Toxicology

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Toxicology
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Toxicology Industrial Hygiene

• Toxicology
• A qualitative and quantitative study of the
  adverse effects of toxicants on biological
  organism.
• Industrial Hygiene
• Industrial hygiene is the science of
  anticipating, recognizing, evaluating, and
  controlling workplace conditions that may cause
  workers' injury or illness.

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Toxicology

• The way toxicants enter biological organism
• The way toxicants are eliminated from biological
  organism
• The effect of toxicants on biological organism

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Fundamental Principle of Toxicology
There are no harmless substance, only harmless
ways of using substances
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Toxicants

• A chemical agents
• A physical (dusts, fibers, noise, and radiation)
  agents, e.g. asbestos
• Toxicity is a property of toxicant that describe
  its effect on biological organism.
• Toxic hazards is the likelihood of damage to
  biological organism based on exposure resulting
  from the use/transport/storage of the toxicants
  (hazardous material).

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Toxic Effect can be classified according to

• Reversible Vs Irreviersible
• Acute Vs Chronic (Duration of Exposure)
• local Vs systemic (Location of the effect)

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Reversible/Irreversible

• Irreversible
• Carcinogen-cause cancer
• Mutagen-cause chromosome (gene) damage
• Teratogen- cause birth defects
• May or may not be irreversible
• Dermatotoxic affects skin
• Hemotoxic affects blood
• Hepatotoxic- affects liver
• Nephrotoxic affects kidneys
• Neutotoxic affects nervous system
• Pulmonotoxic- affects lungs

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Acute / Chronic

• Acute exposure
• High Dosage (e.g. due to accidental release
• The effect is immediate
• Chronic Exposure
• Normally lower dose
• The effect only noticed/detected following long
  exposure
• Sometimes, the worker could not recall the
  exposure.

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Local/Systemic

• Local
• Damage to the part of the body that comes in
  contact with the substance.
• Systemic
• Chemical is absorbed by the body and attacks a
  target organ.

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Source of Toxicants

• Toxic Release
• Vapour/gas/liquid release from source
• Fire and Explosion
• Fire and radiation
• Toxic release following explosion

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Route of Entry

• Injection through cuts or hypodermic needles
  into the skin, usually cause highest blood level
  concentration.
• Inhalation through mouth/nose into the lungs
  (respiratory system), 2nd highest blood level
  concentration.
• Ingestion through mouth into stomach and
  gastrointestinal tract, 2nd lowest in blood level
  concentration.
• Dermal (Skin) absorption through skin membrane,
  lowest in blood level concentration, note
  absorption of phenol could result in death

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Route of Entry for Toxicants
ENTRY
ROUTE
CONTROL
Ingestion mouth, stomach rules on
eating, drinking, smoking
Inhalation mouth, nose ventilation,
hoods, protection equipment

Injection cuts in skin protective
clothing

Dermal Absorption skin protective clothing
industrially most significant
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RESPIRATORY SYSTEM

• Upper respiratory
• Nose, sinuses, mouth, pharynx, larynx and tracea
• Filtering, heating, and humidifying the air
• Affected by toxicants that are soluble in water
• These toxicants will react or dissolve in the
  mucus to form acids or bases
• E.g. hydrogen halides, oxides, hydroxides, sodium
  dusts

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Human Respiratory System
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Respiratory System Lower Respiratory System

• Lungs (bronchial tubes and alveoli for gas
  exchange with blood)
• Toxicants affect the function of alveoli by
  blocking the transfer of gases or by reaction
  with alveoli wall to produce corrosive/toxic
  substances.
• E.g. monomers (acrylonitrile), halides
  (Chlorine),hydrogen sulfide, methyl cynaide etc

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Respiratory System

• Effect of dust and insoluble materials
• The smaller the dust particles, the farther it
  penetrate into respiratory system
• Particles gt5 µ m are filtered in the upper
  respiratory system.
• 5µmgtParticlesgt2 µm can reach bronchial system
• Particleslt1 µm can reach the alveoli

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How toxicant are eliminated from biological
organism

• Excretion- through kidneys (blood to urine),
  liver (selectively excrete certain chemicals
  indigestive tract to bile), lungs , skin
  (sweats), hair, nail or other organ
• Detoxification-change the chemical into something
  less harmful by biotransformation through liver,
  can also occur in blood, intestinal wall, skin,
  kidney
• Storage- in fatty tissue. Can create problem when
  fatty deposits are metabolized and released the
  toxic (e.g. during reduced food supply). Also
  store in bone, blood, liver, and kidney.
• Massive exposure to hazardous chemical can damage
  major organs (kidney, lung, liver), reduces their
  ability to excrete.

