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The Science of the Total Environment Dec 2022No human studies have evaluated early life organophosphate ester (OPE) exposures with bone health outcomes, despite evidence of osteotoxicity.
BACKGROUND
No human studies have evaluated early life organophosphate ester (OPE) exposures with bone health outcomes, despite evidence of osteotoxicity.
OBJECTIVES
We assessed associations of urinary OPE metabolites measured across early life with areal bone mineral density (aBMD) and bone mineral content (BMC) at age 12 years.
METHODS
Among 223 mother-child dyads enrolled in the Health Outcomes and Measures of the Environment (HOME) Study, we quantified concentrations of bis-2-chloroethyl phosphate (BCEP), bis-(1,3-dichloro-2-propyl) (BDCIPP), di-n-butyl phosphate (DnBP), and diphenyl phosphate (DPHP) in urine collected from mothers during pregnancy and children at ages 1, 2, 3, 5, and 8 years. At age 12 years, we performed dual energy x-ray absorptiometry and calculated aBMD and BMC z-scores at six skeletal sites. We estimated overall and sex-stratified BMD/BMC z-score differences per interquartile range (IQR) increase in OPE concentrations at multiple exposure timepoints: gestation (average) and 1-3 (average), 5, and 8 years.
RESULTS
In adjusted models, overall associations of BCEP and BDCIPP with total hip and 1/3rd distal radius aBMD and BMC varied significantly by exposure timepoint, as did BDCIPP with whole body aBMD. For example, differences (95 % CI) in total hip aBMD z-score per IQR increase in BDCIPP were 0.33 (0.01, 0.64), -0.10 (-0.34, 0.14), -0.18 (-0.40, 0.05), and 0.14 (-0.09, 0.38) for concentrations during gestation and at 1-3, 5, and 8 years, respectively. Overall DnBP and DPHP associations were generally null at all timepoints. We observed sex-specific associations for some timepoints and skeletal sites. For example, an IQR increase in 8-year DPHP was associated with a 0.21 (0.05, 0.38) greater total hip aBMD z-score among females but -0.19 (-0.43, 0.05) lower z-score among males.
DISCUSSION
Early life OPE exposures may be associated with sex- and exposure period-dependent alterations in early adolescent bone mineral accrual and strength.
Topics: Adolescent; Male; Pregnancy; Female; Humans; Child; Bone Density; Organophosphates; Phosphates; Esters; Outcome Assessment, Health Care
PubMed: 36030851
DOI: 10.1016/j.scitotenv.2022.158246 -
International Journal of Hygiene and... May 2023Organophosphate esters (OPEs), widely used as flame retardants and plasticizers for commercial and residential purposes, are suspected of being neurotoxic. We aimed to...
Organophosphate esters (OPEs), widely used as flame retardants and plasticizers for commercial and residential purposes, are suspected of being neurotoxic. We aimed to assess exposure to an OPE mixture in early life and its relationship to parent-reported child behavior. We measured urinary concentrations of three OPE metabolites, bis-2-chloroethyl phosphate (BCEP), bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), and diphenyl phosphate (DPHP), at pregnancy (16 and 26 weeks of gestation and delivery) and postnatal time points (ages 1, 2, 3, and 5 years) in the Health Outcomes and Measures of the Environment Study, a longitudinal pregnancy and birth cohort in Cincinnati, Ohio, USA (enrolled 2003-2006, n = 219). We used latent variable analysis in structural equations models and quantile g-computation to investigate associations of a mixture of the three OPE metabolites with parent-reported child behaviors at 3 and 8 years, measured using the Behavioral Assessment System for Children, Second Edition. Higher log-transformed urinary OPE latent variable values at 16 weeks were associated with fewer externalizing problem behaviors (ß = -5.74; 95% CI = -11.24, -0.24) and fewer overall behavioral problems at age 3 years (ß = -5.26; 95% CI = -10.33, -0.19), whereas having higher OPEs at delivery was associated with poorer overall behavioral problems at age 3 years (ß = 2.87; 95% CI = 0.13, 5.61). OPE latent variable values at 16 weeks, 26 weeks, and delivery were not associated with child behavior at 8 years. However, higher OPE latent variable values at 3 years were associated with fewer externalizing behaviors at 8 years (ß = -2.62; 95% CI = -5.13, -0.12). The quantile g-computation estimates had directions largely consistent with the latent variable analysis results. Pregnancy and postnatal urinary OPE metabolite mixtures were associated with child internalizing, externalizing, and overall negative behaviors at 3 and 8 years, but we did not identify a consistent pattern in terms of the direction of the effects or a particularly sensitive time point.
