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Birth Defects Research. Part B,... Apr 2015The U.S. Environmental Protection Agency's (EPA's) Toxicity Forecaster (ToxCast) is a potential tool for chemical prioritization, hazard identification, and risk... (Comparative Study)
Comparative Study
A Comparison of ToxCast Test Results with In Vivo and Other In Vitro Endpoints for Neuro, Endocrine, and Developmental Toxicities: A Case Study Using Endosulfan and Methidathion.
INTRODUCTION
The U.S. Environmental Protection Agency's (EPA's) Toxicity Forecaster (ToxCast) is a potential tool for chemical prioritization, hazard identification, and risk assessment. We conducted a case study to compare ToxCast data with endpoints from other in vitro and in vivo studies for two data-rich pesticides: endosulfan and methidathion.
METHODS
ToxCast assays for endocrine disruption, development (zebrafish), and neurotoxicity were qualitatively compared to traditional neurotoxicity, developmental and reproductive toxicity findings. We also used in vitro-in vivo extrapolation to convert half-maximal activity concentrations in active ToxCast assays to rat oral equivalent doses, and quantitatively compared these to the lowest observable effect level (LOEL) from in vivo studies.
RESULTS
Endosulfan was inactive for GABAA R, unlike in vivo; but active with dopamine transporter assays and was neurotoxic in zebrafish as expected. Methidathion was not active for these endpoints in vivo or in vitro. Acetylcholinesterase inhibition was ToxCast-inactive, although both pesticides are inhibitors in vivo. ToxCast results were generally inactive for endosulfan estrogen receptor agonism and androgen receptor antagonism unlike in vivo. Calculated oral equivalent doses for estrogen receptor and androgen receptor pathways and for zebrafish assays for both compounds were generally consistent with in vivo LOELs. Endosulfan showed neurotoxicity and both pesticides showed developmental effects in the zebrafish assays, although methidathion is not developmentally toxic in vivo.
CONCLUSIONS
ToxCast's predictions showed concordance on some endpoints and nonconcordance, consisting mainly of false inactives, in several critical endpoints, likely due to a lack of metabolic activation and limitations in assay design. Zebrafish assays were good predictors of developmental toxicity and neurotoxicity for endosulfan.
Topics: Animals; Embryo, Nonmammalian; Embryonic Development; Endocrine System; Endosulfan; High-Throughput Screening Assays; Humans; In Vitro Techniques; Insecticides; Mice; Nervous System; Organothiophosphorus Compounds; Rabbits; Rats; Risk Assessment; Toxicity Tests; Zebrafish
PubMed: 26017137
DOI: 10.1002/bdrb.21140 -
Frontiers in Pharmacology 2021In the present study, 168 pesticides in 1,017 samples of 10 Chinese herbal medicines (CHMs) were simultaneously determined by high-performance liquid (HPLC-MS/MS) and...
In the present study, 168 pesticides in 1,017 samples of 10 Chinese herbal medicines (CHMs) were simultaneously determined by high-performance liquid (HPLC-MS/MS) and gas (GC-MS/MS) chromatography-tandem mass spectrometry. A total of 89.2% of the samples encompassed one or multiple pesticide residues, and the residue concentrations in 60.5% of samples were less than 0.02 mg kg, revealing the relatively low residue levels. The hazard quotient and hazard index methods were used to estimate the health risk for consumers. For a more accurate risk assessment, the exposure frequency and exposure duration of CHMs were involved into the exposure assessment, which was obtained from a questionnaire data of 20,917 volunteers. The results of chronic, acute, and cumulative risk assessment indicated that consumption of CHMs is unlikely to pose a health risk to consumers. Ranking the risk of detected pesticides revealed that phorate, BHC, triazophos, methidathion, terbufos, and omethoate posed the highest risk. Our results also showed that pollution of the aboveground medicinal part was more serious. Although exposure to pesticides in tested CHMs was below dangerous levels, more strict controlled management should be carried out for banned pesticides due to the high detection rate and illegal use in the actual planting practice.
