Ferre et al., 2018
Ferre, D. M., Quero, A. A. M., Hernandez, A. F., Hynes, V., Tornello, M. J., Luders, C., & Gorla, N. B. M., “Potential risks of dietary exposure to chlorpyrifos and cypermethrin from their use in fruit/vegetable crops and beef cattle productions,” Environmental Monitoring and Assessment, 2018, 190(5), 292. DOI 10.1007/s10661-018-6647-x.
ABSTRACT:
The active ingredients (a.i.) used as pesticides vary across regions. Diet represents the main source of chronic exposure to these chemicals. The aim of this study was to look at the pesticides applied in fruit, vegetable, and beef cattle productions in Mendoza (Argentina), to identify those that were simultaneously used by the three production systems. Local individuals (n = 160), involved in these productions, were interviewed. Glyphosate was the a.i. most often used by fruit-vegetable producers, and ivermectin by beef cattle producers. Chlorpyrifos (CPF) and cypermethrin (CYP) were the only a.i. used by the three production systems. The survey revealed that CPF, CYP, alpha CYP, and CPF+CYP were used by 22, 16, 4, and 20% of the fruit and vegetable producers, respectively. Regarding beef cattle, CYP was used by 90% of producers, CYP + CPF formulation by 8%, and alpha CYP by 2%. The second approach of this study was to search the occurrence of CYP and CPF residues in food commodities analyzed under the National Plan for Residue Control (2012-2015). CYP residues found above the LOD were reported in 4.0% and CPF in 13.4% of the vegetable samples tested, as well as in 1.2 and 28.8%, respectively, of the fruit samples tested. Regarding beef cattle, CYP residues were reported in 2.3% and organophosphates (as a general pesticide class) in 13.5% of samples tested. In conclusion, consumers may be exposed simultaneously to CPF and CYP, from fruits, vegetables, and beef intake. Accordingly, the policy for pesticide residues in food and human risk assessment should account for the combined exposure to CPF and CYP. Moreover, appropriate toxicological studies of this mixture (including genotoxicity) are warranted.
Feat-Vetel et al., 2018
Feat-Vetel, Justyne, Larrigaldie, Vanessa, Meyer-Dilhet, Geraldine, Herzine, Ameziane, Mougin, Camille, Laugeray, Anthony, Gefflaut, Thierry, Richard, Olivier, Quesniaux, Valerie, Montecot-Dubourg, Celine, & Mortaud, Stephane, “Multiple effects of the herbicide glufosinate-ammonium and its main metabolite on neural stem cells from the subventricular zone of newborn mice,” NeuroToxicology, 2018, 69, 152-163. DOI: 10.1016/j.neuro.2018.10.001.
ABSTRACT:
The globally used herbicide glufosinate-ammonium (GLA) is structurally analogous to the excitatory neurotransmitter glutamate, and is known to interfere with cellular mechanisms involved in the glutamatergic system. In this report, we used an in vitro model of murine primary neural stem cell culture to investigate the neurotoxicity of GLA and its main metabolite, 4-methylphosphinico-2-oxobutanoic acid (PPO). We demonstrated that GLA and PPO disturb ependymal wall integrity in the ventricular-subventricular zone (V-SVZ) and alter the neuro-glial differentiation of neural stem cells. GLA and PPO impaired the formation of cilia, with reduced Celsr2 expression after PPO exposure. GLA promoted the differentiation of neuronal and oligodendroglial cells while PPO increased B1 cell population and impaired neuronal fate of neural stem cells. These results confirm our previous in vivo report that developmental exposure to GLA alters neurogenesis in the SVZ, and neuroblast migration along the rostral migratory stream. They also highlight the importance of investigating the toxicity of pesticide degradation products. Indeed, not only GLA, but also its metabolite PPO disrupts V-SVZ homeostasis and provides a novel cellular mechanism underlying GLA-induced neurodevelopmental toxicity. Furthermore, we were able to demonstrate a neurotoxic activity of a metabolite of GLA different from that of GLA active substance for the very first time. FULL TEXT
EPA, 2018
Environmental Protection Agency, “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table,” Office of Pesticide Programs, 2018, Available at: https://www.epa.gov/pesticide-science-and-assessing-pesticide-risks/exposure-surrogate-reference-table-pesticide-risk.
SUMMARY:
The Exposure Surrogate Reference Table provides pesticide exposure information for risk assessment based on exposure scenarios, exposure routes and applicable personal protective equipment. FULL TEXT
EPA, 2017
Environmental Protection Agency, “Revised Glyphosate Issue Paper: Evaluation of Carcinogenic Potential,” Office of Pesticide Programs, December 12, 2017, Available at: https://cfpub.epa.gov/si/si_public_record_Report.cfm?Lab=OPP&dirEntryId=337935.
SUMMARY:
Not available. FULL TEXT
DeVito, 2017
DeVito, Michael, “Update on NTP Studies of Glyphosate,” Presented at the National Toxicology Program (NTP) Board of Scientific Counselors Meeting, December 7-8, 2017.
