TOXICOLOGY Question and Answer bank is aimed to make the study of toxicology simple and understandable
Absorption
Q. Define absorption
Absorption is defined as the process of movement of unchanged
compound from its sites of administration or exposure to the blood stream.
Q.
Define distribution of xenobiotics?
Distribution may be defined as a process by which xenobiotics
move throughout the body and reach their site of action (extracellular fluid
and tissues).
Explanation: Once absorbed, a toxicant typically enters the
interstitial fluid at the site of absorption and then passes into the tissue
cells or enters the blood and/or lymph. Blood is moved rapidly through the body
by the cardiovascular circulatory system and this process constitutes the major
mechanism whereby absorbed chemicals are distributed to the various organs and
tissues of the body. The entrance of xenobiotics to some tissues is restricted
by special barriers (e.g., blood–brain barrier, blood–testes barrier and
blood–placenta barrier) that form continuous cellular layers with tight
junctions that prevent movement of toxicants into tissues by passive diffusion
through intercellular spaces. To gain entry into these protected tissues,
toxicants must pass through lipid cell membranes, either by penetrating the
lipid membranes directly, or by active or facilitated transport through
trans-membrane transporter proteins.
Q. Define excretion of
xenobiotics.
Excretion may be defined as
a process by which toxicants and/or their metabolites are irreversibly
transferred from body to external environment. Thus excretion is one of the
primary mechanisms of protecting the body from the toxic effects of toxicants
through the elimination of these compounds from the body. Compounds that are
rapidly eliminated are less likely to accumulate in tissues and damage critical
cells. Although the terms elimination and excretion are sometimes used
synonymously, the former term encompasses all the processes that decrease the
amount of parent compound in the body, including biotransformation.
Q. Define ADME?
ADME is an abbreviation in pharmacokinetics
and pharmacology for "absorption, distribution, metabolism, and
excretion," and describes the disposition of a pharmaceutical compound
within an organism.
Q. What are the
primary routes of exposure for toxic substances?
Following are the routes of exposure
a) oral
b) respiratory
c) dermal.
d) parentral
Explanation: Oral or gastrointestinal (GI), respiratory, and
dermal systems are lined with epithelia that present significant barriers to
the entry of foreign substances due to tight junctions between their cells, or
continuous lipid layers in the case of skin.. The onset, duration and intensity
of a substance’s toxic effects are therefore dependent on the toxicant’s
ability to permeate lipid cell membranes directly, and its interactions with
transporter proteins. Dermal penetration is unique in the sense that the outer
epithelial cellular layers (corneocytes) are non-viable and do not contain
transporter proteins. Absorption, in this case, is therefore dependent on the
ability of toxicants to penetrate the intercellular lipid matrix found between
corneocytes.
The plasma membranes surrounding all these cells are
remarkably similar (such as the stratified epithelium of the skin, the thin
cell layers of the lungs or the GI tract, capillary endothelium, and ultimately
the cells of the target organ The plasma membranes surrounding all these cells
are remarkably similar.
Q.
What is plasma membrane?
The biological cell has a fundamental structure, the cell membrane
or, as it is often called, the plasma membrane. The thickness of the membranes
is of the order of 100Å.
Explanation: The majority of chemicals to which most of the
population is exposed are organic acids or bases. An acid with a low pKa is a
strong acid and one with a high pKa is a weak acid. Conversely, a base with a
low pKa is a weak base and one with a high pKa is a strong base. The weak acids
are absorbed readily from the stomach because they all are almost completely
non ionized at the gastric pH. Weak bases are not absorbed well; indeed, they
would tend to accumulate within the stomach at the expense of the chemical
agent in the blood stream. Naturally, in the more alkaline intestine, bases
would be absorbed better, acids more poorly.
The concentration
of a chemical that is in ionized or in non-ionized form depends on both pKa of
the chemical and the pH of the solution in which it is dissolved. The
relationship may be derived by mathematical transformation of Henderson
Hasselbalch equation:
It is therefore
assumed that the gastric mucosal wall acts as a simple lipoid barrier which is
permeable only to the lipid-soluble, non-dissociated form of the acid. Thus, in
plasma, the ratio of non-ionized to ionized drug is 1:1000; in gastric juice, the
ratio is 1:0.001. The total concentration ratio between the plasma and the
gastric sides of the barrier is therefore 1000:1. For a weak base with a pKa of
4.4, the ratio is reversed.
