ORIGINAL ABSTRACT

Canine multicentric lymphoma (CML) is one of the most common malignancies in dogs. Although breed risk is important, environmental factors such as herbicides have also been implicated. The objective of this study was to determine whether genotoxic exposures to the herbicides 2,4-D and glyphosate are associated with CML, using dogs from the Golden Retriever Lifetime Study cohort. We measured urinary concentrations of glyphosate and 2,4-D in golden retrievers with CML and matched unaffected controls at two time points: at the time of diagnosis and 1 year prior to diagnosis. To assess the genotoxic potential of herbicide exposures, we used reverse dosimetry from urinary concentrations to estimate plasma concentrations. We then assessed the genotoxicity of these herbicide concentrations towards healthy canine peripheral blood mononuclear cells (PBMC's) in vitro using the CometChip assay, with and without canine liver microsomes. All dogs had detectable urinary exposures to 2,4-D (7.3-42.9 ng/mg creat) and glyphosate (0.4-80.7 ng/mg creat), with no differences between cases and controls at either time point. Both 2,4-D and glyphosate were genotoxic to canine PBMCs at concentrations of 0.10 μM and higher, with no consistent effects of canine liver microsomes on herbicide genotoxicity. No dogs reached estimated genotoxic plasma concentrations for glyphosate, but 4 of 30 golden retrievers with CML (13.3%) and 2 of 30 control dogs (6.7%) reached estimated genotoxic 2,4-D exposures (p = 0.67).