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TESTING FOR DEPARTURES FROM ADDITIVITY FOR A 2:1 MIXTURE OF CHLORPYRIFOS AND CARBARYL ON CHOLINESTERASE ACTIVITY IN BRAIN, PLASMA, AND RED BLOOD CELLS OF LONG EVANS RATS.
Citation:
Stork, L., T. Coffey, C. Gennings, W. H. Carter, J E. Simmons, AND D W. Herr. TESTING FOR DEPARTURES FROM ADDITIVITY FOR A 2:1 MIXTURE OF CHLORPYRIFOS AND CARBARYL ON CHOLINESTERASE ACTIVITY IN BRAIN, PLASMA, AND RED BLOOD CELLS OF LONG EVANS RATS. Presented at Society of Toxicology, Baltimore, MD, 3/21-25/2004.
Description:
Detecting and characterizing interactions among chemicals is an important environmental issue. This study was conducted to test for the existence of a significant departure from additivity for a mixture of two cholinesterase (ChE)-inhibiting pesticides: chlorpyrifos (CPF), an organophosphate; and carbaryl (CARB), a carbamate. The effects of CPF and CARB on ChE activity in the brain, plasma, and red blood cells of male Long Evans rats were evaluated using single chemical dose-response curves (CPF: 0, 3, 10, 20, 30 and 50 mg/kg; CARB: 0, 10, 30, 50, 100 and 175 mg/kg; po; 5 rats per group) and a 2:1 (CPF:CARB) mixing ratio (total dose: 0, 28 and 35 mg/kg; 6 rats per group) evaluated at the time of near maximal ChE inhibition by the mixture (4 h after dosing). Nonlinear additivity models estimated from the single chemical data were fit for each outcome. Nonlinear mixture models estimated from the mixture data were compared to that predicted using the additivity model along the 2:1 mixture ray. A significant difference between the mixture and additivity models is considered evidence of interaction. A significant dose-response effect was detected for the single chemical and mixture data. Using a likelihood ratio test, departure from additivity was not detected for any of the three endpoints. While the additivity model was estimated from data in the active range of the dose-response curves, the mixture data included only two doses above control, which were generally near optimal effect. Hence, generalizing these conclusions to the low-dose region of the mixture ray should be made with caution. For further investigation, the existing data are useful in determining an optimal design associated with maximum power for detecting interactions. Supported by T32 ES07334-01A1 (NIEHS, NIH) and CR-828-11401 (U.S. EPA). This is an abstract of a proposed presentation and does not necessarily reflect EPA policy.