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Kidney
Your kidneys receive the blood from the renal
artery, process it, return the processed blood to
the body through the renal vein and remove the
wastes and other unwanted substances in the
urine. Urine flows from the kidneys through the
ureters to the bladder.
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Liver
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TLV

• Refer to airborne concentrations that correspond
  to condition under which no adverse effects are
  normally expected during workers lifetime. The
  body is able to detoxify and eliminate the agent
  without any detectable effects.
• Units
• ppm (by volume), mg/m3,
• for dust mg/m3 and mppcf (millions of particles
  per ft3 air)
• The TLV assumes that workers are exposed only
  during normal eight-hour workday

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TLV

• The American Conference of Governmental
  Industrial Hygienists (ACGIH) established 3
  different types of TLV
• TLV-TWA
• TLV-STEL
• TLV-C

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TLV-TWA

• Time-weighted average for a normal 8-hour workday
  or 40- hour work week, to which nearly all
  workers can be exposed, day after day, without
  adverse effects.
• PEL (Permissible exposure level) defined by OSHA
  (USA) generally follow closely TLV-TWA
• More TLV-TWA data are available than TWA-STEL and
  TWA-C
• See Table 2.8 (Crowl Louvar) for variety of
  TLV-TWA and PEL for a variety of chemical
  substances. Compare with schedule 1 in USECHH in
  OSHA 1994.

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TLV - STEL

• Short-term exposure limit. The maximum
  concentration to which workers can be exposed for
  a period of up to 15 minutes continuously without
  suffering
• (1) intolerable irritation
• (2) chronic or irreversible tissue change
• (3) narcosis of sufficient degree to increase
  accident proneness, impair self-rescue, or
  materially reduce worker efficiency, provided
  that no more than 4 excursions per day are
  permitted, with at least 60 minutes between
  exposure periods, and provided that the daily
  TLV-TWA is not exceeded
• Compare with definition of maximum exposure limit
  in USECHH, OSHA 1994?

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TLV-C

• Ceiling limit. The concentration that should not
  be exceeded, even instantaneously.
• Some values are tabulated in Table 2.8
• Compare with ceiling limit in schedule 1 in
  USECHH, OSHA 1994?

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Dose vs response

• Toxicological test are done on a target
  population
• Individual target response different for the same
  dose (depends on age, sex, weight, diet, gen
  health)
• The results are statistically analyzed
• The results are reported as,
• LD lethal dose for ingestion or injection or skin
  absorption
• TD toxic dose for not lethal but irreversible
• ED effective dose for minor and reversible
• LC lethal concentration for gaseous inhalation
• LD50 means lethal dose for 50 of the subjects or
  expt. animal population.

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LD-50
LD50 is commonly used for assessment of toxicity
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Response vs. Dose
Average Response
Not very useful
Dose
Better at low doses, much more useful
Average Response
Log ( Dose )
Can also use a probit transformation to change
s-shaped curve into a straight line.
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Probit Analysis

• The dose level of the various hazard events
  against fatality can be conveniently determined
  using Probit Analysis.
• It is a graphical and Look-up Table approach to
  determine probability of fatality

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Probit Analysis

• The probit variable Y is computed from
• Y k1 k2 ln V
• Values of constants k1, k2 and causative variable
  V (representing the dose) are given in table
• Once the probit is obtained, it can be converted
  into fatality

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Probit Toxic Release
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Probit Fire and Explosion
Here, te is the effective time duration (s), t
is the time duration of pool burning (sec), Ie
is the effective radiation intensity (W/m2), I
is the radiation intensity from pool burning
(W/m2), te is the effective time duration (s),
p0 is peak overpressure (N/m2), J is impulse
(Ns/m2), C is concentration (ppm) and T is time
interval (min).
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Conversion of Probit to Fatality data
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Medical test to determine exposure before
symptoms appear

• Compare results with a medical baseline results
  (usually done on new employees before employment)
• Respiratory problem (using spirometer) astha,
  broncitis, emphysema
• Nervous system disorder mental status, motor
  system reflexes, sensory system
• Skin texture, hair, nail, vascularity (blood
  vessel)
• Blood count (red/white cell, hemoglobin, platelet
  count)
• Kidney (test for quantity and for sugar and
  proteins in urine)
• Liver (through chemical test on urine and blood)

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Toxicology study

• To quantify the effects of toxicant on target
  organism
• Usually done on animals (lung, kidney, liver) and
  the results are extrapolated to human. For
  genetic effect, the study is on single-cell
  organism.
• Different routes requires different toxicological
  study

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Toxicological study

• Involve identifying,
• The toxicant
• The target or test organism
• The effect or response to be monitored
• The dose range
• Ingestion or injection , mg toxicant/kg of body
  weight
• Gaseous Inhalation, ppm or mg/m3 air
• Particle inhalation, millions of particle per
  cubic foot (mppcf) or mg/m3 air
• The period of the test (mostly acute tocixity
  study)
• Acute toxicity, single exposure or series of
  exposure in a short time
• Chronic toxicity, multiple exposure over a long
  period of time, also difficult to perform