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Environmental Health Perspectives Oct 2023Widespread insecticide exposure might be a risk factor for neurodevelopment of our children, but few studies examined the mixture effect of maternal coexposure to...
BACKGROUND
Widespread insecticide exposure might be a risk factor for neurodevelopment of our children, but few studies examined the mixture effect of maternal coexposure to organophosphate insecticides (OPPs), pyrethroids (PYRs), and neonicotinoid insecticides (NNIs) during pregnancy on child neurodevelopment, and critical windows of exposure are unknown.
OBJECTIVES
We aimed to evaluate the association of prenatal exposure to multiple insecticides with children's neurodevelopment and to identify critical windows of the exposure.
METHODS
Pregnant women were recruited into a prospective birth cohort study in Wuhan, China, from 2014-2017. Eight metabolites of OPPs (mOPPs), three metabolites of PYRs (mPYRs), and nine metabolites of NNIs (mNNIs) were measured in 3,123 urine samples collected at their first, second, and third trimesters. Children's neurodevelopment [mental development index (MDI) and psychomotor development index (PDI)] was assessed using the Bayley Scales of Infant Development at 2 years of age (). Multivariate linear regression models, generalized estimating equation models, and weighted quantile sum (WQS) regression were used to estimate the association between the insecticide metabolites and Bayley scores. Potential sex-specific associations were also examined.
RESULTS
Single chemical analysis suggested higher urinary concentrations of some insecticide metabolites at the first trimester were significantly associated with lower MDI and PDI scores, and the associations were more prominent among boys. Each 1-unit increase in ln-transformed urinary concentrations of two mOPPs, 3,5,6-trichloro-2-pyridinol and 4-nitrophenol, was associated with a decrease of 3.16 points [95% confidence interval (CI): , ] and 3.06 points (95% CI: , ) respectively in boys' MDI scores. Each 1-unit increase in that of -3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarboxylic acid (-DCCA; an mPYR) was significantly associated with a decrease of 2.24 points (95% CI: , ) in boys' MDI scores and 1.90 points (95% CI: , ) in boys' PDI scores, respectively. Significantly positive associations of maternal urinary biomarker concentrations [e.g., dimethyl phosphate (a nonspecific mOPP) and desmethyl-clothianidin (a relatively specific mNNI)] with child neurodevelopment were also observed. Using repeated holdout validation, a 1-quartile increase in the WQS index of the insecticide mixture (in the negative direction) at the first trimester was significantly associated with a decrease of 3.02 points (95% CI: , ) in MDI scores among the boys, and -DCCA contributed the most to the association (18%).
CONCLUSIONS
Prenatal exposure to higher levels of certain insecticides and their mixture were associated with lower Bayley scores in children, particularly in boys. Early pregnancy may be a sensitive window for such an effect. Future studies are needed to confirm our findings. https://doi.org/10.1289/EHP12097.
Topics: Male; Infant; Humans; Child; Female; Pregnancy; Insecticides; Pyrethrins; Prospective Studies; Cohort Studies; Prenatal Exposure Delayed Effects; Organophosphates; Child Development; Neonicotinoids; Maternal Exposure
PubMed: 37856202
DOI: 10.1289/EHP12097 -
International Journal of Palliative... Feb 2024Synopses of a selection of recently published research articles of relevance to palliative care.
Synopses of a selection of recently published research articles of relevance to palliative care.
