Concerns over use of glyphosate-based herbicides and risks associated with exposures: a consensus statement
TL;DR: GBHs are the most heavily applied herbicide in the world and usage continues to rise; Worldwide, GBHs often contaminate drinking water sources, precipitation, and air, especially in agricultural regions and regulatory estimates of tolerable daily intakes for glyphosate in the United States and European Union are based on outdated science.
Abstract: 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.
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TL;DR: Glyphosate will likely remain the most widely applied pesticide worldwide for years to come, and interest will grow in quantifying ecological and human health impacts, according to published global pesticide use data.
Abstract: Accurate pesticide use data are essential when studying the environmental and public health impacts of pesticide use. Since the mid-1990s, significant changes have occurred in when and how glyphosate herbicides are applied, and there has been a dramatic increase in the total volume applied. Data on glyphosate applications were collected from multiple sources and integrated into a dataset spanning agricultural, non-agricultural, and total glyphosate use from 1974–2014 in the United States, and from 1994–2014 globally. Since 1974 in the U.S., over 1.6 billion kilograms of glyphosate active ingredient have been applied, or 19 % of estimated global use of glyphosate (8.6 billion kilograms). Globally, glyphosate use has risen almost 15-fold since so-called “Roundup Ready,” genetically engineered glyphosate-tolerant crops were introduced in 1996. Two-thirds of the total volume of glyphosate applied in the U.S. from 1974 to 2014 has been sprayed in just the last 10 years. The corresponding share globally is 72 %. In 2014, farmers sprayed enough glyphosate to apply ~1.0 kg/ha (0.8 pound/acre) on every hectare of U.S.-cultivated cropland and nearly 0.53 kg/ha (0.47 pounds/acre) on all cropland worldwide. Genetically engineered herbicide-tolerant crops now account for about 56 % of global glyphosate use. In the U.S., no pesticide has come remotely close to such intensive and widespread use. This is likely the case globally, but published global pesticide use data are sparse. Glyphosate will likely remain the most widely applied pesticide worldwide for years to come, and interest will grow in quantifying ecological and human health impacts. Accurate, accessible time-series data on glyphosate use will accelerate research progress.
1,153 citations
TL;DR: It is hypothesized that the selection pressure for glyphosate-resistance in bacteria could lead to shifts in microbiome composition and increases in antibiotic resistance to clinically important antimicrobial agents, which would have an impact on plant, animal and human health.
571 citations
Wageningen University and Research Centre1, Humboldt State University2, Katholieke Universiteit Leuven3, Agricultural & Applied Economics Association4, Leibniz Association5, University of Gloucestershire6, Polish Academy of Sciences7, University of Bergen8, Aberystwyth University9, Swedish University of Agricultural Sciences10, Université Paris-Saclay11, Tuscia University12, Technical University of Madrid13, University of National and World Economy14
TL;DR: In this paper, the authors define resilience of a farming system as its ability to ensure the provision of the system functions in the face of increasingly complex and accumulating economic, social, environmental and institutional shocks and stresses, through capacities of robustness, adaptability and transformability.
277 citations
TL;DR: In this paper, the use of nanomaterials in agriculture as nanofertilizers, nanopesticides, or nano-enabled sensors to increase crop yield is gaining increasing interest.
Abstract: The use of nanomaterials in agriculture as nanofertilizers, nanopesticides, or nano-enabled sensors to increase crop yield is gaining increasing interest. Engineered nanomaterials (ENMs) can improve crop productivity by influencing fertilizer nutrient availability in soil and uptake by plants. These materials can suppress crop diseases by directly acting on pathogens through a variety of mechanisms, including the generation of reactive oxygen species (ROS). ENMs may also suppress disease indirectly by improving crop nutrition and enhancing plant defense pathways. Efficient use of ENMs may complement or replace conventional fertilizers and pesticides, subsequently reducing the environmental impact of agricultural practices. This review evaluates the current literature on ENMs used as pesticides and fertilizers, and highlights critical knowledge gaps that must be addressed to ensure sustainable application of nanotechnology in agriculture so as to achieve global food security.
269 citations
TL;DR: The estimated exports clearly indicate that particulate transport can contribute to human and environmental exposure to herbicide residues and Residue threshold values in soils are urgently needed to define potential risks for soil health and off site effects related to export by wind and water erosion.
238 citations
Cites background from "Concerns over use of glyphosate-bas..."
...Currently, there is strong debate about the potential harmfulness of glyphosate (e.g., EFSA, 2015; IARC, 2015; Myers et al., 2016), with some studies associating its use with cancer and endocrine disruption in humans and acute and chronic toxicity to aquatic species (Annett et al., 2014; Gasnier et…...
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...Currently, there is strong debate about the potential harmfulness of glyphosate (e.g., EFSA, 2015; IARC, 2015; Myers et al., 2016), with some studies associating its use with cancer and endocrine disruption in humans and acute and chronic toxicity to aquatic species (Annett et al....
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References
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TL;DR: It is concluded that when nonmonotonic dose-response curves occur, the effects of low doses cannot be predicted by the effects observed at high doses, and fundamental changes in chemical testing and safety determination are needed to protect human health.
Abstract: For decades, studies of endocrine-disrupting chemicals (EDCs) have challenged traditional concepts in toxicology, in particular the dogma of “the dose makes the poison,” because EDCs can have effects at low doses that are not predicted by effects at higher doses. Here, we review two major concepts in EDC studies: low dose and nonmonotonicity. Low-dose effects were defined by the National Toxicology Program as those that occur in the range of human exposures or effects observed at doses below those used for traditional toxicological studies. We review the mechanistic data for low-dose effects and use a weight-of-evidence approach to analyze five examples from the EDC literature. Additionally, we explore nonmonotonic dose-response curves, defined as a nonlinear relationship between dose and effect where the slope of the curve changes sign somewhere within the range of doses examined. We provide a detailed discussion of the mechanisms responsible for generating these phenomena, plus hundreds of examples from...
