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Introduction and Principles of Toxicology Flashcards

1
Q

What is toxicology?

A

study of adverse effects of xenobiotics on living systems

toxicon = poison
logos = scientific study
STUDY OF POISONS

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2
Q

What is the difference between toxins and toxicants?

A

TOXIN = poison produced by living organisms (botulinum neurotoxin)

TOXICANT = man-made poisonous substance (organophosphates)

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3
Q

What are xenobiotics?

A

any substances foreign to an organism, or any compound no found within the normal metabolic pathways of a biologic system

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4
Q

What is the universal symbol of poisonous substances?

A

skull and crossbones

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5
Q

Toxicology is multidisciplinary. What 4 fields greatly contribute?

A
  1. chemistry
  2. physiology
  3. biochemistry
  4. pathology
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6
Q

What is mechanistic toxicology? Descriptive toxicology? Regulatory toxicology?

A

MECHANISTIC: study of cellular, biochemical, and molecular mechanisms of action

DESCRIPTIVE: toxicity testing for safety and regulatory purposes

REGULATORY: assessment of chemical risk from available data

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7
Q

What is forensic toxicology? Clinical toxicology? Environmental toxicology?

A

FORENSIC: medical-legal aspects of poisoning (CSI)

CLINICAL: diagnosis and treatment of toxicoses

ENVIRONMENTAL: effects of chemicals and pollutants in the environment on nonhuman subjects

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8
Q

Why is toxicology considered as old as humanity? Who where the early toxicologists?

A

early humans knew what to eat without harm and were able to recognize poisonous plants and animals and used their extracts for hunting and warfare

herbalists, witches, philosophers, alchemists

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9
Q

What is the oldest documentation of medicine?

A

Ebers Papyrus from 1500 BC, which contains >800 magical formulae and remedies with information on toxic plants and metals

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10
Q

Who is considered the father of toxicology? Why?

A

Paracelsus

advocated focus on “toxicon” and pioneered the dose-response relationship

all things are poisonous, it is only the dose that makes a thing not a poison

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11
Q

What 3 concepts were advanced by Paracelsus?

A
  1. need for experimentation in examining response to chemicals
  2. need to distinguish between therapeutic and toxic properties of chemicals based on dose
  3. specificity of therapeutic and toxic effects of chemicals
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12
Q

Who was Orfila? What did he discover?

A

pioneered quantitative toxicology to relate chemical content and toxicity and introduced experimental and forensic toxicology

used autopsy material and chemical analysis for legal proof of arsenic poisoning - Marsh Test (cause and effect)

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13
Q

What did Francois Magendie do?

A

pioneered mechanistic toxicology to determine the mechanisms of action of strychnine, emetine, and arrow poisons

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14
Q

What was the 1960s considered with regard to toxicology? What important agency was discovered?

A

era of public awareness - birth defects, pesticides wiping out bird populations (Rachel Carson and Silent Spring)

launch of the Environmental Movement lead to the development of the US Environmental Protection Agency

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15
Q

How has toxicology developed from the pre-20th century to the mid-20th century? Today?

A

PRE-20TH CENTURY - observational; mostly focused on domestic animals used for food, fiber, transportation, and power (plant toxicoses and their antidotes)

MID-20TH CENTURY - experimental; increased population of companion animals, large-scale food animal production, and reduced use of animal power

TODAY - mechanistic; comparative approach driven by concerns for human health

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16
Q

What makes something poisonous?

A

the dose

all substances are poisons, the dose differentiates a poison from remedy

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17
Q

What is LD50? What are 3 important limitations?

A

dose lethal to 50% of exposed animals

  1. does not reflect full spectrum of toxicity (low acute toxicity may be carcinogenic or teratogenic)
  2. tells us nothing about the nature or severity of effects in survivors
  3. specific to exposure conditions (species, age, sex, size, route and duration of exposure, environment and physiological conditions)
18
Q

Some of the most toxic agents are ______.

19
Q

When are substances generally recognized as safe (GRAS)?