Topics: Humans; Glyphosate; Palliative Care
PubMed: 38407154
DOI: 10.12968/ijpn.2024.30.2.100 -
Cancer Chemotherapy and Pharmacology May 2024Tazemetostat, a novel oral selective inhibitor of enhancer of zeste homolog 2 (EZH2), was approved by the Food and Drug Administration (FDA) in 2020 for use in patients... (Review)
Review
Tazemetostat, a novel oral selective inhibitor of enhancer of zeste homolog 2 (EZH2), was approved by the Food and Drug Administration (FDA) in 2020 for use in patients with advanced epithelioid sarcoma or relapsed/refractory (R/R) EZH2-mutated follicular lymphoma. These indications were approved by the FDA trough accelerated approval based on objective response rate and duration of response that resulted from phase 2 clinical trials. Tazemetostat competes with S-adenosylmethionine (SAM) cofactor to inhibit EZH2, reducing the levels of trimethylated lysine 27 of histone 3 (H3K27me3), considered as pharmacodynamic marker. Tazemetostat is orally bioavailable, characterized by rapid absorption and dose-proportional exposure, which is not influenced by coadministration with food or gastric acid reducing agents. It highly distributes in tissues, but with limited access to central nervous system. Tazemetostat is metabolized by CYP3A in the liver to 3 major inactive metabolites (M1, M3, and M5), has a short half-life and is mainly excreted in feces. Drug-drug interactions were shown with moderate CYP3A inhibitors as fluconazole, leading the FDA to recommend a 50% dose reduction, while studies investigating coadministration of tazemetostat with strong inhibitors/inducers are ongoing. No dosage modifications are recommended based on renal or hepatic dysfunctions. Overall, tazemetostat is the first-in-class EZH2 inhibitor approved by the FDA for cancer treatment. Current clinical studies are evaluating combination therapies in patients with several malignancies.
Topics: Humans; Morpholines; Drug Interactions; Biphenyl Compounds; Pyridones; Enhancer of Zeste Homolog 2 Protein; Sulfonamides; Antineoplastic Agents; Animals; Organophosphates; Benzamides
PubMed: 38520556
DOI: 10.1007/s00280-024-04658-4 -
Molecular Pharmaceutics Nov 2023Amifostine (AMF, also known as WR-2721) is the only approved broad-spectrum small-molecule radiation protection agent that can combat hematopoietic damage caused by... (Review)
Review
Amifostine (AMF, also known as WR-2721) is the only approved broad-spectrum small-molecule radiation protection agent that can combat hematopoietic damage caused by ionizing radiation and is used as an antitumor adjuvant and cell protector in cancer chemotherapy and radiotherapy. Amifostine is usually injected intravenously before chemotherapy or radiotherapy and has been used in the treatment of head and neck cancer. However, the inconvenient intravenous administration and its toxic side effects such as hypotension have severely limited its further application in clinic. In order to reduce the toxic and side effects, scientists are trying to develop a variety of drug administration methods and are devoted to developing a wide application of amifostine in radiation protection. This paper reviews the research progress of amifostine for radiation protection in recent years, discusses its mechanism of action, clinical application, and other aspects, with focus on summarizing the most widely studied amifostine injection administration and drug delivery systems, and explored the correlation between various administrations and drug efficacies.
Topics: Humans; Amifostine; Radiation Protection; Radiation-Protective Agents; Administration, Intravenous; Adjuvants, Immunologic; Drug-Related Side Effects and Adverse Reactions
PubMed: 37747899
DOI: 10.1021/acs.molpharmaceut.3c00600 -
Environmental Research Jul 2024Organophosphate esters (OPEs) are a class of chemicals now widely used as flame retardants and plasticizers after the phase-out of polybrominated diphenyl ethers... (Review)
Review
Organophosphate esters (OPEs) are a class of chemicals now widely used as flame retardants and plasticizers after the phase-out of polybrominated diphenyl ethers (PBDEs). However, OPEs carry their own risk of developmental toxicity, which poses concern for recent birth cohorts as they have become ubiquitous in the environment. In this review, we summarize the literature evaluating the association between OPE exposure and maternal, perinatal, and child health outcomes. We included original articles investigating associations of OPE exposure with any health outcome on pregnant women, newborns, children, and adolescents. We found 48 articles on this topic. Of these, five addressed maternal health and pregnancy outcomes, 24 evaluated prenatal OPE exposure and child health, 18 evaluated childhood OPE exposure and child/adolescent health, and one article evaluated both prenatal and childhood OPE exposure. These studies suggest that OPE exposure is possibly associated with a wide range of adverse health outcomes, including pregnancy loss, altered gestational duration and smaller birthweight, maternal and neonatal thyroid dysfunction, child metabolic dysregulation and abnormal growth, impaired neurodevelopment, and changes in immune response. Many of the reported outcomes associated with OPE exposure varied by child sex. Findings also varied substantially by OPE metabolite and exposure time. The OPEs most frequently measured, detected, and found to be associated with health outcomes were triphenyl phosphate (TPHP, metabolized to DPHP) and tris(1,3-dichloro-2-propyl) phosphate (TDCIPP, metabolized to BDCIPP). The extensive range of health outcomes associated with OPEs raises concern about their growing use in consumer products; however, these findings should be interpreted considering the limitations of these epidemiological studies, such as possible exposure misclassification, lack of generalizability, insufficient adjustment for covariates, and failure to consider chemical exposures as a mixture.