PubMed: 35177984
DOI: 10.3389/fphar.2021.818268 -
The Science of the Total Environment Mar 2021The buds and initial flowers of honeysuckle (Lonicera japonica Thunb.) are most widely used in traditional Chinese medicines (TCMs). In recent years, the problem of...
The buds and initial flowers of honeysuckle (Lonicera japonica Thunb.) are most widely used in traditional Chinese medicines (TCMs). In recent years, the problem of pesticide residues in honeysuckle has attracted much attention. This research aimed to study pesticide residual situation of honeysuckle in China and estimate the potential health risks for consumers using the HQ (hazard quotient) and HI (hazard index) methods. A reliable and robust method was established to determine and quantify 137 pesticide residues simultaneously by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) for 151 honeysuckle samples from different planting bases in China in 2017 and 2018. Fifty-four pesticides were detected in total, including 10 unauthorized pesticides (chlorpyrifos, fipronil, carbofuran, omethoate, isofenphos-methyl, triazophos, methomyl, dimethoate, methidathion, and methamidophos). One hundred and fifty (99.3%) samples contained at least 1 and up to 31 pesticides and/or their metabolites, with concentrations ranging from 0.001 to 3.087 mg/kg. Carbendazim, chlorbenzuron, imidacloprid, chlorpyrifos, and acetamiprid were the most frequently detected pesticides in 2017 and 2018, and the corresponding detection rates were 95.31%, 64.06%, 65.63%, 53.13%, 57.81%, and 98.85%, 88.51%, 70.11%, 77.01%, 57.47%, respectively. The acute hazard quotient (HQ) of carbofuran was 1.54 for specific population (fetus, infants, and pregnant or nursing women), which indicated that it posed a potential acute health risk. In the cumulative risk assessment, the acute hazard index (HI) of insecticides in honesuckle for children and the specific population were 1.34 and 3.36, respectively, suggesting that they posed potential acute cumulative health risks. These results were of theoretical and practical value for evaluating the safety of honeysuckle and improving its quality and safety.
Topics: Child; China; Food Contamination; Humans; Lonicera; Pesticide Residues; Risk Assessment; Tandem Mass Spectrometry
PubMed: 33121779
DOI: 10.1016/j.scitotenv.2020.142747 -
Chemosphere Mar 2023Pesticide registration in developing countries like Ethiopia is often not supported by substantiated risk assessment procedures. In this study, we evaluated the PRIMET...
Pesticide registration in developing countries like Ethiopia is often not supported by substantiated risk assessment procedures. In this study, we evaluated the PRIMET (Pesticide Risks in the Tropics for Man, Environment and Trade) Registration_Ethiopia_1.1 model which is a tool developed to assess the risks to non-target protection goals. All the 103 registered active ingredients (a.i.) in Ethiopia, except those used for flower and storage pest control purposes, were evaluated on their environmental risks. Data on physico-chemical characteristics, toxicity and pesticide use patterns were mined from either the information given in the dossier or public databases. Together with scenarios specifically developed for Ethiopia, these data were used to perform a risk assessment for the aquatic and terrestrial environment as well as for vertebrates including humans via contaminated drinking water exposure. Results indicated that 11 and 16% of the a.i.s are indicated to pose high acute risk and 7.3 and 11% high chronic risks for fish and aquatic invertebrates, respectively. Similarly, 5.5 and 8.7% high acute risks and 6.8 and 3.9% high chronic risks were observed for the soil ecosystem and birds, respectively. 23% of the evaluated active ingredients were indicated to be highly risky to bees when beehives are present inside the sprayed crop while 7.8% of them are highly risky when beehives are present outside the field of the sprayed crop. The fungicide metalaxyl, the herbicides acetochlor, alachlor, mecoprop and tembotrion, and the insecticides carbaryl, chlorpyrifos, diazinon and methidathion were predicted to pose high acute or chronic risks to humans or other vertebrates if surface water is used as a source of drinking water. Future studies should give emphasis on how the risk assessment results of this study can be implemented to aid the registration process.
