Transcript dosage & toxicity

DOSAGE & TOXICITY
• A lack of understanding of these principles
can lead to improperly labeling as toxic
ingredients that are beneficial when used
in the proper doses.
• Every natural substance that is used for
therapeutic benefit also has a toxic dose.
• Even medications often found at a
pharmacy or grocery store shelves have a
dose at which toxicity occurs.
• For example, Vitamin C (as well as
• some of the other compounds in citrus fruit)
will cause diarrhea (腹瀉), stomach upset
(反胃), and even vomiting (嘔吐), if
ingested in extremely large amounts.
While this might be toxicity, no one would
suggest that vitamin C should never be
used for therapeutic benefit.
• All substances have what is termed an
LD50 (半數致死劑量).
• This is the dose that, when administered
to a large group of animals (or humans),
will cause lethality (death) in 50% of that
group.
• If the LD50 is less than the average
therapeutic dose, then toxicity occurs
before therapeutic effects and the
substance should be avoided.
• If the LD50 is much greater than the
therapeutic dose, then the substance is
very safe and can be administered to a
patient in large amounts without fear of
toxicity.
• Penicillin, which has an LD50 approaching infinity
and a therapeutic dose that is much lower.
• If LD50 is very close to the average therapeutic
dose, then the medicine must be managed
carefully.
• Digoxin (地高辛) is a medicine commonly used
for some heart conditions, congestive heart
failure, and to regulate the heart rate.
• Propylene glycol (丙烯乙二醇) is used in
antifreeze and it should never be used on the
body in any form.
• The natural hormones (such as progesterone
(黃體激素), estrogen (雌激素), DHEA (青春素),
or testosterone (睪丸素) ) are placed in a
pharmaceutical base containing propylene glycol
because it is one of the very best substances for
increasing absorption of natural hormone
through the skin.
• In fact, if Propylene glycol were not used,
the medicine would not be absorbed
effectively.#
Units used to measure chemicals in
the environment
• ppm: parts per million
1 cent in $ 10, 000
• ppb: parts per billion
1 cent in $ 10, 000, 000
• ppt: parts per trillion
1 cent in $ 10, 000, 000, 000
Important Relationship
• For water at STP (standard temparature
[23C] and pressure [15psi])
• 1cc = 1ml = 1g
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1 liter of water = 1 kg
1 mg / kg = 1 ppm
1 mm3 / liter = 1 ppm
1 mg / liter = 1 ppm
Measures of Toxicity
• Toxicity of chemicals is determined in the
laboratory.
• The normal procedure is to expose test
animals by ingestion, application to the
skin, by inhalation, gavage, or some other
method which introduces the test item into
the body.
• Toxicity is measured as clinical “endpoints”
which include:
• Mortality (death)
• Teratogenecity (birth defects)
• Carcinogenicity (cancer)
• Mutagenecity (DNA damage)
The Median Lethal Dosage
(LD50 and LC50)
• LD50
The dose of a chemical which produces
death in 50% of a population of test
animals to which it is administered by a
specified method.
Normally expressed as mg/kg (milligrams
of substance per kilogram of animal body
weight)
LC50
• LC50
The concentration of a chemical in air or
water which produces death in 50% of an
exposed population of test animals in a
specified time frame.
Normally expressed as mg/kg (milligrams
of substance per liter of air or water [or as
ppm])#
Routes of exposure (暴露途徑)
• There are three primary routes by which
organisms are exposed to certain material
(solvents, pesticides, )：
• Oral (口服) ：Taken in through the mouth
and passes through gastrointestinal tract.
• Dermal (皮膚)：Most common route of
human exposure.
• Inhalation (呼吸)：Breathed into the lungs
through nose or mouth.#
Duration of Exposure
(持續暴露時間)
• Three terms are commonly used to
describe the duration of doses：
• Acute (急毒性)：Application of a short-term
[generally less than a day] dosing.
• Chronic (慢性)：Repeated exposure to a
chemical in doses regularly applied to
organism for a time greater than half of its
life-expectancy.
• Subchronic (亞慢性)：
• The less you need to cause a toxic effect,
the more toxic the substance is. Thus, an
LD50 of 15 mg/kg is more toxic than is one
of 250 mg/kg.#
Signal words (警語標示)
• Caution (小心)：Reflects the lowest degree
of relative toxicity. All pesticides with an
LD50 > 500 mg/kg must display this word
on their label. Actually includes two groups:
500 - 5,000 mg/kg (slightly toxic, 輕毒性)
> 5,000 mg/kg (relatively nontoxic, 相對無毒
性)
• Warning (警誡)： Reflects an intermediate
degree of relative toxicity. All pesticides
with an LD50 that is 500 > LD50 > 50
mg/kg must display this word on their label.
Pesticides in this category are classified
as “moderately toxic (中等毒)”
• Danger (危險)： Reflects the highest
degree of relative toxicity. All pesticides
with an LD50 < 50 mg/kg must display this
word on their label.
Pesticides in this category are classified
as “highly toxic (劇毒)”
• Poison (毒物)：Any pesticide with an
LD50 < or = 50 mg/kg , the label must
have the signal word “DANGER” plus the
word “POISON”.
• Also, the label must display the skull and
crossbones icon.
• Organisms can’t differentiate between
“natural” and “synthetic” chemicals.
• “synthetic (合成)” does not mean toxic or
poisonous.
• “natural (天然)” does not mean safe or
even low risk.
• Chemicals must evaluated in their
biological context of behavior in organisms.
• Mode of action, not source, is the concern
and informed the users of pesticides.
• Most herbicides act on biological pathways
not present in humans.#
Insecticides (殺蟲劑)
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TCDD (Dioxin)
Parathion (巴拉松)
Nicotine (尼古丁)
Carbaryl (加保利)
Malathion (馬拉松)
0.1 mg/kg
13.0 mg/kg
50.0 mg/kg
270.0 mg/kg
370.0 mg/kg
Herbicides (除草劑)
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Paraquat (巴拉刈)
2,4-D (二四地)
2,4-DP (N/A)
Triclopyr (三氯比)
Dicamba (N/A)
Hexazinone (N/A)
Glyphosate (嘉磷塞)
95 mg/kg
375 mg/kg
532 mg/kg
630 mg/kg
755 mg/kg
1,690 mg/kg
4,320 mg/kg
Highly Toxic (劇毒)
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Botulinus toxin
Dioxin
Parathion
Nicotine
0.00001 mg/kg
0.1 mg/kg
13.0 mg/kg
50.0 mg/kg
Moderately Toxic (中等毒)
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Paraquat
Caffeine
Carbaryl
Marathion
2,4-D
95 mg/kg
200 mg/kg
270 mg/kg
370 mg/kg
375 mg/kg
Are all substances toxic?
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All are toxic to some degree.
Sugar has an LD50 of 30,000 mg/kg.
Ethanol has an LD50 of 13,700 mg/kg.
Even water has a recognized LD50 of
slightly > 80,000 mg/kg.
• All materials should be treated with care
and proper respect!!!