Occurrence and potential risks of organophosphate esters in agricultural soils: A case study of Fuzhou City, Southeast China.

Fifty agricultural soil samples collected from Fuzhou, southeast China, were first investigated for the occurrence, distribution, and potential risks of twelve organophosphate esters (OPEs). The total concentration of OPEs (ΣOPEs) in soil ranged from 1.33 to 96.5 ng/g dry weight (dw), with an average value of 17.1 ng/g dw. Especially, halogenated-OPEs were the predominant group with a mean level of 9.75 ng/g dw, and tris(1-chloro-2-propyl) phosphate (TCIPP) was the most abundant OPEs, accounting for 51.1% of ΣOPEs. The concentrations of TCIPP and ∑OPEs were found to be significantly higher (P < 0.05) in soils of urban areas than those in suburban areas. In addition, the use of agricultural plastic films and total organic carbon had a positive effect on the occurrence of OPE in this study. The positive matrix factorization model suggested complex sources of OPEs in agricultural soils from Fuzhou. The ecological risk assessment demonstrated that tricresyl phosphate presented a medium risk to land-based organisms (0.1 ≤ risk quotient < 1.0). Nevertheless, the carcinogenic and non-carcinogenic risks for human exposure to OPEs through soil ingestion and dermal absorption were negligible. These findings would facilitate further investigations into the pollution management and risk control of OPEs.

Migration patterns of organophosphate esters from plastic food packaging simulants to foods: Donors, behaviours, and influencing factors.

In recent years, organophosphate esters (OPEs) have been widely produced and used as flame retardants and plasticizer additives, posing significant ecological and health risks. Dietary intake is considered to be the primary route of human exposure to OPEs. Plastic food packaging materials are considered a crucial source for contamination of OPEs in food. However, the migration behaviour of OPEs from plastic food packaging materials into foods has received limited attention. In this study, we employed a novel method to prepare migration donors containing 13 kinds of OPEs. The migration behaviours of OPEs from food packaging simulants (polypropylene) to foods (full-fat milk powder) were simulated, and factors influencing the migration of OPEs were examined, including the properties of the target compounds, migration temperature, fat content of the migration receptors, and mass transfer mode. The results indicated that OPEs exhibited a significant migration tendency. Low molecular weight OPEs (< 300 Da) had faster migration efficiency compared to high molecular weight OPEs. The mean migration efficiencies of various OPEs showed a significant negative correlation with their molecular weights (p < 0.01) and a significant positive correlation with temperature (p < 0.01). Except for resorcinol bis(diphenyl phosphate) (RDP), which showed almost no migration, the mean migration efficiencies of other OPEs at 25 °C, 40 °C, and 60 °C were 3.1-37.5 %, 9.0-60.0 %, and 23.9-80.4 %, respectively. Most of the OPEs demonstrated higher migration efficiency in high-fat content food than low-fat content food. The migration of OPEs from food packaging simulants to foods primarily occurred through contact rather than gas-phase mass transfer. Overall, this study uncovers the migration behaviours of OPEs from food packaging simulants to foods and scrutinized the relevant factors influencing the migration. It is expected that the research in terms of the contamination control of OPEs in food will benefit from this work.

Spatial variation, emissions, transport, and risk assessment of organophosphate esters in two large petrochemical complexes in southern China.

Organophosphate esters (OPEs) serve as significant flame retardants and plasticizers in various petrochemical downstream products. The petrochemical industry could be a potential source of atmospheric OPEs, but their emissions from this industry are poorly understood. The present study revealed the spatial variation, emission, and atmospheric transport of traditional and novel OPEs (TOPEs and NOPEs, respectively) in atmospheric particulate matter (PM) across Hainan and Guangdong petrochemical complexes (HNPC and GDPC, respectively) in southern China. The total concentrations of TOPEs ranged from 232 to 46,002 pg/m3 and from 200 to 20,347 pg/m3 in the HNPC and GDPC, respectively, which were substantially higher than those of NOPEs (HNPC: 23.5-147 pg/m3, GDPC: 13.9-465 pg/m3). Enterprises involved in the production of downstream petrochemical products presented relatively high concentrations of OPEs, indicating evident emissions of these pollutants in the petrochemical industry. The correlations of PM-bound OPEs in the atmosphere are determined mainly by their coaddition to industrial products or their coexistence in technical mixtures. The annual emissions of TOPEs and NOPEs in the HNPC were 42.6 kg and 0.34 kg, respectively, and those in the GDPC were 116 kg and 1.85 kg, respectively. OPEs from the HNPC can reach Vietnam, Cambodia, and Guangxi Province, China, and those from the GDPC can reach Guangxi Province and Hunan Province via atmospheric transmission after 24 h of emission. The OPE concentrations reaching the receptor regions were generally less than 3.20 pg/m3. Risk assessment revealed that OPE inhalation exposure on two petrochemical complexes likely poses minor risks for people living in the study areas, but the risk resulting from two chlorinated OPEs should be noted since they are close to the threshold values. This study has implications for enhancing control measures for OPE emissions to reduce health risks related to the petrochemical industry.

