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International Journal of Molecular... Apr 2022Glyphosate, a non-selective systemic biocide with broad-spectrum activity, is the most widely used herbicide in the world. It can persist in the environment for days or... (Review)
Review
Glyphosate, a non-selective systemic biocide with broad-spectrum activity, is the most widely used herbicide in the world. It can persist in the environment for days or months, and its intensive and large-scale use can constitute a major environmental and health problem. In this systematic review, we investigate the current state of our knowledge related to the effects of this pesticide on the nervous system of various animal species and humans. The information provided indicates that exposure to glyphosate or its commercial formulations induces several neurotoxic effects. It has been shown that exposure to this pesticide during the early stages of life can seriously affect normal cell development by deregulating some of the signaling pathways involved in this process, leading to alterations in differentiation, neuronal growth, and myelination. Glyphosate also seems to exert a significant toxic effect on neurotransmission and to induce oxidative stress, neuroinflammation and mitochondrial dysfunction, processes that lead to neuronal death due to autophagy, necrosis, or apoptosis, as well as the appearance of behavioral and motor disorders. The doses of glyphosate that produce these neurotoxic effects vary widely but are lower than the limits set by regulatory agencies. Although there are important discrepancies between the analyzed findings, it is unequivocal that exposure to glyphosate produces important alterations in the structure and function of the nervous system of humans, rodents, fish, and invertebrates.
Topics: Animals; Central Nervous System Depressants; Glycine; Herbicides; Neurotoxicity Syndromes; Glyphosate
PubMed: 35562999
DOI: 10.3390/ijms23094605 -
Mutation Research. Reviews in Mutation... 2019Glyphosate is the most widely used broad-spectrum systemic herbicide in the world. Recent evaluations of the carcinogenic potential of glyphosate-based herbicides (GBHs)... (Meta-Analysis)
Meta-Analysis
Glyphosate is the most widely used broad-spectrum systemic herbicide in the world. Recent evaluations of the carcinogenic potential of glyphosate-based herbicides (GBHs) by various regional, national, and international agencies have engendered controversy. We investigated whether there was an association between high cumulative exposures to GBHs and increased risk of non-Hodgkin lymphoma (NHL) in humans. We conducted a new meta-analysis that includes the most recent update of the Agricultural Health Study (AHS) cohort published in 2018 along with five case-control studies. Using the highest exposure groups when available in each study, we report the overall meta-relative risk (meta-RR) of NHL in GBH-exposed individuals was increased by 41% (meta-RR = 1.41, 95% confidence interval, CI: 1.13-1.75). For comparison, we also performed a secondary meta-analysis using high-exposure groups with the earlier AHS (2005), and we calculated a meta-RR for NHL of 1.45 (95% CI: 1.11-1.91), which was higher than the meta-RRs reported previously. Multiple sensitivity tests conducted to assess the validity of our findings did not reveal meaningful differences from our primary estimated meta-RR. To contextualize our findings of an increased NHL risk in individuals with high GBH exposure, we reviewed publicly available animal and mechanistic studies related to lymphoma. We documented further support from studies of malignant lymphoma incidence in mice treated with pure glyphosate, as well as potential links between glyphosate / GBH exposure and immunosuppression, endocrine disruption, and genetic alterations that are commonly associated with NHL or lymphomagenesis. Overall, in accordance with findings from experimental animal and mechanistic studies, our current meta-analysis of human epidemiological studies suggests a compelling link between exposures to GBHs and increased risk for NHL.
Topics: Carcinogens; Glycine; Herbicides; Humans; Lymphoma, Non-Hodgkin; Risk; Glyphosate
PubMed: 31342895
DOI: 10.1016/j.mrrev.2019.02.001 -
Toxics Apr 2022Rheumatoid arthritis (RA) is a disease that affects people all over the world and can be caused by a variety of factors. Exposure to pesticides is one of the risk... (Review)
Review
Rheumatoid arthritis (RA) is a disease that affects people all over the world and can be caused by a variety of factors. Exposure to pesticides is one of the risk factors for the development of RA. However, the evidence of exposure to pesticides linked with the development of RA is still controversial. This study aimed to investigate the association between exposure to pesticides and RA by a systematic review of relevant literature and a meta-analysis. Full-text articles published in PubMed, Web of Science, Scopus, and Google Scholar between 1956 and 2021 were reviewed and evaluated. A total of eight studies were eligible for inclusion (two cohort studies, four case-control studies, and two cross-sectional studies). The adjusted odds ratio for pesticide exposure on RA was 1.20 for insecticides (95% CI = 1.12-1.28), 0.98 for herbicides (95% CI = 0.89-1.08), 1.04 for fungicides (95% CI = 0.86-1.27), and 1.15 in for non-specific pesticides (95% CI = 1.09-1.21). There is some evidence to suggest that exposure to insecticides (especially fonofos, carbaryl, and guanidines) contributes to an increased risk of RA. However, the evidence is limited because of a small number of studies. Therefore, further epidemiological studies are needed to substantiate this conclusion.