Distribution
Q.
Describe factors that determine a compound’s rate and extent
of distribution.
Factors that influence distribution include:
(a)
Molecular size i.e. physicochemical properties of compound
(b)
Lipophilicity
(c)
Plasma protein and tissue binding
(d)
Blood flow and organ size
(e)
Special compartmental and barriers e.g. blood-brain barrier;
blood-cerebrospinal barrier; placental barrier and other barriers
(f)
Availability of special transport system
(g)
The ability to interact with trans-membrane transporter
proteins , and
(h)
Disease state, etc.
Explanation: After absorption into the blood stream, the
chemicals penetrate in the various fluid compartments- (i) plasma, (ii)
interstitial fluid, (iii) transcellular fluid, and (iv) cellular fluids. The
non-ionized lipid/soluble fractions penetrate most readily. Some chemicals may
accumulate in various areas as a result of binding or due to their affinity for
fat.
Q.
Describe important blood organ barriers for transport of xenobiotics.
For
transport of xenobiotics, the effective tight junction occurs at the level of
capillary endothelium e.g., brain, placenta and thymus barriers. These barriers are called blood-organ barriers. In blood-bile
barriers, the blood has direct access to the membranes of the hepatocytes.
Tight junctions formed by adjacent hepatocytes constitute the physical barrier
immediately interposed between blood and bile. Some of the so called
blood-organ barriers do not directly involve the blood. For example, in
blood-urine barrier tight junction occurs near the luminal surface of bladder
epithelial cells and in the blood testes barriers within the seminiferous
tubules. Thus blood-testes barrier resembles the blood-urine barriers more than
the blood-brain barriers with which it is often compared. A few important
barriers are:
a)
Blood-Brain Barrier
b)
Placental Barrier
c)
Blood-Testes Barrier
Q.
Describe in brief different factors that affect distribution and tissue
retention of drugs
The
following factors affect the distribution and retention of drugs:
a) blood flow
b) volume of
distribution
c)
enzyme induction
d)
chemical interaction
e)
age and sex differences
f)
genetic factors
g)
binding with proteins
h)
storage in various body
tissues including brain and fat
Q.
Discuss briefly routes of excretion of xenobiotics?
The principal organs of
excretion, is called renal excretion, excretion by organs other than kidneys is
known as extra-renal or non renal excretion.
The biliary route of excretion plays a major role in the
elimination of anions, cations, and non-ionized molecules containing both polar
and lipophilic groups. The biliary excretion of foreign compounds varies with
species and is generally highest in the dog and rat. The hepatic excretory
system is not fully developed in the infants and is additional reason for some
compounds being more toxic in infants than in the adults. More information is
required to see if increased toxicity of some compounds in the infants is due
to this reason.
In
addition to renal excretion, there are non renal or extra renal excretion
through GI tract, expired air, sweat, saliva, milk, vaginal
secretions and other route such as lachrymal
fluid, intestinal fluid, tracheobronchial secretions, etc.
Biotransformation
Q. What is disposition of a
chemical?
The disposition of a chemical or
xenobiotic is defined as the composite actions of its absorption, distribution, biotransformation, and elimination.
Explanation
To reach the target site, the toxicant must be absorbed
effectively into blood stream, distributed efficiently to site of action, and
subsequently metabolized and excreted from the body. The processes of absorption and distribution
are responsible for placement or deployment of these toxicants in the body, and
metabolism and excretion, for elimination of the toxicant from the body. All
these processes involve passage across biological membranes.
Q. What are the functions of
biotransformation. Give suitable examples
Biotransformation
performs the following functions
(a)
It causes conversion of an active compound to less active
called inactivation or detoxification. Examples are phenobarbitone to
p-hydroxyphenobarbitone; DDT to metabolite products
DDE and DDA
(b)
It causes conversion of an active compound to more active
metabolite(s) called bioactivation. Examples are malathion to malaoxon or parathion to paraoxon
and acetonitrile to cyanide
(c)
It causes conversion of an inactive compound (i.e. pro-drug
or precursor compound) to active metabolite(s) called activation. Examples are phenacetin to paracetamol, thiocyanates to cyanide
(d)
It causes conversion of an active compound to equally active
metabolite(s) (no change in the activity). Examples are dichrotophos to
monochrotophos, digitoxin to digoxin
(e)
It causes conversion of an active compound to active
metabolite(s) having entirely pharmacological/toxicological activity (change in
activity). Examples are Iproniazid (antidepressant) to isoniazid
(antitubercular), Alflatoxin B1 (hepatotoxin) to aflatoxin M1 (carcinogen).
