The in vitro evaluation of the toxicities of three related herbicide formulations containing ester derivatives of 2,4,5-T and 2,4-D using sub-mitochondrial particles.
The aim of this investigation was to determine the contribution made by the different components of herbicide formulations to the overall toxicity of the formulations. Three related herbicide formulations were chosen. The first, Agent Orange, consisted only of the butyl esters of 2,4,5-T and 2,4-D. The second was Agent Orange diluted with diesel fuel and the third formulation tested was a tree and blackberry killer, which consisted of the butyl ester of 2,4,5-T, the ethyl ester of 2,4-D, diesel fuel and two surfactants. The potential toxic effects of these three formulations were evaluated by determining their inhibitory effects on the oxidative functions of submitochondrial particles prepared from beef heart mitochondria. The effective concentration that caused a 50% inhibition of the activities of the submitochondrial particles was determined for all three formulations. When the toxicity of the individual components of these formulations was evaluated, it was established that the so-called 'inert' components i.e. diesel fuel and surfactants contributed approximately 50% of the overall toxicity of the complete formulations. Hence the results confirm the importance of evaluating the toxicity of complete formulations, rather than only focussing on the active components. While cellular and sub-cellular assays cannot account for pharmacokinetic and pharmacodynamic changes that may affect the toxicity of xenobiotics, the sub-mitochondrial particle test is useful as an initial screening assay.
Oakes
D J
DJ
Department of Anatomy and Histology, University of Sydney, NSW 2006, Sydney, Australia.
Pollak
J K
JK
D015085:2,4,5-Trichlorophenoxyacetic Acid / Q000633:toxicity*; D015084:2,4-Dichlorophenoxyacetic Acid / Q000633:toxicity*; D004121:Dimethyl Sulfoxide / Q000633:toxicity; D004579:Electron Transport / Q000187:drug effects; D005742:Gasoline / Q000633:toxicity; D006540:Herbicides / Q000633:toxicity*; D013367:Submitochondrial Particles / Q000187:drug effects*; D013501:Surface-Active Agents / Q000633:toxicity
D005742:Gasoline; D006540:Herbicides; D013501:Surface-Active Agents; D015084:2,4-Dichlorophenoxyacetic Acid; D015085:2,4,5-Trichlorophenoxyacetic Acid; D004121:Dimethyl Sulfoxide