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Sieke et al., 2018

Sieke, C., Michalski, B., & Kuhl, T.; “Probabilistic dietary risk assessment of pesticide residues in foods for the German population based on food monitoring data from 2009 to 2014;” Journal of Exposure Analysis and Environmental Epidemiology, 2018, 28(1), 46-54; DOI: 10.1038/jes.2017.7.

ABSTRACT:

Dietary risks for the German population owing to pesticide residues in foods were assessed based on food monitoring data, consumption surveys for children and adults and compound specific toxicological reference values or general thresholds of toxicological concern. A tiered probabilistic modelling was conducted to screen 700 pesticides for significant long- and short-term dietary exposures. Especially for the short-term dietary exposure, the probabilistic methodology used allows simultaneous consideration of the complete daily consumption, whereas most regulatory bodies still rely on single commodity approaches. After screening, refined exposure assessments were conducted for 19 compounds under consideration of conversion factors for toxicologically relevant metabolites, processing information, experimentally derived variability factors and the edible portion for each food item. In total, for 693 compounds the dietary exposure was unlikely to present a chronic or acute public health concern for the German population. In contrast, the refined assessments indicate that the short-term dietary exposure for chlorpyrifos and the cumulative short-term dietary exposure for dimethoate and omethoate may present a public health concern. For copper, owing to exposure assessment limitations, as well as for dimethylvinphos, halfenprox and tricyclazole, which exceeded the thresholds of toxicological concern, the dietary risk assessment remained inconclusive. FULL TEXT

Nougadere et al., 2020

Nougadere, A., Sirot, V., Cravedi, J. P., Vasseur, P., Feidt, C., Fussell, R. J., Hu, R., Leblanc, J. C., Jean, J., Riviere, G., Sarda, X., Merlo, M., & Hulin, M.; “Dietary exposure to pesticide residues and associated health risks in infants and young children – Results of the French infant total diet study;” Environment International, 2020, 137, 105529; DOI: 10.1016/j.envint.2020.105529.

ABSTRACT:

A total diet study (TDS) was undertaken to estimate the chronic dietary exposure to pesticide residues and health risks for the French infants and young children below 3 years old. As a whole, 516 pesticides and metabolites were analysed in 309 food composite samples including 219 manufactured baby foods and 90 common foods, which cover 97% of infants and young children’s diet. These composite samples were prepared using 5,484 food products purchased during all seasons from 2011 to 2012 and processed as consumed. Pesticide residues were detected in 67% of the samples and quantified in 27% of the baby food samples and in 60% of the common foods. Seventy-eight different pesticides were detected and 37 of these quantified at levels ranging from 0.02 to 594 microg/kg. The most frequently detected pesticides (greater than 5% samples) were (1) the fungicides 2-phenylphenol, azoxystrobin, boscalid, captan and its metabolite tetrahydrophthalimide, carbendazim, cyprodinil, difenoconazole, dodine, imazalil, metalaxyl, tebuconazole, thiabendazole, (2) the insecticides acetamiprid, pirimiphos-methyl and thiacloprid, (3) the herbicide metribuzin and (4) the synergist piperonyl butoxide. Dietary intakes were estimated for each of the 705 individuals studied and for 431 pesticides incl. 281 with a toxicological reference value (TRV). In the lower-bound scenario, which tends to underestimate the exposure, the TRV were never exceeded. In the upper-bound scenario that overestimates exposure, the estimated intakes exceeded the TRV for dieldrin and lindane (two persistent organic pollutants) and propylene thiourea, a metabolite of propineb. For these three substances, more sensitive analyses are needed to refine the assessment. For 17 other detected and/or prioritised pesticides, the risk could not be characterised due to the lack of a valid TRV, of certain food analyses or the absence of analytical standards for their metabolites. FULL TEXT

Mesnage and Antoniou, 2020

Mesnage, Robin, & Antoniou, Michael N.; “Computational modelling provides insight into the effects of glyphosate on the shikimate pathway in the human gut microbiome;” Current Research in Toxicology, 2020, 1, 25-33; DOI: 10.1016/j.crtox.2020.04.001.

