The mechanism of DNA damage induced by Roundup 360 PLUS, glyphosate and AMPA in human peripheral blood mononuclear cells - genotoxic risk assessement

Woźniak, Ewelina; Sicińska, Paulina; Michałowicz, Jaromir; Woźniak, Katarzyna; Reszka, Edyta; Huras, Bogumiła; Zakrzewski, Jerzy; Bukowska, Bożena

doi:10.1016/j.fct.2018.07.035

Cited by 81 publications

(53 citation statements)

References 32 publications

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“…In PBMCs, RoundUp V R , glyphosate, and AMPA induced single-strand breaks, and both RoundUp V R and high doses of glyphosate caused double-strand breaks too, which are repaired after 2 h, except for the highest RoundUp V R concentration (Kwiatkowska et al 2017;Wo zniak et al 2018). Another study comparing genotoxicity in lymphocytes from populations exposed to GBH spraying showed a slightly higher frequency of binucleated cells with micronuclei (Bolognesi et al 2009); as this effect decreased 4 months after the last GBH spraying, the authors concluded GBH caused low transient genotoxicity.…”

Section: Genotoxicitymentioning

confidence: 99%

The impact and toxicity of glyphosate and glyphosate-based herbicides on health and immunity

Peillex

Pelletier

2020

Journal of Immunotoxicology

174

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Glyphosate, or N-phosphomethyl(glycine), is an organophosphorus compound and a competitive inhibitor of the shikimate pathway that allows aromatic amino acid biosynthesis in plants and microorganisms. Its utilization in broad-spectrum herbicides, such as RoundUp V R , has continued to increase since 1974; glyphosate, as well as its primary metabolite aminomethylphosphonic acid, is measured in soils, water, plants, animals and food. In humans, glyphosate is detected in blood and urine, especially in exposed workers, and is excreted within a few days. It has long been regarded as harmless in animals, but growing literature has reported health risks associated with glyphosate and glyphosate-based herbicides. In 2017, the International Agency for Research on Cancer (IARC) classified glyphosate as "probably carcinogenic" in humans. However, other national agencies did not tighten their glyphosate restrictions and even prolonged authorizations of its use. There are also discrepancies between countries' authorized levels, demonstrating an absence of a clear consensus on glyphosate to date. This review details the effects of glyphosate and glyphosate-based herbicides on fish and mammal health, focusing on the immune system. Increasing evidence shows that glyphosate and glyphosate-based herbicides exhibit cytotoxic and genotoxic effects, increase oxidative stress, disrupt the estrogen pathway, impair some cerebral functions, and allegedly correlate with some cancers. Glyphosate effects on the immune system appear to alter the complement cascade, phagocytic function, and lymphocyte responses, and increase the production of pro-inflammatory cytokines in fish. In mammals, including humans, glyphosate mainly has cytotoxic and genotoxic effects, causes inflammation, and affects lymphocyte functions and the interactions between microorganisms and the immune system. Importantly, even as many outcomes are still being debated, evidence points to a need for more studies to better decipher the risks from glyphosate and better regulation of its global utilization.

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Section: Genotoxicitymentioning

confidence: 99%

The impact and toxicity of glyphosate and glyphosate-based herbicides on health and immunity

Peillex

Pelletier

2020

Journal of Immunotoxicology

174

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“…EPA regards such differences as "hypothesized, " despite many studies reporting that GBHs are, in general, more toxic than glyphosate technical [30][31][32], and sometimes by large margins [33,34], as shown in Table 3. The examples of differential toxicity in Table 3 are based on the levels of glyphosate technical triggering a defined, positive genotoxicity response in a given assay, in contrast to the amount of glyphosate in a GBH that triggers the same response.…”

Section: Differential Toxicitymentioning

confidence: 99%

How did the US EPA and IARC reach diametrically opposed conclusions on the genotoxicity of glyphosate-based herbicides?