Distribution patterns and origins of organophosphate esters in soils from different climate systems on the Tibetan Plateau.

Organophosphate esters (OPEs) are extensively applied in various materials as flame retardants and plasticizers, and have high biological toxicity. OPEs are detected worldwide, even in distant polar regions and the Tibetan Plateau (TP). However, few studies have been performed to evaluate the distribution patterns and origins of OPEs in different climate systems on the TP. This study investigated the distribution characteristics, possible sources, and ecological risks of OPEs in soils from the different climate systems on the TP and its surroundings. The total concentrations of OPEs in soil varied from 468 to 17,451 pg g-1 dry weight, with greater concentrations in southeast Tibet (monsoon zone), followed by Qinghai (transition zone) and, finally, southern Xingjiang (westerly zone). OPE composition profiles also differed among the three areas with tri-n-butyl phosphate dominant in the westerly zone and tris(2-butoxyethyl) phosphate dominant in the Indian monsoon zone. Correlations between different compounds and altitude, soil organic carbon, or longitude varied in different climate zones, indicating that OPE distribution originates from both long-range atmospheric transport and local emissions. Ecological risk assessment showed that tris(2-chloroethyl) phosphate and tri-phenyl phosphate exhibited medium risks in soil at several sites in southeast Tibet. Considering the sensitivity and vulnerability of TP ecosystems to anthropogenic pollutants, the ecological risks potentially caused by OPEs in this region should be further assessed.

Estimated daily intake and cumulative risk assessment of organophosphate esters and associations with DNA damage among e-waste workers in Hong Kong.

Organophosphate esters (OPEs) are extensively used as additives in various products, including electronic equipment, which becomes e-waste when obsolete. Nevertheless, no study has evaluated OPEs exposure levels and the related health risks among e-waste workers in Hong Kong. Therefore, 201 first-spot morning urine samples were collected from 101 e-waste workers and 100 office workers to compare eight urinary OPE metabolites (mOPEs) levels in these groups. The concentrations of six mOPEs were similar in e-waste workers and office workers, except for significantly higher levels of diphenyl phosphate (DPHP) in e-waste workers and bis(1-chloro-2propyl) phosphate (BCIPP) in office workers. Spearman correlation analysis showed that most non-chlorinated mOPEs were correlated with each other in e-waste workers (i.e., nine out of ten pairs, including di-p-cresyl phosphate (DpCP) and di-o-cresyl phosphate (DoCP), DpCP and bis(2-butoxyethyl) phosphate (BBOEP), DpCP and DPHP, DpCP and dibutyl phosphate (DBP), DoCP and BBOEP, DoCP and DPHP, DoCP and DBP, BBOEP and DPHP, DPHP and DBP), indicating that handling e-waste could be the exposure source of specific OPEs. The median values of estimated daily intake (EDI) and hazard quotient (HQ) suggested that the health risks from OPEs exposures were under the recommended thresholds. However, linear regression models, Quantile g-computation, and Bayesian kernel machine regression found that urinary mOPEs elevated 8-hydroxy-2-deoxyguanosine (8-OhdG) levels individually or as a mixture, in which DPHP contributed prominently. In conclusion, although e-waste might not elevate the internal OPEs levels among the participating Hong Kong e-waste workers, attention should be paid to the potential DNA damage stimulated by OPEs under the currently recommended thresholds.

Exposure to organophosphate esters and maternal-child health.

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.

Organophosphate esters (OPEs) in corals of the South China Sea: Occurrence, distribution, and bioaccumulation.