SUMMARY:
Not available. FULL TEXT
Dellaferrera et al., 2018
Dellaferrera, Ignacio, Cortés, Eduardo, Panigo, Elisa, De Prado, Rafael, Christoffoleti, Pedro, & Perreta, Mariel, “First Report of Amaranthus hybridus with Multiple Resistance to 2,4-D, Dicamba, and Glyphosate,” Agronomy, 2018, 8(8). DOI: 10.3390/agronomy8080140.
ABSTRACT:
In many countries, Amaranthus hybridus is a widespread weed in agricultural systems. The high prolificacy and invasive capacity as well as the resistance of some biotypes to herbicides are among the complications of handling this weed. This paper reports on the first A. hybridus biotypes with resistance to auxinic herbicides and multiple resistance to auxinic herbicides and the EPSPs inhibitor, glyphosate. Several dose response assays were carried out to determine and compare sensitivity of six population of A. hybridus to glyphosate, 2,4-D, and dicamba. In addition, shikimic acid accumulation and piperonil butoxide effects on 2,4-D and dicamba metabolism were tested in the same populations. The results showed four populations were resistant to dicamba and three of these were also resistant to 2,4-D, while only one population was resistant to glyphosate. The glyphosate-resistant population also showed multiple resistance to auxinic herbicides. Pretreatment with piperonil butoxide (PBO) followed by 2,4-D or dicamba resulted in the death of all individual weeds independent of herbicide or population. FULL TEXT
Defarge et al., 2018
Defarge, N., Spiroux de Vendomois, J., & Seralini, G. E., “Toxicity of formulants and heavy metals in glyphosate-based herbicides and other pesticides,” Toxicology Reports, 2018, 5, 156-163. DOI: 10.1016/j.toxrep.2017.12.025.
ABSTRACT:
The major pesticides of the world are glyphosate-based herbicides (GBH), and their toxicity is highly debated. To understand their mode of action, the comparative herbicidal and toxicological effects of glyphosate (G) alone and 14 of its formulations were studied in this work, as a model for pesticides. GBH are mixtures of water, with commonly 36-48% G claimed as the active principle. As with other pesticides, 10-20% of GBH consist of chemical formulants. We previously identified these by mass spectrometry and found them to be mainly families of petroleum-based oxidized molecules, such as POEA, and other contaminants. We exposed plants and human cells to the components of formulations, both mixed and separately, and measured toxicity and human cellular endocrine disruption below the direct toxicity experimentally measured threshold. G was only slightly toxic on plants at the recommended dilutions in agriculture, in contrast with the general belief. In the short term, the strong herbicidal and toxic properties of its formulations were exerted by the POEA formulant family alone. The toxic effects and endocrine disrupting properties of the formulations were mostly due to the formulants and not to G. In this work, we also identified by mass spectrometry the heavy metals arsenic, chromium, cobalt, lead and nickel, which are known to be toxic and endocrine disruptors, as contaminants in 22 pesticides, including 11 G-based ones. This could also explain some of the adverse effects of the pesticides. In in vivo chronic regulatory experiments that are used to establish the acceptable daily intakes of pesticides, G or other declared active ingredients in pesticides are assessed alone, without the formulants. Considering these new data, this assessment method appears insufficient to ensure safety. These results, taken together, shed a new light on the toxicity of these major herbicides and of pesticides in general. FULL TEXT
de Souza et al., 2017
de Souza, Janaina Sena, Kizys, Marina Malta Letro, da Conceicao, Rodrigo Rodrigues, Glebocki, Gabriel, Romano, Renata Marino, Ortiga-Carvalho, Tania Maria, Giannocco, Gisele, da Silva, Ismael Dale Cotrim Guerreiro, Dias da Silva, Magnus Regios, Romano, Marco Aurelio, & Chiamolera, Maria Izabel, “Perinatal exposure to glyphosate-based herbicide alters the thyrotrophic axis and causes thyroid hormone homeostasis imbalance in male rats,” Toxicology, 2017, 377, 25-37. DOI: 10.1016/j.tox.2016.11.005.