PubMed: 35622621
DOI: 10.3390/toxics10050207 -
Systematic Reviews Aug 2021Sarcomas are a rare and heterogeneous group of tumors originating from mesenchymal or connective tissue. They represent less than 1% of all adult cancers. The etiology... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Sarcomas are a rare and heterogeneous group of tumors originating from mesenchymal or connective tissue. They represent less than 1% of all adult cancers. The etiology and epidemiology of sarcomas remain understudied and poorly understood. The main objective of our study was to systematically assess the association between various occupational exposures and risk of sarcomas.
METHODS
We performed a systematic literature search using the PubMed, Scopus, EMBASE and Cochrane databases to identify relevant cohort and case-control studies. A meta-analysis method was applied on the incidence and mortality outcomes where the estimate with 95% confidence interval (CI) was obtained.
RESULTS
We included a total of 50 publications in our systematic review and 35 in meta-analysis. For exposures to phenoxy herbicides and chlorophenols, the pooled odds ratio (OR) for sarcoma was 1.85 (95% CI: 1.22, 2.82), based on 16 studies with 2254 participants, while the pooled standardized mortality ratio was 40.93 (95% CI 2.19, 765.90), based on 4 cohort studies with 59,289 participants. For exposure to vinyl chloride monomers the pooled risk ratios for angiosarcoma of the liver and other STS were 19.23 (95% CI 2.03, 182.46) and 2.23 (95 CI 1.55, 3.22) respectively based on 3 cohort studies with 12,816 participants. Exposure to dioxins was associated with an increased STS mortality; the pooled standardized mortality ratio was 2.56 (95% CI 1.60, 4.10) based on 4 cohort studies with 30,797 participants. Finally, woodworking occupation was associated with an increased risk of STS with the pooled OR of 2.16 (95% CI 1.39, 3.36).
CONCLUSIONS
Our findings suggest a positive association between higher exposure to dioxins and increased mortality from STS, between cumulative exposure to vinyl chloride monomers and increased mortality from angiosarcoma of the liver and STS, and between woodworking occupation and STS incidence. These findings were all statistically significant.
Topics: Adult; Cohort Studies; Humans; Incidence; Occupational Diseases; Occupational Exposure; Sarcoma
PubMed: 34389054
DOI: 10.1186/s13643-021-01769-4 -
BMC Public Health Jun 2016A study in frog and chicken embryos, and reports of a high incidence of birth defects in regions of intensive GM-soy planting have raised concerns on the teratogenic... (Review)
Review
BACKGROUND
A study in frog and chicken embryos, and reports of a high incidence of birth defects in regions of intensive GM-soy planting have raised concerns on the teratogenic potential of glyphosate-based herbicides. These public concerns prompted us to conduct a systematic review of the epidemiological studies testing hypotheses of associations between glyphosate exposure and adverse pregnancy outcomes including birth defects.
METHODS
A systematic and comprehensive literature search was performed in MEDLINE, TOXLINE, Bireme-BVS and SCOPUS databases using different combinations of exposure and outcome terms. A case-control study on the association between pesticides and congenital malformations in areas of extensive GM soy crops in South America, and reports on the occurrence of birth defects in these regions were reviewed as well.
RESULTS
The search found ten studies testing associations between glyphosate and birth defects, abortions, pre-term deliveries, small for gestational date births, childhood diseases or altered sex ratios. Two additional studies examined changes of time-to-pregnancy in glyphosate-exposed populations. Except for an excess of Attention Deficit Hyperactivity Disorder - ADHD (OR = 3.6, 1.3-9.6) among children born to glyphosate appliers, no significant associations between this herbicide and adverse pregnancy outcomes were described. Evidence that in South American regions of intensive GM-soy planting incidence of birth defects is high remains elusive.
CONCLUSIONS
Current epidemiological evidence, albeit limited to a few studies using non-quantitative and indirect estimates and dichotomous analysis of exposures, does not lend support to public concerns that glyphosate-based pesticides might pose developmental risks to the unborn child. Nonetheless, owing to methodological limitations of existing analytical observational studies, and particularly to a lack of a direct measurement (urine and/or blood levels), or an indirect estimation of exposure that has proven valid, these negative findings cannot be taken as definitive evidence that GLY, at current levels of occupational and environmental exposures, brings no risk for human development and reproduction.
