SciCombinator

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Concept: Glyphosate

220

The broad-spectrum herbicide glyphosate (common trade name “Roundup”) was first sold to farmers in 1974. Since the late 1970s, the volume of glyphosate-based herbicides (GBHs) applied has increased approximately 100-fold. Further increases in the volume applied are likely due to more and higher rates of application in response to the widespread emergence of glyphosate-resistant weeds and new, pre-harvest, dessicant use patterns. GBHs were developed to replace or reduce reliance on herbicides causing well-documented problems associated with drift and crop damage, slipping efficacy, and human health risks. Initial industry toxicity testing suggested that GBHs posed relatively low risks to non-target species, including mammals, leading regulatory authorities worldwide to set high acceptable exposure limits. To accommodate changes in GBH use patterns associated with genetically engineered, herbicide-tolerant crops, regulators have dramatically increased tolerance levels in maize, oilseed (soybeans and canola), and alfalfa crops and related livestock feeds. Animal and epidemiology studies published in the last decade, however, point to the need for a fresh look at glyphosate toxicity. Furthermore, the World Health Organization’s International Agency for Research on Cancer recently concluded that glyphosate is “probably carcinogenic to humans.” In response to changing GBH use patterns and advances in scientific understanding of their potential hazards, we have produced a Statement of Concern drawing on emerging science relevant to the safety of GBHs. Our Statement of Concern considers current published literature describing GBH uses, mechanisms of action, toxicity in laboratory animals, and epidemiological studies. It also examines the derivation of current human safety standards. We conclude that: (1) GBHs are the most heavily applied herbicide in the world and usage continues to rise; (2) Worldwide, GBHs often contaminate drinking water sources, precipitation, and air, especially in agricultural regions; (3) The half-life of glyphosate in water and soil is longer than previously recognized; (4) Glyphosate and its metabolites are widely present in the global soybean supply; (5) Human exposures to GBHs are rising; (6) Glyphosate is now authoritatively classified as a probable human carcinogen; (7) Regulatory estimates of tolerable daily intakes for glyphosate in the United States and European Union are based on outdated science. We offer a series of recommendations related to the need for new investments in epidemiological studies, biomonitoring, and toxicology studies that draw on the principles of endocrinology to determine whether the effects of GBHs are due to endocrine disrupting activities. We suggest that common commercial formulations of GBHs should be prioritized for inclusion in government-led toxicology testing programs such as the U.S. National Toxicology Program, as well as for biomonitoring as conducted by the U.S. Centers for Disease Control and Prevention.

Concepts: Epidemiology, Agriculture, Animal testing, Toxicology, Carcinogen, Herbicide, Glyphosate, Roundup

113

Glyphosate-based herbicides (GBH) are the major pesticides used worldwide. Converging evidence suggests that GBH, such as Roundup, pose a particular health risk to liver and kidneys although low environmentally relevant doses have not been examined. To address this issue, a 2-year study in rats administering 0.1 ppb Roundup (50 ng/L glyphosate equivalent) via drinking water (giving a daily intake of 4 ng/kg bw/day of glyphosate) was conducted. A marked increased incidence of anatomorphological and blood/urine biochemical changes was indicative of liver and kidney structure and functional pathology. In order to confirm these findings we have conducted a transcriptome microarray analysis of the liver and kidneys from these same animals.

Concepts: Kidney, Liver, Renal cortex, Renin, Offal, Herbicide, Glyphosate, Roundup

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Use of glyphosate-based herbicides (GBHs) increased ∼100-fold from 1974 to 2014. Additional increases are expected due to widespread emergence of glyphosate-resistant weeds, increased application of GBHs, and preharvest uses of GBHs as desiccants. Current safety assessments rely heavily on studies conducted over 30 years ago. We have considered information on GBH use, exposures, mechanisms of action, toxicity and epidemiology. Human exposures to glyphosate are rising, and a number of in vitro and in vivo studies challenge the basis for the current safety assessment of glyphosate and GBHs. We conclude that current safety standards for GBHs are outdated and may fail to protect public health or the environment. To improve safety standards, the following are urgently needed: (1) human biomonitoring for glyphosate and its metabolites; (2) prioritisation of glyphosate and GBHs for hazard assessments, including toxicological studies that use state-of-the-art approaches; (3) epidemiological studies, especially of occupationally exposed agricultural workers, pregnant women and their children and (4) evaluations of GBHs in commercially used formulations, recognising that herbicide mixtures likely have effects that are not predicted by studying glyphosate alone.

