CHAPTER 3 BIOACCUMULATION

AND BIODISPOSITION OF
TOXICANTS
• Bioaccumulation of Persistent Environmental
Toxicants
• Uptake and Distribution of Toxicants
• Metabolism/ Biotransformation of Xenobiotics
• Adverse Action/Toxic Response
• Factor and Conditions Affecting Toxicity

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Learning Outcome
• 2.1 Definition of Bioaccumulation and Toxic Equivalency
(TEQ)
• 2.2 Factors Influencing Bioaccumulation
• 2.3 Uptake and Distribution of Toxicants
• 2.4 Absorption of Toxicants3 Uptake and Distribution of
Toxicants
• 2.5 Distribution and Excretion of Toxicants
• 2.6 Metabolism and Biotransformation of Xenobiotics
• 2.7 Adverse Action and Toxic Response
• 2.8 Factors and Conditions Affecting Toxicity
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Part 1: Bioaccumulation of Persistent
Environmental Toxicants
• Bioaccumulation – accumulation of substances in
living organism
• When contaminants can not degraded in the
environment, its potential persistent toxicants in the
environment. Its subject to “Bioconcentration”
• Bioconcentration – process uptake and retention of a
toxicant in an organism’s tissues can eventually be
much higher than its concentration in the surrounding
environment

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Part 1: Bioaccumulation of Persistent
Environmental Toxicants

• Bioaccumulation when organism’s uptake and retention of

a toxicant from all sources (all site/route/medium such as
water or soil).
• When this organism eaten by its predator cause
biomagnification.
• Because toxicant is now bioaccumulated in predator, with
its concentration magnifying in a food chain (since
predator likely to consume more than one similar prey).
• Toxicants tend to concentrate in fatty tissues and become
abundant on higher trophic level of food chain.
• Ex: Bioaccumulation of POC in seafood
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 Part 1: Bioaccumulation of Persistent
Environmental Toxicants
• Bioaccumulation & Bioconcentration occur when exist
of chemical, organism under conducive environment.
• Using passive transport: chemical tend to diffuse
passively from area of high concentration to low
concentration.
• Factor Influencing Bioaccumulation are:

Lipophilicity Dynamic
Metabolic Environmental
and Equilibrium
Potential Mobility
Bioavailability Effect

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 Part 1: Bioaccumulation of Persistent
Environmental Toxicants

(a) Lipophilicity and Bioavailability

• Lipophilicity- (LIPID/FAT LOVING) Certain chemicals (eg:
POC) do not mixed well with water.
• Lipophilic substances tend to move out of water and into
the cells of living organism that they come in contact
with.
Toxicants level
rapidly to body The chemical Unbound
Chemical ready organ and bound/unboun chemical are
enter organism tissues via d to plasma biologically
body bloodstream & proteins of active lead to
lymphatic tissues bioavailability
system.

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 Toxicants level
The chemical Unbound chemical
Chemical ready rapidly to body
bound/unbound to are biologically
enter organism organ and tissues
plasma proteins of active lead to
body via bloodstream &
tissues bioavailability
lymphatic system.

(a) Lipophilicity and Bioavailability

Bioavailability caused uptake of chemical in cell.
Factor high bioavailability of are
Types of plasma Plasma flow rate Temporary attached of
protein (weak binding Concentrations (caused uptake slowly Binding kinetic chemical to protein
of chemical) or discontinued) sites.

High water solubility of

chemical (caused
chemical not readily
enter the cells of
organism).