Metabolizing
enzymes
Q. What are xenobiotic metabolizing
enzymes?
These enzymes can be divided
into two main groups:
(a)
Microsomal enzymes
(b)
Non-microsomal enzymes
Microsomal enzymes: These enzymes are present in the
endoplasmic reticulum (ER) (especially smooth) of liver and other tissues.
Non-microsomal enzymes: Enzymes occurring in organelles/sites
other than microsomes are called non-microsomal enzymes. These are usually
present in the cytoplasm, plasma, and mitochondria.
Q. Describe briefly fine pathways
of biotransformation
The major transformation reactions for xenobiotics are
divided into two phases known as Phase I and Phase II.
a)
Phase I Reactions
(Non-synthetic or Non-conjugative Phase)
Phase I reactions modify the compound’s
structure by adding a functional group. This allows the substance to interact
with a reactive group, such as –OH, SH, -NH2 or –COOH. Most of these
reactions involve different types of microsomal enzymes, except a few where reactions involve non-microsomal enzymes. Phase I reactions usually yield products with decreased
activity. However, some may give rise to products with similar or even greater
activity.
Oxidation:
It is the most common reaction and may take place in a number of ways such as
hydroxylation, deamination, desulfurization, dealkylation or sulfoxide
formation, etc.
In the biotransformation of
lipophilic xenobiotics, microsomal oxidation is the most prominent reaction
where microsomal enzymes associated with smooth endoplasmic reticulum of
hepatocytes are involved and the enzyme cytrochrome P-450, a heme-protein, which is a part of an enzyme system termed as
mixed function oxidase (MFO) system, plays an important role.
The other enzyme systems of Phase I biotransformation are
involved in metabolism when the appropriate functional groups are available
e.g. alcohol dehydrogenase is involved in the biotransformation of alcohols and
aldehydes, monomine oxidase is a flavine adenine dinucleotide (FAD)-containing
enzyme that catalyses the oxidative deamination. Epoxide hydrolases are enzymes
that add water across epoxide bonds to form diols. A number of carbroxyl
esterases are responsible for biotransformation of certain compounds including
organophosphates. The extent to which these metabolic reactions take place
appear to vary with the species.
Reduction: Reduction is acceptance of one or more electrons(s)
or their equivalent from another substrate. Biotransformation by reduction is
also capable of generating polar functional groups such as hydroxyl and amino
groups which can undergo further biotransformation or conjugation. Many
reductive reactions are exact opposite of oxidative reactions.
Hydrolysis:
It is the process of cleaving of a foreign compound by the addition of water.
It occurs both in the cytoplasm and smooth endoplasmic reticulum. It is an
important metabolic pathway for compounds with an ester linkage (-CO, O-) or an
amide (-CO, HN-) bond. The cleavage of esters or amides generates nucleophilic
compounds which undergo conjugation.
b)
Phase II Reactions or Conjugation/Synthetic Reactions
Phase II reactions (conjugation/synthetic reactions) includes
reactions that catalyses conjugation of xenobiotics or their Phase I
metabolites with endogenous substances with a water soluble molecule. In Phase
II, most of the reactions involve non-microsomal process (except a few that
involve microsomal enzyme). Due to biotransformation, the water solubility of a
compound is typically increased.
Synthetic reactions
may take place when a xenobiotic or with a polar metabolite of phase I
metabolism containing –OH, -COOH, -NH2 or –SH group that undergoes further
transformation to generate non-toxic products of high polarity which are highly
water soluble and readily excretable by combining with some hydrophilic
endogenous moieties Conjugating agents
are glucuronic acid, acetyl, sulphate, glycine, cysteine, methionine and
glutathione which conjugate with different functional groups of xenobiotics.
Most of the phase-II biotransforming enzymes are located in the
cytosol with the exception of uridine diphosphate glucuronyl transferase
(UDPGT) which is a microsomal enzyme.
Q.
What do you understand by induction or Inhibition of metabolizing enzymes?
a) Induction of Enzymes
Several drugs and chemicals have ability to increase the
metabolizing activity of enzymes called enzyme induction. Microsomal enzyme induction by drugs and chemicals
usually require repetitive administration of the inducing agent over a period
of several days and the induction, once started, may continue for several days.
