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Environment International Aug 2023Maternal pesticide exposure might be associated with adverse pregnancy outcomes through triggering inflammation and oxidative stress and disrupting endocrine functions.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Maternal pesticide exposure might be associated with adverse pregnancy outcomes through triggering inflammation and oxidative stress and disrupting endocrine functions. Yet the association between prenatal pesticide exposure and risk of preterm birth remains inconclusive.
OBJECTIVES
To conduct a systematic review and meta-analysis of human observational studies using the Office of Health Assessment and Translation (OHAT) framework to explore the association of per ten-fold increase of pesticide concentrations in maternal biological samples during pregnancy with risk of preterm birth and length of gestational age at birth.
DATA SOURCE
Five English (PubMed, Embase, Cochrane Library, Web of Science and Scopus) and 3 Chinese databases (China national knowledge infrastructure (CNKI), Wanfang Data, and Chinese Biomedical Literature Database (CBM)) were searched till Jan 18th, 2023.
STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTIONS
To be included, pesticide exposure should be measured in maternal biological samples during pregnancy and in log-transformed forms. The primary outcome was preterm birth and the secondary outcome was gestational age at birth.
STUDY APPRAISAL, SYNTHESIS METHODS AND CONFIDENCE ASSESSMENT
Quality of studies was evaluated using OHAT Risk of Bias Tool. Evidence was quantitatively synthesized with Correlated and Hierarchical Effects (CHE) model. The confidence rating in the body of evidence was done using OHAT.
RESULTS
A total of 21 studies reported by 18 papers were included, with 7 studies for preterm birth and 19 for gestational age at birth. The meta-analysis found a ten-fold increase of pesticide concentrations was potentially associated with risk of preterm birth (pooled OR = 1.28; 95%CI: 0.93, 1.78) and shortened gestational age at birth (β = -0.10; 95%CI: -0.21, 0.01). Sampling biospecimens in different trimesters was identified as a potential modifier in the association between pesticide exposure and length of gestational age (F = 2.77, P < 0.05). For studies that collected samples at any time during pregnancy, pesticide exposure was found to be associated with shortened length of gestational age (β = -0.43; 95%CI: -0.81, -0.06). The confidence rating in the body of evidence was "moderate" and "very low" for preterm birth and gestational age at birth, respectively.
CONCLUSION
Our result suggested moderate evidence of an association between pesticide exposure and higher risk of preterm birth. Yet more studies are still needed with larger sample size and careful considerations of confounders and accuracy of outcome measurements. Attention is also required on other pesticide compounds in addition to organochlorine and organophosphorus pesticides, and on windows of susceptibility.
Topics: Pregnancy; Female; Infant, Newborn; Humans; Premature Birth; Pesticides; Organophosphorus Compounds; Pregnancy Outcome; Gestational Age
PubMed: 37364307
DOI: 10.1016/j.envint.2023.108043 -
Environmental Health : a Global Access... Oct 2023Research on the effect of pesticide exposure on health has been largely focused on occupational settings. Few reviews have synthesized the associations between dietary... (Review)
Review
BACKGROUND
Research on the effect of pesticide exposure on health has been largely focused on occupational settings. Few reviews have synthesized the associations between dietary pesticide exposure and health outcomes in non-occupationally exposed adults.
OBJECTIVE
We aim to summarize the evidence regarding dietary pesticide exposure and non-communicable diseases (NCD) in adults, using a systematic review of prospective studies.
METHODS
Electronic and manual searches were performed until July 2023. The inclusion criteria were the following: 1) adults aged ≥ 18years, 2) (non)-randomized trials, prospective cohort studies, 3) dietary exposure to pesticides. A bias analysis was carried out using the Nutrition Evidence Systematic Review guidelines based on the Cochrane ROBINS-I.
RESULTS
A total of 52 studies were retrieved and 6 studies that met the above criteria were included. Studies were conducted either in France or in the United States. The studies investigated the risk of cancer (n = 3), diabetes (n = 1), cardiovascular diseases (n = 1), and mortality (n = 1). The quality of the studies varied with overall grades derived from the bias analysis ranging from low to moderate bias. The level of evidence was estimated as low for the risk of cancer while the grading was not assignable for other outcomes, as only one study per outcome was available.