ABSTRACT:

The herbicide active ingredient glyphosate can affect the growth of microorganisms, which rely on the shikimate pathway for aromatic amino acid biosynthesis. However, it is uncertain whether glyphosate exposure could lead to perturbations in the population of human gut microbiota. We have addressed this knowledge gap by analysing publicly available datasets to provide new insights into possible effects of glyphosate on the human gut microbiome. Comparison of the abundance of the shikimate pathway in 734 paired metagenomes and metatranscriptomes indicated that most gut bacteria do not possess a complete shikimate pathway, and that this pathway is mostly transcriptionally inactive in the human gut microbiome. This suggests that gut bacteria are mostly aromatic amino acid auxotrophs and thus relatively resistant to a potential growth inhibition by glyphosate. As glyphosate blocking of the shikimate pathway is via inhibition of EPSPS, we classified E. coli EPSPS enzyme homologues as class I (sensitive to glyphosate) and class II (resistant to glyphosate). Among 44 subspecies reference genomes, accounting for 72% of the total assigned microbial abundance in 2144 human faecal metagenomes, 9 subspecies have class II EPSPS. The study of publicly available gut metagenomes also indicated that glyphosate might be degraded by some Proteobacteria in the human gut microbiome using the carbon–phosphorus lyase pathway. Overall, there is limited experimental evidence available for the effects of glyphosate on the human gut microbiome. Further investigations using more advanced molecular profiling techniques are needed to ascertain whether glyphosate and glyphosate-based herbicides can alter the function of the gut microbiome with consequent health implications. FULL TEXT

Almeida et al., 2017

Almeida, L. L., Teixeira, A. A. C., Soares, A. F., Cunha, F. M. D., Silva, V. A. D. Junior, Vieira Filho, L. D., & Wanderley-Teixeira, V.; “Effects of melatonin in rats in the initial third stage of pregnancy exposed to sub-lethal doses of herbicides;” Acta Histochemica, 2017, 119(3), 220-227; DOI: 10.1016/j.acthis.2017.01.003.

ABSTRACT:

Exposure to the herbicides Paraquat (PQ) and Roundup((R)) may cause cell lesions due to an increase in oxidative stress levels in different biological systems, even in the reproductive system.

OBJECTIVE: Evaluate the possible changes in reproductive parameters and hepatic, as well as its prevention by simultaneous application of melatonin.

METHODS: Thirty-five female rats at the age of 3 months were divided into seven groups: three groups exposed to sub-lethal doses of the herbicides PQ (50mg/kg) and Roundup((R)) (500mg/kg) (n=5, G2, G3 and G4); three groups exposed to herbicides and simultaneous treatment with 10mg/kg of Melatonin (n=5, G5, G6 and G7) and control group (n=5, G1) from the first to the seventh day of pregnancy. On the seventh day of pregnancy, the rats were anesthetized and euthanized, followed by laparotomy to remove their reproductive tissues and liver. Body and ovary weights were taken and the number of implantation sites, corpora lutea, preimplantation losses, implantation rates were counted and histopathology of the implantation sites, morphometry of the surface and glandular epithelia of endometrium and hepatic oxidative stress were undertaken.

RESULTS: The present study shows the decrease in body and ovary weight, decrease in the number of implantation sites, implantation rate, in the total number of corpora lutea and increase of preimplantation percentages were observed when compared to the G1: Fig. 1 and Table 1, (p>0.001 ANOVA/Tukey). The histopathological analysis of the implantation sites showed a disorder of the cytotrophoblast and cell degeneration within the blastocyst cavity in Fig. 4. Morphometry revealed a reduction in surface and glandular epithelia and in the diameter of the endometrial glands (Table 2; p>0.05 ANOVA/Tukey), whereas in liver, serum levels of thiobarbituric acid reactive substances (TBARS) were found to be significantly elevated (Fig. 2; p>0.001; p>0.05 ANOVA/Tukey), and serum level of reduced glutathione (GSH) was significantly lower (Fig. 3; p>0.001 ANOVA/Tukey). However, treatments with melatonin exhibited improvements in reproductive parameters, as well as reduced lesions in the implantation sites (Fig. 4.) and in serum levels TBARS (Fig. 2; p>0.001 ANOVA/Tukey), serum levels GSH (Fig. 3; p>0.001; p>0.05 ANOVA/Tukey).

CONCLUSIONS: These results reveal that melatonin is a protective agent against experimentally induced maternal/embryo toxicity with herbicides and favoring normalization of reproductive parameters and hepatic.

FULL TEXT

Brehm and Flaws, 2019

Brehm, E., & Flaws, J. A.; “Transgenerational Effects of Endocrine-Disrupting Chemicals on Male and Female Reproduction;” Endocrinology, 2019, 160(6), 1421-1435; DOI: 10.1210/en.2019-00034.

