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ANALYSIS OF FUNCTIONAL EFFECTS OF A MIXTURE OF FIVE PESTICIDES USING A RAY DESIGN
Citation:
Gennings, C., W. H. Carter, M. Casey, V C. Moser, R. A. Carchman, AND J E. Simmons. ANALYSIS OF FUNCTIONAL EFFECTS OF A MIXTURE OF FIVE PESTICIDES USING A RAY DESIGN. ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY. Elsevier Science Ltd, New York, NY, 18(2):115-125, (2004).
Description:
Abstract
The protection of human health from the adverse effects of cumulative environmental exposure to chemical mixtures is an important issue. Of particular interest is the potential detection and characterization of interaction among chemicals in complex mixtures. Response surface methodology, often supported by factorial designs, is the classical statistical experimental approach. Fixed-ratio ray designs, which may include the use of single chemical data in addition to data along mixture ray(s), have been proposed as an alternative approach. Such designs permit a reduction in the amount of experimental effort when the region of interest can be restricted to exposure-relevant mixing ratios. A 'single agent required' (SAR) approach and a 'single agent not required' (SANR) approach are both described.
The methods are illustrated using a five-pesticide mixture. The pesticides chosen for these studies were based on usage patterns (i.e., pesticides used on the same or similar crops) and market share (i.e., highest volume pesticides), and were acephate, diazinon, chlorpyrifos, malathion and dimethoate. The fixed-ratio ray under study was chosen based on the relative dietary human exposure estimates of each chemical as projected by the U.S. EPA Dietary Exposure Evaluation Model (DEEM) and its mixing proportions are given by (0.040: 0.002: 0.031: 0.825: 0.102) for acephate, diazinon, chlorpyrifos, malathion, and dimethoate, respectively.
The methods developed here are demonstrated using a dichotomized gait score as an indication of toxicity. The overall test indicated that significant departures from additivity exist when all five chemicals are together in the mixture (i.e., synergy). Malathion alone was not active in the dose range under study. This lack of activity motivated examination of interaction along a second fixed ratio ray whose mixing proportions are given by (0.229: 0.011: 0.177: 0: 0.583), where malathion is removed from the mixture and the remaining four chemicals are at the same relative proportions as those considered along the full fixed-ratio ray. There was not a significant departure from additivity along the ray with the four remaining pesticides omitting malathion. Further, although malathion was not dose-responsive alone, it significantly interacted with the other pesticides.