Topics: Abortion, Spontaneous; Agriculture; Case-Control Studies; Congenital Abnormalities; Environmental Exposure; Epidemiologic Studies; Female; Glycine; Herbicides; Humans; Incidence; Infant, Newborn; Male; Pregnancy; Pregnancy Outcome; South America; Glyphosate
PubMed: 27267204
DOI: 10.1186/s12889-016-3153-3 -
Medical Sciences (Basel, Switzerland) Apr 2018Nowadays, there seems to be a consensus about the multifactorial nature of autism spectrum disorders (ASD). The literature provides hypotheses dealing with numerous... (Review)
Review
Nowadays, there seems to be a consensus about the multifactorial nature of autism spectrum disorders (ASD). The literature provides hypotheses dealing with numerous environmental factors and genes accounting for the apparently higher prevalence of this condition. Researchers have shown evidence regarding the impact of gut bacteria on neurological outcomes, altering behavior and potentially affecting the onset and/or severity of psychiatric disorders. Pesticides and agrotoxics are also included among this long list of ASD-related environmental stressors. Of note, ingestion of glyphosate (GLY), a broad-spectrum systemic herbicide, can reduce beneficial bacteria in the gastrointestinal tract microbiota without exerting any effects on the Clostridium population, which is highly resistant to this herbicide. In the present study, (i) we performed a systematic review to evaluate the relationship between Clostridium bacteria and the probability of developing and/or aggravating autism among children. For that purpose, electronic searches were performed on and databases for identification of relevant studies published in English up to December 2017. Two independent researches selected the studies and analyzed the data. The results of the present systematic review demonstrate an interrelation between Clostridium bacteria colonization of the intestinal tract and autism. Finally, (ii) we also hypothesize about how environmental GLY levels may deleteriously influence the gut-brain axis by boosting the growth of Clostridium bacteria in autistic toddlers.
PubMed: 29617356
DOI: 10.3390/medsci6020029 -
Ecotoxicology and Environmental Safety Aug 2021Studies investigating the association between pesticide exposure and colorectal cancer (CRC) risk have been inconclusive.
BACKGROUND
Studies investigating the association between pesticide exposure and colorectal cancer (CRC) risk have been inconclusive.
OBJECTIVES
Investigate the association between pesticide exposure and CRC risk through a systematic literature review.
METHODS
CRC has the fourth-highest rate of cancer-caused death in the US after lung cancer, breast cancer in women, and prostate cancer in men. Here we have conducted a systematic literature search on studies examining the association between any pesticide exposure and CRC risk using PubMed, MEDLINE via EBSCO host, and Embase according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist.
RESULTS
Following the review, 139 articles were included for qualitative evaluation. Study participants were farmers, pesticide applicators, pesticide manufacturers, spouses of pesticide applicators, farm residents, Korean veterans of the Vietnam War, rural communities, and those who consumed food with pesticide residues. The studies' results were split between those with significant positive (39 significant results) and inverse (41 significant results) associations when comparing pesticide exposure and CRC risk.
DISCUSSION
From our literature review, we have identified a similar number of significant positive and inverse associations of pesticide exposure with CRC risk and therefore cannot conclude whether pesticide exposure has a positive or inverse association with CRC risk overall. However, certain pesticides such as terbufos, dicamba, trifluralin, S-ethyl dipropylthiocarbamate (EPTC), imazethapyr, chlorpyrifos, carbaryl, pendimethalin, and acetochlor are of great concern not only for their associated elevated risk of CRC, but also for the current legal usage in the United States (US). Aldicarb and dieldrin are of moderate concern for the positive associations with CRC risk, and also for the illegal usage or the detection on imported food products even though they have been banned in the US. Pesticides can linger in the soil, water, and air for weeks to years and, therefore, can lead to exposure to farmers, manufacturing workers, and those living in rural communities near these farms and factories. Approximately 60 million people in the US live in rural areas and all of the CRC mortality hotspots are within the rural communities. The CRC mortality rate is still increasing in the rural regions despite the overall decreasing of incidence and mortality of CRC elsewhere. Therefore, the results from this study on the relationship between pesticide exposure and CRC risk will help us to understand CRC health disparities.
Topics: Adult; Colorectal Neoplasms; Farmers; Female; Herbicides; Humans; Incidence; Male; Middle Aged; Occupational Exposure; Pesticide Residues; Pesticides
PubMed: 34029839
DOI: 10.1016/j.ecoenv.2021.112327 -
International Archives of Occupational... Jan 2023Human health risk assessments of glyphosate have focused on animal toxicology data for determining neurotoxic potential. Human epidemiological studies have not yet been... (Review)
Review
PURPOSE
Human health risk assessments of glyphosate have focused on animal toxicology data for determining neurotoxic potential. Human epidemiological studies have not yet been systematically reviewed for glyphosate neurotoxicity hazard identification. The objective of this systematic literature review was to summarize the available epidemiology of glyphosate exposure and neurological outcomes in humans.