A

relatively harmless at > 15 g/kg

20
Q

What is the dose-response (D-R) relationship?

A

correlative relationship that brings together the characteristics of exposure and the spectrum of effects

21
Q

What does the toxicant-receptor interaction depend on?

A

configuration and accessibility (must be compatible)

22
Q

What are the 5 fundamentals to the dose-response (D-R) relationship?

A
  1. response is due to the chemical administered or the toxicant to which the animal is exposed
  2. the chemical interacts with a molecular or receptor site to produce a response
  3. degree of response is correlated with the concentration of the toxicant at the receptor site
  4. concentration of the toxicant at the receptor site(s) is related to the dose of the toxicant received
  5. there exist methods of measuring and expressing toxic effects
23
Q

What is included in toxicokinetics?

A

Absorption
Distribution
Metabolism
Excretion

external exposure —> internal dose —> target dose

24
Q

What is toxicodynamics?

A

interaction of toxicant with target site

target dose —> toxic effect

25
What condition must be met for toxicity to occur?
uptake (K1) must exceed elimination (K2) leading to accumulation of the toxicant K1 > K2 when a xenobiotic or its metabolite reaches appropriate sites in the body at adequate concentrations and at an adequate length of time
26
What are some exposure, toxicant, animal, and environment-related factors that influence toxic response?
EXPOSURE - dose, route, site, duration and frequency of exposure, concentration at the site of action, prior exposure TOXICANT - physical and chemical properties, formulation ANIMAL - species, strain, age, size, sex, metabolism, nutritional status, health ENVIRONMENT - temperature, humidity, wind, drought, time of year
27
How does response time, difficulty linking toxicant, and importance change up the levels of biologic organization?
- increases - increases - increases
28
How do the lower and higher levels of biological organization give information about toxicants?
LOWER = explains mechanisms HIGHER = provides significance
29
Are effects at all levels of biological organization significant?
YES
30
How are dose-response relationships illustrated graphically? What are the 2 main types?
D-R curves 1. QUANTAL - distribution of responses to different doses in a population of organisms in an all-or-nothing way (responders or not responders) 2. GRADED - response of a biological system to varying doses of a chemical in a continuous and gradual way from minimum detectable to a maximal response
31
What do quantal dose-response curves look like? How are they applied?
sigmoidal prediction of the proportion of a population that respond in a specified manner to doses of the toxicant - relating dose to frequency of response
32
Within a population how will a majority of respond to a given toxicant dose?
the majority will respond similarly
33
What do graded dose-response curves look like? How are they applied?
a curve that plateaus relates dose to the intensity of response
34
What is EC50?
value on a graded dose-response curve that is half the maximal concentration
35
What are the 4 major uses of graded dose-response curves?
1. therapeutic dose 2. potency and efficacy 3. safety 4. mechanisms of action
36
What is potency? Efficacy?
POTENCY = amount required to elicit an effect of a given magnitude (typically calculated as 1/EC50) EFFICACY = maximal response (effectiveness)
37
What is the NOEL and LOEL in graded dose-response curves? Threshold dose?
NOEL = no observed effect level LOEL = lowest observed effect level THRESHOLD = beginning of a response
38
Label the graded dose-response curve.
1 = NOEL 2 = threshold (response) 3 = LOEL blue line = linear = something that is always a toxicant, not matter the dose (ionizing radiation)
39
What does the dose-response curve for trace elements, like vitamins and metals, look like?
U-shaped with responses at deficiency levels and toxic levels - within the U and below the adverse effect threshold is at homeostasis
40
What is hormesis? What does the graph look like? What are 3 common toxicants that fall into this category?
low-dose stimulation, high-dose inhibition - beneficial at low doses, dangerous at high doses regular or inverted curve beginning at 0 alcohol, dioxin, cancer drugs
41
Inverted hormesis dose-response curve:
42
What are non-monotonic dose responses (NMDR)?
dose-response relationship in which the direction changes with increasing or decreasing dose

Veterinary Toxicology (29 decks)

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