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Ecotoxicology and Environmental Safety Jun 2024Organophosphate esters (OPEs) are used extensively as flame retardants and plasticizers. Laboratory studies have shown that OPEs exhibit osteotoxicity by inhibiting...
BACKGROUND
Organophosphate esters (OPEs) are used extensively as flame retardants and plasticizers. Laboratory studies have shown that OPEs exhibit osteotoxicity by inhibiting osteoblast differentiation; however, little is known about how OPEs exposure is associated with bone health in humans.
OBJECTIVES
We conducted a cross-sectional study to investigate the association between OPEs exposure and bone mineral density (BMD) in adults in the United States using data from the 2011-2018 National Health and Nutrition Examination Survey (NHANES).
METHODS
Multivariate linear regression models were used to assess the association between concentrations of individual OPE metabolites and BMDs. We also used the Bayesian kernel machine regression (BKMR) and quantile g-computation (qgcomp) models to estimate joint associations between OPE mixture exposure and BMDs. All the analyses were stratified according to gender.
RESULTS
A total of 3546 participants (median age, 40 years [IQR, 30-50 years]; 50.11% male) were included in this study. Five urinary OPE metabolites with a detection rate of > 50% were analyzed. After adjusting for the potential confounders, OPE metabolite concentrations were associated with decreased total-body BMD and lumbar spine BMD in males, although some associations only reached significance for bis(1-chloro-2-propyl) phosphate (BCPP), dibutyl phosphate (DBUP), and bis(2-chloroethyl) phosphate (BCEP) (β = -0.013, 95% CI: -0.026, -0.001 for BCPP and total-body BMD; β = -0.022, 95% CI: -0.043, -0.0001 for DBUP and lumbar spine BMD; β=-0.018, 95% CI: -0.034, -0.002 for BCEP and lumbar spine BMD). OPE mixture exposure was also inversely associated with BMD in males, as demonstrated in the BMKR and qgcomp models.
CONCLUSIONS
This study provides preliminary evidence that urinary OPE metabolite concentrations are inversely associated with BMD. The results also suggested that males were more vulnerable than females. However, further studies are required to confirm these findings.
Topics: Humans; Adult; Male; Bone Density; Female; Middle Aged; United States; Nutrition Surveys; Cross-Sectional Studies; Organophosphates; Esters; Flame Retardants; Environmental Exposure; Environmental Pollutants
PubMed: 38714086
DOI: 10.1016/j.ecoenv.2024.116414 -
The Journal of Pharmacology and... Jan 2024Sex differences are common in human epilepsy. Although men are more susceptible to seizure than women, the mechanisms underlying sex-specific vulnerabilities to seizure...
Sex differences are common in human epilepsy. Although men are more susceptible to seizure than women, the mechanisms underlying sex-specific vulnerabilities to seizure are unclear. The organophosphate (OP) diisopropylfluorophosphate (DFP) is known to cause neurotoxicity and status epilepticus (SE), a serious neurologic condition that causes prolonged seizures and brain damage. Current therapies for OP poisoning and SE do not consider neuronal variations between male and female brains. Therefore, we investigated sex-dependent differences in electrographic seizure activity and neuronal injury using the DFP model of refractory SE in rats. Electroencephalogram recordings were used to monitor DFP-induced SE, and the extent of brain injury was determined using fluoro-jade-B staining to detect cellular necrosis. After DFP exposure, we observed striking sex-dependent differences in SE and seizure activity patterns as well as protective responses to midazolam treatment. Following acute DFP exposure, male animals displayed more severe SE with intense epileptiform spiking and greater mortality than females. In contrast, we observed significantly more injured cells and cellular necrosis in the hippocampus and other brain regions in females than in males. We also observed extensive neuronal injury in the somatosensory cortex of males. The anticonvulsant effect of midazolam against SE was limited in this model and found to be similar in males and females. However, unlike males, females exhibited substantially more protection against neuronal damage after midazolam treatment. Overall, these results demonstrate significant sex-dependent differences in DFP-induced refractory SE and neuronal damage patterns, suggesting that it may be possible to develop sex-specific neuroprotective strategies for OP intoxication and refractory SE. SIGNIFICANCE STATEMENT: Sex-dependent differences in neurotoxicity and status epilepticus (SE) are key biological variables after organophosphate (OP) exposure. Here, we investigated sex-dependent differences in SE and brain injury after acute diisopropylfluorophosphate exposure. Male rats had more severe SE and less survival than females, while females had more neuronal damage. Females had more neuroprotection to midazolam than males, while both sexes had similar but partial anticonvulsant effects. These findings suggest that a sex-specific therapeutic approach may prevent neurological complications of OP-induced SE.