Organophosphate esters (OPEs) have garnered significant attention in recent years. In view of the enormous ecosystem services value and severe degradation of coral reefs in the South China Sea, this study investigated the occurrence, distribution, and bioaccumulation of 11 OPEs in five coral regions: Daya Bay (DY), Weizhou Island (WZ), Sanya Luhuitou (LHT), Xisha (XS) Islands, and Nansha (NS) Islands. Although OPEs were detected at a high rate, their concentration in South China Sea seawater (1.56 ± 0.89 ng L-1) remained relatively low compared to global levels. All OPEs were identified in coral tissues, with Luhuitou (575 ± 242 ng g-1 dw) showing the highest pollution levels, attributed to intense human activities. Coral mucus, acting as a defense against environmental stresses, accumulated higher ∑11OPEs (414 ± 461 ng g-1 dw) than coral tissues (412 ± 197 ng g-1 dw) (nonparametric test, p < 0.05), and their compositional characteristics varied greatly. In the case of harsh aquatic environments, corals increase mucus secretion and then accumulate organic pollutants. Tissue-mucus partitioning varied among coral species. Most OPEs were found to be bioaccumulative (BAFs >5000 L kg-1) in a few coral tissue samples besides Triphenyl phosphate (TPHP). Mucus' role in the bioaccumulation of OPEs in coral shouldn't be ignored.

OPEs-ID: A software for non-targeted screening of organophosphate esters based on liquid chromatography-high-resolution mass spectrometry.

Organophosphate esters (OPEs) are widely used as flame retardants and plasticizers, presenting a potential threat to the environment and human health. To date, no automatic software exists for the nontargeted screening of OPEs. In this study, OPEs-ID, a user-friendly software, was developed for the identification of OPEs using liquid chromatography-high-resolution mass spectrometry. The main workflow of OPEs-ID included fragments-dependent precursor ion screening, elemental composition determination, extracted ion chromatograms (EIC) comparison, and molecular structure identification via MetFrag strategy. A mixture of 17 OPE standards was identified with an identification rate of 100% by OPEs-ID. OPEs-ID demonstrated a rate of 94.1% for correctly ranking within the top 1 candidate in a local database (41.2% in PubChem) for the 17 OPE standards, which remarkably improved the identification when compared to conventional in silico fragmentation algorithms. Using a pooled airborne fine particle sample (PM2.5), OPEs-ID could automatically retrieve 22 valid molecules with structure candidates. The detection frequencies of 9 newly identified OPEs were between 13% and 100% in the 32 PM2.5 samples. Their semi-quantification concentrations were comparable to those of some traditional OPEs. Overall, OPEs-ID offers a powerful tool to significantly enrich our understanding of the OPEs present in the environment.

[Pollution Level and Risk Assessment of OPEs in Typical River Basins of China].

Organophosphate esters(OPEs), as a substitute for brominated flame retardants, are widely used in production and life, and their environmental pollution and toxic effects have attracted widespread attention. In this study, the concentrations and distribution characteristics of OPEs in seven major drainage basins of China were sorted out. The average daily dose of OPEs in Chinese adults, adolescents, and children was calculated to assess the health risks, and the reliability of the results was evaluated using Monte Carlo simulation. The toxic effect concentrations of 12 OPEs on aquatic organisms were investigated, and the species sensitivity distribution(SSD) curve was constructed to assess the ecological risk. The results showed that the 5th percentile concentration of ΣOPEs in the seven drainage basins was 52.61 ng·L-1 under the low exposure scenario. The median concentration of ΣOPEs in the seven basins was 499.74 ng·L-1, with trichloroethyl phosphate(TCEP), triethyl phosphate(TEP), and triethyl phosphate(1,3-dichloro-2-propyl) esters(TDCP) as the main contaminants. Under the high exposure scenario, the 95th percentile concentration of ΣOPEs in the seven basins was 1904.4 ng·L-1, 3.8 times that of the intermediate exposure scenario, and the Yangtze River Basin had the highest ΣOPEs concentration under the high exposure scenario. The health risk assessment showed that the non-carcinogenic risk of OPEs exposure through drinking water was within acceptable limits for different populations. Trimethyl phosphate(TMP), triisobutyl phosphate(TiBP), and TCEP were the main contributors to cancer risk. The results of ecological risk assessment showed that TCEP had medium ecological risk at the high exposure level, tributyl phosphate(TnBP) had medium ecological risk under the intermediate exposure scenario, and there was higher ecological risk under the high exposure scenario. Triphenyl phosphate(TPhP) had a risk quotient greater than 1 under the low, intermediate, and high exposure scenarios, and there was a high ecological risk, which requires special attention.

Associations between exposure to organophosphate esters and overactive bladder in U.S. adults: a cross-sectional study.