Metabolizing enzyme induction has great clinical importance because it affects
the plasma half-life and duration of action of xenobiotics.
c)
Inhibition of Enzymes
Contrary to metabolizing enzyme induction, several drugs and
chemicals have ability to decrease the metabolizing activity of certain enzymes
called enzyme inhibition. Enzyme inhibition can be either non-specific of chromosomal
enzymes, or specific of some non-microsomal enzymes (e.g. monoamine oxidase,
cholinesterase and aldehyde dehydrogenase). The inhibition of hepatic
microsomal enzymes mainly occurs due to administration of hepatotoxic agents,
which cause either rise in the rate of enzyme degradation (e.g. carbon
tetrachloride and carbon disulphide) or fall in the rate of enzyme synthesis
(e.g. puromycin and dactinomycin). Enzyme inhibition may also produce
undesirable xenobiotic interactions.
Bioactivation
Q. Describe briefly bioactivation
Formation of harmful or highly reactive metabolic from relatively
inert/non toxic chemical compounds is called bioactivation or toxication. The bioactive metabolites often interact with the body
tissues to precipitate one or more forms of toxicities such as carcinogenesis,
teratogenesis, tissue necrosis, etc.
The bioactivation reactions are generally catalyzed by
cytochrome P-450-dependent monooygenase systems, but some other enzymes like
those in intestinal flora are also involved in some cases. The reactive
metabolites primarily belong to
three main categories-electrophiles, free radicals and nucleophiles. The formation of electrophiles and free radicals from
relatively harmless substances/xenobiotics account for most toxicities.
Electrophiles
Q.
Define electrophiles
Electrophiles are molecules which
are deficient in electrons pair with a positive charge that allows them to
react by sharing electron pairs with electron-rich atoms in nucleophiles.
Important electrophiles are epoxides, hydroxyamines, nitroso and azoxy
derivatives, nitrenium ions and elemental sulfur. These eletrophiles form
covalent binding to nucleophilic tissue components such as macromolecules
(proteins, nucleic acids and lipids) or low molecular weight cellular
constituents to precipitate toxicity. Covalent binding to DNA is responsible
for carcinogenicity and tumor formation.
Q. Define free radicals
Free radicals are molecules which
contain one or more unpaired electrons (odd number of electrons) in their outer
orbit.
Q. Define nucleophiles
Nucleophiles are molecules with
electron-rich atoms. Formation of nucleophiles is a relatively uncommon
mechanism for toxicants. Examples of toxicity induced through nucleophiles
include formation of cyanides from amygdalin, acrylonitrile and sodium
nitroprusside and generation of carbon monoxide from dihalomethane.
Toxicokinetics
Q. What is toxicokinetics?
Toxicokinetics (often abbreviated as 'TK') is the
description of what rate a chemical will enter the body and what happens to it
once it is in the body.
Q. What do you mean by extravascular
administration (EV)?
Drug or toxicant administration by any other route than the intravenous route is called EV
administration.
Q. Define minimum effective
concentration (MEC)
Minimum effective concentration
(MEC) is the minimum concentration of drug in plasma
required to produce the desirable pharmacological/therapeutic response. In case
of antimicrobials, the term minimum inhibitory concentration (MIC) is used,
which may be defined as the minimum concentration of antimicrobial agent in
plasma required to inhibit the growth of microrganims.
Q. Define maximum safe
concentration (MSC) or minimum toxic concentration (MTC)
Maximum safe concentration
(MSC) or minimum toxic concentration (MTC) is the concentration of drug in plasma above
which toxic effects are produced. Concentration of drug above MSC is said to be
in toxic level. The drug concentration between MEC and MSC represents the
therapeutic range.
Q. Define maximum plasma
concentration/Peak plasma concentration (Cmax or Cpmax).
Maximum plasma
concentration/Peak plasma concentration is the point of maximum concentration of drug
in plasma. The maximum plasma concentration depends on administered dose and rates
of absorption (absorption rate constant, Ka) and elimination
(elimination rate constant, β). The peak represents the point of time when
absorption equals elimination rate of the drug. It is often expressed as
g/ml.
Q. Define area under curve (AUC).
Area under curve (AUC) is the total integrated area under the plasma
drug concentration-time curve. It expresses the total amount of drug that come
into systemic circulation after administration of the drug
Q. Define peak effect
Peak effect is the maximal or peak
pharmacological or toxic effect produced by the drug. It is generally observed
at peak plasma concentration.