Topics: Humans; Female; Male; Rats; Animals; Benzodiazepines; Anticonvulsants; Midazolam; Isoflurophate; Organophosphates; Sex Characteristics; Rats, Sprague-Dawley; Status Epilepticus; Seizures; Brain; Organophosphate Poisoning; Brain Injuries; Necrosis
PubMed: 37770202
DOI: 10.1124/jpet.123.001747 -
Parasites & Vectors Mar 2024Indoor residual spraying (IRS) was first implemented in the Atacora department, Benin from 2011 to 2012 using bendiocarb (carbamate) followed by annual spraying with...
The frequency of kdr and ace-1 alleles in Anopheles gambiae s.l. before and during indoor residual spraying (IRS) implementation and four years after IRS withdrawal in three districts in Atacora, Benin.
BACKGROUND
Indoor residual spraying (IRS) was first implemented in the Atacora department, Benin from 2011 to 2012 using bendiocarb (carbamate) followed by annual spraying with pirimiphos-methyl (organophosphate) from 2013 to 2018. Before and after IRS implementation in Atacora, standard pyrethroid insecticide-treated bed nets were the main method of vector control in the area. This study investigated the knockdown resistance (kdr) gene (L1014F) and the acetylcholinesterase (ace-1) gene (G119S), before and during IRS implementation, and 4-years after IRS withdrawal from Atacora. This was done to assess how changes in insecticide pressure from indoor residual spraying may have altered the genotypic resistance profile of Anopheles gambiae s.l.
METHOD
Identification of sibling species of An. gambiae s.l. and detection of the L1014F mutation in the kdr gene and G119S mutation in ace-1 genes was done using molecular analysis. Allelic and genotypic frequencies were calculated and compared with each other before and during IRS implementation and 4 years after IRS withdrawal. The Hardy-Weinberg equilibrium and genetic differentiation within and between populations were assessed.
RESULTS
Prevalence of the L1014F mutation in all geographic An. gambiae s.l. (An. gambiae s.s., Anopheles. coluzzii, Anopheles. arabiensis, and hybrids of "An. gambiae s.s. and An. coluzzii") populations increased from 69% before IRS to 87% and 90% during and after IRS. The G119S allele frequency during IRS (20%) was significantly higher than before IRS implementation (2%). Four years after IRS withdrawal, allele frequencies returned to similar levels as before IRS (3%). Four years after IRS withdrawal, the populations showed excess heterozygosity at the ace-1 gene and deficit heterozygosity at the kdr gene, whereas both genes had excess heterozygosity before and during IRS (F < 0). No genetic differentiation was observed within the populations.
CONCLUSIONS
This study shows that the withdrawal of IRS with bendiocarb and pirimiphos-methyl may have slowed down the selection of individual mosquitoes with ace-1 resistance alleles in contrast to populations of An. gambiae s.l. with the L1014F resistance allele of the kdr gene. This may suggest that withdrawing the use of carbamates or organophosphates from IRS or rotating alternative insecticides with different modes of action may slow the development of ace-1 insecticide-resistance mutations. The increase in the prevalence of the L1014F mutation of the kdr gene in the population, despite the cessation of IRS, could be explained by the growing use of pyrethroids and DDT in agriculture and for other domestic use. More observational studies in countries where carbamates or organophosphates are still being used as public health insecticides may provide additional insights into these associations.
Topics: Animals; Insecticides; Anopheles; Benin; Alleles; Acetylcholinesterase; Mosquito Vectors; Pyrethrins; Insecticide Resistance; Carbamates; Organophosphates; Mosquito Control; Phenylcarbamates
PubMed: 38454494
DOI: 10.1186/s13071-024-06206-8 -
The Science of the Total Environment Jul 2023Organophosphate esters (OPEs) are widely used in numerous consumer products for their flame retardant and plasticizing properties. Despite potential widespread exposure,...