CONCLUSIONS
Although further research is warranted to examine more in depth the relationships between low-dose chronic exposure to pesticides through diet and NCD outcomes in non-occupationally-exposed adults, studies suggest a possible role of exposure to dietary pesticide on health. Standardized methodological guidelines should also be proposed to allow for comparison across studies.
Topics: Humans; Adult; Prospective Studies; Noncommunicable Diseases; Pesticides; Dietary Exposure; Neoplasms
PubMed: 37907942
DOI: 10.1186/s12940-023-01020-8 -
PloS One 2023Maternal exposures to environmental hazards during pregnancy are key determinants of birth outcomes that affect health, cognitive and economic status later in life. In... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Maternal exposures to environmental hazards during pregnancy are key determinants of birth outcomes that affect health, cognitive and economic status later in life. In Ethiopia, various epidemiological evidences have suggested associations between environmental exposures such as household air pollution, cigarette smoking, and pesticide exposure and pregnancy outcomes such as low birth weight, preterm birth, and birth defects.
OBJECTIVE
This review aimed at generating summarized evidence on the association between maternal exposure to environmental factors (household air pollution, cigarette smoking, and pesticide) and pregnancy outcomes (birth weight, preterm birth, and birth defects) in Ethiopia.
METHOD
A systematic literature search was performed using PubMed, Google Scholar, and the Cochrane Library databases. All observational study designs were eligible for inclusion in the review. Quality assessment was conducted using the Newcastle-Ottawa Scale (NOS) quality assessment tools adopted for case-control and cross-sectional studies. The random-effects model was applied in computing the pooled estimates and their corresponding 95% confidence interval (CI). Funnel and Doi plots were used for detecting the potential publication bias. All statistical analyses were performed using comprehensive meta-analysis (CMA 2.0) and MetaXL version 5.3 software.
RESULT
The pooled estimates revealed that prenatal biomass fuel use increased the risk of giving a low birth weight baby by twofold (OR = 2.10, 95% CI: 1.33-3.31), and has no separate kitchen increases the risk of having low birth weight baby nearly by two and half times (OR = 2.48, 95% CI: 1.25-4.92). Overall, using biomass fuel as the main energy source for cooking and /or having no separate kitchen from the main house is 2.37 times more likely to give low birth weight babies (OR = 2.37, 95% CI: 1.58-3.53). Active cigarette smoker women were 4 times (OR = 4.11, 95% CI: 2.82-5.89) more prone to have low birth weight babies than nonsmokers; and passive smoker women were 2.6 times (OR = 2.63, 95% CI: 1.09-6.35) more risked to give low birth weight babies. It was also estimated that active cigarette smoker women were nearly 4 times (OR = 3.90, 95% CI: 2.36-6.45) more likely to give preterm birth babies. Pesticide exposure during pregnancy also increases the risk of the birth defect 4 times (OR = 4.44, 95% CI: 2.61-7.57) compared with non-exposed pregnant women.
CONCLUSION
Household air pollution from biomass fuel use, active and passive cigarette smoking, and pesticide exposures are significantly associated environmental risk factors for low birth weight, preterm birth, and birth defects in Ethiopia. Therefore, Pregnant and lactating women should be aware of these environmental hazards during pregnancy. Promoting clean energy and improved and efficient stoves at the household level will help to reduce household air pollution-related adverse health effects.
TRIAL REGISTRATION
PROSPERO 2022: CRD42022337140.
Topics: Infant, Newborn; Pregnancy; Infant; Female; Humans; Pregnancy Outcome; Premature Birth; Cross-Sectional Studies; Ethiopia; Lactation; Environmental Exposure; Observational Studies as Topic
PubMed: 37437038
DOI: 10.1371/journal.pone.0288240 -
The Lancet. Planetary Health Nov 2023High-level exposure to indoor air pollutants (IAPs) and their corresponding adverse health effects have become a public concern in China in the past 10 years. However,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
High-level exposure to indoor air pollutants (IAPs) and their corresponding adverse health effects have become a public concern in China in the past 10 years. However, neither national nor provincial level burden of disease attributable to multiple IAPs has been reported for China. This is the first study to estimate and rank the annual burden of disease and the financial costs attributable to targeted residential IAPs at the national and provincial level in China from 2000 to 2017.