Topics: Child; Pregnancy; Female; Humans; Child, Preschool; Esters; Organophosphates; Child Behavior; Phosphates; Flame Retardants
PubMed: 36989997
DOI: 10.1016/j.ijheh.2023.114162 -
Journal of Environmental and Public... 2022Intentional ingestion of organophosphate (OP) and carbamate is a significant health issue worldwide. It causes adverse health effects on the liver. This study aimed to...
BACKGROUND
Intentional ingestion of organophosphate (OP) and carbamate is a significant health issue worldwide. It causes adverse health effects on the liver. This study aimed to determine liver transaminases (AST and ALT) and bilirubin levels to assess the severity of poisoning in patients with acute OP and carbamate poisoning.
METHODS
A descriptive cross-sectional study was conducted on patients admitted to a selected hospital in Sri Lanka with acute OP and carbamate poisoning. The severity of poisoning was measured by RBC cholinesterase and Peradeniya Organophosphorus Poisoning scale (POP), where six clinical features were assessed based on a 3-point scale. A score of 0-3 was considered mild, 4-7 to be moderate, and 8-11 to be severe poisoning. Liver parameters such as AST, ALT, and total and direct bilirubin were measured.
RESULTS
Among the 188 screened patients, 166 were recruited. Majority were males (112, 67.5%). Kruskal-Wallis test showed significant differences in AST and ALT on admission and AST on discharge, across POP groups (( (2, = 166) = 26.48, ≤ 0.001), ( (2, = 166) = 14.31, =0.001), and ( (2, = 157) = 11.34, =0.003), respectively)). Mann-Whitney test showed significantly higher AST and ALT in the moderate POP group compared to the mild POP group (AST: = 1709, = -4.50, ≤ 0.001, = 0.36; ALT: = 2114, = -3.04, =0.002, = 0.26) on admission. In addition, the treatment outcomes (duration of hospital stay and duration of ventilator assistance) were significantly correlated ( ≤ 0.001) with the severity of poisoning and serum AST and ALT at the time of admission.
CONCLUSION
AST and ALT levels on admission and AST level at discharge showed significant correlations with the severity of poisoning. Treatment outcomes significantly correlated with the severity of poisoning and serum AST and ALT levels.
Topics: Bilirubin; Carbamates; Cross-Sectional Studies; Female; Humans; Liver; Male; Organophosphates; Prospective Studies
PubMed: 35755887
DOI: 10.1155/2022/7826396 -
Rural and Remote Health Jan 2020Organophosphates are a class of insecticides used globally by the agricultural industry for insect control. Acute consequences of organophosphate exposures are well... (Review)
Review
INTRODUCTION
Organophosphates are a class of insecticides used globally by the agricultural industry for insect control. Acute consequences of organophosphate exposures are well known, while there has been limited research on their long-term effects. The objective of this review was to discuss the health effects of chronic organophosphate exposure in farmers.
METHODS
Medline, Scopus and Web of Science were searched to find the relevant articles. Articles published only in English and until December 2018 were reviewed. The selected articles were then categorised as neurological (neurobehaviour, neurodevelopmental, neurological signs and symptoms) or non-neurological subheadings.
RESULTS
A total of 53 articles for neurological effects and 17 articles for non-neurological effects were identified. Chronic organophosphates exposure was associated with deficits in the neurobehaviour subsets of attention and short-term memory, increased incidence of neurodegenerative diseases and effects on peripheral nerves and neurodevelopment. However, research to support non-neurological effects such as respiratory symptoms, increased cancer risk, endocrine disruption, cardiac issues, chronic fatigue and infertility was limited.
CONCLUSION
Chronic organophosphate exposure was found to affect four of the five areas of described neurological effects in the literature. A large proportion of the research in this area was not methodologically strong, therefore few recommendations can be conclusively made. Future research is warranted to investigate the non-neurological effects of chronic exposure to ensure the occupational risks of low-level chronic exposure are clearly communicated to farmers and farm workers.
Topics: Agricultural Workers' Diseases; Farmers; Humans; Insecticides; Occupational Exposure; Organophosphates
PubMed: 31902214
DOI: 10.22605/RRH4508 -
Environmental Research Jun 2023Organophosphate esters (OPEs) are used as flame retardants and plasticizers in various consumer products. Limited prior research suggests sex-specific effects of...
Sex-specific effects of prenatal organophosphate ester (OPE) metabolite mixtures and adverse infant birth outcomes in the maternal and developmental risks from environmental and social stressors (MADRES) pregnancy cohort.
BACKGROUND
Organophosphate esters (OPEs) are used as flame retardants and plasticizers in various consumer products. Limited prior research suggests sex-specific effects of prenatal OPE exposures on fetal development. We evaluated overall and sex-specific associations between prenatal OPE exposures and gestational age (GA) at birth and birthweight for gestational age (BW for GA) z-scores among the predominately low-income, Hispanic MADRES cohort.