Background: The relationship between exposure to organophosphate esters (OPEs) and the risk of developing overactive bladder (OAB) is uncertain. The purpose of this study is to examine the potential link between urinary metabolites of organophosphate esters and OAB. Method: Data from the National Health and Nutrition Examination Survey (NHANES) database of the 2011-2016 cycles were utilized. Four urinary metabolites of organophosphate esters: diphenyl phosphate (DPHP), bis (1,3-dichloro-2-propyl) phosphate (BDCPP), bis (2-chloroethyl) phosphate (BCEP), and dibutyl phosphate (DBUP) were included in the study. Multivariate logistic regression and restricted cubic spline (RCS) were used to evaluate the relationship between urinary OPEs metabolites and OAB. Interaction analysis was conducted on subgroups to confirm the findings. Results: A total of 3,443 United States (US) adults aged 20 years or older were included in the study, of whom 597 participants were considered to have OAB. After adjusting for potential confounding factors, we found a positive association between DPHP and the risk of overactive bladder. The risk of overactive bladder increased with increasing DPHP concentrations compared with quartile 1 (quartile 2, OR = 1.19, 95% CI, 0.82-1.73, P = 0.34; quartile 3, OR = 1.67, 95% CI, 1.10-2.53, P = 0.02; Q4, OR = 1.75, 95% CI, 1.26-2.43, P = 0.002). However, after dividing the participants by gender, only the female group retained consistent results. Additionally, restricted cubic spline analysis revealed a nonlinear dose-response correlation between DPHP and OAB in female participants. In the subgroup analysis based on age, race, body mass index (BMI), recreational activity, smoking status, drinking status, hypertension, diabetes, and stroke, the interaction analysis revealed that the findings were uniform. Conclusion: Our findings indicate that exposure to DPHP could elevate the risk of OAB in US adult females. Further experimental studies are needed to explore the underlying mechanism in the future.

Organophosphate esters (OPEs) in plastic food packaging: non-target recognition, and migration behavior assessment.

Organophosphate esters (OPEs) are widely used as plasticizers in plastic food packaging; however, the migration of OPEs from plastic to food is largely unstudied. We do not even know the specific number of OPEs that exist in the plastic food packaging. Herein, an integrated target, suspect, and nontarget strategy for screening OPEs was optimized using ultrahigh-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS). The strategy was used to analyze 106 samples of plastic food packaging collected in Nanjing city, China, in 2020. HRMS allowed full or tentative identification of 42 OPEs, of which seven were reported for the first time. Further, oxidation products of bis(2,4-di-tert-butylphenyl) pentaerythritol diphosphite (AO626) in plastics were identified, implying that the oxidation of organophosphite antioxidants (OPAs) could be an important indirect source of OPEs in plastics. The migration of OPEs was examined with four simulated foods. Twenty-six out of 42 OPEs were detected in at least one of the four simulants, particularly isooctane, in which diverse OPEs were detected at elevated concentrations. Overall, the study supplements the list of OPEs that humans could ingest as well as provides essential information regarding the migration of OPEs from plastic food packaging to food.

The aomogeneous and heterogeneous oxidation of organophosphate esters (OPEs) in the atmosphere: Take diphenyl phosphate (DPhP) as an example.

Organophosphate esters (OPEs) are widely detected in the atmosphere. However, the atmospheric oxidative degradation mechanism of OPEs has not been closely examined. This work took density functional theory (DFT) to investigate the tropospheric ozonolysis of organophosphates, represented by diphenyl phosphate (DPhP), including adsorption mechanisms on the surface of titanium dioxide (TiO2) mineral aerosols and oxidation reaction of hydroxyl groups (·OH) after photolysis. Besides, the reaction mechanism, reaction kinetics, adsorption mechanism, and ecotoxicity evaluation of the transformation products were also studied. At 298 K, the total reaction rate constants kO3, kOH, kTiO2-O3, and kTiO2-OH are 5.72 × 10-15 cm3 molecule-1 s-1, 1.68 × 10-13 cm3 molecule-1 s-1, 1.91 × 10-23 cm3 molecule-1 s-1, and 2.30 × 10-10 cm3 molecule-1 s-1. The atmospheric lifetime of DPhP ozonolysis in the near-surface troposphere is 4 min, much lower than that of hydroxyl radicals (·OH). Besides, the lower the altitude is, the stronger the oxidation is. The TiO2 clusters carry DPhP promoting ·OH oxidation but inhibiting ozonolysis of DPhP. Finally, the main transformation products of this process are glyoxal, malealdehyde, aromatic aldehydes, etc., which are still ecotoxic. The findings shed new light on the atmospheric governance of OPEs.

[Occurrence Distribution and Risk Assessment of Organophosphate Esters in A Typical Area of the Estuary in the Yellow River Basin].

