Pesticides: formulants, distribution pathways and effects on human health - a review.
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ABSTRACT:
SUBMITTER: Kalyabina VP
PROVIDER: S-EPMC8193068 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: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.
| S-EPMC5756058 | biostudies-literature
Project description:Abstract: The impact of pesticide residues on human health is a worldwide problem, as human exposure to pesticides can occur through ingestion, inhalation, and dermal contact. Regulatory jurisdictions have promulgated the standard values for pesticides in residential soil, air, drinking water, and agricultural commodity for years. Until now, more than 19,400 pesticide soil regulatory guidance values (RGVs) and 5400 pesticide drinking water maximum concentration levels (MCLs) have been regulated by 54 and 102 nations, respectively. Over 90 nations have provided pesticide agricultural commodity maximum residue limits (MRLs) for at least one of the 12 most commonly consumed agricultural foods. A total of 22 pesticides have been regulated with more than 100 soil RGVs, and 25 pesticides have more than 100 drinking water MCLs. This research indicates that those RGVs and MCLs for an individual pesticide could vary over seven (DDT drinking water MCLs), eight (Lindane soil RGVs), or even nine (Dieldrin soil RGVs) orders of magnitude. Human health risk uncertainty bounds and the implied total exposure mass burden model were applied to analyze the most commonly regulated and used pesticides for human health risk control. For the top 27 commonly regulated pesticides in soil, there are at least 300 RGVs (8% of the total) that are above all of the computed upper bounds for human health risk uncertainty. For the top 29 most-commonly regulated pesticides in drinking water, at least 172 drinking water MCLs (5% of the total) exceed the computed upper bounds for human health risk uncertainty; while for the 14 most widely used pesticides, there are at least 310 computed implied dose limits (28.0% of the total) that are above the acceptable daily intake values. The results show that some worldwide standard values were not derived conservatively enough to avoid human health risk by the pesticides, and that some values were not computed comprehensively by considering all major human exposure pathways.
| S-EPMC5551264 | biostudies-literature
Project description:Plant Protection Products, more commonly referred to as pesticides and biocides, are used to control a wide range of yield-reducing pests including insects, fungi, nematodes, and weeds. Concern has been raised that some pesticides may act as endocrine disrupting chemicals (EDCs) with the potential to interfere with the hormone systems of non-target invertebrates and vertebrates, including humans. EDCs act at low doses and particularly vulnerable periods of exposure include pre- and perinatal development. Of critical concern is the number of pesticides with the potential to interfere with the developing nervous system and brain, notably with thyroid hormone signaling. Across vertebrates, thyroid hormone orchestrates metamorphosis, brain development, and metabolism. Pesticide action on thyroid homeostasis can involve interference with TH production and its control, displacement from distributor proteins and liver metabolism. Here we focused on thyroid endpoints for each of the different classes of pesticides reviewing epidemiological and experimental studies carried out both in in vivo and in vitro. We conclude first, that many pesticides were placed on the market with insufficient testing, other than acute or chronic toxicity, and second, that thyroid-specific endpoints for neurodevelopmental effects and mixture assessment are largely absent from regulatory directives.
| S-EPMC6915086 | biostudies-literature
Project description:With thousands of pesticides registered by the United States Environmental Protection Agency, it not feasible to sample for all pesticides applied in agricultural communities. Hazard-ranking pesticides based on use, toxicity, and exposure potential can help prioritize community-specific pesticide hazards. This study applied hazard-ranking schemes for cancer, endocrine disruption, and reproductive/developmental toxicity in Yuma County, Arizona. An existing cancer hazard-ranking scheme was modified, and novel schemes for endocrine disruption and reproductive/developmental toxicity were developed to rank pesticide hazards. The hazard-ranking schemes accounted for pesticide use, toxicity, and exposure potential based on chemical properties of each pesticide. Pesticides were ranked as hazards with respect to each health effect, as well as overall chronic health effects. The highest hazard-ranked pesticides for overall chronic health effects were maneb, metam-sodium, trifluralin, pronamide, and bifenthrin. The relative pesticide rankings were unique for each health effect. The highest hazard-ranked pesticides differed from those most heavily applied, as well as from those previously detected in Yuma homes over a decade ago. The most hazardous pesticides for cancer in Yuma County, Arizona were also different from a previous hazard-ranking applied in California. Hazard-ranking schemes that take into account pesticide use, toxicity, and exposure potential can help prioritize pesticides of greatest health risk in agricultural communities. This study is the first to provide pesticide hazard-rankings for endocrine disruption and reproductive/developmental toxicity based on use, toxicity, and exposure potential. These hazard-ranking schemes can be applied to other agricultural communities for prioritizing community-specific pesticide hazards to target decreasing health risk.