Concepts: Epidemiology, In vivo, Toxicology, In vitro fertilisation, In vitro, Herbicide, Glyphosate, Roundup

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Glyphosate is the most commonly used herbicide worldwide, with both residential and agricultural uses. In 2015, the International Agency for Research on Cancer classified glyphosate as “probably carcinogenic to humans,” noting strong mechanistic evidence and positive associations for non-Hodgkin lymphoma (NHL) in some epidemiologic studies. A previous evaluation in the Agricultural Health Study (AHS) with follow-up through 2001 found no statistically significant associations with glyphosate use and cancer at any site.

Concepts: Epidemiology, Cancer, Agriculture, Statistics, Lymphoma, Carcinogen, International Agency for Research on Cancer, Glyphosate

39

Our recent work (Séralini et al., 2012) remains to date the most detailed study involving the life-long consumption of an agricultural genetically modified organism (GMO). This is true especially for NK603 maize for which only a 90-day test for commercial release was previously conducted using the same rat strain (Hammond et al., 2004). It is also the first long term detailed research on mammals exposed to a highly diluted pesticide in its total formulation with adjuvants. This may explain why 75% of our first criticisms arising within a week, among publishing authors, come from plant biologists, some developing patents on GMOs, even if it was a toxicological paper on mammals, and from Monsanto Company who owns both the NK603 GM maize and Roundup herbicide ®. Our study has limits like any one, and here we carefully answer to all criticisms from agencies, consultants and scientists, that were sent to the Editor or to ourselves. At this level, a full debate is biased if the toxicity tests on mammals of NK603 and R obtained by Monsanto Company remain confidential and thus unavailable in an electronic format for the whole scientific community to conduct independent scrutiny of the raw data. In our article, the conclusions of long-term NK603 and Roundup toxicities came from the statistically highly discriminant findings at the biochemical level in treated groups in comparison to controls, because these findings do correspond in an blinded analysis to the pathologies observed in organs, that were in turn linked to the deaths by anatomopathologists. GM NK603 and R cannot be regarded as safe to date.

Concepts: Scientific method, Molecular biology, Genetically modified organism, Genetically modified food, Ice-minus bacteria, Glyphosate, Roundup, Monsanto

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Pesticide formulations contain declared active ingredients and co-formulants presented as inert and confidential compounds. We tested the endocrine disruption of co-formulants in six glyphosate-based herbicides (GBH), the most used pesticides worldwide. All co-formulants and formulations were comparably cytotoxic well below the agricultural dilution of 1% (18-2000 times for co-formulants, 8-141 times for formulations), and not the declared active ingredient glyphosate (G) alone. The endocrine-disrupting effects of all these compounds were measured on aromatase activity, a key enzyme in the balance of sex hormones, below the toxicity threshold. Aromatase activity was decreased both by the co-formulants alone (polyethoxylated tallow amine-POEA and alkyl polyglucoside-APG) and by the formulations, from concentrations 800 times lower than the agricultural dilutions; while G exerted an effect only at 1/3 of the agricultural dilution. It was demonstrated for the first time that endocrine disruption by GBH could not only be due to the declared active ingredient but also to co-formulants. These results could explain numerous in vivo results with GBHs not seen with G alone; moreover, they challenge the relevance of the acceptable daily intake (ADI) value for GBHs exposures, currently calculated from toxicity tests of the declared active ingredient alone.

