Impact of atrazine on chlorpyrifos toxicity in four aquatic vertebrates.

Atrazine has been shown previously to potentiate chlorpyrifos toxicity in selected invertebrates. This study examined interactions of atrazine and chlorpyrifos in four aquatic vertebrates. Organisms were exposed to binary mixtures of atrazine and chlorpyrifos during toxicity bioassays. Inhibition of cholinesterase (ChE) enzyme activity and chlorpyrifos uptake kinetics were also examined with and without atrazine exposure. Atrazine alone did not affect organisms at concentrations up to 5000 microg/L; however, the presence of atrazine at 1000 microg/L did result in a significant increase in the acute toxicity of chlorpyrifos in Xenopus laevis. Mixed results were encountered with Pimephales promelas; some bioassays showed greater than additive toxicity, while others showed an additive response. No effect of atrazine on chlorpyrifos toxicity was observed for Lepomis macrochirus and Rana clamitans. Atrazine did not affect ChE activity or chlorpyrifos uptake rates, indicating that these toxicodynamic and toxicokinetic parameters may not be related to the mechanism of atrazine potentiation of chlorpyrifos toxicity. Based on the results of this study, it does not appear that a mixture toxicity of atrazine and chlorpyrifos at environmentally relevant concentrations presents a risk to the vertebrate organisms examined in this study.

Direct measurement of unfractionated heparin using a biochemical assay.

A number of investigations have noted that functional biological assays for heparin are not always reliable and may not reflect the actual biochemical level of heparin in patients receiving anticoagulant therapy. This creates the possibility that patients receiving anticoagulant treatment may have an excess or deficiency of circulating levels of heparin. To address this problem, we have developed a direct biochemical measurement of heparin. The heparin assay uses fluorophore-assisted carbohydrate electrophoresis (FACE) to directly measure the predominate disaccharide of unfractionated heparin. In this study, unfractionated heparin was measured in vitro throughout a wide range of heparin concentrations in plasma. Seven in vivo pharmacokinetic studies in five normal subjects given 3,000 USP units of unfractionated heparin intravenously showed a three-phase elimination process with higher peak plasma levels and shorter elimination times than predicted from previous studies. At these doses, heparin is largely eliminated intact through urinary excretion. Body weight has a significant effect on heparin kinetics. When we compared the direct biochemical assay with two biological clotting assays, we found the latter can overestimate biochemical heparin concentrations. The FACE assay, due to its sensitivity, is also able to measure circulating levels of endogenous heparin in plasma and urine. Direct heparin measurement using the FACE technique is practical and useful for studies of the correlation of biochemical and biological activities.