TOXICOLOGY

FOR
OCCUPATIONAL HYGIENE
INTRODUCTION TO TOXICOLOGY

HAZARDOUS WASTE
START DATE:______________
AMOUNT:__________________
CONTENTS:________________
HANDLE WITH CARE

THE
STUDY
OF
POISONS
INTRODUCTION TO TOXICOLOGY
(Continued)

“ALL THINGS ARE POISONS, OR

THERE IS NOTHING WITHOUT
POISONOUS QUALITIES. IT IS
ONLY THE DOSE WHICH MAKES A
THING POISON.”

PARACELSUS
(1493 - 1541)
 INTRODUCTION TO TOXICOLOGY
(Continued)

TOXIN - Any of a group of poisonous, usually unstable

compounds generated by microorganisms, plants or
animals. Certain toxins are produced by specific
pathogenic microorganisms and are the causative
agents in various diseases, such as tetanus, diphtheria,
etc.

The effect a specific quantity or dosage of a specific

toxin has on a living microorganism. This is not an
TOXICITY - absolute!
 GENERAL CONCEPTS OF TOXICOLOGY

EXPOSURE TERMINOLOGY

Hazardous Material. A Material That Falls Into One or More Of the

Following Categories. Hazardous Materials Can Have One or Many
Characteristics That Can Add to the Intensity of the Toxic Action of a
Particular Solid, Liquid, or Gas.

 Ignitability Is Flammable or Combustible.

 Reactivity Can React With Itself or Other Materials.
 Corrosivity Can Deteriorate Another Substance.
 Toxicity In Its Normal State Is Harmful to Living Things.
 GENERAL CONCEPTS OF TOXICOLOGY
(Continued)

EVERYTHING IS TOXIC;
IT ALL DEPENDS ON THE DOSE

How Well the Body Accepts a Substance Depends on:

 The Type of Substance.

 The Amount (Dose) Absorbed.
 The Period of Time Over Which It Is Absorbed.
 The Susceptibility/Sensitivity of the Person Exposed.
 FOUR PRIMARY ROUTES

INHALATION
INGESTION
ABSORPTION
INJECTION
INHALATION
(Continued)
Breathing and smoking causes us to inhale substances which enter the
lungs. Substance inhaled into the lungs are readily absorbed into the
blood stream.

 INHALATION
 INGESTION
 ABSORPTION
 INJECTION
INGESTION
Swallowing a substance causes penetration into the blood stream
via the stomach and small intestine.

 INHALATION
 INGESTION
 ABSORPTION
 INJECTION
 (Continued)

FOOD CHAIN EXPOSURE

We Could Potentially Eat Toxic Food

START

GROUND CONTAMINATION BARLEY

ABSORPTION
(Continued)
Entering the body through the skin causes substances to enter the blood
stream at a slower rate than by inhalation or absorption. However, the
resulting entry and distribution within the body is the same.

 INHALATION
 INGESTION
 ABSORPTION
 INJECTION
INJECTION
GENERAL CONCEPTS OF TOXICOLOGY
(Continued)

Injection occurs when substances are forced through this

skin. This can occur as a result of such means as
compressed air, or by having the skin abraded by a
penetrating object.

 INHALATION
 INGESTION
 ABSORPTION
 INJECTION
 EXPOSURE LIMITS

SOURCES INCLUDE:

 American Conference of Gov. Industrial

Hygienists (ACGIH)

 Occupational Safety and Health Administration

(OSHA)

 National Institute for Occupational Safety and

Health (NIOSH)
 American Conference of Government
Industrial Hygienists:

 Threshold Limit Values (TLV). (Respiratory)

 Biological Exposure Indices (BEI). (Dermal)
 8 Hour Time Weighted Averages (TWA).
- How Much a Worker Can Be Exposed to in an 8 Hr.
Shift.
 Published by ACGIH Annually, Provides Exposure
Levels.
 Legally Enforceable.
 Occupational Safety and Health Act 1994
(USECHH Regulations 2000):

 Permissible Exposure Limits (PEL’s)

Establishes OSH’s Exposure Levels
 Legally Enforceable
 THRESHOLD LIMIT VALUE

TLV - Threshold Limit Value: One of three categories of

chemical exposure levels - TLV-TWA, TLV-STEL or TLV-C.

TLV-TWA - Threshold Limit Value Time-Weighted Average:

The time weighted average concentration for a normal 8-
hour workday and a 40 hour work week to which nearly all
workers may be repeatedly exposed without adverse effect.
Should be used as an exposure guide rather than an
absolute.
 THRESHOLD LIMIT VALUE
(Continued)

TLV-STEL - Threshold Limit Value - Short Term Exposure

Limit: A 15 minute time-weighted average exposure that
should not be exceeded at any time during the work day.

