Chapter 1 (exam 1) Flashcards
Toxicology
study adverse effects of chemicals or organisms
Toxicant
substance that causes harm when in contact with organism at a sufficiently high dose
toxin
a toxicant produced by an organism
Xenobiotic
foreign to life, evolutionary time scale
Dose
amount administered and internalized by organism
Dosage
dose per unit body weight
Anthropogenic
manmade. from human activity
Potency
measure ability of material to cause effect
Method of exposure
inhalation
ingestion
dermal
injection
Principles of Tox
- Response has specific chemical cause
- Magnitude related to dose
- receptor interaction with toxicant
- Concentration at the receptor is related to the conc. of exposure
Response Pathway
exposure - uptake - metabolism (maybe) - distribution - excretion
Why Tox?
Environmental effects Workplace exposure Nontarget effects Understand mechanisms Crime Develop better targeted
Tox Goals
Hazard ID - extent and nature of effect, ID the toxicant
Dose Response/Risk Assessment - assess probablility of effects depending on the exposure
Exposure Duration
Acute - single dose (1-2 days)
Subacute - little longer than acute
Subchronic - little less than chronic
Chronic - multiple doses (weeks to years), dependent on the lifespan of the organism
Duration Effects/Factors
Longer-more uptake, more interaction with the receptor
Different endpoints
Dependent on the half life
Rate at which compound is removed
Accumulation
Increase in the concentration over time in a tissue
NOAEL
No observable adverse effects level
- acute requires greater amount
- chronic requires smaller amount
- highest conc/dose that is not different from the control
Why use Rats/Mice Experiments
- easy to handle
- similar physiology to human, uptake and reproduction
- similar receptors
- metabolism
Interested Organisms
human, fish, rats/mice, plants, birds, insects, algae, crops
Drawbacks of lab experiments
- skips distribution
- technical expertise
- wrong target site
- metabolism
Endpoints
mortality, reproduction, organ function, metabolism, growth, mobility/behavior, a bio function
in vivo and in vitro
in vivo - in organism
in vitro - “in glass” in the lab
LD50
median lethal dose, produces mortality of 50% of the tested population
LC50
concentration that produces mortality in 50% of the exposure.
- easier to measure than dose in each organism
- concentration in the exposure
ED50 or EC50
effective dose or concentration for 50% of the population
- used when effect is increasing
- beneficial effect of pharmaceutical
ID50 or IC50
Inhibitory dose or concentration for 50% of the population
- used when effect is decreasing
- example - pain with medication
Rank EC and LC values
Low (EC always lower than any LC) EC10 EC50 LC50 96 hr LC50 12 hr high
Therapeutic Index
LD50/ED50 larger index is safer
Margin of Safety
LD1/ED99
-if less than 1, people are dying before it is effective
Dose - Response relationship
- log scale x-axis
- sigmoidal
- Zero dose is control
- non zero intercept because some organisms will die without the dose
Threshold
Cumulative vs response graphs
Cumulative is sigmoidal and response is bell curve
Cumulative can also be a valley shape
-example - copper is necessary for survival, deficiency is fatal, but so is an excess
LOAEL
Lowest observable adverse effect level
-lowest observable dose/conc that is different from the control
NOEC and LOEC
no/lowest observable effects concentration
Why compare across species and challenges
-cant use humans
-nontarget species
-endangered species
-minimize organisms tested
Challenges - physiology, receptor, metabolism differences
Variability in responses graph
- genetics, gender, age, exposure, health status, chemical interactions
- Narrower curve will have lower uncertainty in LC50 estimate
- More variability is more realistic in actual population
- narrow curve will have less noise, better baseline
Humans and Pesticides (something that kills a pest)
- Greater phylogenetic similarity, greater chance of similar response
- herbicide/fungicide< molluscicides < nematocides < rodenticides
Pesticide Design
goal-control pests w/o harming nontarget
selective-highly toxic to pest, low tox to nontarget
effective-low dose to achieve control of pest
Additivity
response to mixture us equal to sum of responses to individual exposures
2+3=5
Antagonism
response to mix is less than sum of responses to individual exposures
10+2 = 4 or 10+0=4
Synergism
Response to mix is greater than sum of responses to individual exposures
2+10=20
Potentiation
same as synergism but one component is nontoxic
2+0=10
Piperonyl butoxide
nontoxic but interferes with metabolic enzyme
- In pesticides to limit metabolism and cause accumulation.
- more economical for the pesticide
Functional Interaction
Both chemicals impact the same physiological function
-Increase blood pressure and decrease blood pressure id functional antagonism
Chemical interactions (antagonism example)
EDTA and Metals
Form complex
EDTA neutralizes metal
Dispositional interactions
Absorbtion, distribution, metabolism , or excretion of one chemical modified another
- charcoal and EtOH
- Receptor interactions-chemicals bind to the same receptor
- -Cu, Zn, Pb on fish gill ion transport proteins
- -Cu out complexes Zn at the receptor
How to obtain tox data
- controlled lab tox testing
- epidemiology-info from uncontrolled sources (more noise and factors)
- Test the general population