Topics: Humans; Female; Pregnancy; Organophosphates; Child; Esters; Child Health; Flame Retardants; Maternal Exposure; Adolescent; Infant, Newborn; Environmental Pollutants; Prenatal Exposure Delayed Effects; Maternal Health; Environmental Exposure; Child, Preschool
PubMed: 38640988
DOI: 10.1016/j.envres.2024.118955 -
The Science of the Total Environment Sep 2023Human beings are widespread exposed to organophosphate esters (OPEs), but little is known about their effects on respiratory health.
BACKGROUND
Human beings are widespread exposed to organophosphate esters (OPEs), but little is known about their effects on respiratory health.
OBJECTIVES
To investigate the associations of exposure to OPEs with lung function and airway inflammation among U.S. participants from NHANES, 2011-2012.
METHODS
A total of 1636 participants aged 6-79 years were included. Concentrations of OPE metabolites were measured in urine and lung function was assessed with spirometry. Fractional exhaled nitric oxide (FeNO) and blood eosinophils (B-Eos), two important inflammatory biomarkers, were also measured. Linear regression was performed to examine the relationships of OPEs with FeNO, B-Eos and lung function. Bayesian kernel machine regression (BKMR) was used to evaluate the joint associations between OPEs mixtures and lung function.
RESULTS
Three of seven OPE metabolites had detection frequencies > 80 %, including diphenyl phosphate (DPHP), bis (1,3-dichloro-2-propyl) phosphate (BDCPP), bis-2-chloroethyl phosphate (BCEP). A 10-fold increase in DPHP concentrations were associated with 1.02 mL decreases in FEV (β = -0.01, 95 % CIs = -0.02, -0.003) and FVC (β = -0.01, 95 % CIs = -0.02, -0.003), respectively, and the similar, modest decreases were seen for BDCPP. For each 10-fold increase in BCEP concentration, FVC was also reduced by 1.02 mL (β = -0.01, 95 % CIs = -0.02, -0.002). Moreover, the negative associations were only found in non-smokers aged >35 years. The aforementioned associations were confirmed by BKMR, but we cannot definitively identify a constituent driving this association. B-Eos was negatively associated with FEV and FEV/FVC, but not with OPEs. No associations were found of FeNO with OPEs and lung function.
CONCLUSIONS
Exposure to OPEs was associated with modest decrements in lung function, although the observed decrease in FVC and FEV is unlikely to be of real clinical relevance for the majority of subjects in this series. Moreover, those associations presented age and smoking status-dependent pattern. Unexpectedly, the adverse effect was not mediated by FeNO/B-Eos.
Topics: Humans; Cross-Sectional Studies; Nutrition Surveys; Bayes Theorem; Flame Retardants; Organophosphates; Phosphates; Esters; Lung
PubMed: 37301401
DOI: 10.1016/j.scitotenv.2023.164755 -
Ecotoxicology and Environmental Safety Sep 2023Heavy metals are pervasive pollutants found in water, soil, and solid wastes. Bio-solidification offers an environmentally friendly approach to immobilize heavy metal... (Review)
Review
Heavy metals are pervasive pollutants found in water, soil, and solid wastes. Bio-solidification offers an environmentally friendly approach to immobilize heavy metal ions using two types of bacteria: urease-producing bacteria (UPB) and phosphatase-producing bacteria (PPB). UPB, exemplified by Sporosarcina pasteurii, secretes urease to hydrolyze urea and generate CO ions, while PPB, like Bacillus subtilis, produces alkaline phosphatase to hydrolyze organophosphate monoester (ROP) and produce PO ions. These ions react with heavy metal ions, effectively reducing their concentration by forming insoluble carbonate or phosphate precipitates. The success of bio-solidification is influenced by various factors, including substrate concentration, temperature, pH, and bacterial density. Optimal operational conditions can significantly enhance the remediation performance of heavy metals. UPB and PPB hold great potential for remediating heavy metal pollution in diverse contaminated areas such as tailings ponds, electroplating sewage, and garbage incineration plants. In conclusion, harnessing the power of these microbial methods can provide effective solutions for remediating heavy metal-induced pollution across a range of environmental conditions.
