Dose Responses Flashcards
Hazard
intrinsic toxic properties of a toxicant mixture
Risk
Probability of an adverse outcome based on the exposure and potency of the hazardous toxicants
risk assessment
characterization of the probability of potentially adverse health effects from human exposures to hazardous agents
risk management
process by which policy actions are chosen to control hazards
epidemiology
studies the patterns, causes, and effects of health and disease conditions in defined populations
epidemiology data
correlative
correlation
- whether two variables are changing together
- correlation does not indicate causation
bioassays
- prove causation
- quantitative estimation of the intensity or concentration of a biologically active chemical
- measured via some biological response under standardized conditions
goals of toxicity testing
- determine the range of doses over which the toxic responses are produced
- identify the nature of the responses to a toxicant
- extrapolate these results for risk assessment analyses for human exposure
uses of bioassays in environment toxicology
- determine of the most sensitive species or life stage in an assemblage of organisms
- compare effects of different pollutants on a single organism
- compare effects of other environmental factors acting with the pollutant that modify its effects
- determine the maximum level of a pollutant that may occur in the environment without causing biological change
dose-response
-quantify the relationships between the exposure concentration and a defined endpoint
endpoints
whatever we are most interested in measuring
dose-response relationships
- standardize the doses to body weight
- duration and frequency important
- often the endpoint is mortality
- compare relative toxicity of toxicants
- ranked into toxicity classes
acute exposure
hours to days
chronic exposure
months to years
lethal concentration
how long an individual was exposed to a toxicant to reach the endpoint
lethal dose
taken orally
graded dose response
- use a continuous variable and occur in a single individual
- characterized by a dose-related increase in the severity of the response
quantal dose response
- occur in a population
- individual is classified as a “responder” or “non-responder”
route of exposure
- change dose-response curves
- injection, inhalation, ingestion, dermal
- speed of the response is related to how quickly a toxicant enters the bloodstream
linear relationships
- y-axis converted to “probits”
- Normal equivalent deviation
- 5=50% of the population
effective dose (ED50)
where the drug is doing what we want it to do in 50% of the population
toxic dose (TD50)
where bad things start happening in 50% of the population
lethal dose (LD50)
lethal in 50% of the population
therapeutic index (TI)
- ratio of TD50 and ED50
- high values drug is relatively safe
- low values rejection of the drug from further clinical testing
potency
the amount required to produce an effect of given intensity
efficacy
refers to the maximum response achievable
No observable effect concentration (NOEC)
highest concentration with no mortality
Lowest observable effect concentration (LOEC)
point of first effect or mortality
vehicle or carrier
- distribute the contaminant to the animals
- contaminants are usually hydrophobic
u-shaped curves
essential nutrients can have adverse effects at low and high doses
hormesis
compounds that are beneficial/stimulatory at low doses but toxic at high doses
nonmonotonic dose-response curves
- toxicants have effects at low levels
- low levels they interact with a hormonal receptor
- high levels receptor can burn out, response decreases
sub-lethal responses
toxic events occur before the animals die
subchronic bioassay
- high dose that causes toxicity but not more than 10% fatalities
- an intermediate dose
- low dose that should cause no toxic effects
- exposure for longer periods of time
why do a sub chronic test
- information on all types of sub chronic toxicity that might occur
- establish dose regimens for chronic studies
- provide data which will allow an estimate to be made of the MTD (maximum tolerable dose), no significant impairment of growth
- biomarkers of exposure
observed during the study
- altered growth rate
- behavioural changes
after the exposure period see what deviates from normal
- mass
- blood chemistry
- biochemical
- cell membrane permeability
- enzyme activity
- organ and tissue damage
Biomarker
a cellular or biochemical response to a toxicant that is measurable in a biological system or sample
biomarkers include
- enzyme activity
- changes in cellular receptor amount and activity
- changes in hormone levels
- increased/decreased expression of genes that respond to toxicants
- changes in the histology of cells to detect cellular damage
carcinogens
- classified based upon what is known from humans and animals
- experiments are expensive
reasons for low testing of chemicals
- not required
- lack of funds
- expensive
- difficult to test interactions
test results and who does them
- considered innocent until proven guilty
- government does not test
- industry conducts tests and gives the results to the government