| S-EPMC3769516 | biostudies-literature
Project description:ObjectiveHealth information technology (HIT) interventions include electronic patient records, prescribing, and ordering systems. Clinical pathways are multidisciplinary plans of care that enable the delivery of evidence-based healthcare. Our objective was to systematically review the effects of implementing HIT-supported clinical pathways.Materials and methodsA systematic review protocol was developed including Medline, Embase, and CENTRAL database searches. We recorded data relating to study design, participants, intervention, and outcome characteristics and formally assessed risk of bias.ResultsForty-four studies involving more than 270 000 patients were included. Investigation methodologies included before-after (n = 16, 36.4%), noncomparative (n = 14, 31.8%), interrupted time series (n = 5, 11.4%), retrospective cohort (n = 4, 9.1%), cluster randomized (n = 2, 4.5%), controlled before-after (n = 1, 2.3%), prospective case-control (n = 1, 2.3%), and prospective cohort (n = 1, 2.3%) study designs. Clinical decision support (n = 25, 56.8%), modified electronic documentation (n = 23, 52.3%), and computerized provider order entry (n = 23, 52.3%) were the most frequently utilized HIT interventions. The majority of studies (n = 38, 86.4%) reported benefits associated with HIT-supported pathways. These included reported improvements in objectively measured patient outcomes (n = 15, 34.1%), quality of care (n = 29, 65.9%), and healthcare resource utilization (n = 10, n = 22.7%).DiscussionAlthough most studies reported improvements in outcomes, the strength of evidence was limited by the study designs that were utilized.ConclusionsOngoing evaluations of HIT-supported clinical pathways are justified but would benefit from study designs that report key outcomes (including adverse events) and minimize the risk of bias.
| S-EPMC7647175 | biostudies-literature
Project description:Consumers of fruits and vegetables are frequently exposed to small amounts of hormonally active pesticides, some of them sharing a common mode of action such as the activation of the human estrogen receptor α (hERα) or β (hERβ). Therefore, it is of particular importance to evaluate risks emanating from chemical mixtures, in which the individual pesticides are present at human-relevant concentrations, below their corresponding maximum residue levels. Binary and ternary iso-effective mixtures of estrogenic pesticides at effect concentrations eliciting a 1 or 10% effect in the presence or absence of 17β-estradiol were tested experimentally at the hERα in the yeast-based estrogen screen (YES) assay as well as in the human U2-OS cell-based ERα chemical-activated luciferase gene expression (ERα CALUX) assay and at the hERβ in the ERβ CALUX assay. The outcome was then compared to predictions calculated by means of concentration addition. In most cases, additive effects were observed with the tested combinations in all three test systems, an observation that supports the need to expand the risk assessment of pesticides and consider cumulative risk assessment. An additional testing of mixture effects at the hERβ showed that most test substances being active at the hERα could also elicit additive effects at the hERβ, but the hERβ was less sensitive. In conclusion, effects of the same ligands at the hERα and the hERβ could influence the estrogenic outcome under physiological conditions.
| S-EPMC4728068 | biostudies-literature
Project description:BackgroundNumerous studies have identified detectable levels of neonicotinoids (neonics) in the environment, adverse effects of neonics in many species, including mammals, and pathways through which human exposure to neonics could occur, yet little is known about the human health effects of neonic exposure.ObjectiveIn this systematic review, we sought to identify human population studies on the health effects of neonics.MethodsStudies published in English between 2005 and 2015 were searched using PubMed, Scopus, and Web of Science databases. No restrictions were placed on the type of health outcome assessed. Risk of bias was assessed using guidance developed by the National Toxicology Program's Office of Health Assessment and Translation.ResultsEight studies investigating the human health effects of exposure to neonics were identified. Four examined acute exposure: Three neonic poisoning studies reported two fatalities (n = 1,280 cases) and an occupational exposure study of 19 forestry workers reported no adverse effects. Four general population studies reported associations between chronic neonic exposure and adverse developmental or neurological outcomes, including tetralogy of Fallot (AOR 2.4, 95% CI: 1.1, 5.4), anencephaly (AOR 2.9, 95% CI: 1.0, 8.2), autism spectrum disorder [AOR 1.3, 95% credible interval (CrI): 0.78, 2.2], and a symptom cluster including memory loss and finger tremor (OR 14, 95% CI: 3.5, 57). Reported odds ratios were based on exposed compared to unexposed groups.ConclusionsThe studies conducted to date were limited in number with suggestive but methodologically weak findings related to chronic exposure. Given the wide-scale use of neonics, more studies are needed to fully understand their effects on human health. Citation: Cimino AM, Boyles AL, Thayer KA, Perry MJ. 2017. Effects of neonicotinoid pesticide exposure on human health: a systematic review. Environ Health Perspect 125:155-162; http://dx.doi.org/10.1289/EHP515.
