Herbicide resistance and biodiversity: agronomic and environmental aspects of genetically modified herbicide-resistant plants
Glyphosate
Glyphosate (C3H8NO5P; N-(phosphonomethyl) glycine), a polar, water soluble organic acid, is a potent chelator that easily binds divalent cations (e.g. Ca, Mg, Mn, and Fe) and forms stable complexes [23]. In addition to the active ingredient (a.i.) that can be present in various concentrations, herbicides usually contain adjuvants or surfactants that facilitate penetration of the active ingredient through the waxy surfaces of the treated plants. The best known glyphosate containing herbicides, the Roundup product line, often contain as a surfactant polyethoxylated tallow amine (POEA), a complex mixture of di-ethoxylates of tallow amines characterized by their oxide/tallow amine ratio, that is significantly more toxic than glyphosate [24]. The toxicity of formulations to human cells varies considerably, depending on the concentration (and homologue) of POEA [25]. Data from toxicity studies performed with glyphosate alone and over short periods of time may thus conceal adverse effects of the herbicides. Glyphosate degradation is reported to be rapid (half-lives up to 130 days) [3], but its main metabolite aminomethylphosphonic acid (AMPA) degrades more slowly. Both substances are frequently and widely found in US soils, surface water, groundwater, and precipitation [26]. Recently, the widespread occurrence of POEA and the persistence of POEA homologues in US agricultural soils have been reported [27] with currently unknown and unexplored consequences.
Inhibition of the enzyme EPSPS and disruption of the shikimate pathway impacts protein synthesis and production of phenolics, including defence molecules, lignin derivatives, and salicylic acid [28]. Glyphosate impacts plant uptake and transport of micronutrients (e.g. Mn, Fe, Cu, and Zn) whose undersupply can reduce disease resistance and plant growth [20, 23]. In Argentine soils, residue levels of up to 1500 µg/kg (1.5 ppm) glyphosate and 2250 µg/kg (2.25 ppm) AMPA have been found [29].
Glyphosate affects the composition of the microflora in soil and gastrointestinal tracts differently, suppressing some microorganisms and favouring others [30, 31]. This is likely linked to varying sensitivities of bacterial EPSPS enzymes to glyphosate [32]. In the RoundupReady soybean system, the bacterial-dependent nitrogen fixation and/or assimilation can be reduced [33]. Impacts of glyphosate on fungi vary also, depending on study sites, species, pathogen inoculum, timing of herbicide application, soil properties, and tillage [28]. Mycorrhizal fungi seem to be sensitive to glyphosate [34], while others, including pathogenic Fusarium fungi, may be favoured under certain conditions since glyphosate may serve as nutrient and energy source [30]. The microbial community of the gastrointestinal tract of animals and humans may be severely affected, if, as reported by Shehata et al. for poultry microbiota in vitro [31], pathogenic bacteria (e.g. Salmonella and Clostridium) are less sensitive to glyphosate than beneficial bacteria, e.g. lactic acid bacteria. For this reason, studies on glyphosate effects on the gut microbiome of other species are needed.
Glyphosate-based herbicides can affect aquatic microorganisms both negatively (e.g. total phytoplankton and nitrifying community) and positively (e.g. cyanobacteria) [35, 36], with surfactants such as POEA being significantly more toxic than the active ingredient itself [37]. In studies where Daphnia magna were fed glyphosate residues for the whole life-cycle, the parameters growth, reproductive maturity, and offspring number were impaired [38]. Amphibians are particularly at risk, since shallow temporary ponds are areas where pollutants can accumulate without substantial dilution. Sublethal concentrations of glyphosate herbicides can cause teratogenic effects and developmental failures in amphibians and impact both larval and adult stages [39]. Environmentally relevant levels of exposure to both glyphosate and Roundup have led to major changes in the liver transcriptome of brown trout, reflective of oxidative stress, and cellular stress response [40]. Simultaneous exposure to glyphosate-based herbicides and other stressors can induce/increase adverse impacts on fish [41] and amphibians [42].
Glyphosate application reduced the number and mass of casts and reproductive success of earthworm species that inhabit agroecosystems [43]. Impacts on arthropods, among them beneficial land predators and parasites, vary [44]. Exposure to sublethal glyphosate doses impairs behaviour and cognitive capacities of honey bees [45]. Acute toxicity of glyphosate to mammals is lower relative to other herbicides. In recent years, however, glyphosate-based herbicides have been reported to be toxic to human and rat cells, impact chromosomes and organelle membranes, act as endocrine disruptors, and lead to significant changes in the transcriptome of rat liver and kidney cells [25, 46, 47]. Negative effects of glyphosate on embryonic development after injection into Xenopus laevis and chicken embryos have been linked to interference of glyphosate with retinoic acid signalling that plays an important role in gene regulation during early vertebrate development, also showing that damage can occur at very low levels of exposure [48]. The International Agency for Research on Cancer (IARC) concluded in a recent report that glyphosate is probably carcinogenic to humans [49]. When mandated by the European Commission to consider IARCS’s conclusion, EFSA identified some data gaps, but argued that, based on its own calculations about glyphosate doses humans may be exposed to, glyphosate is unlikely to pose a carcinogenic hazard to humans [50]. The current concerns over the use of glyphosate-based herbicides are summarized in a recent paper [51], which concludes that glyphosate-based herbicides should be prioritized for further toxicological evaluation and for biomonitoring studies.