Topics: Humans; Animals; Bees; Pesticides; Ecosystem; Drinking Water; Ethiopia; Risk Assessment; Environmental Monitoring; Water Pollutants, Chemical
PubMed: 36638923
DOI: 10.1016/j.chemosphere.2023.137794 -
Soudni Lekarstvi 2019We present an autopsy case involving ingestion of methidathion, an organothiophosphate pesticide. A headspace gas chromatography mass spectrometry system was used for...
We present an autopsy case involving ingestion of methidathion, an organothiophosphate pesticide. A headspace gas chromatography mass spectrometry system was used for screening of volatile compounds. Subsequent toxicological analysis was performed using liquid chromatography tandem mass spectrometry. Xylene and ethylbenzene were detected in stomach contents. We also identified methidathion at concentrations of 3.07 and 2240 µg/ml in femoral venous blood and stomach contents, respectively. We concluded that the victim ingested methidathion insecticide, with an estimated dose of at least 9.2 g.
Topics: Autopsy; Gas Chromatography-Mass Spectrometry; Humans; Insecticides; Organothiophosphorus Compounds
PubMed: 31842549
DOI: No ID Found -
Analytical Biochemistry May 2021Intentional or unintentional intake of anticholinesterase pesticides became common due to their extensive use in agricultural and domestic purposes, resulting in...
Intentional or unintentional intake of anticholinesterase pesticides became common due to their extensive use in agricultural and domestic purposes, resulting in numerous poisoning cases. A simple, accurate, and sensitive gas chromatography-ion trap mass spectrometry-based method for the quantification of 12 anticholinesterase pesticides (monocrotophos, dimethoate, dichlorvos, azinphos-methyl, carbofuran, chlorpyrifos, dialifos, diazinon, malathion, parathion, methidathion, and terbufos) in serum was developed, and its utility in patients with alleged pesticides poisoning was assessed. The quantification was performed using liquid-liquid extraction by toluene/chloroform (4:1,v/v) with 500 μL of serum. On column limit of detection and limit of quantification were less than 50.00 μg/L. The recovery ranged from 97.54 to 103.23%. The calibration curves were linear (R > 0.9937). Accuracy was found to be between - 7.1 and 7.2%. Intra-day and inter-day reproducibility was less than 17% for the spiked quality control serum samples. The level of pesticide in serum quantified by the validated method correlated with clinical signs and symptoms, pseudo-cholinesterase activity, total atropine dose, length of hospital stay, and clinical outcome in 15 patients with alleged pesticide poisoning. The validated method may be used for monitoring and prognosis in patients with pesticide poisoning and diagnosis of poisoning in forensic toxicology.
Topics: Calibration; Cholinesterase Inhibitors; Gas Chromatography-Mass Spectrometry; Humans; Liquid-Liquid Extraction; Pesticides; Reproducibility of Results; Spectrometry, Mass, Electrospray Ionization
PubMed: 33705722
DOI: 10.1016/j.ab.2021.114158 -
Chemosphere Feb 2016In this study, we evaluated the toxic effects of a glyphosate-based herbicide (GBH) and a methidathion-based insecticide (MBI), individually and in combination, on...
Integrated assessment of biochemical markers in premetamorphic tadpoles of three amphibian species exposed to glyphosate- and methidathion-based pesticides in single and combination forms.
