TOXICOLOGY

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TOXICOLOGY

• The study of chemical or physical agents and
  their interaction with biologic systems to
  produce a response in a organism.
• The dose makes the poison!

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TOXICOLOGY

• DOSE AMOUNT
• Units
• mg/Kg (per unit weight)
• mg/cm2 (per area of skin surface)
• ppm (per unit volume of air inhaled (gas/vapor))
• mg/m3 (for solids inhaled in air)

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TOXICOLOGY

• Types of Exposure
• Acute
• amount of substance which is capable of causing
  an immediate reaction (less than 24 hours)
• Chronic
• small amount which does not cause an immediate
  reaction but is accumulated in the body to cause
  a delayed reaction over a longer period of time.

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TOXICOLOGY

• Routes of Exposure
• oral
• dermal
• inhalation
• injection

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TOXICOLOGY

• Toxicity Tests
• goal is to select a test species that is a good
  model of humans, a response that is not
  subjective and can be consistently determined,
  and a test period that is relatively short.

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TOXICOLOGY

• Dose-Response Curve

test organisms responding
Dose
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TOXICOLOGY

• DOSE - RESPONSE TERMS
• Toxic dose low (TLlo) lowest dose introduced by
  any route (except inhalation) reported to produce
  any toxic effect in humans or to produce
  tumorigenic or reproductive effects in animals.

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TOXICOLOGY

• DOSE - RESPONSE TERMS
• - Toxic Concentration Low (TClo) - Lowest
  concentration of substance in air to which humans
  or animals have been exposed and has produced any
  toxic effect

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TOXICOLOGY

• DOSE - RESPONSE TERMS
• Lethal Dose low (LDl0) Lowest dose of a substance
  introduced by any route (except inhalation) which
  has been reported to have caused death in humans
  or animals.

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TOXICOLOGY

• DOSE - RESPONSE TERMS
• Lethal Dose 50 (LD50) - Calculated dose of a
  substance which is expected to cause death of 50
  of the entire defined experimental population.

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TOXICOLOGY

• DOSE - RESPONSE TERMS
• Lethal Concentration 50 (LC50) Calculated
  concentration of a substance in air to which is
  expected to cause the death of 50 of an entire
  defined experimental population.
• (Table 1.)

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TOXICOLOGY

• USING DOSE - RESPONSE INFORMATION
• Can compare LD50 of chemicals gives a relative
  rating of toxicity (Table 2.)
• Use LD50 (mg/Kg) and multiply by 70 gives a rough
  estimate of toxic potential for humans.

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TOXICOLOGY

• DOSE - RESPONSE
• AND SAFETY FACTORS

LD50
TLV
ED50
Percent Response
Dose
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TOXICOLOGY

• FACTORS INFLUENCING TOXICITY
• ROUTE OF EXPOSURE
• Route determines how much is absorbed and
  which organs are exposed to the highest
  concentrations.

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TOXICOLOGY

• FACTORS INFLUENCING TOXICITY
• GENDER
• Some substances are more toxic to one gender
  than another.

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TOXICOLOGY

• FACTORS INFLUENCING TOXICITY
• AGE
• Older people have different blood, hepatic
  systems, musculature, metabolism, and excretory
  patterns than younger people. This can influence
  disposition and toxic effects of chemicals.

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TOXICOLOGY

• FACTORS INFLUENCING TOXICITY
• SYNERGISM - 1 1 3
• ANTAGONISM - 1 1 1/2
• POTENTIATION - Type of Synergism

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TOXICOLOGY

• FACTORS INFLUENCING TOXICITY
• GENETICS
• Not all people are created equal genetically!

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TOXICOLOGY

• FACTORS INFLUENCING TOXICITY
• SPECIES VARIATION
• Physiological differences between species can
  lead one to over or under estimate toxic effects
  of a chemical when comparing results from one to
  another species.

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TOXICOLOGY

• EXPOSURE GUIDELINES
• ACGIH - American Conference of
• Governmental Industrial
  Hygienists
• Develop and Publish - Threshold Limit
• 
  Values (TLVs)

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TOXICOLOGY

• TLV - based on the concept that there is a
  threshold dose or concentration below
  which there is no adverse effects.
• - Developed for use in the workplace

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TOXICOLOGY

• TLVs
• Refer to airborne concentrations
• Represent conditions under which nearly all
  workers may be repeatedly exposed day after day
  without adverse effects.
• Limited healthy working age individuals

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Toxicology

• TLV TYPES
• TLV-TWA Time Weighted Average
• time weighted average concentration for a
• normal eight-hour work day
• TLV-STEL Short Term Exposure Limit
• 15 minute time weighted average exposure
  repeated exposure no more than four times
  per 8 hour work shift

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TOXICOLOGY

• TLV TYPES
• TLV-C Ceiling
• Concentration that should not be exceeded,
  even instantaneously.

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TOXICOLOGY

• EXPOSURE GUIDELINES
• OSHA - PELs Permissible Exposure Limits
• PELs are legally enforceable and apply to all
  private industries and the Federal government.
• 29 CFR 1910.1000 lists PELs for specific
  compounds

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TOXICOLOGY

• EXPOSURE TYPES
• IDLH - Immediately Dangerous to Life and Health
• represent maximum concentrations from which one
  could escape within 30 minutes without any
  irreversible health effects

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TOXICOLOGY

• BODY RESPONSE
• TO TOXIC CHEMICALS
• Respiratory Tract
• upper - nasopharyngeal
• middle - tracheobronchial
• lower - pulmonary acinus

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TOXICOLOGY

• BODY RESPONSE
• TO TOXIC CHEMICALS
• Types of inhaled toxicants
• Asphyxiants gases that deprive the body of
  oxygen
• Simple asphyxiants (nitrogen, helium, methane)
• Chemical asphyxiants (cyanide, Carbon Monoxide)

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TOXICOLOGY

• BODY RESPONSE
• TO TOXIC CHEMICALS
• Irritants
• chemicals that irritate the air passages, causing
  constriction of airways and edema (liquid in the
  lungs) and infection.
• (ammonia, chlorine, HF, HCl)

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TOXICOLOGY

• BODY RESPONSE
• TO TOXIC CHEMICALS
• Necrosis Producers
• chemicals that result in cell death and edema.
• (ozone, nitrogen dioxide)

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TOXICOLOGY

• BODY RESPONSE
• TO TOXIC CHEMICALS
• Fibrosis producers
• chemicals that produce fibrotic tissue which if
  massive, block airways and decrease lung
  capacity.
• (asbestos, silicates, beryllium)

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TOXICOLOGY

• BODY RESPONSE
• TO TOXIC CHEMICALS
• Allergens
• chemicals that induce allergic response
  characterized by bronhoconstriction and pulmonary
  disease.
• (isocyanates, sulfur dioxide)

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TOXICOLGY

• BODY RESPONSE
• TO TOXIC CHEMICALS
• Carcinogens
• chemicals associated with lung cancer
• (cigarette smoke, coke emissions,
• asbestos, arsenic)

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TOXICOLOGY

• BODY RESPONSE
• TO TOXIC CHEMICALS
• SKIN
• natural barrier prevents absorption
• Sebaceous glands secrete fatty acids
• Melanocytesprotects from UV
• Sweat galnds regulate heat

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TOXICOLOGY

• BODY RESPONSE
• TO TOXIC CHEMICALS
• EYES
• CENTRAL NERVOUS SYSTEM
• LIVER
• KIDNEYS
• BLOOD

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TOXICOLOGY

• TERATOGENS
• MUTAGENS
• CARCINOGENS