Reanalysis with optimized power of red blood cell acetylcholinesterase activity from a 1-year dietary treatment of dogs to chlorpyrifos

• Published in: Toxicology (Amsterdam) Vol. 160; no. 1; pp. 155 - 164
• Main Authors: Mattsson, J.L., Holden, L., Eisenbrandt, D.L., Gibson, J.E.
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 07.03.2001; Amsterdam Elsevier Science
• Subjects: Acetylcholinesterase - metabolism; Analysis of Variance; Animals; Biological and medical sciences; Chlorpyrifos; Chlorpyrifos - toxicity; Cholinesterase Inhibitors - toxicity; Data Interpretation, Statistical; Dogs; Erythrocytes - drug effects; Erythrocytes - enzymology; Female; Insecticides - toxicity; Male; Medical sciences; No-Observed-Adverse-Effect Level; Pesticides, fertilizers and other agrochemicals toxicology; Red blood cell acetylcholinesterase inhibition; Sample Size; Toxicology; Chlorpyrifos; Red blood cell acetylcholinesterase inhibition; Dogs; Insecticide; Toxicity; Esterases; Acetylcholinesterase; Blood plasma; Dose activity relation; Statistical test; Enzymatic activity; Exposure time; Dog; Fissipedia; Carnivora; Enzyme; Pesticides; Oral administration; Red blood cell; No observed effect level; Carboxylic ester hydrolases; Vertebrata; Mammalia; Diet; Animal; Hydrolases; Organophosphorus compounds
• ISSN: 0300-483X; 1879-3185
• DOI: 10.1016/S0300-483X(00)00446-7

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 α=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.