Transcript TOXIC EFFECTS OF CHEMICALS - Plymouth State University

Toxic Effects of Chemicals
ALL CHEMICALS ARE TOXIC AT
SOME LEVEL.
ALL CHEMICALS SHOULD BE
CONSIDERED TOXIC UNTIL PROVEN
OTHERWISE.
EVEN CHEMICALS WHICH ARE
RELATIVELY “SAFE” CAN BE
HARMFUL IN COMBINATIONS.
OSHA says hazardous chemicals
are ones which are…
toxic, corrosive, irritants, strong
sensitizers, carcinogenic, flammable or
reactive, or
specifically listed by OSHA in 29 CFR
1910, Subpart Z, or
have been assigned a TLV by the
ACGIH.
Toxicity of chemicals
Definitions
Acute toxicity occurs from a single
exposure and results in damage within
a few days.
Chronic toxicity results from repeated,
often low-level, exposures over months
to decades. Effects may not appear
until long after exposure has ceased.
Types of Chronic Toxicity
Mutagens act on DNA, genes or
chromosomes of cells; may lead to death of
the cell or cancer. If the cell is a sperm or
egg, may lead to birth defects.
Carcinogens are cancer-causing after a
latency period.
Embryotoxins cause problems for a
developing fetus when the mother is exposed
during pregnancy, includes teratogens.
Fertility depressants are substances which
lower the odds of conception.
Toxicology Studies
Routes of exposure
Transport within the body
Transformation within the body
Modes of attack
Storage
Elimination
Routes of Exposure
INHALATION
INGESTION
SKIN or MUCOUS MEMBRANE
ABSORPTION
EYE ABSORPTION
INJECTION
Routes of Exposure (cont’d)
Inhalation: vapors, mists, gases or dusts can produce irritation
by contact and systemic poisoning by absorption into the blood
stream. The most common [and usually most dangerous] route
of entry. We breath 10 m3 of air every eight hours and this air
comes in contact with 140 m2 of capillary surface.
Ingestion: hazards as for inhalation. Generally of minor
importance except for very toxic agents because of normal
precautions taken with respect to eating, drinking, smoking, etc.
in presence of chemicals. Chemicals are not as readily
absorbed from GI tract as in lung. Can occur as a side effect of
inhalation through cilliary action and swallowing.
Skin and eye contact: hazards as for inhalation. Skin provides
some protection but is the most common point chemical contact.
Some solvents pass directly through the skin. The eyes are
especially sensitive, acting like sponges to liquids and easily
scratched by solids.
Injection: can occur from cuts by contaminated materials such
as broken glass or by accidental syringe wounds.
Dose-effect Curves
Biological organisms show differences
in sensitivity to toxic materials. The
variations are small within species
compared to between species. A
frequency of response curve would
theoretically look like a “normal”
distribution.
Number beginning to show effect
Dose-effect Curve
Dose
Cumulative Response Curve
It is more conventional to use a
cumulative response curve to report
toxicological data. The slope of the
rising portion of the curve is related to
the margin of safety. If the effect being
plotted is death, it is an easy matter to
obtain the LD50 from the graph.
Cumulative Response Curve
Lethal Doses
Compound
Test animal
Route
ethanol
mouse
oral
10,000
sodium chloride
rat
oral
3,000
aspirin
rat
oral
1,500
DDT
rat
oral
150
potassium cyanide
rat
oral
10
nicotine
rat
iv
1
dioxin
guinea pig
iv
0.001
botulinus toxin
rat
iv
0.00001
Some terms encountered which express toxicity verbally include:

extremely toxic

moderately toxic


relatively harmless

>15000 mg/kg
LD50 <1 mg/kg
50-500 mg/kg
LD50 (mg/kg)
Interactive Effects
Additivity – the total effect is the simple sum
of the individual effects.
Synergism – the total effect is greater than
the simple sum of the individual effects.
Antagonism – the total effect is less than the
simple sum of the individual effects.
Potentiation – one chemical has the effect of
setting the organism up for an effect by a
following chemical.
Epidemiological studies are carried
out on large groups of human
subjects either retrospectively or
prospectively
Strengths: natural exposures; longterm, low-level exposures can be found;
no need to extrapolate from animals.
Weaknesses: many variables which
cannot be controlled for; difficult to
determine causation (as opposed to
association)
Clinical studies are carried out on
carefully controlled groups of human
subjects
Strengths: much more knowledge
about exposure conditions, fewer
uncontrolled variables, often-possible to
assess cause-effect.
Weaknesses: artificial exposures,
generally only acute studies, ethics of
group control.
Toxicological studies are performed
on animals, tissues, cells,
biochemicals
Strengths: maximum exposure control,
exact response can be determined,
cause-effect probably determinable.
Weaknesses: extrapolation to humans
required when animals used, often
difficult to study chronic effects due to
short lifetime of animal subjects, ethics
of subjecting animals to tests.
Exposure Limit Terminology
PEL = permissible exposure limit
(OSHA). This may be given as a timeweighted average (TWA, for 8-hr shift
over 40-hr week) limit, or a short-term
exposure limit (STEL, not to be
exceeded for more than 15 min. any
time during a work day) or a ceiling limit
(CL, not to be exceeded any time).
Exposure Limit Terminology
REL = Recommended exposure limit
(NIOSH). Highest airborne level not expected
to produce injury in workers, generally TWA
for 10-hr day, but may be a CL.
IDLH = immediately dangerous to life
(NIOSH). Maximum concentration which
could be tolerated for 30 min. (in case of
respirator failure) without impairing ability to
escape or causing permanent damage.
Exposure Limit Terminology
AL = action level (OSHA). Exposure level at
which OSHA regulations to protect workers
(air monitoring, medical monitoring, etc.) kick
in, generally half the PEL.
TLV = threshold limit value (ACGIH).
Designed to protect “average” healthy worker.
May be expressed in any of the same ways
as PEL’s above. Traditionally were TWA’s.