ABSTRACT:

Endocrine-disrupting chemicals are known to interfere with normal reproductive function and hormone signaling. Phthalates, bisphenol A, pesticides, and environmental contaminants such as polychlorinated biphenyls and dioxins are known endocrine-disrupting chemicals that have been shown to negatively affect both male and female reproduction. Exposure to these chemicals occurs on a daily basis owing to these compounds being found in plastics, personal care products, and pesticides. Recently, studies have shown that these chemicals may cause transgenerational effects on reproduction in both males and females. This is of concern because exposure to these chemicals prenatally or during adult life can negatively impact the reproductive health of future generations. This mini-review summarizes the endocrine-disrupting chemicals that humans are exposed to on a daily basis and what is known about the transgenerational effects that these chemicals may have on male and female reproduction. FULL TEXT

Dechartres et al., 2019

Dechartres, J., Pawluski, J. L., Gueguen, M. M., Jablaoui, A., Maguin, E., Rhimi, M., & Charlier, T. D.; “Glyphosate and glyphosate-based herbicide exposure during the peripartum period affects maternal brain plasticity, maternal behaviour and microbiome;” Journal of Neuroendocrinology, 2019, 31(9), e12731; DOI: 10.1111/jne.12731.

ABSTRACT:

Glyphosate is found in a large array of non-selective herbicides such as Roundup(R) (Monsanto, Creve Coeur, MO, USA) and is by far the most widely used herbicide. Recent work in rodent models suggests that glyphosate-based herbicides during development can affect neuronal communication and result in altered behaviours, albeit through undefined mechanisms of action. To our knowledge, no study has investigated the effects glyphosate or its formulation in herbicide on maternal behaviour and physiology. In the present study, relatively low doses of glyphosate (5 mg kg(-1) d(-1) ), Roundup(R) (5 mg kg(-1) d(-1) glyphosate equivalent), or vehicle were administered by ingestion to Sprague-Dawley rats from gestational day (GD) 10 to postpartum day (PD)22. The treatments significantly altered licking behaviour toward pups between PD2 and PD6. We also show in the dams at PD22 that Roundup exposure affected the maturation of doublecortin-immunoreactive new neurones in the dorsal dentate gyrus of the hippocampus of the mother. In addition, the expression of synaptophysin was up-regulated by glyphosate in the dorsal and ventral dentate gyrus and CA3 regions of the hippocampus, and down-regulated in the cingulate gyrus. Although a direct effect of glyphosate alone or its formulation on the central nervous system is currently not clear, we show that gut microbiota is significantly altered by the exposure to the pesticides, with significant alteration of the phyla Bacteroidetes and Firmicutes. This is the first study to provide evidence that glyphosate alone or in formulation (Roundup) differentially affects maternal behaviour and modulates neuroplasticity and gut microbiota in the mother. FULL TEXT

Lorenz et al., 2019

Lorenz, V., Milesi, M. M., Schimpf, M. G., Luque, E. H., & Varayoud, J.; “Epigenetic disruption of estrogen receptor alpha is induced by a glyphosate-based herbicide in the preimplantation uterus of rats;” Molecular and Cellular Endocrinology, 2019, 480, 133-141; DOI: 10.1016/j.mce.2018.10.022.

ABSTRACT:

Previously, we have shown that perinatal exposure to a glyphosate-based herbicide (GBH) induces implantation failures in rats. Estrogen receptor alpha (ERalpha) is critical for successful implantation. ERalpha transcription is under the control of five promoters (E1, OT, O, ON, and OS), which yield different transcripts. Here, we studied whether perinatal exposure to a GBH alters uterine ERalpha gene expression and prompts epigenetic modifications in its regulatory regions during the preimplantation period. Pregnant rats (F0) were orally treated with 350mg glyphosate/kg bw/day through food from gestational day (GD) 9 until weaning. F1 females were bred, and uterine samples were collected on GD5 (preimplantation period). ERalpha mRNA levels and its transcript variants were evaluated by RT-qPCR. Enzyme-specific restriction sites and predicted transcription factors were searched in silico in the ERalpha promoter regions to assess the methylation status using the methylation-sensitive restriction enzymes-PCR technique. Post-translational modifications of histones were studied by the chromatin immunoprecipitation assay. GBH upregulated the expression of total ERalpha mRNA by increasing the abundance of the ERalpha-O transcript variant. In addition, different epigenetic changes were detected in the O promoter. A decrease in DNA methylation was observed in one of the three sites evaluated in the O promoter. Moreover, histone H4 acetylation and histone H3 lysine 9 trimethylation (H3K9me3) were enriched in the O promoter in GBH-exposed rats, whereas H3K27me3 was decreased. All these alterations could account for the increase in ERalpha gene expression. Our findings show that perinatal exposure to a GBH causes long-term epigenetic disruption of the uterine ERalpha gene, which could be associated with the GBH-induced implantation failures. FULL TEXT

Meftaul et al.; 2020

Meftaul, I. M., Venkateswarlu, K., Dharmarajan, R., Annamalai, P., Asaduzzaman, M., Parven, A., & Megharaj, M.; “Controversies over human health and ecological impacts of glyphosate: Is it to be banned in modern agriculture?;” Environmental Pollution, 2020, 263(Pt A), 114372; DOI: 10.1016/j.envpol.2020.114372.