Q.
Define time of maximum concentration/Time of peak concentration (tmax):
Time
of maximum concentration/ time of peak concentration is the time required for a drug to reach peak
concentration in plasma. The faster is the absorption rate, the lower is the tmax.
It is also useful in assessing efficacy of drugs used to treat acute conditions
(e.g., pain) can be treated by a single dose. It is expressed in hours.
Q.
Define onset of action
Onset
of action: It is the beginning of
pharmacological or toxicological effect or
response produced by the drug. It occurs when the plasma drug
concentration just exceeds the MEC.
Q. Define onset time
Onset time is the time required for the drug to start
producing pharmacological or toxic response. It usually corresponds to the time
for the plasma concentration to reach MEC after administration of the drug.
Q. Define duration of action
Duration
of action is the time period for which pharmacological
or toxic response is produced by the drug. It usually corresponds to the
duration for which the plasma concentration of drug remains above the MEC level.
Q. What is zero order
process or kinetic?
Zero-order
process/zero-order kinetics or constant-rate kinetics is defined as a
toxicokinetic process whose rate is independent of the concentration of the
xenobiotic/chemical i.e., the rate of toxicokinetic process remains constant
and cannot be increased further by increasing their concentration of
xenobiotic.
Q. What is first order
process or kinetic?
First-order process
(first-order kinetics or linear kinetics) is defined as a toxicokinetic process whose rate is
directly proportionate to the concentration of the xenobiotic/chemical i.e.,
greater the concentration, faster is the process.
Q. What is mixed process or mixed order kinetic?
Mixed- process (mixed- order kinetics, non-linear
kinetic or dose-dependent kinetics) is defined as a toxicokinetic process whose
rate is a mixture of both zero order and first-order processes. The mixed order
process follows zero-order kinetics at high concentration and the first order
kinetics at lower concentration of the xenobiotic. This type of kinetics is
usually observed at increased or multiple doses of some chemicals.
Toxicokinetic models
Q.
Name three toxicokinetic models that are commonly used
i)
classic toxicokinetics (traditional)
ii)
non compartment models/non compartment analysis and
iii)
physiological models
Q.
What are classic toxicokinetic models?
Classic
toxicokinetic modeling (traditional) is simplest mean of gathering information
on absorption, distribution, metabolism, and elimination of a compound and to
examine the time course of blood or plasma toxicant concentration over time. In
this approach the body represents as a system of one or two compartments
(sometimes more than two compartments) even though the compartments do not have
exact correspondence to anatomical structures or physiologic processes.
Q.
What are the advantages of classic models?
(a)
they
do not require information on tissue physiology or anatomic structure;
(b)
they
are useful in predicting the toxicant concentrations in blood at different
doses;
(c)
they
are useful in establishing the time course of accumulation of the
toxicant, either in its parent form or
as biotransformed products during continuous or episodic exposures, in defining
concentration–response (vs. dose–response) relationships and,
(d)
provide
help/guidance in the choice of effective dose and design of dosing regimen in
animal toxicity studies.
Q.
Define One-Compartment Open Model
One-compartment open model is the simplest model, which
considers the whole body as a single, kinetically homogeneous unit, in this
model, the final distribution equilibrium between the chemical in plasma and
other body fluids is attained rapidly and maintained at all times.
Q. Define two-compartment open model
Two-compartment Open Model assumes that body is composed of
two compartments-the centra l compartment and peripheral
compartment. The central compartment (compartment 1) consists of blood
and highly perfused organs like liver and, kidney, lungs, heart, brain , etc;
the less perfused tissues (compartment 2) like skin, muscles, bone, cartilage,
etc. make the peripheral compartment.
Q. Describe the shape of time curve in two
compartment model
In two-compartment open model,
after intravenous (IV) bolus or extravascular administration of a single dose
of toxicant the curve is biexponential. As shown in figure below linear
terminal portion is elimination phase β.
Q. Describe three-compartment open model
The toxicokinetic behavior of some
chemicals, which have a high affinity for a particular tissue and are under
redistribution, is best interpreted according to a three compartment open
model. Body is conceived as consisting of three compartments – one central and
two peripheral compartments. The central compartment (compartment 1) comprises of plasma and highly
perfused organs, whereas peripheral compartments 2 comprises of moderately (e.g., skin and
muscles) and compartment 3 poorly perfused tissues (e.g., bone, teeth,
ligaments, hair, and fat). If any chemical is administered by IV, it is first
distributed immediately into the highly perfused tissues (compartment 1), then slowly into the moderately perfused tissues
(compartment 2) and thereafter very slowly to the poorly perfused tissues
(compartment 3). If plasma level-time
profile is plotted on semi-logarithmic graph, it gives triexponential
appearance.