In this study, we evaluated the toxic effects of a glyphosate-based herbicide (GBH) and a methidathion-based insecticide (MBI), individually and in combination, on premetamorphic tadpoles of three anuran species: Pelophylax ridibundus, Xenopus laevis, and Bufotes viridis. Based on the determined 96-h LC50 values of each species, the effects of a series of sublethal concentrations of single pesticides and their mixtures after 96-h exposure and also the time-related effects of a high sublethal concentration of each pesticide were evaluated, with determination of changes in selected biomarkers: glutathione S-transferase (GST), glutathione reductase (GR), acetylcholinesterase (AChE), carboxylesterase (CaE), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH). Also, the integrated biomarker response (IBR) was used to assess biomarker responses and quantitatively evaluate toxicological effects. Isozyme differences in CaE inhibition were assessed using native page electrophoresis; results showed that GBH to cause structural changes in the enzyme but not CaE inhibition in P. ridibundus. In general, single MBI and pesticide mixture exposures increased GST activity, while single GBH exposures decreased GST activity in exposed tadpoles. The AChE and CaE activities were inhibited after exposure to all single MBI and pesticide mixtures. Also, higher IBR values and GST, GR, AST, and LDH activities were determined for pesticide mixtures compared with single-pesticide exposure. This situation may be indicative of a synergistic interaction between pesticides and a sign of a more stressful condition.
Topics: Acetylcholinesterase; Animals; Aspartate Aminotransferases; Biomarkers; Bufonidae; Carboxylesterase; Cholinesterase Inhibitors; Glutathione Reductase; Glutathione Transferase; Glycine; Herbicides; Insecticides; L-Lactate Dehydrogenase; Larva; Organothiophosphorus Compounds; Ranidae; Water Pollutants, Chemical; Xenopus laevis; Glyphosate
PubMed: 26595308
DOI: 10.1016/j.chemosphere.2015.10.125 -
Analytical Chemistry May 2021Most of the fluorescence sensors require choline oxidase or quenchers to detect organophosphorus pesticides (OPs) based on a single hydrolysate and suffer from high...
Most of the fluorescence sensors require choline oxidase or quenchers to detect organophosphorus pesticides (OPs) based on a single hydrolysate and suffer from high cost, complex procedures, weak stability, and low sensitivity. Here, we proposed a brand-new fluorescence strategy for highly sensitive detection of OPs based on both hydrolysate-response disulfide bond-functionalized gold nanoclusters (S-S-AuNCs) without additional substances. S-S-AuNCs were synthesized via a facile one-step redox reaction and emitted bright red light with ultrasmall size and high water dispersion. Interestingly, S-S-AuNCs displayed a unique response to thiol compounds and low pH values and were thus pioneered as a high-efficiency sensor for OPs based on acetylcholinesterase (AChE)-catalyzed hydrolysis of acetylthiocholine into thiocholine and CHCOOH and OP inhibition of AChE activity. Further, S-S-AuNCs were employed to monitor the residue, distribution, and metabolization of methidathion in pakchoi with acceptable results. We believe that this work supplies a simpler and more highly sensitive approach for OP assay than the known ones and opens a new avenue to development of multistimulus-responsive and high-performance fluorescence substances.
Topics: Acetylcholinesterase; Biosensing Techniques; Disulfides; Gold; Hydrogen-Ion Concentration; Organophosphorus Compounds; Oxidation-Reduction; Pesticides
PubMed: 33961403
DOI: 10.1021/acs.analchem.1c01414 -
Journal of Chromatography. B,... Feb 2022A sensitive assay was developed to evaluate inhibitory effects of aqueous solution on acetylcholinesterase (AChE) activity via measuring hydrolysis rates of...
