous poisons

In addition, there are other types of classifications that are based up on the environmental and public health considerations and so on.

1.5 Toxicity Rating

Q. Describe briefly the term “Toxicity rating”.

A system of “toxicity rating” has been evolved for common poisons. The higher the toxicity rating for a particular substance (over a range of 1-6), the greater is the potency. The toxicity rating based on toxic potential of substances (super toxic, extremely toxic, very toxic, moderately toxic, slightly toxic and practically non-toxic.

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PK Gupta Series 10: TOXICOLOGY Question and Answer bank

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Gupta's series 3:TOXICOLOGY Question and Answer bank

General Toxicology: Continued, FROM SERIES 2

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