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Part 1: Bioaccumulation of Persistent
Environmental Toxicants
(b) Metabolic Potential
• Metabolism – ability of organism’s body break
down the chemical that has been entered its cell or
tissues.
• Metabolic for
• each organisms varies among species and
• depend on chemical’s physiochemical properties
• Ex: natural pyrethrins (insecticides derived from
plants) fat soluble but easily degraded.
• Its will not accumulate in organism / persistent in
aquatic/microorganism/organism

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Part 1: Bioaccumulation of Persistent
Environmental Toxicants

(d) Environmental Mobility

• Bioaccumulation influenced by chemical’s mobility in the
environment as long-range transport via animal migration (called as
biotransport).
• Ex: Pacific salmon deposit egg in freshwater and then migrate
downstream to ocean to spend their lifecycle there.
• Migration to freshwater for spawning- accumulate lipid for energy for
migration and gonadal development.
• However, at ocean found that the lipid accumulated in salmon body have
been contaminated by DDT and PCBs.
• Biotransport of pollutant occur due to
• large volume local contaminants load at freshwater
• high bioavailability (stowed in organism plasma protein/lipid)
• less vulnerable to environmental degradation (protected from oxidation process or UV
radiation)

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 Part 1: Bioaccumulation of
Persistent Environmental Toxicants
(e) Dynamic Equilibrium Effect
• Dynamic equilibrium between organism’s exposure to a toxicant and its
uptake, storage and degradation inside the organism effect excreted
from body.
Metabolism
Toxicant enter Distribution and
the cells of and storage in elimination
organism cell within
organism

• Persistent lipophilic toxicants posing a

• Resistant to metabolic inside an organism (due high lipophilicity caused toxicant
stored in fat for years)
• great threat of bioaccumulation within an ecosystem.

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Part 2: Uptake and Distribution of
Toxicants
• Fate and transport of toxicants entering the body of
an organism, particularly on human and
mammalian.
• Two types of effect due to uptake and distribution
of toxicants
a) Localized effect of non-systemic action
b) Disposition of systemic/ internal organ toxicants

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 Part 2: Uptake and Distribution of
Toxicants
Localized Effect of Non-Systemic Action
• High level of toxicants within the
microenvironment outside of an
organism
• cause acute effect on outer structure
(skin, surface respiratory tract)
• Ex: Pesticide residues cause localized
rash/ irritation of skin
Disposition of Systemic/ Internal Organ
Toxicants
• Disposition of Xenobiotic (foreign
substance from chemical substance
that found in body or has taken into
body) in biological system may be
broadly divided in a series of
biochemical events or phases.
• Eg: applies also in plant which can
excrete wastes (eg: minerals) via roots,
shoots or leaves. Different plants,
secreted waste differently.
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 Part 2: Uptake and Distribution of Toxicants

Mechanism of Entry
• Disposition of Xenobiotics inside a biological system
caused disposition

Distribution
Exposure Uptake Metabolism Excretion
and storage

Disposition of Xenobiotic insides a biological system

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Part 2: Uptake and Distribution of Toxicants
Mechanism of Entry
• Xenobiotic actively penetrates a cellular membrane on the host
organism’s outer structure (cellular membrane). But, for many
xenobiotics passive transport is the predominant entry
mechanism.
1. Structure
of cellular • Biomembranes
membrane
• Passive Diffusion
2. Common • Active Transport
Mechanism • Filtration
of Entry • Facilitated Diffusion
• Endocytosis

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Mechanism of Entry

Structure of Cellular Membranes

• Biomembrane
• Protect a cell from outside environment/ separate the compartments inside a
cell to safeguard important biological process
• Permeable to certain toxicant
Biomembrane part Function
Phospholipid Bilayer embedded with protein
- polar/water soluble head
- non polar fatty acid hydrocarbon tail

Peripheral Protein Safeguard membrane surface, regulate cell signalling

Integral Protein Transport substances such as ions & macromolecules
across phospholipid bilayer

Glycolipid and Steroid Glycolipid have more carbohydrate group attached

Steroid are cholesterol due alcoholic hydroxyl (OH)
group- interact with water, rigidity/stability to the
biomembrane

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 Mechanism of Entry
Common Mechanism of Entry
• 5 mechanisms of entry enabling/aiding Xenobioticx to
get inside an organism’s body or cross cellular
membranes

