Reanalysis with optimized power of red blood cell acetylcholinesterase activity from a 1-year dietary treatment of dogs to chlorpyrifos.
A no-observed-effect level (NOEL) of 0.1 mg/kg/day was reported for inhibition of red blood cell (RBC) acetylcholinesterase (AChE) in two groups of Beagle dogs fed chlorpyrifos (0, 0.01, 0.03, 0.1, 1 or 3 mg/kg/day) in the diet for 1 or 2 years (McCollister et al., Food Cosmet. Toxicol. 12 (1974) 45-61). The statistical analyses were by t-test that had low statistical power due to small sample sizes. Common time points for blood samples in both phases allowed a reanalysis of the grouped data over a 1-year time period. The reanalysis increased statistical power by increasing the sample size to n=14 from n=3 or 4, and decreasing the variance, by statistical step-by-step aggregation of the data from both phases, both sexes, and four sample periods. Factors retained in the ANOVA were dose, sex, and phase (sex-by-dose was not significant). Contrasts with one-sided t-tests indicated the 1 and 3 mg/kg/day groups had significantly inhibited RBC AChE (P<0.0001). At alpha=0.05, the uncorrected one-sided model had 80% power to detect a 12% decrease, 93% power for a 15% decrease, and 99.5% power for a 20% decrease in AChE activity. Overall, the reanalysis had high power to detect a clinically significant decrease in RBC AChE activity, and substantiated the original NOEL for chronic treatment of dogs to dietary chlorpyrifos at 0.1 mg/kg/day.
Mattsson
J L
JL
Dow AgroSciences LLC, 9330 Zionsville Road, Building 306/2B, Indianapolis, IN 46268, USA. jlmattsson@dowagro.com
Holden
L
L
Eisenbrandt
D L
DL
Gibson
J E
JE
D000110:Acetylcholinesterase / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D004390:Chlorpyrifos / Q000633:toxicity*; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D003627:Data Interpretation, Statistical; D004285:Dogs; D004912:Erythrocytes / Q000187:drug effects* / Q000201:enzymology; D005260:Female; D007306:Insecticides / Q000633:toxicity*; D008297:Male; D019055:No-Observed-Adverse-Effect Level; D018401:Sample Size
D002800:Cholinesterase Inhibitors; D007306:Insecticides; D000110:Acetylcholinesterase; D004390:Chlorpyrifos