Q. Define the term half-life
Half-life (T½) may be defined as the time taken for the
concentration of a compound/ toxicant in plasma to decline by ½ or 50% of its
initial value (or it may be defined as the time required for the body to
eliminate half of the chemical). This value is determined during the
elimination phase of a chemical; therefore, it is called as elimination
half-life.
Q. What is bioavailability?
After oral or EV routes,
often only a fraction of the total dose to which an animal or human is exposed
gets absorbed systemically. This fraction is referred to as the bioavailability
(F). Bioavailability is
determined by measuring the area under plasma drug concentration versus time
curve (AUC) after oral or EV
routes. This is compared with AUC measured after IV bolus administration of the
same drug.
Bioavailability is
a useful parameter, which is used to predict the drug efficacy after different
routes of administration.
Q. What is the influence of route of administration of
drug/toxicant on bioavailability?
It is generally in the following order:
IV > oral route > topical route
Q. Define volume of distribution (Vd)
The total volume of fluid in
which a toxic substance must be dissolved to account for the measured plasma
concentrations is known as the apparent volume of distribution (Vd). If a compound is
distributed only in the plasma fluid, the Vd is small and plasma concentrations are
high. Conversely, if a compound is distributed to all sites in the body, or if
it accumulates in a specific tissue such as fat or bone, the Vd becomes large
and plasma concentrations are low.
Q. Define total body
clearance, term used in kinetic studies of toxicants.
In toxicology, the clearance is a pharmacokinetic measurement of
the volume of plasma that is completely cleared off of a substance per unit
time. The usual units are mL/min. The total
body clearance will be equal to
the renal clearance + hepatic clearance + lung clearance.
Flip-flop kinetics
Q. Define flip-flop kinetics
Flip-flop kinetics refers to a situation when the rate of
absorption of a compound is significantly slower than its rate of elimination
from the body. The compound’s persistence in the body therefore becomes
dependent on absorption rather than elimination processes. This sometimes
occurs when the route of exposure is dermal.
Q. Define PBTK
It is a physiological based toxico-kinetic
(PBTK) model. These models are mathematical stimulation of physiological
processes that determine the rate and extent of xenobiotics/toxicant
absorption, distribution, metabolism and excretion. The primary difference
between physiologic compartmental models and classic compartmental models lies
in the basis for assigning the rate constants that describe the transport of
chemicals into and out of the compartments. In classic kinetics, the rate
constants are defined by the data; thus, these models are often referred to as
data-based models. In PBTK models, the rate constants represent known or
hypothesized biological processes, and these models are commonly referred to as
physiologically based toxicokinetic models.
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 11th edition,
Merck & Co. Inc Whitehouse Station, NJ, USA 2969-99
The Merck Veterinary Manual (2016). Chapter “Pentachlorophenol
Poisoning” by PK GUPTA 11th 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.
https://www.linkedin.com/.../series-3-toxicology-question-answer-bank-dr-pawan-ku...Jan
26, 2018 -
https://www.linkedin.com/.../series-4-toxicology-question-answer-bank-dr-pawan-ku...Feb
4, 2018 - Feb 4, 2018 Cont'd from series 3.
https://www.linkedin.com/.../series-5-risk-assessment-toxicology-question-answer-ban...Series 5: Risk
Assessment. Cont'd from series 4.
Gupta PK (2018) Series 6: (Multiple choice
questions)TOXICOLOGY Question and Answer bank https://www.linkedin.com/pulse/series-6-multiple-choice-questionstoxicology-question-gupta/
Gupta PK (2018) Dr Pawan K (PK) Gupta Series7: Multiple
Choice Questions and fill in blanks TOXICOLOGY Question and Answer bank
https://www.linkedin.com/pulse/dr-pawan-k-pk-gupta-series7-multiple-choice-questions-gupta/
Gupta PK (2018) Dr Pawan K (PK) Gupta Series8: Fill in blanks TOXICOLOGY Question and Answer bank https://www.linkedin.com/pulse/dr-pawan-k-pk-gupta-s
To be cont’d -Series 10
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