Passive
Facilitated
diffusion/passive Active Transport
Diffusion
transport

Filtration Endocytosis

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 Common Mechanism of Entry
• Passive Diffusion
• Molecule movement across cell membrane
without expenditure of energy by cell
• Facilitated Diffusion
• Molecule movement across a cell
membrane using special transport protein
(Integral protein) as carriers that embedded
within cellular membrane
• Active Transport
• Molecule movement against concentration
gradient or electrical potential in direction
opposite to passive diffusion.
• Require expenditure of energy by the cell

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 Common Mechanism of Entry

• Filtration
• Movement of molecule across cell
membrane due to hydrostatic pressure
generated by cardiovascular system (high
pressure to low pressure)
• Endocytosis
• Cells absorb molecule from outside cell by
engulfing these molecule with their
membrane.
• Ingested molecules are solid:
phagocytosis
• If liquid: pinocytosis

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 Part 2: Uptake and Distribution of Toxicants

Uptake and
Distribution Excretion
Absorption

Distribution
Renal Fecal Pulmonary
Plant Human via
Excretion Excretion Excretion
Bloodstream

Shoot Root
Skin Respiratory Gastrointestinal
(above (below Penetration Uptake Absorption
ground) ground)

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 Uptake and Absorption of
Toxicants

Uptake by Plant
(a)Plant Leaves
(b)Plant Root

Internal anatomy of leaf

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Uptake and Absorption of Toxicants
– uptake via Plant Leaves

• Dermal tissues – comprised

epidermal cells closely packed to
shield the outer surface of
herbaceous plants. Internal anatomy of leaf
Anatomy of Leaf Character/ function
Cuticle Waxy
To reduce water loss from leaf
Palisade parenchyma cells Rich Chloroplast for photosynthesis,
storage and support
Spongy mesophyll Transporting food, water, minerals,
parenchyma cells hormones and other materials within a
plant.

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 Uptake and Absorption of Toxicants
– uptake via Plant Leaves
• Amount of contaminants enter plant are in solution (pesticide, spray, liquid
aerosol) rather than in gas form which cause plant damage.
• Stomata most significant structure component cause plant damage.
• Stomata responsible regulating the passage of pollutants into the leaf cells.
• Opening of stomata regulate by meteorological (temperature, light),
physiochemical condition in guard cell, starch content and accumulation potassium
(K+) in guard cells
• Physiochemical properties of pollutant along the leaf surface
• The flow of pollutant may be hindered by leaf’s morphology.
• The reaction of chemical scavengers occur within the leaf or by air movement
across the leaf.
• This factor affect the polluted air’s flux to the leaf surface

“Permeability of solution on leaf surface depend on moistening of the leaf

surface, surface tension of liquid, morphology of stomata”

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Uptake and Absorption of Toxicants
– uptake via Plant Roots
• Roots of many plants also have stomata serving as
crucial passage for soil contaminants.
• Indirect damage retarding plant growth cause disturbance of
water or nutrient uptake.
• Acidified contaminated soil by decayed material or acid
rain
• Metallic ions (Pb, Cd) in the soil become more mobile toward
the plant roots
• These ions may damage plant’s root and then its lead by
disturpting its uptake of water and nutrients.
• Leaching of nutrients cause lead nutrient deficiency or
growth disturbance

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 Uptake and Absorption of Toxicants
– uptake via Plant Roots
• As water can enter the root via
epidermis,
• minerals can enter the root by dissolved
in water or
• entering on their own as free molecules
root hair
• Mineral can enter the root against
their concentration gradient via active
transport.

