S07-03 Impact of Glyphosate and its Mixture with 2,4-D and Dicamba on Gut Biochemical Function, Intestinal Barrier Integrity and Microbiome Composition in Adult Rats with Prenatal Commencement of Exposure

Background:

Large scale use of glyphosate herbicides in genetically modified (GM) glyphosate-tolerant cropping and non-GM cropping applications has resulted in the spread of many glyphosate-resistant weed species. As a result, the agricultural biotechnology industry has launched GM crops tolerant to glyphosate plus 2,4-D and to glyphosate plus dicamba. Consequently, people are increasingly exposed to a mixture of glyphosate, 2,4-D and dicamba.

Objectives:

Our objective was to investigate the effects of glyphosate alone and in combination with 2,4-D and dicamba, using regulatory relevant doses, on gut structure and function in rats.

Methods:

Pregnant Wistar rats were administered via drinking water from day-6 of gestation with glyphosate at the European Union (EU) no observed adverse effect level (NOAEL; 50 mg/kg bw/day) and acceptable daily intake (ADI; 0.5 mg/kg bw/day), and with a mixture of glyphosate, 2,4-D and dicamba, with each at the ADI (0.3 mg/kg bw/day dicamba; 0.02 mg/kg bw/day 2,4-D; 0.5 mg/kg bw/day glyphosate). Offspring continued on this regimen for 13 weeks post-weaning, at which point large and small intestinal tissues and gut content were isolated and analysed for inflammation, gut epithelial integrity, oxidative stress, microbiota composition and histopathology.

Results:

Treatment with theglyphosate, dicamba and 2,4-D mixture resulted in increased gut inflammation and permeability (leaky gut), which was associated with oxidative stress and alterations in microbial community composition. The glyphosate NOAEL dose gave similar though less prominent gut inflammation and integrity outcomes but was also associated with oxidative stress. Histological analysis confirmed structural alterations and inflammation in large and small intestine. Effects were more pronounced in the large intestine but no major, significant differences were observed between sexes.

Discussion:

Our results indicate that exposure to a mixture of glyphosate, 2,4-D and dicamba at their respective EU ADI constitutes a potential health hazard with respect to gut structure and function. Our data also suggests that safety (ADI) limits for pesticides should be based on mixtures and not individual “active substances” as currently practised. Outcomes seen from treatment with the EU glyphosate NOAEL dose add to evidence that this value may be incorrect and thus the ADI too high.