METHODS
We first did a systematic review and meta-analysis of 117 articles from 37 231 articles identified in major databases, and obtained exposure-response relationships for the candidate IAPs. The exposure levels to these IAPs were then collected by another systematic review of 1864 articles selected from 52 351 articles. After the systematic review, ten IAPs with significant and robust exposure-response relationships and sufficient exposure data were finally targeted: PM, nitrogen dioxide, sulphur dioxide, ozone, carbon monoxide, radon, formaldehyde, benzene, toluene, and p-dichlorobenzene. The annual exposure levels in residences were then evaluated in all 31 provinces in mainland China continuously from 2000 to 2017, using the spatiotemporal Gaussian process regression model to analyse indoor originating IAPs, and the infiltration factor method to analyse outdoor originating IAPs. The disability-adjusted life-years (DALYs) attributable to the targeted IAPs were estimated at both national and provincial levels in China, using the population attributable fraction method. Financial costs were estimated by an adapted human capital approach.
FINDINGS
From 2000 to 2017, annual DALYs attributable to the ten IAPs in mainland China decreased from 4620 (95% CI 4070-5040) to 3700 (3210-4090) per 100 000. Nevertheless, in 2017, IAPs still ranked third among all risk factors, and their DALYs and financial costs accounted for 14·1% (95% CI 12·3-15·6) of total DALYs and 3·45% (3·01-3·82) of the gross domestic product. Specifically, the rank of ten targeted IAPs in order of their contribution to DALYs in 2017 was PM, carbon monoxide, radon, benzene, nitrogen dioxide, ozone, sulphur dioxide, formaldehyde, toluene, and p-dichlorobenzene. The DALYs attributable to IAPs were 9·50% higher than those attributable to outdoor air pollution in 2017. For the leading IAP, PM, the DALYs attributable to indoor origins are 18·3% higher than those of outdoor origins.
INTERPRETATION
DALYs attributed to IAPs in China have decreased by 20·0% over the past two decades. Even so, they are still much higher than those in the USA and European countries. This study can provide a basis for determining which IAPs to target in various indoor air quality standards and for estimating the health and economic benefits of various indoor air quality control approaches, which will help to reduce the adverse health effects of IAPs in China.
FUNDING
The National Key Research and Development Program of China and the National Natural Science Foundation of China.
Topics: Humans; Air Pollutants; Carbon Monoxide; Sulfur Dioxide; Benzene; Nitrogen Dioxide; Formaldehyde; Cost of Illness; Particulate Matter; Radon; Ozone; Toluene
PubMed: 37940210
DOI: 10.1016/S2542-5196(23)00215-2 -
The Cochrane Database of Systematic... Aug 2023Insecticide-based interventions, such as long-lasting insecticide-treated nets (LLINs) and indoor residual spraying (IRS), remain the backbone of malaria vector control.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Insecticide-based interventions, such as long-lasting insecticide-treated nets (LLINs) and indoor residual spraying (IRS), remain the backbone of malaria vector control. These interventions target mosquitoes that prefer to feed and rest indoors, but have limited capacity to prevent transmission that occurs outdoors or outside regular sleeping hours. In low-endemicity areas, malaria elimination will require that these control gaps are addressed, and complementary tools are found. The use of topical repellents may be particularly useful for populations who may not benefit from programmatic malaria control measures, such as refugees, the military, or forest goers. This Cochrane Review aims to measure the effectiveness of topical repellents to prevent malaria infection among high- and non-high-risk populations living in malaria-endemic regions.
OBJECTIVES
To assess the effect of topical repellents alone or in combination with other background interventions (long-lasting insecticide-treated nets, or indoor residual spraying, or both) for reducing the incidence of malaria in high- and non-high-risk populations living in endemic areas.
SEARCH METHODS
We searched the following databases up to 11 January 2023: the Cochrane Infectious Diseases Group Specialised Register; CENTRAL (in the Cochrane Library); MEDLINE; Embase; CAB Abstracts; and LILACS. We also searched trial registration platforms and conference proceedings; and contacted organizations and companies for ongoing and unpublished trials.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) and cluster-randomized controlled trials (cRCTs) of topical repellents proven to repel mosquitoes. We also included non-randomized studies that complied with pre-specified inclusion criteria: controlled before-after studies (CBA), controlled interrupted time series (ITS), and controlled cross-over trials.