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Uptake and Absorption by Human
• Enter of xenobiotic into human body are
• Dermal
• Respiratory
• Gastrointestinal
• Secondary routes : eyes, injection, sexual, wound

(Xenobiotic: used for a foreign substance/chemical that is

found in body or has taken into body. May produce
beneficial effect (pharmaceuticals) or may toxic (metallic
ion such as lead)

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 Uptake and Absorption by Human
Dermal/ Skin Penetration
• Penetration and distribution of xenobiotic via
human skin which is complex, multi-layered
structure.
• Skin is biomembrane relatively impermeable to
most ion and aqueous solution
• due to epidermis as physical barrier to most chemical
penetration.
• Many toxicants still can find their way deep into
human skin (pesticides).
• When xenobiotics is lipid-soluble compound given then
biomembrane are largely phospholipids which highly
lipophilic (easier dissolve in lipid/fat)

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Uptake and Absorption by Human

Dermal Contact

Epidermis

Blood and Lymph

System
Dermis

Subcutaneous

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• Dermis provide maximum opportunity for transport
of toxicant once they have penetrated through
epidermis.
• This opportunity owes to the fact that dermis is
place that most of the blood vessel and nerves.

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Uptake and Absorption by Human
Respiratory Uptake
• Unavoidable contact with air pollutant
• Exchange gases between bloodstream and the air
present in the alveoli.
• This organ also furnished with mechanical and
immunological mechanism (filtration in nasal cavity,
sneezing) devoted to keeping itself free from
invading particles or microorganism.
• Cilia (small hair like appendages) in respiratory
tract can sweep foreign particles out of the airways
and up to the throat through which foreign
particles may enter the gastrointestinal (GI)

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Uptake and Absorption by Human

Gastrointestina
Inhalation / Exhalation l Tract

Upper Respiratory Tract

Blood and Lymph

(Nose, pharynx, larynx)

Lower Respiratory Tract

( trachea, bronchi, alveoli)

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Uptake and Absorption by Human
Gastrointestinal (GI) Absorption
• GI tract treated as a long tube running from the
mouth to the anus, with its content external to the
rest of the organism’s body system
• Aside from dietary exposure, the oral route of
toxicological concern is generally limited to
accidental or deliberate ingestion of toxicants

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Uptake and Absorption by Human

Ingestion
Bile

Gastrointestinal
Tract
(mouth, esophagus, Liver
stomach, intestines)

Feces Blood and Lymph

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Distribution and Excretion of
Toxicants
• Distribution via
• Bloodstream
• Excretions via
• Renal Excretion
• Fecal Excretion
• Pulmonary Excretion

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 Distribution of Toxicants via Bloodstream

• Body fluid in human composed 3 main

components
• Intracellular fluid (40% of human body weight)
• Interstitial fluid/ Tissues fluid (20% of body
weight)
• Intravascular fluid/ Blood plasma (4% of body
weight)
• Intravascular fluid/Blood plasma responsible
in distribution of absorbed toxicants
• Lymph flow slower than blood flow.
• Toxicants frequently distributed along with
plasma proteins

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Distribution of Toxicants via Bloodstream
• If toxicants is bound to plasma protein, usually becomes
immobilized away from the site of action (toxic).
• Toxicants frequently distributed to the
• site of storage (bone, fat),
• liver or kidney for metabolic process or
• the site of action (binding to haemoglobin).
• Lipophilic compound such as dioxin, DDT, PCBs are stored in
fats and bones
• It is important to note that whenever there is a large amount
of toxicants stored in one of the depots, it is potential health
hazard.
• Because when biochemical or physiological disturbance occur,
large amount of stored toxicants can be suddenly released to
become available for body distribution to overload the site of
action
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 Excretion of Toxicants
(Elimination of toxicants/ removed from body)

Renal Excretion
• Main function of kidney is to
• remove urea, mineral salt, waste material from
blood.
• retention of water, salts and electrolytes (K+)
and
• regulate blood pressure.
• eliminating toxicants from body, in keeping the
blood clean, regulating amount of fluid in body.
• Nephron have million number in 2 human
kidney function unit responsible for renal
excretion

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 Renal Excretion
• 3 region as primary route of
excretion
• Glomerulus
• Proximal tubule
• Distal tubule
• Urine compose water, certain
electrolyte and waste
molecules.
• Urine formation by
• Glomerulus filtration
• Tubular reabsorption

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 Renal Excretion

• Glomerulus filtration
• 25% of cardiac output passes through kidney.
• 20% filtrate by glomerus pores (~70nm)
• small molecules polar or lipid soluble able pass through
• Large molecules/ bind with protein must altered or
eliminated by other processes/mechanism.