METHODS
Nine OPE metabolite concentrations were measured in 421 maternal urine samples collected during a third trimester visit (GA = 31.5 ± 2.0 weeks). We examined associations between single urinary OPE metabolites and GA at birth and BW for GA z-scores using linear regression models and Generalized Additive Models (GAMs) and effects from OPE mixtures using Bayesian Kernel Machine Regression (BKMR). We also assessed sex-specific differences in single metabolite analyses by evaluating statistical interactions and stratifying by sex.
RESULTS
We did not find significant associations between individual OPE metabolites and birth outcomes in the full infant sample; however, we found that higher bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) was associated with earlier GA at birth among male infants (p = 0.04), and a nonlinear, inverted U-shape association between the sum of dibutyl phosphate and di-isobutyl phosphate (DNBP + DIBP) and GA at birth among female infants (p = 0.03). In mixtures analysis, higher OPE metabolite mixture exposures was associated with lower GA at birth, which was primarily driven by female infants. No associations were observed between OPE mixtures and BW for GA z-scores.
CONCLUSION
Higher BDCIPP and DNBP + DIBP concentrations were associated with earlier GA at birth among male and female infants, respectively. Higher exposure to OPE mixtures was associated with earlier GA at birth, particularly among female infants. However, we saw no associations between prenatal OPEs and BW for GA. Our results suggest sex-specific impacts of prenatal OPE exposures on GA at birth.
Topics: Pregnancy; Infant, Newborn; Humans; Male; Infant; Female; Bayes Theorem; Organophosphates; Phosphates; Flame Retardants; Esters
PubMed: 36934865
DOI: 10.1016/j.envres.2023.115703 -
Viruses May 2021Viral entry into host cells is a critical step in the viral life cycle. HIV-1 entry is mediated by the sole surface envelope glycoprotein Env and is initiated by the... (Review)
Review
Viral entry into host cells is a critical step in the viral life cycle. HIV-1 entry is mediated by the sole surface envelope glycoprotein Env and is initiated by the interaction between Env and the host receptor CD4. This interaction, referred to as the attachment step, has long been considered an attractive target for inhibitor discovery and development. Fostemsavir, recently approved by the FDA, represents the first-in-class drug in the attachment inhibitor class. This review focuses on the discovery of temsavir (the active compound of fostemsavir) and analogs, mechanistic studies that elucidated the mode of action, and structural studies that revealed atomic details of the interaction between HIV-1 Env and attachment inhibitors. Challenges associated with emerging resistance mutations to the attachment inhibitors and the development of next-generation attachment inhibitors are also highlighted.
Topics: Animals; Anti-HIV Agents; HIV Infections; HIV-1; Humans; Organophosphates; Piperazines; Virus Internalization
PubMed: 34066522
DOI: 10.3390/v13050843 -
International Journal of Environmental... Jul 2020Organophosphate pesticides (OPs) are one of the most commonly used classes of insecticides in the U.S., and metabolites of OPs have been detected in the urine of >75% of... (Review)
Review
BACKGROUND
Organophosphate pesticides (OPs) are one of the most commonly used classes of insecticides in the U.S., and metabolites of OPs have been detected in the urine of >75% of the U.S.
POPULATION
While studies have shown that OP exposure is associated with risk of neurological diseases and some cancers, the relationship between OP exposure and breast cancer risk is not well understood.
METHODS
The aim of this rapid review was to systematically evaluate published literature on the relationship between OP exposure and breast cancer risk, including both epidemiologic and laboratory studies. Twenty-seven full-text articles were reviewed by searching on Pubmed, EMBASE, and Cochrane databases.
RESULTS
Some human studies showed that malathion, terbufos, and chlorpyrifos were positively associated with human breast cancer risk, and some laboratory studies demonstrated that malathion and chlorpyrifos have estrogenic potential and other cancer-promoting properties. However, the human studies were limited in number, mostly included agricultural settings in several geographical areas in the U.S., and did not address cumulative exposure.
CONCLUSIONS
Given the mixed results found in both human and laboratory studies, more research is needed to further examine the relationship between OP exposure and breast cancer risk, especially in humans in non-agricultural settings.
Topics: Animals; Breast Neoplasms; Cohort Studies; Female; Humans; Insecticides; Organophosphates; Organophosphorus Compounds; Pesticides; Prospective Studies
PubMed: 32668751
DOI: 10.3390/ijerph17145030 -
Environmental Health Perspectives Oct 2021To date, the toxicity of organophosphate esters has primarily been studied regarding their use as pesticides and their effects on the neurotransmitter...
BACKGROUND
To date, the toxicity of organophosphate esters has primarily been studied regarding their use as pesticides and their effects on the neurotransmitter acetylcholinesterase (AChE). Currently, flame retardants and plasticizers are the two largest market segments for organophosphate esters and they are found in a wide variety of products, including electronics, building materials, vehicles, furniture, car seats, plastics, and textiles. As a result, organophosphate esters and their metabolites are routinely found in human urine, blood, placental tissue, and breast milk across the globe. It has been asserted that their neurological effects are minimal given that they do not act on AChE in precisely the same way as organophosphate ester pesticides.