Concepts: Pharmacology, Toxicology, Cytotoxicity, Toxicity, Poison, Biological activity, Glyphosate, Pesticide formulation

32

High crop yields depend on the continuous input of orthophosphate (PO(4)(−3))-based fertilizers and herbicides. Two major challenges for agriculture are that phosphorus is a nonrenewable resource and that weeds have developed broad herbicide resistance. One strategy to overcome both problems is to engineer plants to outcompete weeds and microorganisms for limiting resources, thereby reducing the requirement for both fertilizers and herbicides. Plants and most microorganisms are unable to metabolize phosphite (PO(3)(−3)), so we developed a dual fertilization and weed control system by generating transgenic plants that can use phosphite as a sole phosphorus source. Under greenhouse conditions, these transgenic plants require 30–50% less phosphorus input when fertilized with phosphite to achieve similar productivity to that obtained by the same plants using orthophosphate fertilizer and, when in competition with weeds, accumulate 2–10 times greater biomass than when fertilized with orthophosphate.

Concepts: Photosynthesis, Ammonia, Fertilizer, Phosphate, Nitrogen, Phosphorus, Weed, Glyphosate

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Abstract 1. The objective of this study was to evaluate the effects of dietary supplementation with phytase transgenic corn (maize) (PTC) which has a phytase activity of 21 000 units (U) phytase per kg of maize on productive performance, egg quality, tibia bone quality and phosphorus (P) excretion in laying hens. 2. In the experiment, 1800 44-week-old Hy-line brown laying hens were divided into 5 groups with 6 replicates per group and 60 hens per replicate. The experiment lasted for 12 weeks. The layers in the control group (control) were given a basal diet with 0.36% non-phytate P (NPP), while the treatment groups received diets containing 360 U of exogenous phytase/kg with 0.26% NPP (EP) or 360 phytase U of PTC/kg diet with 0.26% (PTC1), 0.21% (PTC2) or 0.16% (PTC3) NPP. 3. The results showed that there was no significant difference in egg production, average daily feed intake, feed efficiency, rate of broken or soft-shell egg production or egg mass among the treatments. There was no significant difference in eggshell thickness or eggshell strength. On the other hand, no differences in any of the bone variables were found between treatments. The faecal P percentage content in EP, PTC1, PTC2 and PTC3 groups was significantly lower than the control group. 4. In summary, the PTC could be used in the feed of laying hens instead of EP to reduce P excretion without effecting production and bone mineralisation.

Concepts: Effect, Food, Femur, Chicken, Maize, Genetically modified food, Glyphosate, Transgenic maize

26

Missouri is an agriculturally intensive state, primarily growing corn and soybeans with additional rice and cotton farming in some southeastern counties. Communities located in close proximity to pesticide-treated fields are known to have increased exposure to pesticides and may be at increased risk of adverse birth outcomes. The study aims were to assess the relationship between county-level measures of crop-specific agricultural production and adverse birth outcomes in Missouri and to evaluate the most appropriate statistical methodologies for doing so.

Concepts: Agriculture, Green Revolution, Crop rotation, Glyphosate, Arable land

25

Genetically modified (GM) crops have been and continue to be a subject of controversy despite their rapid adoption by farmers where approved. For the last two decades, an important matter of debate has been their impact on pesticide use, particularly for herbicide-tolerant (HT) crops. Some claim that these crops bring about a decrease in herbicide use, while others claim the opposite. In fact, since 1996, most cultivated GMOs have been GMHT crops, which involve the use of an associated herbicide, generally glyphosate. In their very first years of adoption, HT crops often led to some decrease in herbicide use. However, the repetition of glyphosate-tolerant crops and of glyphosate only applications in the same fields without sufficient alternation and herbicide diversity has contributed to the appearance of glyphosate-resistant weeds. These weeds have resulted in a rise in the use of glyphosate and other herbicides. This article explores this situation and the impacts of herbicide-resistant weeds, using an interdisciplinary approach and drawing on recent data. The paper analyzes the spread of GMHT crops worldwide and their consequences on herbicide use in the USA in particular. It then addresses the global development of glyphosate-resistant weeds and their impact, particularly focusing on the USA. Finally, the last section explores how industry, farmers, and weed scientists are coping with the spread of resistant weeds. The concluding comments deal more widely with trends in GM crops.

Concepts: Agriculture, Pesticide, Abstraction, Genetically modified organism, Weed, Herbicide, Glyphosate, Roundup