• Tubular reabsorption
• in proximal tubule (less crucial)
• All water, glucose, K+ and amino acid lost during first phase will
re-entered the blood from nephron section by passive diffusion
(high concentration to lower concentration in the capillaries
surrounding tubule)

• Secretion
• Solute may secreted into kidney at distal tubule via active
transport from peritubular capillaries into tubular.
• H+, K+ polar and nonpolar substances.

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 Fecal Excretion
• Bile is complex fluid flowing
through biliary tract into small
intestine.
• Contain water, electrolytes, host
of organic molecules (bile acid,
cholesterol, phospholipid)
• Waste product (bilirubin)
removed from body by hepatic
secretion into bile and into
duodenum (beginning small
intestine) for feces excretion.

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 Fecal Excretion
• Substances secreted into and from the bile are
water soluble.
• Therefore, those substance not likely to
reabsorbed from small intestine back to liver.
• Enzymes in intestinal capable hydrolysing
some glucuronide and sulphate conjugates to
produce smaller or less water soluble
compound.
• Which can reabsorbed along the proximal and
distal ileum.

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Pulmonary Excretion
• Lower respiratory tract particularly alveolar region as
pathway for excretion of many volatile substances
including gaseous metabolites.
• Alveoli used for exchange of oxygen from air with
carbon dioxide from blood.
• These gaseous exchange known as pulmonary
respiration.
• By passive diffusion following concentration gradient.
• Gaseous compound with low solubility in blood rapidly
eliminated than those high solubility.
• Volatile liquid dissolved in blood readily excreted as exhaled
air.
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 Uptake and Absorption Distribution and Excretion

Toxicant

Metabolism/biotransformation

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Metabolism/ Biotransformation of
Xenobiotics
• Many environmental toxicants that human body exposed are
lipophilic
• Biochemical property that enable many toxicant penetrate
various cellular membranes.
• In human, following uptake and distribution, xenobiotics are
distributed via bloodstream and lymphatic system to various body
parts (include excretory organ) where the xenobiotics can be
eliminated.
• Xenobiotics in body tissues and organ, may undergo
biotransformation (a process whereby a substance is transformed
from one chemical to another one or more biochemical reaction.
• Biotransformation = metabolism (enzymatic)

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 Metabolism/ Biotransformation of
Xenobiotics
• Metabolism as biochemical reaction to ensure
• Maintaining a homeostatic environment
• Constant energy supply to body cell
• Constant body temperature
• Constant blood sugar level

• Metabolic reaction have

• Catabolism : breaks down large molecule into small unit to release energy
• Anabolism : synthesize molecules from smaller unit, powered by energy released from catabolism.

• Require enzyme. Enzyme is protein; able catalysing biochemical reaction of metabolic reaction.
• Enzyme are target of environmental toxicants to have biotransformation.
• Factor affecting biotransformation
• Genetic Polymorphism
• Enzyme Inhibitor (xenobiotic able to inhibit catalytic activities)
• Enzyme Inducer (induce catalytic activities

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 Uptake and Absorption Distribution and Excretion

Toxicant
Metabolism/
Toxic Response
biotransformation

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Toxicodynamics of Toxicants
• Toxicodynamics (IUPAC, 1997)
• Is study of toxic actions on living system, including the
reaction with and binding to cell constituent, and the
biochemical and physiological consequences of these
actions.
• Two types of toxicodynamics:

Basic and
Specific based
nonspecific types
adverse effects
of adverse effects

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Basic and nonspecific types of adverse effects
Types of Characteristics
effects/response

Local Toxic effect/response occurring at site of contact with toxicant

Systemic Toxic effect to/response by the entire body or particular body region other than the
portal of entry

Reversible Effect than is temporarily, reparable form (tissues) injury, or otherwise reversible
Irreversible Effect that is permanents, not reparable from (tissues) injury
Immediate Response or effect that develops rapidly after acute or a single exposure
Delayed Response that develops following a short latent period from typically an acute
exposure

Acute Similar to immediate effect, but typically reserved for the kind that is usually of the
severe types.