Organophosphate esters (OPEs) are widely used in numerous consumer products for their flame retardant and plasticizing properties. Despite potential widespread exposure, biomonitoring data during critical windows of development are scarce and limited to the most widely studied metabolites. We quantified urinary concentrations of multiple OPE metabolites in a vulnerable Canadian population. Using data and biobanked specimens from the Maternal-Infant Research on Environmental Chemicals (MIREC) study (2008-2011), we measured first trimester urinary concentrations of 15 OPE metabolites as well as one flame retardant metabolite and quantified associations with sociodemographic and sample collection characteristics in 1865 pregnant participants. We applied 2 different analytical methods to quantify OPEs, one using UItra-Performance Liquid Chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) and the other using Atmospheric Pressure Gas Chromatography coupled to mass spectrometry (APGC-MS/MS) with sensitive limits of detection (0.008-0.1 μg/L). We modelled associations between sociodemographic and sample collection characteristics and specific gravity-standardized chemical concentrations. Six OPE metabolites were detected in the majority (68.1-97.4 %) of participants. Bis-(2-chloroethyl) hydrogen phosphate had the highest detection rate (97.4 %). Diphenyl phosphate had the highest geometric mean concentration (0.657 μg/L). Metabolites of tricresyl phosphate were detected in few participants. Associations between sociodemographic characteristics varied according to each OPE metabolite. Pre-pregnancy body mass index tended to be positively associated with OPE metabolite concentrations whereas age tended to be inversely associated with OPE concentrations. OPE concentrations were, on average, higher in urine samples collected in the summer than other seasons the winter. We present the largest biomonitoring study of OPE metabolites in pregnant people to date. These findings demonstrate widespread exposure to OPEs and their metabolites and identify subpopulations who may experience heightened exposure.
Topics: Pregnancy; Female; Humans; Flame Retardants; Tandem Mass Spectrometry; Chromatography, Liquid; Esters; Canada; Gas Chromatography-Mass Spectrometry; Organophosphates; Phosphates
PubMed: 37030364
DOI: 10.1016/j.scitotenv.2023.163327 -
Globalization and Health Nov 2023Glyphosate is the world's most used herbicide and a central component of modern industrial agriculture. It has also been linked to a variety of negative health and...
BACKGROUND
Glyphosate is the world's most used herbicide and a central component of modern industrial agriculture. It has also been linked to a variety of negative health and environmental effects. For instance, the International Agency for Research on Cancer classified glyphosate as "probably carcinogenic to humans" in 2015. This has motivated widespread political demands for stricter glyphosate regulation but so far few governments have followed through.
METHODS
We conduct a case study of Sri Lanka, which in 2015 became the first and so far only country in the world to adopt and implement a complete glyphosate ban. But this ban proved to be short-lived, as it was partially reversed in 2018 (and later fully revoked in 2022). To explain the political causes of Sri Lanka's pioneering glyphosate ban and its subsequent reversal, we employ process tracing methods drawing on publicly available documents. Our analysis is theoretically guided by the multiple streams framework and the concept of self-undermining policy feedback.
RESULTS
Glyphosate regulation rose to the top of the Sri Lankan political agenda in 2014 when a local scientist linked glyphosate exposure to an epidemic of Chronic Kidney Disease of Unknown Origin (CKDu). A glyphosate ban was eventually adopted in June 2015 by the newly elected government of Maithripala Sirisena. The ban was a political commitment made to the Buddhist monk Rathana Thero and his party, which had supported Sirisena during his presidential campaign. The ban's partial reversal in 2018, implemented through sectoral exceptions, was the result of continued lobbying by export-oriented plantation industries and increased political concerns about potential negative effects on the large and structurally powerful tea sector. The reversal was further aided by the scientific community's failure to corroborate the hypothesized link between glyphosate and CKDu.
CONCLUSIONS
The case of Sri Lanka suggests that strict glyphosate regulation becomes more likely when coupled with locally salient health risks and when decision-making authority is de-delegated from regulatory agencies back to the political executive. Meanwhile, the short-lived nature of the Sri Lankan ban suggests that strict glyphosate regulation faces political sustainability threats, as the apparent lack of cost-effective alternative herbicides motivates persistent business lobbying for regulatory reversal.
Topics: Humans; Sri Lanka; Herbicides; Glycine; Politics; Glyphosate
PubMed: 37957659
DOI: 10.1186/s12992-023-00981-2 -
Journal of Food Protection Oct 2023Dissipation, residue levels, and ingestion risks of carbendazim in peach (Amygdalus persica L.) were investigated with individual and joint applications in the present...
Dissipation, residue levels, and ingestion risks of carbendazim in peach (Amygdalus persica L.) were investigated with individual and joint applications in the present study. The dissipation kinetics of carbendazim, chlorpyrifos, prochloraz, and imidacloprid were evaluated by the first-order kinetics. When carbendazim was individually applied, the final residual concentration was 2.97 mg kg and the half-life was 17.4 d. In the joint application of carbendazim with chlorpyrifos, prochloraz, and imidacloprid, the residual concentrations at 35 d after spraying were 7.16, 7.50, and 4.26 mg kg and the half-lives were 30.8, 23.7, and 23.2 d, respectively, which showed an increase of 1.3-1.8 times compared with the single application of carbendazim. In addition, the effects of household processing of rinsing and peeling were investigated, and a high removal rate of 54.6% and 76.5% were found. Furthermore, the carbendazim ingestion risk assessment was conducted, which indicated that the acute health risk (aHI) and hazard quotient (HQ) of carbendazim were all within acceptable levels ranging from 21.7% to 40.9%. However, a higher ingestion risk of carbendazim was found under the joint application. This study provides some preliminary guidance for the joint application and risk assessment of carbendazim in peach, which is worth further investigation.