DATA COLLECTION AND ANALYSIS
Four review authors independently assessed trials for inclusion, and extracted the data. Two authors independently assessed the risk of bias (RoB) using the Cochrane RoB 2 tool. A fifth review author resolved any disagreements. We analysed data by conducting a meta-analysis, stratified by whether studies included populations considered to be at high-risk of developing malaria infection (for example, refugees, forest goers, or deployed military troops). We combined results from cRCTs with RCTs by adjusting for clustering and presented results using forest plots. We used the GRADE framework to assess the certainty of the evidence. We only included data on Plasmodium falciparum infections in the meta-analysis.
MAIN RESULTS
Thirteen articles relating to eight trials met the inclusion criteria and were qualitatively described. We included six trials in the meta-analysis (five cRCTs and one RCT). Effect on malaria incidence Topical repellents may slightly reduce P falciparum infection and clinical incidence when both outcomes are considered together (incidence rate ratio (IRR) 0.74, 95% confidence interval (CI) 0.56 to 0.98; 3 cRCTs and 1 RCT, 61,651 participants; low-certainty evidence); but not when these two outcomes were considered independently. Two cRCTs and one RCT (12,813 participants) evaluated the effect of topical repellents on infection incidence (IRR 0.76, 95% CI 0.56 to 1.02; low-certainty evidence). One cRCT (48,838 participants) evaluated their effect on clinical case incidence (IRR 0.66, 95% CI 0.32 to 1.36; low-certainty evidence). Three studies (2 cRCTs and 1 RCT) included participants belonging to groups considered at high-risk of being infected, while only one cRCT did not include participants at high risk. Adverse events Topical repellents are considered safe. The prevalence of adverse events among participants who used topical repellents was very low (0.6%, 283/47,515) and limited to mild skin reactions. Effect on malaria prevalence Topical repellents may slightly reduce P falciparum prevalence (odds ratio (OR) 0.81, 95% CI 0.67 to 0.97; 3 cRCTs and 1 RCT; 55,366 participants; low-certainty evidence). Two of these studies (1 cRCT and 1 RCT) were carried out in refugee camps, and included exclusively high-risk populations that were not receiving any other background vector control intervention.
AUTHORS' CONCLUSIONS
There is insufficient evidence to conclude that topical repellents can prevent malaria in settings where other vector control interventions are in place. We found the certainty of evidence for all outcomes to be low, primarily due to the risk of bias. A protective effect was suggested among high-risk populations, specially refugees, who might not have access to other standard vector control measures. More adequately powered clinical trials carried out in refugee camps could provide further information on the potential benefit of topical repellents in this setting. Individually randomized studies are also likely necessary to understand whether topical repellents have an effect on personal protection, and the degree to which diversion to non-protected participants affects overall transmission dynamics. Despite this, the potential additional benefits of topical repellents are most likely limited in contexts where other interventions are available.
Topics: Animals; Humans; Insecticides; Mosquito Vectors; Malaria, Falciparum; Controlled Before-After Studies; Culicidae
PubMed: 37602418
DOI: 10.1002/14651858.CD015422.pub2 -
Journal of Neurosciences in Rural... 2023Pesticide application has become necessary to increase crop productivity and reduce losses. However, the use of these products can produce toxic effects. Farmers are... (Review)
Review
OBJECTIVES
Pesticide application has become necessary to increase crop productivity and reduce losses. However, the use of these products can produce toxic effects. Farmers are individuals occupationally exposed to pesticides, thus subject to associated diseases as well as cognitive impairment. However, this relation is not well established in the literature, requiring further investigation. To assess the potential association between farmers' pesticide exposure and cognitive impairment, we followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines, considering participants, interventions, comparators, outcomes, and study strategies.
MATERIALS AND METHODS
This study included articles published between 2000 and 2021 on the Scopus, Web of Science, ScienceDirect, and PubMed databases, retrieved by the terms "" and "."