Benbrook

2019

Environ Sci Eur

134

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Background: The US EPA considers glyphosate as "not likely to be carcinogenic to humans. " The International Agency for Research on Cancer (IARC) has classified glyphosate as "probably carcinogenic to humans (Group 2A). " EPA asserts that there is no convincing evidence that "glyphosate induces mutations in vivo via the oral route. " IARC concludes there is "strong evidence" that exposure to glyphosate is genotoxic through at least two mechanisms known to be associated with human carcinogens (DNA damage, oxidative stress). Why and how did EPA and IARC reach such different conclusions? Results: A total of 52 genotoxicity assays done by registrants were cited by the EPA in its 2016 evaluation of technical glyphosate, and another 52 assays appeared in the public literature. Of these, one regulatory assay (2%) and 35 published assays (67%) reported positive evidence of a genotoxic response. In the case of formulated, glyphosatebased herbicides (GBHs), 43 regulatory assays were cited by EPA, plus 65 assays published in peer-reviewed journals. Of these, none of the regulatory, and 49 published assays (75%) reported evidence of a genotoxic response following exposure to a GBH. IARC considered a total of 118 genotoxicity assays in six core tables on glyphosate technical, GBHs, and aminomethylphosphonic acid (AMPA), glyphosate's primary metabolite. EPA's analysis encompassed 51 of these 118 assays (43%). In addition, IARC analyzed another 81 assays exploring other possible genotoxic mechanisms (mostly related to sex hormones and oxidative stress), of which 62 (77%) reported positive results. IARC placed considerable weight on three positive GBH studies in exposed human populations, whereas EPA placed little or no weight on them. Conclusions: EPA and IARC reached diametrically opposed conclusions on glyphosate genotoxicity for three primary reasons: (1) in the core tables compiled by EPA and IARC, the EPA relied mostly on registrant-commissioned, unpublished regulatory studies, 99% of which were negative, while IARC relied mostly on peer-reviewed studies of which 70% were positive (83 of 118); (2) EPA's evaluation was largely based on data from studies on technical glyphosate, whereas IARC's review placed heavy weight on the results of formulated GBH and AMPA assays; (3) EPA's evaluation was focused on typical, general population dietary exposures assuming legal, food-crop uses, and did not take into account, nor address generally higher occupational exposures and risks. IARC's assessment encompassed data from typical dietary, occupational, and elevated exposure scenarios. More research is needed on real-world exposures to the chemicals within formulated GBHs and the biological fate and consequences of such exposures.

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“…For these reasons, recently, the cytotoxic and genotoxic effects were also evaluated on glyphosate-based herbicides, such as Roundup®. Roundup® has been found able to cause genomic damage to human peripheral blood mononuclear cells at a concentration of 5 μM, a value lower than that observed for glyphosate, which was found to induce DNA lesions starting from a concentration of 500 μM (Woźniak et al 2018). The genotoxic effect of glyphosate-based herbicides has already been tested with MN assay on some vertebrate taxa, such as fish (Grisolia 2002;Cavalcante et al 2008), reptiles (Poletta et al 2009;Schaumburg et al 2016), and amphibians (Bosch et al 2011).…”

Section: Introductionmentioning

confidence: 99%

A micronucleus assay detects genotoxic effects of herbicide exposure in a protected butterfly species

2020

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Lycaena dispar Hawort (Lepidoptera: Lycaenidae), a protected butterfly, is declining in Europe, but it thrives in rice fields in northern Italy. Here, agrochemical usage could threaten its long-term survival. We investigated, by micronucleus (MN) assay, the genotoxic effect of glyphosate, a common herbicide, on L. dispar larvae. Micronuclei (MNi) are DNA fragments separated from the main nucleus and represent the result of genomic damage that has been transmitted to daughter cells. In a control/treatment experiment, we extracted epithelial cells from last-instar larvae fed with Rumex spp. plants sprayed with a solution containing 3.6 g/L of glyphosate, and from larvae fed with unsprayed plants. MNi and other chromosomal aberrations—nuclear buds (NBUDs) and bi-nucleated cells—were then scored in 1000 cells/subject. Significant differences were found between glyphosate-exposed and control groups in terms of MNi and total genomic damage, but not in terms of NBUDs or bi-nucleated cells. We reported a possible genomic damage induced by glyphosate on larvae of L. dispar. For the first time, a MN assay was used in order to evaluate the genomic damage on a phytophagous invertebrate at the larval stage. Increased levels of MNi reflect a condition of genomic instability that can result in reduced vitality and in an increased risk of local extinction. Therefore, farmland management compatible with wildlife conservation is needed.

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The mechanism of DNA damage induced by Roundup 360 PLUS, glyphosate and AMPA in human peripheral blood mononuclear cells - genotoxic risk assessement

Cited by 81 publications

References 32 publications

The impact and toxicity of glyphosate and glyphosate-based herbicides on health and immunity

The impact and toxicity of glyphosate and glyphosate-based herbicides on health and immunity

How did the US EPA and IARC reach diametrically opposed conclusions on the genotoxicity of glyphosate-based herbicides?

A micronucleus assay detects genotoxic effects of herbicide exposure in a protected butterfly species

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