Chemistry Reference
In-Depth Information
response relationships rather than dose-effect relation-
ships. For the dose-response relationship the sigmoid
model, therefore, represents the cumulative frequency
distribution of subjects showing an effect as a function
of dose. A graphical representation of this statement is
given in Figure 11. It is obvious that biological systems
may include complexities that prevent any simple gen-
eralization by a graph or mathematical expression.
On the other hand, understanding and communica-
tion of scientifi c observations are greatly enhanced by
the presentation of general principles and models or
mechanisms for observations.
and is seen as either an inverted U- or J-shaped curve
is common in the biomedical/toxicological literature,
and is highly generalizable according to biological
model tested, endpoint measured, and chemical class/
physical agent used (Calabrese, 2002).
The form of this dose-response curve may be either
of an inverted U or a J shape, depending on the end-
point measured. In cases of endpoints such as growth,
longevity, fecundity, and cognitive function, the res-
ponse would be seen as an inverted U shape. In the
case of disease incidence, it would be seen as a J shape
(Figure 12) (Calabrese, 2005).
In some situations, hormetic dose response is a nor-
mal component of the array of traditional dose-response
relationships. Above NO(A)EL doses the hormetic dose
response and the traditional sigmoidal dose response
are the same. At below NO(A)EL doses the threshold
response model assumes there is no real treatment-related
difference between the control group response and the
exposed group response below the NO(A)EL treatment.
2.3 Hormesis—Inverted U- or J-Shaped Curves
There is evidence to suggest that some toxic sub-
stances may also impart benefi cial or stimulatory
effects at low doses, but that at higher doses they pro-
duce adverse effects. This term “hormesis” (meaning
to excite) was fi rst coined in 1943 by Southam and
Ehrlich (1943) in studies dealing with the effects of red
cedar extracts on fungal metabolism and was later used
more extensively to describe radiation effects. Numer-
ous articles have been published that indicate that the
hormetic dose-reponse model, which is characterized
by a low-dose stimulation and a high-dose inhibition
2.4 U-Shaped Curves and Essentiality
The dose-response relationship for an essential
substance such as vitamin or essential trace element
A
100
Response
80
Cumulative
frequency
distribution
60
B
40
Response
20
Frequency
distribution
Dose
FIGURE 12
(A) The most common form of the hormetic dose-
response curve depicting low-dose stimulatory and high-dose
inhibitory response, the inverted U-shaped curve. Endpoints
displaying this curve include growth, fecundity, and longevity. (B)
The hormetic dose-response curve depicting low-dose reduction and
high-dose enhancement of adverse effects. Endpoints displaying this
curve include carcinogenesis, mutagenesis, and disease incidence.
0
50
70
100
200
Dose (mg)
FIGURE 11
The relationship between the frequency distribution
curve and the S-shaped cumulative frequency distribution curve
(from Goodman and Gilman, 1975).
