Chemistry Reference
In-Depth Information
in a continuum of biological changes that can be quan-
titatively measured to provide an “effect” or (2) by the
presence of a specifi ed change in a certain proportion of
the individuals in a population providing “response.”
This distinction in terminology is needed for a clear
and precise description of changes resulting from a
dose or doses of a chemical. When a population of
individuals receives a dose of a chemical, both effect
and response occur simultaneously (i.e., some indi-
viduals respond with an effect of a certain magnitude,
whereas other individuals respond with a greater or
lesser effect). Furthermore, more than one kind of effect
may occur at the same time. The need to differentiate
the variations in magnitude and kind of effect from the
variations in the number of individuals responding
makes this use of the terms
effect
and
response
valuable.
A set of hypothetical data is used to illustrate the inter-
relationships between effect and response.
4
3
2
1
0
0
1
2
3
4
Dose (D)
FIGURE 1
Hypothetical observations of effect on 10 subjects at
each dose. The line is point-to-point based on the arithmetic mean
of the values for effect.
4
1.2 Interrelationships Among Dose,
Effect, and Response
First, consider the simplest situation for the obser-
vation of a dose-effect relationship. This would be for
an individual subject in which a series of doses of a
chemical would be administered; after each dose, a sin-
gle kind of effect would be quantitatively determined.
One could then plot the magnitude of the dose against
the magnitude of the effect. This situation assumes that
each successive dose is independent (i.e., the subject
returns completely to the original state between doses).
However, in most situations the effect has some residue
that may change the magnitude, and possibly the kind,
of effect resulting from the next dose. Therefore, it is
generally necessary to use populations of individual
subjects to quantity changes due to individual doses
where each time the subject is naive.
Next, consider a study in which a population of 40
subjects is randomly distributed into four groups of 10
each, and each group of 10 is given a different dose of
a chemical. The effect on each subject is then measured
on a quantitative scale, and the values are plotted with
dose as in Figure 1.
With such data as in Figure 1, it may be useful to
make general statements (either graphical or math-
ematical) about the relationship with dose. Specifi cally,
it is useful to interpolate between doses. Thus, one may
plot (see Figure 2) a curvilinear relationship using the
median effect at each dose (the term “median effect”
meaning that 50% of the population responded with this
or a lesser effect). Alternately, one could determine the
percent responding at each dose by a defi ned level of
effect and plot the relationships as shown in Figure 3. In
addition, one could plot the distribution of effect for the
population at a specifi c dose level, as shown in Figure 4.
3
2
1
0
0
1
2
3
4
Dose (D)
FIGURE 2
Point-to-point plots for the dose-effect relationships at
equi-response based on data from Figure 1.
100
75
50
25
0
0
1
2
3
4
Dose (D)
FIGURE 3
Point-to-point plots for the dose-response relation-
ships at equi-effect based on data from Figure 1.
