Lecture 3&4

B.Sc. in Environmental Science

ES 411 Environmental Toxicology

Environmental risk
assessment - I

B. M. R. Bandara
Department of Chemistry
University of Peradeniya
 Risk assessment

Scientific evaluation of risk (potential for

toxicity/adverse effects) when humans and
animals are exposed to a hazardous compound
Risk =
f(inherent toxicity, Evaluation of risk
exposure) Using data from:
• Human epidemiology
Living organisms • Animal toxicity studies
• In vitro studies (cells, cell lines, bacteria)

Study of toxic compounds and

their adverse effects on ENVIRONMENT
living organisms
ENVIRONMENTAL TOXICOLOGY
 Study of toxic compounds and
their adverse effects on
Some basic concepts living organisms

(changes from
Toxic when exposed to Living produce adverse normal sate of
compounds organisms effects organism)

Selective toxic effects

at
toxicity Toxic compound can (poisonous effects)
be selectively toxic to (deleterious effects)
one or few species
but not to others • molecular level
• cellular level
E.g.
• organ level
antibiotics
herbicides • organism level
• community level
 Toxicological paradigm & selective toxicity
Toxic when exposed to Living produce adverse
compound organism effects

What happens to What happens to the Toxicological paradigm:

the toxic compound organism when exposed
Identify adverse effects of a
in the organism? to toxic compound?
substance (& its fate) by
‘Fate of a ‘What a testing its effects on different
chemical in chemical does to routes of exposure (oral,
the organism’ the organism’ inhalation, dermal) and doses
(concentrations & durations)
Toxicokinetics Toxicodynamics
Deals with How a chemical changes Selective toxicity
• absorption structure and function of arises due to
• distribution a cell/organ/organism differences in
ADME
• metabolism leading to toxic effects
• excretion toxicokinetics &
of a chemical toxicodyanmics in
different organisms
 Classification of toxic compounds
according to

Origin Use Target Mode of

organ action
Toxic chemicals Drugs
produced in (fentanyl) Corrosive
biological Liver (acid & alkali)
systems: Food additives hepatotoxins Irritant
(NaNO3) (CCl4) (detergents)
Toxins
(algal toxins, Industrial Kidney Asphyxiant
plant toxins) chemicals (cyanide)
renal toxins
(petroleum) (Cd) Carcinogen
Other toxic (tobacco smoke)
chemicals: Household CNS Mutagen
Toxicants chemicals neurotoxins (NaN3)
(bleach)
(As, paraquat) (EtOH)
Teratogen
(thalidomide)
 Exposure to toxic compounds
Main routes Duration & frequency
of exposure: of exposure:
• Inhalation (nose) Acute exposure – 24 h
• Oral (mouth) • Single dose (very toxic chemical)
• Topical (skin) • Multiple doses (slightly toxic chemical)
• Continuous (inhalation < 24h, ~ 4 h)

Effectiveness of Sub-acute exposure –

route of exposure: up to 1 month
inhale > oral > topical
Sub-chronic exposure –
1 to 3 months
Toxicity can vary with
route of exposure Chronic exposure –
3 months to lifetime
 Toxic effects Toxic chemical or
activated metabolite
Macromolecule
Cell
Target Organ
Biochemical process

Change from At:

its natural state Molecular level
Toxic-Body-Burden.jpg (600×400) (ronandlisa.com)
Cellular level
Tissue damages can be Organism level
Irritations Toxic effect
Allergic reactions CNS
Physiological changes Reproductive system
Reproductive effects Anywhere
Liver
Teratogenic effects in the body
Lungs
Mutagenicity
Carcinogenicity
 Types of toxic responses
Damaged organ:
repaired by itself – liver
• Reversible toxicity vs
not repaired by itself – CNS
irreversible toxicity
Develop rapidly after a single
administration – cyanide, CO
• Immediate toxicity
vs delayed toxicity Develop after a gap of time:
delayed by days – neurotoxicity of
organophosphate insecticides
delayed by months – teratogenic
• Local toxicity vs effects of thalidomide
systemic toxicity delayed by years – cancer due to
asbestos fibres
 Local toxicity vs systemic toxicity
Toxic chemical Adverse health effects
absorption
reacts directly with at a location away from
exposed cells initial point of contact
distribution to
skin, mucous target organs Liver – hepatotoxins
membranes, Kidney – renal toxins
respiratory tract, Lung – pulmonary toxins
GIT, eyes accumulation CNS - neurotoxins
Heart – cardio toxins
Strong acids/alkali Nepron – nephrotoxins
toxic effect on
- can damage skin target organ functional
Inhalation of asbestos fibres unit of kidney
- can cause asbestosis
& lung cancer

IMG_20210309_155400.jpg
(719×568) (bp.blogspot.com)
 Multiple exposure to toxic compounds
xenobiotics
e.g. Environmental
Living Get exposed to
exposure
organisms several chemicals
simultaneously
water air gasoline
• pesticides • automobile vapour
• Each chemical acts independently • heavy metals exhaust mixture of
• A chemical can affect the response • solvents • cigarette chemicals
of another due to interactions smoke
• dioxins

Toxic effect of Toxic effect of Combined Type of POPs in the

chemical A chemical B toxic effect of interaction environment
A&B
20% 30% 50% Additivity
20% 30% 5% Antagonism
0% 20% 50% Potentiation
5% 10% 90% Synergism
 Evaluation of toxic effect
Toxic effect? Assess the risk of the
Data toxicant/chemical
Extent?

