Glyphosate is an active ingredient in a number of commercially available herbicides, including several that are used in concert with genetically modified crops. The herbicidal action of glyphosate derives from its inhibition of a key plant enzyme, 5-enolpyruvylshikimate-3-phosphate synthase, which is involved in the synthesis of aromatic amino acids. Since this enzyme is not present in vertebrates, it has long been believed that glyphosate would not affect non-target species, including humans. However, multiple lines of evidence suggest that this contention is inaccurate.

Methods used in environmental health sciences to examine the potential health effects of chemicals, including pesticides, have undergone substantial changes over the past 30 years. Cutting-edge tools currently employed by federally funded scientists bear little resemblance to the archaic standardised assays required by regulatory agencies and used in formal risk assessments.1 We are concerned that the assays used to assess glyphosate safety, including the toxicity studies requested by the US Environmental Protection Agency (EPA) in 2009, may be insufficient to address the full complement of health effects that could be induced by exposure to glyphosate-based herbicides (GBHs).

In this commentary, we summarise these key findings as well as trends in increased use of GBHs. Since commercial applications of GBHs began four decades ago, their use has diversified and expanded considerably. We offer recommendations on how to reduce significant uncertainties concerning GBH risks.