2,475 citations
"Concerns over use of glyphosate-bas..." refers background in this paper
...Contemporary endocrine science has demonstrated that dose–response relationships will sometimes deviate from a linear increase in the frequency and severity of impacts expected as dose levels rise [19, 63]....
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TL;DR: Glyphosate will likely remain the most widely applied pesticide worldwide for years to come, and interest will grow in quantifying ecological and human health impacts, according to published global pesticide use data.
Abstract: Accurate pesticide use data are essential when studying the environmental and public health impacts of pesticide use. Since the mid-1990s, significant changes have occurred in when and how glyphosate herbicides are applied, and there has been a dramatic increase in the total volume applied. Data on glyphosate applications were collected from multiple sources and integrated into a dataset spanning agricultural, non-agricultural, and total glyphosate use from 1974–2014 in the United States, and from 1994–2014 globally. Since 1974 in the U.S., over 1.6 billion kilograms of glyphosate active ingredient have been applied, or 19 % of estimated global use of glyphosate (8.6 billion kilograms). Globally, glyphosate use has risen almost 15-fold since so-called “Roundup Ready,” genetically engineered glyphosate-tolerant crops were introduced in 1996. Two-thirds of the total volume of glyphosate applied in the U.S. from 1974 to 2014 has been sprayed in just the last 10 years. The corresponding share globally is 72 %. In 2014, farmers sprayed enough glyphosate to apply ~1.0 kg/ha (0.8 pound/acre) on every hectare of U.S.-cultivated cropland and nearly 0.53 kg/ha (0.47 pounds/acre) on all cropland worldwide. Genetically engineered herbicide-tolerant crops now account for about 56 % of global glyphosate use. In the U.S., no pesticide has come remotely close to such intensive and widespread use. This is likely the case globally, but published global pesticide use data are sparse. Glyphosate will likely remain the most widely applied pesticide worldwide for years to come, and interest will grow in quantifying ecological and human health impacts. Accurate, accessible time-series data on glyphosate use will accelerate research progress.
1,153 citations
TL;DR: Recent studies suggest that retinoic acid may act primarily in a paracrine manner and provide insight into the cell-cell signaling networks that control differentiation of pluripotent cells.
994 citations
TL;DR: The importance of developmental stage and the realization that exposure to a presumptive "safe" dose of chemical may impact a life stage when there is normally no endogenous hormone exposure are emphasized, thereby underscoring the potential for very low-dose EDC exposures to have potent and irreversible effects.
Abstract: An endocrine-disrupting chemical (EDC) is an exogenous chemical, or mixture of chemicals, that can interfere with any aspect of hormone action. The potential for deleterious effects of EDC must be considered relative to the regulation of hormone synthesis, secretion, and actions and the variability in regulation of these events across the life cycle. The developmental age at which EDC exposures occur is a critical consideration in understanding their effects. Because endocrine systems exhibit tissue-, cell-, and receptor-specific actions during the life cycle, EDC can produce complex, mosaic effects. This complexity causes difficulty when a static approach to toxicity through endocrine mechanisms driven by rigid guidelines is used to identify EDC and manage risk to human and wildlife populations. We propose that principles taken from fundamental endocrinology be employed to identify EDC and manage their risk to exposed populations. We emphasize the importance of developmental stage and, in particular, the realization that exposure to a presumptive “safe” dose of chemical may impact a life stage when there is normally no endogenous hormone exposure, thereby underscoring the potential for very low-dose EDC exposures to have potent and irreversible effects. Finally, with regard to the current program designed to detect putative EDC, namely, the Endocrine Disruptor Screening Program, we offer recommendations for strengthening this program through the incorporation of basic endocrine principles to promote further understanding of complex EDC effects, especially due to developmental exposures.
839 citations
TL;DR: It is concluded that estrogenic agents are able to act together to produce significant effects when combined at concentrations below their NOECs, highlighting the limitations of the traditional focus on the effects of single agents.
Abstract: We tested whether multicomponent mixtures of xenoestrogens would produce significant effects when each component was combined at concentrations below its individual NOEC or EC01 level. The estrogenic effects of eight chemicals of environmental relevance, including hydroxylated PCBs, benzophenones, parabenes, bisphenol A, and genistein, were recorded using a recombinant yeast estrogen screen (YES). To ensure that no chemical contributed disproportionately to the overall combination effect, a mixture was prepared at a mixture ratio proportional to the potency of each individual component. The performance of four approaches for the calculation of additive combination effects (concentration addition, toxicity equivalency factors, effect summation, and independent action) was compared. Experimental testing of the predictions revealed that concentration addition and its application, the toxicity equivalency factor approach, were valid methods for the calculation of additive mixture effects. There was excellent agreement between prediction and observation. In contrast, independent action and effect summation led to clear underestimations of the experimentally observed responses. Crucially, there were substantial mixture effects even though each chemical was present at levels well below its NOEC and EC01. We conclude that estrogenic agents are able to act together to produce significant effects when combined at concentrations below their NOECs. Our results highlight the limitations of the traditional focus on the effects of single agents. Hazard assessments that ignore the possibility of joint action of estrogenic chemicals will almost certainly lead to significant underestimations of risk.
807 citations
"Concerns over use of glyphosate-bas..." refers background in this paper
...fects that are not predicted from tests of single compounds [40, 41]....
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