A sensitive assay was developed to evaluate inhibitory effects of aqueous solution on acetylcholinesterase (AChE) activity via measuring hydrolysis rates of acetylcholine (ACh) based on ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Upon having identified precursor ions and product ions of the ACh and its hydrolysis products choline (Ch), the separation chromatogram for these two analytes has been established using a 50 mm reverse-phase BEH Shield RP18 column. The total chromatographic separation time is 7 min; limits of detection (LODs) for ACh and Ch are 0.14 µg L and 0.12 µg L, respectively. A simple method for inactivation of AChE and optimization of operational parameters were then sequentially performed. It was found that adjusting solution pH to 2.5 not only can terminate the enzymatic reaction but also solve band shifting and broadening caused by aqueous matrices in chromatographic separation during UPLC-MS/MS detection. Under conditions of 0.00075 U mL AChE, initial concentration of ACh at 100 µg L and 20 min observation time, IC values of the proposed assay for chlorpyrifos-oxon, diazoxon, malaoxon, methidathion oxon, omethoate and paraoxon were 3.5 nM, 16.8 nM, 2.4 nM, 6.8 nM, 270 nM and 36.9 nM, respectively. They are 4.5-51.9 times smaller than those reported in a LC-MS based method, and >120 times lower than those obtained by the traditional Ellman method. The results suggested that, the proposed assay significantly increases the sensitivity of commercial AChE. In addition, inhibition efficiencies of three surface waters, a groundwater and four commercial brands of bottled drinking water samples on AChE activity were firstly measured using this UPLC-MS/MS based method. These water samples were proved to have different inhibitory effects on AChE activity, and the inhibition efficiencies dependent on concentrations of dissolved organic carbon (DOC) but are independent of UV absorbance at 254 nm (UV) values. These results indicate that the proposed method has advantages of high sensitivity over all other conventional methods. It may become a promising AChE inhibition assay for assessing toxicity of aqueous solution containing neurotoxicity contaminants such as organophosphorus pesticides (OPPs) at low levels, or used to evaluate potential inhibition effects of natural waters on AChE activity.
Topics: Acetylcholine; Acetylcholinesterase; Animals; Cholinesterase Inhibitors; Chromatography, High Pressure Liquid; Drinking Water; Electrophorus; Fish Proteins; Groundwater; Hydrolysis; Organophosphorus Compounds; Sensitivity and Specificity; Tandem Mass Spectrometry; Water Pollutants
PubMed: 35030473
DOI: 10.1016/j.jchromb.2022.123101 -
Chemosphere Aug 2023The epidemiological evidence of human exposure to organophosphorus pesticides (OPPs) with type 2 diabetes mellitus (T2DM) and prediabetes (PDM) is scarce. We aimed to...
OBJECTIVE
The epidemiological evidence of human exposure to organophosphorus pesticides (OPPs) with type 2 diabetes mellitus (T2DM) and prediabetes (PDM) is scarce. We aimed to examine the association of T2DM/PDM risk with single OPP exposure and multi-OPP co-exposure.
METHODS
Plasma levels of ten OPPs were measured using the gas chromatography-triple quadrupole mass spectrometry (GC-MS/MS) among 2734 subjects from the Henan Rural Cohort Study. We used generalized linear regression to estimate odds ratios (ORs) or β with 95% confidence intervals (CIs), and constructed quantile g-computation and Bayesian kernel machine regression (BKMR) models to investigate the association of OPPs mixture with the risk of T2DM and PDM.
RESULTS
High detection rates ranged from 76.35% (isazophos) to 99.17% (malathion and methidathion) for all OPPs. Several plasma OPPs concentrations were in positive correlation with T2DM and PDM. Additionally, positive associations of several OPPs with fasting plasma glucose (FPG) values and glycosylated hemoglobin (HbA1c) levels were observed. In the quantile g-computation, we identified significantly positive associations between OPPs mixtures and T2DM as well as PDM, and fenthion had the greatest contribution for T2DM, followed by fenitrothion and cadusafos. As for PDM, the increased risk was largely explained by cadusafos, fenthion, and malathion. Furthermore, BKMR models suggested that co-exposure to OPPs was linked to an increased risk of T2DM and PDM.
CONCLUSION
Our findings suggested that the individual and mixture of OPPs exposure were associated with an increased risk of T2DM and PDM, implying that OPPs might act an important role in the development of T2DM.
Topics: Humans; Bayes Theorem; Cohort Studies; Diabetes Mellitus, Type 2; East Asian People; Fenthion; Gas Chromatography-Mass Spectrometry; Malathion; Organophosphorus Compounds; Pesticides; Tandem Mass Spectrometry
PubMed: 37156283
DOI: 10.1016/j.chemosphere.2023.138865