Dose-Response Relationships Flashcards
the characteristic of exposure and the spectrum of toxic effects come together as
dose-response relationship
two types of dose response relationships
individual dose-response relationship
quantal dose-response relationship
describes the response of and individual organism to varying doses of a chemical
individual dose relationship
characterizes the distribution of individual responses to different does in a population of individual organisms
quantal dose relationship
bell shaped curve
normal frequency distribution
the reason for normal distribution
differences in susceptibility to chemicals among individuals
animals responding to the left end of the curve are
hypersusceptible
animals responding to the right end of the curve are
resistant
the minimally ED of any chemical that evokes a stated all or none response is the ___which cannot be determined experimentally
threshold dose
units of NED are converted by the addition of five to the value to avoid negative numbers
probit units
50% of the population will show an effect from a chemical
ED50
50% of the population will show a toxic dose from a chemical
TD50
50% of the population will die from exposure to a chemical
LD50
the “graded” dose relationship in an individual over the entire dose range is actually
U-shaped
the region of the dose response relationship for essential nutrients is commonly referred to as
deficiency
there is considerable evidence to suggest that some nonnuritional toxic substances may also impart beneficial or stimulatory effects at low doses but that at high doses they produce adverse effects
hormesis
factors to consider when talking about the threshold concept
test population size
time periods
endpoints
ED01 vs NOAEC
important assumptions for generating proper dose-response curves
effects are caused by dosed chemical
magnitude of response is actually related to dose
response can be quantified reliable
three assumptions that cover “magnitude of response is actually related to the dose”
there is a target site with which the chemical interacts
response is related to concentration at target site
concentration at target site is related to dose
the ratio of the dose required to produce a toxic effect to the dose needed to elicit the desired therapeutic response
therapeutic index
the larger the ratio the ____the relative safety
greater
use the ED99 for the desired effect and the TD1 for the undesired effect
Margin of Safety (MOS)
a chemical produces injury to one kind of living matter without harming another form of life even though the two may exist in intimate contact
selective toxicity
generally the first toxicity test performed on a new chemical is
acute toxicity
5 objectives of acute toxicity
- provide estimate for intrinsic toxicity of a substance
- provide information on target organs
- identify species differences and susceptible species
- establish the reversibility of the toxic response
- provide information that will assists the design and dose selection for longer term studies
performed to obtain information on the toxicity of a chemical after repeated administration
subacute toxicity
common duration for subchronic testing
90 days
principle goals of subchronic testing
establish the NOAEC
further identify and characterize specific organ(s) affected by the test compound
use to establish regulatory values for acceptable pollutant levels
reference dose
uses all the experimental data to fit 1 or more dose-response curves
benchmark dose
performed similarly to subchronic studies except that the period of exposure is longer than three months
chronic toxicity
dose that suppresses body weight gain slightly
maximum tolerable dose