RESULTS
In total, ten studies fit the established criteria and were included in the sample. All had farmers occupationally exposed to pesticides in their sample and only one study dispensed with a control group. Of the neurobehavioral tests, four studies used mini-mental state examination, six neurobehavioral core test batteries (tests recognized in the area), and the remaining, other tests. We observed that 90% of articles found an association between cognitive impairment and pesticide exposure. Overall, five studies measured the activity of cholinesterases in their sample, of which three found significant differences between groups, confirming intoxication in those exposed.
CONCLUSION
Despite the limited number of trials, we found scientific evidence to support the existence of adverse effects of pesticides on farmers' cognition. We recommend that future studies research similar projects, expanding knowledge on the subject.
PubMed: 38059229
DOI: 10.25259/JNRP_58_2023 -
Frontiers in Psychiatry 2023Metformin has shown good efficacy in the management of antipsychotic-induced metabolic syndrome (MetS) in patients with schizophrenia or schizoaffective disorders. Its... (Review)
Review
The potential effect of metformin on cognitive and other symptom dimensions in patients with schizophrenia and antipsychotic-induced weight gain: a systematic review, meta-analysis, and meta-regression.
INTRODUCTION
Metformin has shown good efficacy in the management of antipsychotic-induced metabolic syndrome (MetS) in patients with schizophrenia or schizoaffective disorders. Its ability to induce antidepressant behavioural effects and improve cognitive functions has also been investigated: yet information has not been systematized. The aim of this study was therefore to investigate the effects of metformin on cognitive and other symptom dimension in schizophrenic patients treated with antipsychotics through a systematic review and meta-analysis.
METHODS
We searched PubMed, ClinicalTrials.Gov, Embase, PsycINFO, and WHO ICTRP database up to February 2022, Randomised Controlled Trials (RCT) evaluating patients diagnosed with schizophrenia and related disorders, who were treated with metformin as add-on therapy to antipsychotics for the treatment of weight gain and in which changes in psychiatric symptoms and cognitive functions were evaluated.
RESULTS
A total of 19 RCTs met the inclusion criteria. Meta-analysis was performed on 12 eligible studies. We found a positive trend after 24 weeks of treatment in schizophrenic patients with stable conditions [SMD (95%CI) = -0.40 (-0.82;0.01), OR (95%CI) = 0.5 (-2.4;3.4)]. Better performance was detected in the Brief Assessment of Cognition in Schizophrenia and Positive and Negative Syndrome Scale (PANSS) with low heterogeneity among studies. One study reported changes in BACS-verbal memory subdomain in favour of placebo [MD (95%CI) = -16.03 (-23.65;8.42)]. Gastrointestinal disorders, xerostomia, and extrapyramidal syndrome were the most reported adverse effects. Psychiatric adverse events were also described: in particular, symptoms attributable to a relapse of schizophrenia.
CONCLUSION
Some degree of efficacy was found for Metformin in improving cognitive and other symptom dimensions in patients with Schizophrenia. Given the clinical relevance of this potential pharmacological effect, longer specific studies using adequate psychometric scales are strongly recommended. Likewise, how metformin acts in this context needs to be evaluated in order to enhance its efficacy or find more efficacious drugs.
PubMed: 37502816
DOI: 10.3389/fpsyt.2023.1215807 -
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 -
Environmental Health Perspectives Nov 2023Evidence of the negative impacts of contemporary use insecticides on sperm concentration has increased over the last few decades; however, meta-analyses on this topic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Evidence of the negative impacts of contemporary use insecticides on sperm concentration has increased over the last few decades; however, meta-analyses on this topic are rare.
OBJECTIVES
This investigation assessed the qualitative and quantitative strength of epidemiological evidence regarding adult exposure to two classes of contemporary use insecticides-organophosphates (OPs) and -methyl carbamates (NMCs)-and sperm concentration using robust and reproducible systematic review and meta-analysis methods.
METHODS
Three scientific databases (PubMed, Scopus, and Web of Science), two U.S. government databases (NIOSHTIC-2 and Science.gov), and five nongovernmental organization websites were searched for relevant primary epidemiological studies published in any language through 11 August 2022. Risk of bias and strength of evidence were evaluated according to Navigation Guide systematic review methodology. Bias-adjusted standardized mean difference effect sizes were calculated and pooled using a three-level, multivariate random-effect meta-analysis model with cluster-robust variance estimation.