ABSTRACT:

Glyphosate, introduced by Monsanto Company under the commercial name Roundup in 1974, became the extensively used herbicide worldwide in the last few decades. Glyphosate has excellent properties of fast sorption in soil, biodegradation and less toxicity to nontarget organisms. However, glyphosate has been reported to increase the risk of cancer, endocrine-disruption, celiac disease, autism, effect on erythrocytes, leaky-gut syndrome, etc. The reclassification of glyphosate in 2015 as ‘probably carcinogenic’ under Group 2A by the International Agency for Research on Cancer has been broadly circulated by anti-chemical and environmental advocacy groups claiming for restricted use or ban of glyphosate. In contrast, some comprehensive epidemiological studies involving farmers with long-time exposure to glyphosate in USA and elsewhere coupled with available toxicological data showed no correlation with any kind of carcinogenic or genotoxic threat to humans. Moreover, several investigations confirmed that the surfactant, polyethoxylated tallow amine (POEA), contained in the formulations of glyphosate like Roundup, is responsible for the established adverse impacts on human and ecological health. Subsequent to the evolution of genetically modified glyphosate-resistant crops and the extensive use of glyphosate over the last 45 years, about 38 weed species developed resistance to this herbicide. Consequently, its use in the recent years has been either restricted or banned in 20 countries. This critical review on glyphosate provides an overview of its behaviour, fate, detrimental impacts on ecological and human health, and the development of resistance in weeds and pathogens. Thus, the ultimate objective is to help the authorities and agencies concerned in resolving the existing controversies and in providing the necessary regulations for safer use of the herbicide. In our opinion, glyphosate can be judiciously used in agriculture with the inclusion of safer surfactants in commercial formulations sine POEA, which is toxic by itself is likely to increase the toxicity of glyphosate. FULL TEXT

Rattan and Flaws, 2019

Rattan, S., & Flaws, J. A.; “The epigenetic impacts of endocrine disruptors on female reproduction across generationsdagger;” Biology of Reproduction, 2019, 101(3), 635-644; DOI: 10.1093/biolre/ioz081.

ABSTRACT:

Humans and animals are repeatedly exposed to endocrine disruptors, many of which are ubiquitous in the environment. Endocrine disruptors interfere with hormone action; thus, causing non-monotonic dose responses that are atypical of standard toxicant exposures. The female reproductive system is particularly susceptible to the effects of endocrine disruptors. Likewise, exposures to endocrine disruptors during developmental periods are particularly concerning because programming during development can be adversely impacted by hormone level changes. Subsequently, developing reproductive tissues can be predisposed to diseases in adulthood and these diseases can be passed down to future generations. The mechanisms of action by which endocrine disruptors cause disease transmission to future generations are thought to include epigenetic modifications. This review highlights the effects of endocrine disruptors on the female reproductive system, with an emphasis on the multi- and transgenerational epigenetic effects of these exposures. FULL TEXT

Ingaramo et al., 2020

Ingaramo, P., Alarcon, R., Munoz-de-Toro, M., & Luque, E. H.; “Are glyphosate and glyphosate-based herbicides endocrine disruptors that alter female fertility?;” Molecular and Cellular Endocrinology, 2020, 110934; DOI: 10.1016/j.mce.2020.110934.

ABSTRACT:

Numerous evidences have alerted on the toxic effects of the exposure to glyphosate on living organisms. Glyphosate is the herbicide most used in crops such as maize and soybean worldwide, which implies that several non-target species are at a high risk of exposure. Although the Environmental Protection Agency (EPA-USA) has reaffirmed that glyphosate is safe for users, there are controversial studies that question this statement. Some of the reported effects are due to exposure to high doses; however, recent evidences have shown that exposure to low doses could also alter the development of the female reproductive tract, with consequences on fertility. Different animal models of exposure to glyphosate or glyphosate-based herbicides (GBHs) have shown that the effects on the female reproductive tract may be related to the potential and/or mechanisms of actions of an endocrine-disrupting compound. Studies have also demonstrated that the exposure to GBHs alters the development and differentiation of ovarian follicles and uterus, affecting fertility when animals are exposed before puberty. In addition, exposure to GBHs during gestation could alter the development of the offspring (F1 and F2). The main mechanism described associated with the endocrine-disrupting effect of GBHs is the modulation of estrogen receptors and molecules involved in the estrogenic pathways. This review summarizes the endocrine-disrupting effects of exposure to glyphosate and GBHs at low or “environmentally relevant” doses in the female reproductive tissues. Data suggesting that, at low doses, GBHs may have adverse effects on the female reproductive tract fertility are discussed. FULL TEXT

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