Basic Concept on Toxicology for PCOM.pdf

Basic Concept on Toxicology

1. Basic Concepts in Toxicology
Dr. Lynn R. Panganiban
National Poison Management & Control Center
U.P. College of Medicine-
Philippine General Hospital

2. GENERAL INSTRUCTIONAL OBJECTIVE:
To understand the basic principles
of toxicology and their applications

3. Specific Behavioral Objectives:
• To define basic concepts in
toxicology
•  To discuss the factors affecting
responses to toxic agents
•  To know the general classification of
toxic effects
•  To discuss the dose-response
relationship

4. DEFINITION OF TERMS
TOXICOLOGY
the study of the adverse effects of chemical,
physical and biological agents on living organisms
TOXICITY
is the ability of a substance to cause injury to
biologic material

5. DEFINITION OF TERMS
POISON
TOXIN
Poisonous substance produced by plants, animals,
or bacteria
Any agent that is capable of producing
deleterious effect(s) in a biological system,
seriously injuring function or producing death.
XENOBIOTIC
Substance that is not naturally produced within an
organism

6. DEFINITION OF TERMS
TOXICANT
POISONING
An overdose of drugs, medicaments,
chemicals and biological substances
An agent capable of producing symptoms of
intoxication or poisoning

7. DEFINITION OF TERMS
RISK
the potential (likelihood) that injury (biological damage)
will occur in a given situation
EXPOSURE
is the amount of chemical that is available for absorption
SAFETY
is the probability that harm will not occur under specified
conditions (the inverse of risk)

8. RISK = (TOXICITY) x (EXPOSURE)
TOXICITY
is the ability of a substance to cause
injury to biologic material
RISK
the potential (likelihood) that injury
(biological damage)
will occur in a given situation
EXPOSURE
is the amount of chemical that is
available for absorption

9. Factors Affecting Responses to Toxic Agents
Chemical & physical properties of the
substance (physical state, solubility,
reactivity, vapor pressure, etc.)
Exposure situation
(duration, frequency,
route, dosage)
Individual factors
(age, sex, nutritional
status, genetic background,
general health status)
Individual practices

10. CHEMICAL & PHYSICAL PROPERTIES
PHYSICAL STATE: liquid, gas, fume, mist. Dust, vapor, etc.
SOLUBILITY: in biological fluid/material such as water, blood
and lipids (fat)
VAPOR PRESSURE: > 1 mm Hg rapid volatilization
VAPOR DENSITY: > 1 (heavier than air)
REACTIVITY: chemical and biological

11. EXPOSURE SITUATION : DURATION
ACUTE EXPOSURE : is the condition wherein the animal
is exposed to a chemical for less than 24 hours usually as
a single dose or in divided doses within 13 hours; for the
inhalational route, exposure is continuous for 4 hours
SUBACUTE EXPOSURE : involves repeated daily exposure
of the animal to the chemical for less than one month (usually
21 days) by a specific route

12. EXPOSURE SITUATION : DURATION
SUBCHRONIC EXPOSURE : involves repeated
daily exposure of the animal to the chemical for 90 days
or 3 months
CHRONIC EXPOSURE : the animal is exposed to the
chemical throughout its lifetime: for 2 years in rats and mice,
or even longer for dogs and non-human primates

13. EXPOSURE SITUATION : FREQUENCY
Frequency is critical to the concentration levels
of the substance in biological fluids/at target site(s);
may be expressed as number of exposures/time period

14. EXPOSURE SITUATION: ROUTE
The major routes by which toxic substances gain
access to the body are through INGESTION
(gastrointestinal), INHALATION (lungs), DERMAL or
PERCUTANEOUS (skin) and PARENTERAL

15. EXPOSURE SITUATION : ROUTE
Descending order of effectiveness toxicity :
1. Parenteral
2. Inhalational
3. Intraperitoneal
4. Intramuscular
5. Subcutaneous
6. Intradermal
7. Oral and dermal

16. EXPOSURE SITUATION : ROUTE

17. EXPOSURE SITUATION : DOSAGE
Dosage (Dose) is the most critical factor in determining
whether the intrinsic potential of a substance will be
expressed; is the unit of chemical/unit of biological
system (mg/unit body weight; mg/body surface area;
mL/unit body weight, etc.)

