Introduction Flashcards
TOX
The word toxicology is derived from what Greek words?
Toxicology is derived from the Greek words
toxicon (= poison) and logos (= scientific
study): “Study of poisons”
Define the term toxicology.
Definition has changed over time. The most
current definition: “Study of adverse
effects of xenobiotics on living systems”
* Changing definition highlights the evolving
nature of the discipline
Define the term toxin.
Toxin: A poison produced by a living
organism, e.g., botulinum neurotoxin
Define the term toxicant.
Toxicant: A man-made (i.e., not produced
within living organisms) poisonous
substance, e.g., organophosphates
Define the term xenobiotic.
Xenobiotic: Any substance foreign to an
organism (or any compound not found
within the normal metabolic pathways of a
biologic system)
What are the universal symbols of poisonous substances?
- Skull and crossbones
- Symbol may appear with different colors,
borders and supplemental information
What key subjects have contributed greatly to toxicology?
chemistry, biochemistry, physiology, and pathology
Define mechanistic toxicology.
Study of cellular, biochemical & molecular mechanisms of action
Define descriptive toxicology.
Toxicity testing for safety & regulatory purposes
Define regulatory toxicology.
Assessment of chemicals risk from available data
Define forensic toxicology.
Medical-legal aspects of poisoning (CSI toxicology)
Define clinical toxicology.
Diagnosis and treatment of toxicoses
Define environmental toxicology.
Effects of chemicals in the environment on nonhuman subjects such as fish, birds, terrestrial animals, etc.
What knowledge did early humans have of toxic things in the environment?
– Early humans knew what to eat without harm
– Early humans recognized poisonous plants and animals and used their extracts for hunting and warfare
What knowledge did early toxicologists have of toxins?
Early toxicologists:
– Herbalists, witches, philosophers, alchemists
Present day toxicologists.
– Multidisciplinary scientists, medical and
veterinary practitioners
What is Ebers Papyrus?
- Oldest documentation
of medicine - Discovered in 1873
- Contains >800 magical
formulae and remedies - Has information on
toxic plants and metals
Egyptian document now @ University of Leipzig Library
Who is the father of toxicology?
1500 AD: Paracelsus
(Theophrastus Phillipus Auroleus Bombastus von Hohenheim-Paracelsus)
* ‘Father of toxicology’
– Advocated focus on “toxicon”
(the primary toxic agent)
* Pioneered the dose-response
relationship
“What is there that is not a
poison? All things are
poison and nothing is
without poison. It is only
the dose that makes a
thing not a poison”
What concepts were advanced by paracelsus?
- Need for experimentation in examining
responses to chemicals - Need to distinguish between therapeutic
and toxic properties of chemicals based on
dose - Specificity of therapeutic and toxic effects
of chemicals
Who was Orfila?
Marsh test = measure arsenic in humans.
Who was Francois Magendie?
- French physician and experimental physiologist
- Pioneered mechanistic toxicology
– Determined mechanisms of action of strychnine, emetine, and arrow poisons
1960s are described as?
The era of public awareness of toxicology.
Many birth defet cases associated with use of lithomid for morning sickness.
DDT wiping out bird populations
Documented in silent spring by Rachel Carson in 1962. Led to nationwide ban of DDT and grassroots movement –> EPA created.
Why is Aspirin considered a poison?
Taking 30 tablets = severe signs of toxicity: vomiting, hypothermia, confusion
105 tablets = lethal
Describe the spectrum of toxicity.
Spectrum of toxicity varies.
What is the function of LD50?
LD50 has been used to classify chemicals into groups.
x <1 mg/kg = extremely toxic
x > 15 g/kg = harmless
What are the cons of LD50?
Some survivors may have suffered permanent damage and may need to be euthanized.
Toxicant and receptor must be compatible to elicit a response.
What processes affect target dose and toxic effect?
Concentration of toxicant at the target site is the main factor that determines the strength of the effect. Two main processes that determine the type and strength of toxic response: Toxicokinetics, Toxicodynamics.
TK: det. conc, of toxicant at target site and degree of strenght of effect.
TD: type of target site and nature of inte4raction with toicant dete the type of resonse. Target site might be a recpeotr in CNS which is either inhibited or stimulated by todicant resulting in depression or excitation of CNS.
Exposure to potentially toxic substance does not mean toxicity will occur. Explain.
Toxic effects occur over a wide range of biological organization.
effects At ecosystem level ultimately originate from interaction between toxic substance and one or more molecules. Thisinteraiton may alter dcel function, organ cell is apart of. Impaired organ function impacts organism at whole and effect at individual level can effect pop at large and ultimately ecosystem.
Effect at all levels of bio org are significant because each level finds its explanation of mech below and significance in levels above. Key features of toxicant effects at various levels: lower org = shorter time, response time increases are higher levels of bio org.
NT mediate effects occur within seconds at molecular level but within ecosystem or pop it would take years.
freq distribution = blue ; bell shaped and is termed normal distribution.
cum freq = red; each freq from distribution is added to sum of predeccors; sigmoidal.
Reuslt is obtained by determining an endpoint and countin the numebr of animals that reached.
Rate of response initiall fast but becomes progressively slower as dose increases. EVentualy max effect achived and further increase in dose does not produce a response.
If dose range is very wide, can plot on semi-log scale.
Graded D-R curves are used for?
Which drug is more potent?
B b/c have lower EC50.
Which drug is more potent?
red line
black line = more effective
Most substances, toxicity is associated with a trhedhols dose consistent with paraselsus dogma.
Linear = estimates effects of ionixing radiation. effect directly proprtional to doses at all levels of exposure. Radiation is alwasy harmful at all levels of exposure. Sum of several Short duration has same effect as one long duration. No safety threshold. Keep in mind: threhold dose falls between NOEL and LOEL.
Unique dose response curve that is U shaped in nature. Arises fro the fact tht both low and high conc. of a central nutients assocaited with adverse effects. Ad effects asociated with deficney are high at very low doses and as these doses increase thse ad effects of defiivency decrease until disappear. with further increasing dose, othr ad effectw appear and are associated with oxicity. For these substances, conc need to be maintained within hoemostatic range at which there is neitehr sign of defieicney nor toicity.
Characteized by: this type fo dose respons eis assoc with non=nutritional toic substances that may impart some benefiical or stimulatory effects at low doses. high doses = adverse effect.
high Alcohol = liver damage, cancer, serosis.
low alcohol = reduces heart failure and stroke
A: degree of ebenfit increases and starts to decrease with increase in conc of toxicant until adverse effects occurs
B: # of tumors initally decrase with incraseing con. higher con of toxicant –> tumors increase.
Non-monotonic Dose Responses (NMDR) are defined as?
Dose-response relationships in which the
direction of the response changes with
increasing or decreasing dose.
U shaped or inverted U shaped depending on end point.
E.g. stimulationof growth at low dosea and inhib at high doses = inverted u
decrease in tumor incidence at low dose and increase at higher doses = u shaped.