Chronic Response or effect that is developed after repeated exposures or that last for a long
time

Allergic Effect requiring prior sensitization by an agent or by one similar structure or chemical
properties

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Specific and mechanism-based
adverse effects

Narcotic and
Asphyxiation
Irritation Effect Corrosive Effect Anaesthetic
Effect
effect

Effects on Target
Carcinogenic Teratogenic
Body Organs or
Effect Effects
System

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Types of effect Justification

Irritation Inflammation and painful reaction involving cell-lining damage

Irritant : biological (stings); chemical (phenol); mechanical (physical),
thermal (heat) and radioactive stimuli (UV ray)

Corrosive Production of irreversible tissue damage in lining of external tissues

following tropical exposure.
Asphyxiation Body is extreme decrease in oxygen supply
Symptoms of asphyxia : difficult breathing, hypertension (high blood
pressure), cyanosis.

Carcinogenic Normal cells transform into cancer cells. Cause by mutation or adverse
changes of genetic material.

Teratogenic Production of abnormalities prior to birth (birth defects, abnormalities in

embryo/fetus due to the viruses, radiation, chemical

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Factor and Condition Affecting
Toxicity
Intrinsic Factor/
Extrinsic Factors
Biological Factor

Environmental Age, Gender,

Factor Health Status

Species, Strain,
Nutritional
Race and
Factor
Genetics

Physiochemical
Factor

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Environmental Factor
• Level of environmental exposure
• London Fog of 1952
• Uptake of soil cadmium and arsenic
• Frequency and Duration of Exposure
• Medium’s pH
• Temperature
• Humidity
• Light (effect physiochemical properties of toxicants)

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Nutrition Factors
• Malnutrition (caused increase substantially toxicity
of some metals, pesticides)
• Starvation (severe GI, stroke, coma)
• Obesity
• Nutrient ability to modulate the enzymatic
activities and affect toxicity of xenobiotics.
• Macronutrient (protein, carbohydrate, lipid)
• Micronutrient (vitamin, minerals, metal)

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 Physiochemical factors
• Reactivity of chemical/xenobiotics
• Additive effect
• Joint exposure to 1 toxicant with toxicity level of 1 unit and subsequently to another toxicant with
toxicity level of 2 units would result in combined toxicity level of 3 units
• Synergism effect
• Joint effect of 2 toxicants that is greater than additive.
• Combine toxicity level would be greater than 3 units.
• Ex: synergism is lung cancer risk from joint exposure to asbestos and cigarette smoking.
• Potentiation effect
• Being to make more potent or to enhance an effect
• Interaction one substance’s presence make the other substance toxic or more toxic to organ.
• Potentiator/potentiating agent has little or no toxic effect on organ but enhancing effect on the
toxicity of other substance
• Antagonism effect
• Chemical interaction between 2 substances whereby the joint effect is less than what one would
expect from the sum of their individual effects.

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Biological Factor
• Age
• young age (infant) blood brain cellular structure not fully developed to be able
restrict the passage of harmful substances from blood to brain.
• Gender
• depend on case, Ex: gasoline induce kidney tumors only in male but not
female rate
• Health status/ disease condition
• Metabolic activities depend on health condition to react with toxicant
• Disease condition causing slower elimination of pollutant
• Species/Strain
• Difficulty on xenobiotic biotransformation
• Genetics
• Genetic expression will some losing entirely its ability to oxidise/react with
xenobiotics

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