OBJECTIVES
This commentary describes research on the non-AChE neurodevelopmental toxicity of organophosphate esters used as flame retardants and plasticizers (OPEs). Studies in humans, mammalian, nonmammalian, and models are presented, and relevant neurodevelopmental pathways, including adverse outcome pathways, are described. By highlighting this scientific evidence, we hope to elevate the level of concern for widespread human exposure to these OPEs and to provide recommendations for how to better protect public health.
DISCUSSION
Collectively, the findings presented demonstrate that OPEs can alter neurodevelopmental processes by interfering with noncholinergic pathways at environmentally relevant doses. Application of a pathways framework indicates several specific mechanisms of action, including perturbation of glutamate and gamma-aminobutyric acid and disruption of the endocrine system. The effects may have implications for the development of cognitive and social skills in children. Our conclusion is that concern is warranted for the developmental neurotoxicity of OPE exposure. We thus describe important considerations for reducing harm and to provide recommendations for government and industry decision makers. https://doi.org/10.1289/EHP9285.
Topics: Acetylcholinesterase; Child; Environmental Monitoring; Esters; Female; Flame Retardants; Humans; Organophosphates; Placenta; Plasticizers; Pregnancy
PubMed: 34612677
DOI: 10.1289/EHP9285 -
International Journal of Environmental... Jan 2022Organophosphate (OP) pesticides are associated with numerous adverse health outcomes. Pesticide use data are available for California from the Pesticide Use Report...
Organophosphate (OP) pesticides are associated with numerous adverse health outcomes. Pesticide use data are available for California from the Pesticide Use Report (PUR), but household- and individual-level exposure factors have not been fully characterized to support its refinement as an exposure assessment tool. Unique exposure pathways, such as proximity to agricultural operations and direct occupational contact, further complicate pesticide exposure assessment among agricultural communities. We sought to identify influencing factors of pesticide exposure to support future exposure assessment and epidemiological studies. Household dust samples were collected from 28 homes in four California agricultural communities during January and June 2019 and were analyzed for the presence of OPs. Factors influencing household OPs were identified by a data-driven model via best subsets regression. Key factors that impacted dust OP levels included household cooling strategies, secondary occupational exposure to pesticides, and geographic location by community. Although PUR data demonstrate seasonal trends in pesticide application, this study did not identify season as an important factor, suggesting OP persistence in the home. These results will help refine pesticide exposure assessment for future studies and highlight important gaps in the literature, such as our understanding of pesticide degradation in an indoor environment.
Topics: Agriculture; Dust; Environmental Exposure; Housing; Humans; Organophosphates; Pesticides
PubMed: 35055689
DOI: 10.3390/ijerph19020862 -
Ecotoxicology and Environmental Safety Oct 2021In recent years, organophosphate ester flame retardants (OPFRs), which have been regarded as alternatives for brominated flame retardants (BFRs), have become widely used...
In recent years, organophosphate ester flame retardants (OPFRs), which have been regarded as alternatives for brominated flame retardants (BFRs), have become widely used in building materials, textiles, and electric equipment. Elucidating the relationship between OPFRs and tumors holds great significance for the treatment and prevention of diseases. In this work, we found a new method for predicting the correlation between the interactive genes of OPFRs and tumors. Transcriptome profiles and OPFR information were obtained from The Cancer Genome Atlas and the Genotype-Tissue Expression, Comparative Toxicogenomics, and PharmMapper databases. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis showed that interactive genes were mainly enriched in prostate cancer, steroid metabolic process, and steroid hormone regulation. Furthermore, protein-protein interaction network analysis revealed 33 biological hub genes. The operating characteristic curves and survival analysis showed the role of key genes in predicting the prognosis of prostate cancer. Gene target prediction and gene set variation analysis proved that OPFRs and their metabolites exert potential effects on prostate cancer. Colony formation assay showed that the cells with AR, mTOR and DDIT3 knockdown could remarkably mitigate the cell proliferation ability in both PC-3 and LNCap cells. Transwell assay demonstrated that the silencing of AR, mTOR and DDIT3 could significantly inhibit the cell invasion capacity of prostate cells. Triphenyl phosphate (TPP) significantly increase the cell proliferation ability and promote cell invasion capacity. AR, mTOR and DDIT3 in the PC-3 and LNCap cells were significantly upregulated with 10-6 M TPP treated.
Topics: Comprehension; Flame Retardants; Humans; Male; Organophosphates; Organophosphorus Compounds; Prostatic Neoplasms
PubMed: 34358932
DOI: 10.1016/j.ecoenv.2021.112589