Association between organophosphate exposure and hyperactivity?
James Bus1, Jacques Maurissen1, Brian Marable1
& Joel Mattsson2
1 The Dow Chemical Company, Midland, Michigan 48674, USA.
2 Dow AgroSciences, Indianapolis, Indiana 46268, USA.
To the editor:
Winrow and coworkers1 have offered a potentially useful genetically modified mouse model for study of the health implications of altered expression of neuropathy target esterase (Nte). But their primary conclusion that "moderate reduction in Nte activity, by either reducing the amount of Nte protein through genetics or using a potent Nte inhibitor, leads to hyperactivity" is critically flawed. The key data justifying their conclusion, presented in Figure 6c and d, showed that wild-type (Nte+/+) mice treated intraperitoneally with 1 mg ethyl octylphosphonofluoridate (EOPF) per kg body weight had a hyperactivity response equal to or greater than that observed in untreated genetically engineered Nte+/- mice with 40% lower intrinsic Nte enzymatic activity. Although it was quantified in untreated Nte+/- mice, Nte activity was not reported in the EOPF-treated mice. Evidence for Nte inhibition in EOPF-treated mice was only inferred by reference to results of an earlier study2 in which intraperitoneal treatment with 5 mg of EOPF per kg body weight was described as inhibiting NTE activity in mouse brain by 85%. But in the same table that describes this response (Table 4 in ref. 2), intraperitoneal treatment with 1.3 mg EOPF per kg body weight is reported as causing no inhibition of Nte activity in mouse brain (only 1% difference from control). This dose of 1.3 mg per kg body weight is slightly higher than that used in the hyperactivity experiments described by Winrow et al.1.
These data on EOPF and Nte inhibition suggest that activity of Nte in the brain was probably not reduced at the dose used in the experiments ascribing increased hyperactivity to Nte inhibition induced by EOPF treatment. In the absence of measurements of inhibition of Nte activity in the brain at a dose of 1 mg EOPF per kg body weight, and knowing that a dose of 1.3 mg EOPF per kg body weight did not inhibit activity of Nte in the brain in other similar experiments, the hypothesis that organophosphate-induced inhibition of Nte is causally linked to hyperactivity is not plausible.
