(Fig. 5), there was no significant dose-by-age interaction, but a
significant age factor supported a shift to the left of the pup dose–
response. The ED50 values for ChE inhibition (Table 1) in pups was 3.6-
fold and 1.3-fold less than in adults for brain and RBC, respectively,
and were significantly different evidenced by mutually-exclusive
confidence limits. Similarly, the motor activity ED50 value (Table 1) for
pups was 2.9-fold lower than for adults.
3.2. Phosphamidon
For phosphamidon, the time point selected from the range-finding
studies was 40 min for tissue collection, so the rats were placed in the
activity chambers 15 min after dosing. Mild tremors were noted in the
high-dose adult rats, whereas pups showed mild to moderate tremors
and some facial fasciculations (chewing). The dose response for brain
ChE inhibition (Fig. 2) was different in pups compared to adults,
evidenced by a significant dose-by-age interaction. The ED50 estimates
(Table 1) indicated a significant 1.8-fold shift to the left in the
pups. The data for RBC ChE inhibition, however, were not significantly
different, and the ED50 values were close (1.2-fold difference with
overlapping confidence limits). At both ages, all dose groups were
different from control. The motor activity (Fig. 5) data for adult rats
showed a decrease but only at the highest dose. In the pups, activity
levels were highly variable across all the dose groups, and there was a
suggestion of an inverted-U shape; however, there were no
statistically significant differences compared to control. The curve fit
to the adult data revealed that the ED50 was about the same as the
high dose, whereas the parameters did not converge for the pups and
thus a model could not be fit and an ED50 cannot be estimated.