18. “ All substances are
poisons; there is none
which is not a poison.
The right dose differentiates
a poison from a remedy. “
Philippus Aureolus Theophrastus Bombastus von
Hohenheim-Paracelsus (1493-1541)

19. The toxicological tenet that the DOSE
makes the POISON may no longer apply.

20. INDIVIDUAL FACTORS
•  AGE
•  SEX
•  GENETIC BACKGROUND
•  NUTRITIONAL STATUS
•  GENERAL HEALTH STATUS
•  ABSORPTION/DISTRIBUTION/METABOLISM
AND EXCRETION

21. Because regeneration
of germ cells
does not occur
in females,
the outcome(s)
of damage to oocytes
can be significant.
Exposure patterns and
susceptibility are different
Factors: Physical location,
breathing zones, oxygen
consumption, food consumption,
type of food consumed,
growth and development factors
Transplacental and breast milk
Women
Children

23. Improper use of chemicals/drugs
Indoor pesticide spraying

24. Mispackaged drugs/chemicals
Mispackaged
chemicals can lead
to children
accidentally
ingesting
them

25. Availability of chemicals/drugs

26. Improper storage of chemicals/drugs

27. Recycling of containers

28. Home as a toxic environment
HOME
Location of poisoning
(NPMCC 2005 stats)

29. Occupational factors
Family members bring contaminated
working clothes and equipment
at home
“Levels of chlorpyrifos
in house dust in farm
workers’ homes were
5 times higher than
levels in nonfarmworkers’
homes.” (EHP 110:549-553)

30. Improper disposal of c hemicals
and containers

31. General Classification of Toxic Effects
•  Allergic reactions
•  Idiosyncratic reactions
•  Immediate or acute toxicity
•  Delayed or chronic toxicity
•  Reversible effects
•  Irreversible effects
•  Local toxicity
•  Systemic toxicity

32. CHEMICAL INTERACTIONS
•  INDEPENDENT EFFECT
substances qualitatively and quantitatively exert their
own toxicity independent of each other
•  ADDITIVE EFFECTS
the combined effect of exposure to two chemicals
is equal to the sum of the effects of exposure to each
chemical alone (3+5=8)
•  SYNERGISTIC EFFECTS
the combined effect of exposure to two chemicals, given
at the same time, is much greater than the sum of the
effects of each substance given alone (3+5=30)

33. •  is the most fundamental concept
in toxicology.
DOSE-RESPONSE RELATIONSHIP
•  exists when a consistent mathematical
relationship describes the proportion of
test organisms responding to a specific
dose for a given exposure period.

34. TWO TYPES OF D-R RELATIONSHIPS
1. GRADED RESPONSE
describes the response of an individual to varying
doses of a chemical in which a measured effect
is continuous over a range of doses
2. QUANTAL RESPONSE
shows the distribution of a population of individuals
given different doses of a chemical based on a
specific end-point; “all or none”

35. Important Features of a D-R curve
Resistant
Sensitive
Midpoint of the curve
Slope of
the curve

36. Important Features of a D-R curve
Resistant
Sensitive
Midpoint of the curve
Slope of
the curve
THRESHOLD - the dose at which
the first response is observed
as a result of toxicity testing;
below this dose, no responses
are observed

37. Midpoint of the Curve
MEDIAN LETHAL DOSE (LD
50
)
 estimated dose causing death in 50% of the exposed
population under the defined condition of the test
 not a biological constant
 not equivalent to acute toxicity
 provides a measure of the relative toxicity of an agent
compared to other agents

38. TOXICITY RELATIONSHIPS
POTENCY
(the lower
or smaller
dose, the
more potent)
Toxicant A is more potent than toxicant B

39. TOXICITY RELATIONSHIPS
EFFICACY
(Higher efficacy when
the d-r relationship
continues over a
greater range of doses)
Toxicant B is more efficant than toxicant A

40. TOXICITY RELATIONSHIPS
MIXED OR REVERSED
TOXICITY (when one toxicant
is not consistently more potent
over the range of doses tested
as compared to another toxicant)
LD10: B more potent than A
LD50: A more potent than B