METHODS
As of December 2021, 25 eligible epidemiological studies of glyphosate exposure and neurological endpoints were identified and assessed for five quality dimensions using guidance from the U.S. Environmental Protection Agency. Studies that assessed personal use of glyphosate were prioritized, whereas those assessing indirect exposure (other than personal use) were rated as low quality, since biomonitoring data indicate that indirect metrics of glyphosate exposure almost always equate to non-detectable glyphosate doses.
RESULTS
Overall, the scientific evidence on glyphosate and neurotoxicity in humans is sparse and methodologically limited, based on nine included epidemiological studies of neurodegenerative outcomes (two high quality), five studies of neurobehavioral outcomes (two high quality), six studies of neurodevelopmental outcomes (none high quality), and five studies of other and mixed neurological outcomes (one high quality). The five high-quality studies showed no association between glyphosate use and risk of depression, Parkinson disease, or peripheral nerve conduction velocity. Results were mixed among the eight moderate-quality studies, which did not demonstrate consistent associations with any neurological endpoints or categories. Low-quality studies were considered uninformative about possible neurotoxic effects due primarily to questionable assessments of indirect exposure.
CONCLUSIONS
No association has been demonstrated between glyphosate and any neurological outcomes in humans. To move the state of science forward, epidemiological studies should focus on scenarios involving direct and frequent use of glyphosate while collecting information on validated health outcomes, concomitant agricultural exposures, and relevant personal characteristics.
Topics: Animals; Humans; Environmental Exposure; Herbicides; Glycine; Risk Assessment; Neurotoxicity Syndromes; Glyphosate
PubMed: 35604441
DOI: 10.1007/s00420-022-01878-0 -
Ciencia & Saude Coletiva Mar 2011It is a systematic review and meta-analysis of previous observational epidemiologic studies examining the relationship between residential pesticide exposures during... (Meta-Analysis)
Meta-Analysis Review
It is a systematic review and meta-analysis of previous observational epidemiologic studies examining the relationship between residential pesticide exposures during critical exposure time windows (preconception, pregnancy, and childhood) and childhood leukemia. Searches of Medline and other electronic databases were performed (1950-2009). Study selection, data abstraction, and quality assessment were performed by two independent reviewers. Random effects models were used to obtain summary odds ratios (ORs) and 95% confidence intervals (Cis). Of the 17 identified studies, 15 were included in the meta-analysis. Exposures during pregnancy to unspecified residential pesticides insecticides, and herbicides were positively associated with childhood leukemia. Exposures during childhood to unspecified residential pesticides and insecticides were also positively associated with childhood leukemia, but there was no association with herbicides. Positive associations were observed between childhood leukemia and residential pesticide exposures. Further work is needed to confirm previous findings based on self-report, to examine potential exposure-response relationships, and to assess specific pesticides and toxicologically related subgroups of pesticides in more detail.
Topics: Child; Environmental Exposure; Female; Housing; Humans; Leukemia; Maternal Exposure; Pesticides; Pregnancy
PubMed: 21519680
DOI: 10.1590/s1413-81232011000300026 -
BMC Public Health Sep 2023Knowledge surrounding the association between exposure to pesticides and hypothyroidism is inconsistent and controversial. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Knowledge surrounding the association between exposure to pesticides and hypothyroidism is inconsistent and controversial.
METHODS
The aim of present study was, therefore, to review scientific evidence systematically and conduct a meta-analysis into the contribution of exposure to pesticides to hypothyroidism. PubMed, Scopus, Web of Science, and Google Scholar were searched. The findings are presented as OR, HR, PR, IRR, and 95% confidence interval (95%CI). A fixed-effect model using the inverse-variance method and random-effects inverse-variance model with DerSimonian-Laird method were used for estimating the pooled estimates. Cochran Q and I tests were used to confirm the heterogeneity of selected studies.
RESULTS
Twelve studies were included in the systematic review, and 9 studies in the meta-analysis. Epidemiological evidence suggested that exposure to insecticides including organochlorines, organophosphates, and pyrethroids increased risk of hypothyroidism (adjusted odds ratio (aOR) = 1.23, 95%CI = 1.14, 1.33 for organochlorines, aOR = 1.12, 95%CI = 1.07, 1.17 for organophosphates, aOR = 1.15, 95%CI = 1.03, 1.28 for pyrethroids). Exposure to herbicides also increased risk of hypothyroidism (aOR = 1.06, 95%CI = 1.02, 1.10). However, exposure to fungicides and fumigants was not found to be associated with hypothyroidism.
CONCLUSION
To increase current knowledge and confirm evidence to date future research needs to center on large-scale longitudinal epidemiological and biological studies, examination of dose-response relationships, the controlling of relevant confounding variables, using standardized and high sensitivity tools, and investigating the effects of environmental exposure.
Topics: Humans; Pesticides; Insecticides; Environmental Exposure; Hypothyroidism; Pyrethrins
PubMed: 37752464
DOI: 10.1186/s12889-023-16721-5