ABSTRACT:
Glyphosate-based herbicides (GBHs) are widely used in agriculture. Recently, several animal and epidemiological studies have been conducted to understand the effects of these chemicals as an endocrine disruptor for the gonadal system. The aim of the present study was to determine whether GBHs could also disrupt the hypothalamic-pituitary-thyroid (HPT) axis. Female pregnant Wistar rats were exposed to a solution containing GBH Roundup((R))Transorb (Monsanto). The animals were divided into three groups (control, 5mg/kg/day or 50mg/kg/day) and exposed from gestation day 18 (GD18) to post-natal day 5 (PND5). Male offspring were euthanized at PND 90, and blood and tissues samples from the hypothalamus, pituitary, liver and heart were collected for hormonal evaluation (TSH-Thyroid stimulating hormone, T3-triiodothyronine and T4-thyroxine), metabolomic and mRNA analyses of genes related to thyroid hormone metabolism and function. The hormonal profiles showed decreased concentrations of TSH in the exposed groups, with no variation in the levels of the thyroid hormones (THs) T3 and T4 between the groups. Hypothalamus gene expression analysis of the exposed groups revealed a reduction in the expression of genes encoding deiodinases 2 (Dio2) and 3 (Dio3) and TH transporters Slco1c1 (former Oatp1c1) and Slc16a2 (former Mct8). In the pituitary, Dio2, thyroid hormone receptor genes (Thra1 and Thrb1), and Slc16a2 showed higher expression levels in the exposed groups than in the control group. Interestingly, Tshb gene expression did not show any difference in expression profile between the control and exposed groups. Liver Thra1 and Thrb1 showed increased mRNA expression in both GBH-exposed groups, and in the heart, Dio2, Mb, Myh6 (former Mhca) and Slc2a4 (former Glut4) showed higher mRNA expression in the exposed groups. Additionally, correlation analysis between gene expression and metabolomic data showed similar alterations as detected in hypothyroid rats. Perinatal exposure to GBH in male rats modified the HPT set point, with lower levels of TSH likely reflecting post-translational events. Several genes regulated by TH or involved in TH metabolism and transport presented varying degrees of gene expression alteration that were probably programmed during intrauterine exposure to GBHs and reflects in peripheral metabolism. In conclusion, the role of GBH exposure in HPT axis disruption should be considered in populations exposed to this herbicide. FULL TEXT
De Almeida et al., 2018
De Almeida, L. K. S., Pletschke, B. I., & Frost, C. L., “Moderate levels of glyphosate and its formulations vary in their cytotoxicity and genotoxicity in a whole blood model and in human cell lines with different estrogen receptor status,” 3 Biotech, 2018, 8(10), 438. DOI: 10.1007/s13205-018-1464-z.
ABSTRACT:
In vitro studies were conducted to determine the short-term cytotoxic and genotoxic effects of pure glyphosate and two glyphosate formulations (Roundup® and Wipeout®) at concentrations relevant to human exposure using whole blood (cytotoxicity) and various cancer cell lines (cytotoxicity and genotoxicity). Pure glyphosate (pure glyph) and Roundup® (Ro) showed similar non-monotonic toxicological profiles at low dose exposure (from 10 microg/ml), whereas Wipeout® (Wo) demonstrated a monotonic reduction in cell viability from a threshold concentration of 50 microg/ml, when tested in whole blood. We evaluated whether using various cancer cells (the estrogen-E2-responsive HEC1A, MCF7 and the estrogen-insensitive MDA-MB-231) exposed to moderate doses (75-500 microg/ml) would indicate varied toxicity and results indicated significant effects in the HEC1A cancer cells. A non-monotonic reduction in cell viability was observed in HEC1A exposed to pure glyph (75-500 microg/ml) and proliferative effects were observed after exposure to Wo (75, 125 and 250 microg/ml). Genotoxicity assessment (test concentration 500 microg/ml) demonstrated DNA damage in the HEC1A and MDA-MB-231 cells. Adjuvants and/or glyphosate impurities were potential contributing factors of toxicity based on the differential toxicities displayed by Ro and Wo in human whole blood and the HEC1A cells. This study contributes to the existing knowledge about in vitro exposure to moderate concentrations of glyphosate or glyphosate formulations at cytotoxic and genotoxic levels. In addition, a suggestion on the relevance of the estrogen receptor status of the cell lines used is provided, leading to the need to further investigate a potential endocrine disruptive role. FULL TEXT
Davoren and Schiestl, 2018
Davoren, Michael J, & Schiestl, Robert H., “Glyphosate-based herbicides and cancer risk: a post-IARC decision review of potential mechanisms, policy and avenues of research,” Carcinogenesis, 2018, 39:10, 1207-1215. DOI:10.1093/carcin/bgy105.
ABSTRACT:
Since its initial sales in the 1970s, the herbicide glyphosate attained widespread use in modern agriculture, becoming the most commercially successful and widely used herbicide of all time as of 2016. Despite a primary mechanism that targets a pathway absent from animal cells and regulatory studies showing safety margins orders of magnitude better than many other, more directly toxic herbicides, the safety status of glyphosate has recently been brought into question by a slow accumulation of studies suggesting more subtle health risks, especially when considered in combination with the surfactants it is usually applied with. Current, official views of respected international regulatory and health bodies remain divided on glyphosate’s status as a human carcinogen, but the 2015 International Agency for Research on Cancer decision to reclassify the compound as Category 2A (probably carcinogenic to humans) marked a sea change in the scientific community’s consensus view. The goal of this review is to consider the state of science regarding glyphosate’s potential as a human carcinogen and genotoxin, with particular focus on studies suggesting mechanisms that would go largely undetected in traditional toxicology studies, such as microbiome disruption and endocrine mimicry at very low concentrations. FULL TEXT