TLV-C - Threshold Limit Value- Ceiling: The concentration

that should not ever be exceeded, even instantaneously.
 FACTORS INFLUENCING TOXIC ACTION

 RATE OF ENTRY
TOXIC
 ROUTE OF EXPOSURE ACTION

 AGE OF INDIVIDUAL
 STATE OF HEALTH
 PREVIOUS EXPOSURE LEVELS
 WORKPLACE ENVIRONMENTAL FACTORS
 INDIVIDUAL SUSCEPTIBILITY AND HEREDITY
 FACTORS INFLUENCING TOXIC ACTION
(Continued)

An IV Injection Can Be Administered

RATE OF ENTRY Instantaneously Whereas, a Dose Absorbed
Through the Skin May Take Several Minutes
to an Hour to Absorb Into the Bloodstream.
The Body Can Sometimes Defend Itself
Against Dosages Where The Rate of Entry
is Slow.
 FACTORS INFLUENCING TOXIC ACTION
(Continued)

ROUTE OF EXPOSURE A Dose Absorbed Through the

Skin Will Be Deposited in the
Blood Much Slower Than a
Dose Inhaled Through the
Lungs and Transferred Directly
Into the Blood. Four Routes:
INHALATION
INGESTION
ABSORPTION
INJECTION
 FACTORS INFLUENCING TOXIC ACTION
(Continued)

Older Persons Are Often More Sensitive

AGE OF INDIVIDUAL to Toxic Action Than Are Younger
Adults. With Aging Comes a
Diminished Reserve Capacity in the
Face of Toxic Stress.
 FACTORS INFLUENCING TOXIC ACTION
(Continued)

Pre-Existing Disease or Other Medical

STATE OF HEALTH Conditions Can Result in Greater
Sensitivity to Toxic Agents. An Individual
With a Pre-Existing Sensitivity to a
Known Material Should Not Be Placed in
a Work Environment That Might
Compound the Condition.
 FACTORS INFLUENCING TOXIC ACTION
(Continued)

PREVIOUS EXPOSURE Previous Exposure to Work

Place Chemicals or Vapors
Can Sometimes Result in
Cumulative Effects Within
INDIVIDUAL
the Body. In Addition,
EXPOSURE Some People Can Develop
HISTORY a Sensitivity to These
Materials Over Time.
 FACTORS INFLUENCING TOXIC ACTION
(Continued)

WORKPLACE ENVIRONMENTAL In Industries Such As Smelting or

FACTORS Steel Making, High Temperatures
Are Encountered. As Well As Air
Contaminants That Must Be
Controlled.

CAUTION
ENSURE
EXHAUST
VENTILATION
IS OPERATING
 FACTORS INFLUENCING TOXIC ACTION
(Continued)

INDIVIDUAL SUSCEPTIBILITY, Males and Females may

HEREDITY, AND GENDER
respond differently to the
Same Material. Hereditary
Factors Also Can Be of
Importance. Genetic Defects
May Render Certain
Individuals More Sensitive to
a Given Material.
 EXPOSURE TERMINOLOGY

 Acute Exposure:

Usually Minutes, Hours or Several Days.

 Chronic Exposure:

Regular Exposure Over Months, Years, or a Lifetime.

The Toxicity of the Chemical or Material Combined With

the Susceptibility of the Individual Determines Whether
the Exposure Is Acute or Chronic.
 EXPOSURE TERMINOLOGY
(Continued)

 Latent Exposure: An injury or disease that remains

undeveloped until an incubation period has elapsed. The
period of time could be hours, days, months or years.

The Toxicity of the Chemical or Material Combined With

the Susceptibility of the Individual Is a Key Factor.
 EXPOSURE TERMINOLOGY
(Continued)

 Irritant: A chemical substance that injures the tissues of

the respiratory system and lungs, thereby causing
inflammation of the respiratory passages.

The Toxicity of the Chemical or Material Combined With

the Susceptibility of the Individual Is a Key Factor.
 FACTORS AFFECTING EXPOSURE

 The Amount Entering the Body.

 The Length of Time of Exposure.
 The Rate of Absorption Into the Blood.
 The Physical Nature of the Chemical.
 The Chemical Nature of the Chemical.
 The Age of the Individual.
 The Health of the Individual.
MEASUREMENT OF TOXICITY

 PARTS PER MILLION - ppm

 PARTS PER BILLION - ppb
 PARTS PER TRILLION - ppt
 LETHAL DOSE - LD50
 LETHAL CONCENTRATION - LC50
 THRESHOLD LIMIT VALUE - TLV
 IMMEDIATELY DANGEROUS TO
LIFE AND HEALTH - IDLH
 (Continued)

 PARTS PER MILLION - ppm

ONE PART IN ONE MILLION PARTS

 (Continued)

 PARTS PER BILLION - ppb

ONE PART IN ONE BILLION PARTS

 (Continued)

 PARTS PER TRILLION - ppt

ONE PART IN ONE TRILLION PARTS

 MEASUREMENT OF TOXICITY
Lethal Dose - LD50

The LD50 is the dosage, when administrated to laboratory

animals, results in 50% fatalities. The expression is made in
milligrams of the substance administered per body weight of
the animal expressed in kilograms (mg/kg). LD50 typically
refers to dermal dosages.
When extrapolated to humans, the lethal dose of an average
person who weighs w kilograms is LD50 x w.
 MEASUREMENT OF TOXICITY
Lethal Concentration - LC50

The LC50 is the concentration of a material that, normally express as

parts per million (ppm) by volume, that when administrated to
laboratory animals, kill half of them during the period of exposure. LC50
typically refers to airborne dosages.
 THRESHOLD LIMIT VALUE - TLV

The TLV is the upper limit of a toxin concentration to which an

average healthy person may be repeatedly exposed on an all-
day, everyday basis without suffering adverse health effects.
TLV is Typically used for workplace exposure determinations.