Rat, mouse etc

Collect data from:
(environmental • Human epidemiological studies
health toxicology) • Animal toxicity studies
Freshwater/marine/ • In vitro studies (cells, cell lines, bacteria)
terrestrial organisms
(ecotoxicology)
measure
Vary: amount of toxicant Toxic effect
(dose) (response)

DOSE-RESPONSE RELATIONSHIPS
• Exposure limits (maximum allowed toxicant levels)
• Regulations to prevent/minimize risk
 Dose-response relationships
e.g. Paracetamol e.g. Alcohol intoxication
Dose Response No. of
Response
Effective dose Therapeutic effect Drinks

Overdose Death 1 no effect

Chronic use (kids) Liver toxicity 2 giddy/dizzy

3 driving impaired
4 drowsy
dose response 5 sleep
6 deep sleep
7 unconscious
8 laboured breathing
9 death
Chronic
liver toxicity
use

1 drink = 17.4 mL (14 g) of EtOH

 Dose-response relationships
Dose Biological Response
system
Amount of chemical • Pathological changes
– liver cell necrosis,
Human/animal: hepatomegaly
mg (of chemical) per kg (of body weight) • Biochemical changes
mg/kg mg kg-1 – inhibition of an enzyme
• Body weight changes
Cell culture/aquatic environment: • Mortality/death
Concentration of chemical (ppm) in
medium/water
association between the amount of a
Dose-response relationship toxicant administered (dose) and the
extent to which the changes (response)
are observed in a biological system
 Dose-response relationships
Dose Biological Response
system
‘External dose’ A change in the organism or
subsystem (e.g. subpopulation
Amount of chemical
of cells):
administered/measured
• Morphology
in the environment
• Physiology
• Growth that results in
‘Internal dose’ • Development an impairment
Amount of chemical • Reproduction of functional
absorbed and found at the • Lifespan capacity
site of biological activity

‘External dose’ Response Dose-response relationships

‘External dose’ Response Dose-response relationships

Amount of chemical:
• administered to the organism
• measured in the environment

Three assumptions are made

when considering ‘external dose’
in dose-response relationships:
1. The response is caused by the chemical
2. The response is proportional to the concentration
of the chemical at the target site (internal dose)
3. The concentration of the chemical (internal dose) is
proportional to the dose (external dose)
 ‘External dose’ Response

Dose-response relationships
Graded dose-response Quantal dose-response
relationship relationship
(Continuous dose-response Distribution of individual
relationship) responses to different doses
in a population of organisms
Response of an individual
organism to increasing Response: “yes or no”
doses of a chemical Response frequency:
how many “yes” responses
Continuous Quantal
frequency
Response

Response
responses responses
extent

Dose Dose
Graded (continuous) dose-response relationships
a continuous scale an increase in the magnitude
of doses of a specific response

Acetylcholinesterase
activity in rat brain
AclE activity

carboxylesterase
activity in rat brain
CxyE activity

Log (dose)
Chlorpyrifos (OP insecticide) Clpfs
‘a linear-log plot’
(A) Dose–response curve plotted on (B) Same data plotted on
an arithmetic scale a semi-log scale
Cassarett & Doull’s Essential of Toxicology (2021)
 Graded dose-response Relationships
• Response (% inhibition): dose-
related
• At 3 mg/kg, Clpfs inhibits AclE but AclE activity
not CxyE
• At higher doses, Clpfs inhibits both
enzymes CxyE activity
• Primary toxicological response –
directly related to AclE inhibition
• Clinical signs & symptoms of Clpfs
toxicity follow a dose-response Log (dose)
relationship for AclE inhibition Clpfs

Chemicals → multiple sites of toxicity → each site with

its own ‘dose-response’ → subsequent adverse effect
 Quantal dose-response relationships
Graded dose-response relationship
“extent of response”
– in individuals
Quantal dose-response relationship
– in a population “all or none” “yes or no”

For administered to a ‘a responder’

An individual is classified as
any population or
in the
given ‘a non-responder’
population
dose
Cumulative response (%)
Number of Response
Dose Number of responders for
responders (%) frequency (%)
dose 1 & dose 2
1 N1 N1
2 N2 N2 – N1 Number of additional responders
3 N3 N3 – N2 when dose was increased from 1 to 2
4 N4 N4 –N3
 Quantal dose-response relationship
A normal (or Gaussian) distribution
Bell-shaped curve →
Due to differences in susceptibility of a normal frequency distribution
individuals to chemical toxicity
(biological variation):

Few animals responded to

highest doses
(animals are resistant)

Few animals responded to

lowest doses
(animals are hypersusceptible)

Maximum frequency
plotted on a semi-log scale
in the middle