Topics: Urease; Metals, Heavy; Phosphates; Organophosphates; Bacillus subtilis; Soil Pollutants; Soil
PubMed: 37517309
DOI: 10.1016/j.ecoenv.2023.115305 -
Environmental Science and Pollution... Nov 2023Human health is adversely affected by exposure to organophosphate (OP) pesticides. This study aims to investigate the correlation between urinary OP metabolites and the...
Human health is adversely affected by exposure to organophosphate (OP) pesticides. This study aims to investigate the correlation between urinary OP metabolites and the prevalence of asthma. In cross-sectional studies, data from the National Health and Nutrition Examination Survey (NHANES) projects conducted between 2003-2008, 2011-2012, and 2015-2018 were analyzed. Multiple logistic regressions and restricted cubic spline (RCS) regressions were utilized to examine the relationship between four urinary OP metabolites, namely dimethyl phosphate (DMP), diethyl phosphate (DEP), dimethyl phosphorothioate (DMTP), and diethyl phosphorothioate (DETP), and the prevalence of asthma. Additionally, quantile g-computation (QG-C) regression was employed to evaluate the association between urinary OP metabolites (both individual and combined exposures) and asthma prevalence. The results showed that a total of 9316 adults, including 1298 participants with asthma, were included in the analysis. The median age of the participants was 47.37 years, and 50.27% were female. In the comprehensive model, the third tertile of DMP and DEP exhibited a positive association with asthma prevalence compared to the first tertile (odds ratio [95% confidence interval]: 1.26 [1.01-1.57], P = 0.036; and 1.25 [1.07-1.51], P = 0.008, respectively). Moreover, a linear relationship was observed between DMP, DEP, and asthma prevalence (P for nonlinearity = 0.320 and 0.553, respectively). The QG-C regression revealed a positive association between the mixture of urinary OP metabolites and asthma prevalence (OR = 1.04 [1.01-1.07], P = 0.025), with DEP contributing the most substantial effect (weight = 0.564). Our findings suggest that exposure to OP pesticides is associated with an increased prevalence of asthma, with DEP demonstrating the strongest impact.
Topics: Humans; Adult; Female; Middle Aged; Male; Cross-Sectional Studies; Nutrition Surveys; Pesticides; Organophosphorus Compounds; Insecticides; Organophosphates; Environmental Exposure
PubMed: 37847364
DOI: 10.1007/s11356-023-30174-8 -
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 -
Environmental Monitoring and Assessment Dec 2023The general population and workers are exposed to organophosphate insecticides, one of the leading chemical classes of pesticides used in rural and urban areas, in the... (Review)
Review
The general population and workers are exposed to organophosphate insecticides, one of the leading chemical classes of pesticides used in rural and urban areas, in the control of arboviruses and agriculture. These pesticides cause environmental/occupational exposure and associated risks to human and environmental health. The objective of this study was to carry out an integrative review of epidemiological studies that identified and quantified dialkylphosphate metabolites in the urine of exposed populations, focusing on the vector control workers, discussing the application and the results found. Searches utilized the Pubmed, Scielo, and the Brazilian Digital Library of Theses and Dissertations (BDTD) databases between 2000 and 2021. From the 194 selected studies, 75 (39%) were with children/adolescents, 48 (24%) with rural workers, 36 (19%) with the general population, 27 (14%) with pregnant women, and 9 (4%) with vector control workers. The total dialkylphosphate concentrations found in the occupationally exposed population were higher than in the general population. Studies demonstrate that dialkylphosphates are sensitive and representative exposure biomarkers for environmental and occupational organophosphate exposure. The work revealed a lack of studies with vector control workers and a lack of studies in developing countries.
Topics: Child; Humans; Female; Pregnancy; Adolescent; Insecticides; Environmental Monitoring; Pesticides; Organophosphorus Compounds; Environmental Exposure; Occupational Exposure; Organophosphates
PubMed: 38049584
DOI: 10.1007/s10661-023-12184-8