• Gaseous substances in air, are usually express in:

parts per million (ppm).

• Fumes or mists in air, are expressed in:

milligrams per cubic meter (mg/m3).

TLV values are set by the American Conference of Governmental

Industrial Hygienist (ACGIH).
 EXPOSURE MODEL

LC50
LD50
T
I TLV
M PEL
E

SAFE
EXPOSURE
0 DOSE
 TOXINS IN OUR BODY

BRAIN
TOXIN
RESPIRATORY
Inhaled Toxins Can Quickly SYSTEMS
Travel to Vital Organs and the
Brain Causing Either Acute or
Chronic Effects.
HEART

STOMACH
LIVER
INTESTINE
 Distribution and metabolism

•Once a chemical has entered the body it may be metabolized,

excreted or accumulated.
•Usually absorption is most rapid from the lungs, less rapid from
the gastrointestinal tract and least rapid from the skin.
•Chemicals from the lungs, skin and stomach may enter the
general blood circulation directly and be rapidly spread through
the body in an unmodified form.
•Chemicals absorbed from stomach and bowel enter the blood
(hepatic portal system) and are taken to the liver where they may
be modified by a series of reactions.
 This modification process in the
liver is referred to as
biotransformation.

These reactions have also been referred

as detoxification, but this may be
misleading as biotransformation may
also increase the toxicity of a number
of chemicals.
 Types of toxicity

Organ toxicity – certain chemicals have a target organ

specificity (harm a certain organ rather than others)
often because of biotransformation or bio-concentration.
The route of exposure might also be responsible for
specific organ injury.
systemic toxicity – serious, sometimes fatal poisoning
that may occur after contact with certain
organophosphate pesticides, ingestion of high
dose of tranquillizer drugs or inhalation of organic
solvents.
 Liver toxicity

most chemicals are metabolized in the liver. Therefore

the liver becomes a target organ for many substances.
Organic solvents (ethanol), certain trace metals
(copper, cadmium) often cause extensive liver damage

– fatty changes, necrosure, fibrosis alteration of the

structure.
 Kidney toxicity – many xenibiotics are removed
by glomerular filtration and tubular excretion,
while essential elements are reabsorbed in the
tubuli. Agents with kidney toxicity include metals
(e.g. mercury, cadmium, lead) and drugs
(sulphonamides).

Neurotoxicity – functional or organic alterations

of neurotransmitters can cause symptoms of
paralysis (organophosphates, chlorinated organic
compounds, metals etc.)
Skin toxicity – allergic reactions can occur in
sensitive individuals while skin irritation can
occur in anyone exposed to a wide variety of
irritating chemicals.

Immunotoxicity – the immune system ensures

1) non-specific defence mechanism against agents,
for which no previous sensitization occurred, and

2) specific, adaptive mechanism directed against

specific agent, for which the organism has
previously been sensitized or infected.
 BIOLOGICAL EFFECTS

TERATOGEN:

MUTAGEN:
DANGER

CARCINOGENIC: CANCER
CAUSING
AGENT
TERATOGEN: (Latin - “The Study of
Monsters”)
 The Study of Congenital Malformations
 Relatively New Discipline (1941)
 First Correlated German Measles to Birth Defects
 Causes of Congenital Malformations

- Heredity
- Maternal Diseases Like German Measles
- Maternal Viral Infections During Pregnancy
- Maternal Malnutrition
- Physical Injury
- Ionizing Radiation Exposure
- Chemical Exposure
 MUTAGEN:
 Potential to Cause Mutation in the Genetic Code
 Can Cause Changes in Chromosomes
 Review the Respective Material Safety Data Sheet
 Agents Shown to Cause Potential Mutagenic Effects

- Hydrogen Peroxide (a Bleaching Agent)

- Ethyleneimine (an Alkylating Agent)
- Ethylene Oxide (Hospital Sterilant)
- Hydrazine (Used in Rocket Fuel)
- Ionizing Radiation Exposure
- Benzene
 DANGER
CARCINOGEN: CANCER
CAUSING
 Has a Potential to Cause Cancer AGENT
 Can Induce a Malignant Tumor in Humans
 Can Cause or Accelerate Tumors
 Some Confirmed or Suspected Human Carcinogens

- Acrylimide - Beryllium - Nickel Sulfide

- Acrylonitrile - Calcium Chromate - Tetranitromethane
- 4-Aminodiphenyl - Chromium (Vi) - O-Tolidine
- Arsenic - Ethylene Dichloride - Vinyl Bromide
- Benzine - Ethylene Oxide - Xylidine
- Benzidine - Lead Chromate - Zinc Chromates
THE FINAL WORD

NEVER
DISCOUNT
ANY
ROUTE-OF-ENTRY!

THANK YOU