Topics: Prunus persica; Chlorpyrifos; Risk Assessment; Pesticide Residues
PubMed: 37604252
DOI: 10.1016/j.jfp.2023.100145 -
Case Reports in Pediatrics 2023. Organophosphates are chemicals that lead to the accumulation of acetylcholine, causing muscarinic symptoms such as salivation and nicotinic manifestations like muscle...
. Organophosphates are chemicals that lead to the accumulation of acetylcholine, causing muscarinic symptoms such as salivation and nicotinic manifestations like muscle weakness and hypertension and rarely leading to basal ganglia impairment, manifesting as extrapyramidal symptoms. Literature reported that the use of amantadine, an amine that has both antiviral and dopaminergic activities, improves extrapyramidal manifestations. Most of the studies exploring the effect of amantadine were conducted on adults and there are extremely limited data in regards to this topic in Saudi Arabia. Thus, the purpose of this case study is to report the outcome of treating a child who developed extrapyramidal symptoms due to organophosphates poisoning with amantadine. . A 6-year-old boy was found by his family drowsy and drooling with an insecticide bottle beside him. He was brought to the ER and arrested on arrival, and he was eventually revived after 5 minutes of CPR. Then, he developed features of extrapyramidal involvement such as delirium, hyperactivity, akathisia, aphonia, and tremors. He was started on oral amantadine 50 mg once daily and then increased to twice daily for two weeks while admitted. During admission, his symptoms were assessed daily, and an improvement was noticed by his family and the medical team. Upon discharge, he was able to form sentences; tremors were almost resolved; and there was no rigidity or agitation. He was followed up postdischarge and showed significant improvement. He continued amantadine for almost 3 months until the full resolution of his symptoms. . This case illustrates the promising benefits of using amantadine in treating extrapyramidal manifestations following organophosphate ingestion.
PubMed: 37700928
DOI: 10.1155/2023/1632052 -
Environmental Pollution (Barking, Essex... Aug 2023Microplastics (MPs) in soil undergo different aging processes such as photoaging, mechanical abrasion and biodegradation, leading to alterations in the surface...
Microplastics (MPs) in soil undergo different aging processes such as photoaging, mechanical abrasion and biodegradation, leading to alterations in the surface properties of MPs. In this study, we investigated the adsorption-desorption of chlorpyrifos (CPF) on pristine and UV light-aged low-density polyethylene (LDPE) and biodegradable (Bio) MPs that were derived from plastic mulch films. We also tested the bioconcentration of pristine and aged MPs (LDPE- and Bio-MPs aged under UV light and LDPE-MPs aged in three different soils) associated with CPF by earthworms (Lumbricus terrestris). The results showed that UV-aged MPs showed higher CPF adsorption capacities than pristine MPs, with the adsorption capacities at 184.9 ± 5.3, 200.5 ± 1.8, 193.0 ± 8.7, and 215.9 ± 1.1 μg g for pristine LDPE-, UV-aged LDPE-, pristine Bio- and UV-aged Bio-MPs, respectively. The desorption rate of CPF from UV-aged LDPE-MPs within 48 h was lower than the desorption from pristine ones (28.8 ± 7.7% vs. 40.0 ± 3.9%), while both pristine and UV-aged Bio-MPs showed very low CPF desorption rates. A 4-day Petri dish experiment showed that UV-aged MPs were significantly less concentrated in earthworm casts than pristine counterparts (52% and 36% lower for UV-aged LDPE- and Bio-MPs), while UV-aged MPs with adsorbed CPF were concentrated significantly more than UV-aged MPs without CPF. Interestingly, LDPE-MPs aged in soil with a high carbon, nitrogen, and carbon-to-nitrogen ratio were significantly more concentrated in earthworm casts than pristine LDPE-MPs. In conclusion, UV-aged MPs acted as stronger vectors for CPF than pristine MPs. The bioconcentration of MPs differed significantly due to microplastic aging, as well as the combined effect with CPF. Moreover, LDPE-MPs aged in soil with enriched carbon and nitrogen were significantly concentrated in earthworm casts. Further studies on the environmental behaviours of aged MPs associated with other pollutants in soil, especially soils high in carbon and nitrogen, are needed.
