28 BIOLOGICAL EFFECTS OF LOW LEVEL EXPOSURES
Figure 1.18. Gompertz plots for control and ethyl acrylate-treated male F344 rats. Ethyl
acrylate administration (75 ppm inhalation) was begun at 7-9 weeks of age
and continued to 24 months of age (6 hr per day, 5 days per week). Time on
the abscissa refers to the period following initiation of exposure. The
theoretical lines were obtained by simultaneous fitting of Equations 3 and
12, employing weighted least-squares regression analysis. Both longevity
hormesis and irreversible toxicity seem evident (see text for caveat). The
original data came from Miller et al.98 Reprinted from Neafsey et al.,24 p.
390, by permission of Marcel Dekker, Inc.
reside with one data point, lying at 9 months and carrying the lowest weight
of the four data points on the curve. Yet the fit is excellent, and the mixed
longevity hormesis-irreversible toxicity model is consistent with the data.
Obviously, additional studies need be conducted before a more definitive
statement can be made concerning the likelihood of longevity hormesis
being elicited by ethyl acrylate in male rats.
The mortality data illustrated in Figure 1.19 presented a unique opportu
nity to incorporate not only the effects of longevity hormesis and irrevers
ible toxicity, but also the change in mortality pattern induced by caloric
restriction.24 " Chloroform was administered to male rats in their drinking
water at a concentration of 1800 ppm. This apparently caused them to
consume less food and water. Consequently, a second control group was
employed that attempted to mimic food and water consumption of the
chloroform exposed population. The top curve of Figure 1.19 illustrates a
linear Gompertz function for the conventional control population (i.e., the
group permitted ad lib access to food and water). The second control group,
not exposed to chloroform but having reduced food and water intake, was
also characterized by a linear Gompertz function. However, as expected (see
Figure 1.5), it was necessary to reduce a. The chloroform exposed group,
on the other hand, apparently experienced three effects:
- longevity hormesis
- irreversible toxicity
- a reduced a due to reduced caloric intake