| S-EPMC5289916 | biostudies-literature
Project description:We present a model to identify the effects of low toxicant concentrations. Due to inadequate models, such effects have so far often been misinterpreted as random variability. Instead, a tri-phasic relationship describes the effects of a toxicant when a broad range of concentrations is assessed: i) at high concentrations where substantial mortality occurs (LC50), we confirmed the traditional sigmoidal response curve (ii) at low concentrations about 10 times below the LC50, we identified higher survival than previously modelled, and (iii) at ultra-low concentrations starting at around 100 times below the LC50, higher mortality than previously modelled. This suggests that individuals benefit from low toxicant stress. Accordingly, we postulate that in the absence of external toxicant stress individuals are affected by an internal "System Stress" (SyS) and that SyS is reduced with increasing strength of toxicant stress. We show that the observed tri-phasic concentration-effect relationship can be modelled on the basis of this approach. Here we revealed that toxicant-related effects (LC5) occurred at remarkably low concentrations, 3 to 4 orders of magnitude below those concentrations inducing strong effects (LC50). Thus, the ECx-SyS model presented allows us to attribute ultra-low toxicant concentrations to their effects on individuals. This information will contribute to performing a more realistic environmental and human risk assessment.
| S-EPMC6813311 | biostudies-literature
Project description:Excessive reclamation and improper use of agrochemicals in karst areas leads to serious non-point source pollution, which is of great concern and needs to be controlled, since contaminants can easily pollute groundwater due to the thin patchy soil and developed karst structures. The occurrences of organochlorine pesticides (OCPs) in karst soil were investigated by analyzing 25 OCPs in the karst soils near the Three Gorges Dam, China. The total concentrations of OCPs ranged 161-43,100 (6410 ± 9620) pg/g, with the most abundant compounds being p,p'-DDT and mirex. The concentration differences between the orchard and vegetable field and between upstream and downstream presented the influences of land-use type and water transport on the OCP spatial distributions. Composition analysis indicated the possible fresh inputs of lindane, technical DDT, aldrin, endrin, mirex, and methoxychlor. Their illegal uses implied an insufficient agrochemical management system in undeveloped karst areas. Principal component analysis with multiple linear regression analysis characterized the dominant sources from current agricultural use and current veterinary use in the study area. OCPs in the soils might not pose significant cancer risk for the residents, but they need to be controlled due to their illegal uses and bioaccumulation effect via the food chain.
| S-EPMC8582917 | biostudies-literature
Project description:Currently, the authorisation process for plant protection products (PPPs) relies on the testing of acute and topological toxicity only. Contrastingly, the evaluation of active substances includes a more comprehensive set of toxicity studies. Nevertheless, mixture effects of active ingredients and co-formulants may result in increased toxicity. Therefore, we investigated effects of surface active co-formulants on the toxicity of two PPPs focussing on qualitative and quantitative toxicokinetic effects on absorption and secretion. The respective products are based on the active substances abamectin and fluroxypyr-meptyl and were tested for cytotoxicity in the presence or absence of the corresponding surfactants and co-formulants using Caco-2 cells. In addition, the effect of co-formulants on increased cellular permeation was quantified using LC-MS/MS, while potential kinetic mixture effects were addressed by fluorescence anisotropy measurements and ATPase assays. The results show that surface active co-formulants significantly increase the cytotoxicity of the investigated PPPs, leading to more than additive mixture effects. Moreover, analytical investigations show higher efflux ratios of both active substances and the metabolite fluroxypyr upon combination with certain concentrations of the surfactants. The results further point to a significant and concentration-dependent inhibition of Pgp transporters by most of the surfactants as well as to increased membrane fluidity. Altogether, these findings strongly support the hypothesis that surfactants contribute to increased cytotoxicity of PPPs and do so by increasing the bioavailability of the respective active substances.
| S-EPMC8448693 | biostudies-literature