Topics: Animals; Microplastics; Plastics; Chlorpyrifos; Polyethylene; Adsorption; Bioaccumulation; Soil; Oligochaeta
PubMed: 37247767
DOI: 10.1016/j.envpol.2023.121910 -
Toxics Sep 2023The contexts where there are mining and agriculture activities are potential sources of risk to human health due to contamination by chemical mixtures. These contexts...
The contexts where there are mining and agriculture activities are potential sources of risk to human health due to contamination by chemical mixtures. These contexts are frequent in several Colombian regions. This study explored the potential association between the frequency of micronuclei and pesticides and elements in regions with ferronickel (Montelibano, Córdoba) and gold (Nechí, Antioquia) mining, and a closed native mercury mine (Aranzazu, Caldas), with an emphasis in the potential effect of selenium as a potential chelator. A cross-sectional study was carried out with 247 individuals. Sociodemographic, occupational, and toxicological variables were ascertained. Blood and urine samples were taken for pesticide analysis (5 organophosphates, 4 organochlorines, and 3 carbamates), 68 elements were quantified in hair, and micronuclei were quantified in lymphocytes. The mixtures of elements were grouped through principal component analysis. Prevalence ratios were estimated with robust variance Poisson regressions to explore associations. Interactions of selenium with toxic elements were explored. The highest concentrations of elements were in the active mines. The potentially most toxic chemical mixture was observed in the ferronickel mine. Pesticides were detected in a low proportion of participants (<2.5%), except paraoxon-methyl in blood (27.55%) in Montelibano and paraoxon-ethyl in blood (18.81%) in Aranzazu. The frequency of micronuclei was similar in the three mining contexts, with means between 4 to 7 ( = 0.1298). There was great heterogeneity in the exposure to pesticides and elements. The "hormetic effect" of selenium was described, in which, at low doses, it acts as a chelator in Montelibano and Aranzazu, and at high doses, it can enhance the toxic effects of other elements, maybe as in Nechí. Selenium can serve as a protective agent, but it requires adaptation to the available concentrations in each region to avoid its toxic effects.
PubMed: 37888671
DOI: 10.3390/toxics11100821 -
Molecules (Basel, Switzerland) Aug 2023To monitor human exposure to pesticides, experts commonly measure their metabolites in urine, particularly dialkyl phosphates (DAPs), which include diethyl phosphate...
To monitor human exposure to pesticides, experts commonly measure their metabolites in urine, particularly dialkyl phosphates (DAPs), which include diethyl phosphate (DEP), Diethyl thiophosphate (DETP), diethyl dithiophosphate (DEDTP), dimethyl phosphate (DMP), dimethyl thiophosphate (DMTP) and dimethyl dithiophosphate (DMDTP)to monitor the metabolites of organophosphates. These DAP metabolites are a urinary biomarker for assessing pesticide exposure and potential health risks. This study presented a new screening method combining ultrafast liquid chromatography with tandem mass spectrometry (UFLC-MS/MS) to detect six DAP metabolites in human urine. The study also compared standard sample extraction methods, namely, liquid-liquid extraction (LLE); quick, easy, cheap, effective, ruggedand safe (QuEChERS); and lyophilization. After a comprehensive analysis of the methods used to extract the analytes, including recovery rate, repeatability and reproducibility, the liquid-liquid extraction (LLE) method was found to be the best. It had a high recovery rate, was easy to handle, required less sample volume and had a short extraction time. Therefore, the LLE method was chosen for further analysis. The results showed excellent performance with high recoveries between 93% and 102%, precise repeatability (RSD) between 0.62% and 5.46% and acceptable reproducibility values (RSD) between 0.80% and 11.33%. The method also had limits of detection (LOD) ranging from 0.0201 ng/mL to 0.0697 ng/mL and limits of quantification (LOQ) ranging from 0.0609 ng/mL to 0.2112 ng/mL. Furthermore, the UFLC-MS/MS method was validated based on the SANTE guidance and successfully analyzed 150 urine samples from farmers and non-farmers. This validated method proved useful for biomonitoring studies focusing on OP pesticide exposure. It offers several advantages, such as a reduced need for samples, chemicals and materials, and a shorter analysis time. The method is sensitive and selective in detecting metabolites in human urine, making it a valuable approach for the practical and efficient assessment of pesticide exposure.
Topics: Humans; Tandem Mass Spectrometry; Reproducibility of Results; Insecticides; Organophosphates; Pesticides
PubMed: 37570770
DOI: 10.3390/molecules28155800