RESULTS
Across 20 studies, 21 study populations, 42 effect sizes, and 1,774 adult men, the pooled bias-adjusted standardized mean difference in sperm concentration between adult men more- and less-exposed to OP and NMC insecticides was (95% CI: , ; ). Sensitivity and subgroup analyses explored statistical heterogeneity and validated the model robustness. Although the pooled effect estimate was modified by risk of bias, insecticide class, exposure setting, and recruitment setting, it remained negative in direction across all meta-analyses. The body of evidence was rated to be of moderate quality, with sufficient evidence of an association between higher adult OP and NMC insecticide exposure and lower sperm concentration.
DISCUSSION
This comprehensive investigation found sufficient evidence of an association between higher OP and NMC insecticide exposure and lower sperm concentration in adults. Although additional cohort studies can be beneficial to fill data gaps, the strength of evidence warrants reducing exposure to OP and NMC insecticides now to prevent continued male reproductive harm. https://doi.org/10.1289/EHP12678.
Topics: Humans; Male; Adult; Insecticides; Organophosphates; Semen; Carbamates; Spermatozoa
PubMed: 37966213
DOI: 10.1289/EHP12678 -
Chemosphere Oct 2023Glyphosate was classified as a probable human carcinogen (Group 2A) by the International Agency for Research on Cancer (IARC) partially due to strong mechanistic... (Review)
Review
Glyphosate was classified as a probable human carcinogen (Group 2A) by the International Agency for Research on Cancer (IARC) partially due to strong mechanistic evidence in 2015. Since then, numerous studies of glyphosate and its formulations (GBF) have emerged. These studies can be evaluated for cancer hazard identification with the newly described ten key characteristics (KC) of carcinogens approach. Our objective was to assess all in vivo, ex vivo, and in vitro mechanistic studies of human and experimental animals (mammals) that compared exposure to glyphosate/GBF with low/no exposure counterparts for evidence of the ten KCs. A protocol with our methods adhering to PRISMA guidelines was registered a priori (INPLASY202180045). Two blinded reviewers screened all in vivo, ex vivo, and in vitro studies of glyphosate/GBF exposure in humans/mammals reporting any KC-related outcome available in PubMed before August 2021. Studies that met inclusion criteria underwent data extraction conducted in duplicate for each KC outcome reported along with key aspects of internal/external validity, results, and reference information. These data were used to construct a matrix that was subsequently analyzed in the program R to conduct strength of evidence and quality assessments. Of the 2537 articles screened, 175 articles met inclusion criteria, from which we extracted >50,000 data points related to KC outcomes. Data analysis revealed strong evidence for KC2, KC4, KC5, KC6, KC8, limited evidence for KC1 and KC3, and inadequate evidence for KC7, KC9, and KC10. Notably, our in-depth quality analyses of genotoxicity (KC2) and endocrine disruption (KC8) revealed strong and consistent positive findings. For KC2, we found: 1) studies conducted in humans and human cells provided stronger positive evidence than counterpart animal models; 2) GBF elicited a stronger effect in both human and animal systems when compared to glyphosate alone; and 3) the highest quality studies in humans and human cells consistently revealed strong evidence of genotoxicity. Our analysis of KC8 indicated that glyphosate's ability to modulate hormone levels and estrogen receptor activity is sensitive to both exposure concentration and formulation. The modulations observed provide clear evidence that glyphosate interacts with receptors, alters receptor activation, and modulates the levels and effects of endogenous ligands (including hormones). Our findings strengthen the mechanistic evidence that glyphosate is a probable human carcinogen and provide biological plausibility for previously reported cancer associations in humans, such as non-Hodgkin lymphoma. We identified potential molecular interactions and subsequent key events that were used to generate a probable pathway to lymphomagenesis.
Topics: Animals; Humans; Carcinogens; Herbicides; Neoplasms; Lymphoma, Non-Hodgkin; Mammals; Glyphosate
PubMed: 37474029
DOI: 10.1016/j.chemosphere.2023.139572