As a type of emerging pollutant, organophosphate esters (OPEs) have the characteristics of toxicity, persistence, and bioaccumulation. Due to their wide use in production and life, OPEs pose potential risks to ecosystems when they enter the environment. In this study, the concentrations of 14 species of OPEs in surface water were determined using UPLC-MS/MS, and the spatial distribution of the OPEs in the surface water of the estuary of the Yellow River basin was further analyzed. The pollution sources were analyzed using correlation analysis and principal component analysis, and the ecological risk was evaluated. The results indicated that the concentration of Σ14OPEs in surface water ranged from 183.81 to 1674.52 ng·L-1, with an average concentration of 638.25 ng·L-1. Tris(2-chloroethyl) phosphate (TCEP) and tris(1-chloro-2-propanyl) phosphate (TCPP) were the main OPEs. The Xiaoqing River flowing through the urban area differed from the main stream of the Yellow River and other branches in terms of OPEs composition characteristics, which showed a greater impact from human activities. The distribution of Σ14OPEs showed an obvious regional pattern, with a trend of increasing and then decreasing along the direction of the Yellow River inlet. The results of source analysis revealed that human activities such as industrial wastewater discharge from different industries, transportation, and atmospheric deposition were the sources of OPEs in surface water. The ecological risk assessment results indicated that TCEP posed a high risk to aquatic organisms in the main stream of the Yellow River, Xiaoqing River, and Zhimai River, and tri-n-butyl phosphate (TnBP) and triphenyl phosphate (TPhP) posed a low risk at some sites.

Organophosphate ester exposure among Chinese waste incinerator workers: Urinary levels, risk assessment and associations with oxidative stress.

Organophosphate esters (OPEs), which are frequently used as flame retardants and plasticizers in versatile products, are readily released to the external environment. Although workers at municipal waste incineration plants may be extensively exposed to OPEs, only scarce health monitoring and risk assessments have been conducted in this population. In this study, we investigated the levels of eight metabolites of organophosphate esters (mOPEs) and the oxidative stress marker 8-hydroxy-2-deoxyguanosine (8-OHdG) in urine samples from 73 waste incinerator workers and 97 general residents from Shenzhen, China between September 2016 and June 2017. The overall detection rate of mOPEs was 82.2 %-100 %, and higher concentrations of di-p-cresyl phosphate and chlorinated mOPEs [bis(2-chloroethyl) phosphate (BCEP), bis(1-chloro-2propyl) phosphate (BCIPP), bis(1,3-dichloro-2-propyl) phosphate) (BDCIPP)] were found among incinerator workers than among general residents. The incinerator workers also showed significantly higher levels of 8-OHdG than general residents, but the measured levels of most mOPEs were not significantly correlated with the level of 8-OHdG; this may be because co-exposure to multiple toxic compounds can lead to oxidative stress. Risk assessment using Monte Carlo simulations revealed that 95 % of the incinerator workers were free from non-carcinogenic effects due to OPEs exposure (hazard index = 0.27, 95 % CI: 0.09, 0.77). However, the carcinogenic risk of tris(2-chloroethyl) phosphate (TCEP) for incinerator workers was between 10-6 and 10-4. These results indicate that incinerator workers are extensively exposed to OPEs, and better protective measures need to be implemented.

Dietary intake assessment of known and unknown organophosphate esters (OPEs) in foodstuffs via high-resolution mass spectrometry.

We applied an integrated target, suspect, and non-target screening strategy to analyze known and unknown organophosphate esters (OPEs) in 107 foodstuffs collected from Nanjing City, China, in 2020. Twelve out of 19 target OPEs were detectable in at least one of the analyzed samples. Among the nine food categories, meat samples were contaminated the most severely with a mean ΣOPEs concentration of 68.5 ng/g wet weight (ww). In most food categories, tris(2,4-di-tert-butylphenyl) phosphate was the predominant OPE with a mean concentrations of 2.26 ng/g ww. In the food extract samples, suspect and non-target analysis identified other 6 suspect OPEs and 1 non-target OPE, of which two were fully identified as tri-m-cresyl phosphate, and trihexyl phosphate. Based on the measured OPE concentrations, we estimated the daily per capita dietary intakes of ΣOPEs for Nanjing residents to be 423 ng/kg bw/day, which is less than the reference dosage value of each OPE. Collectively, this study provides new information regarding the comprehensive identification of OPEs in foodstuffs, and revealed the importance of dietary risk assessment of this emerging class of contaminants.

Potential adverse outcome pathways with hazard identification of organophosphate esters.

Data-driven analysis and pathway-based approaches contribute to reasonable arrangements of limited resources and laboratory tests for continuously emerging commercial chemicals, which provides opportunities to save time and effort for toxicity research. With the widespread usage of organophosphate esters (OPEs) on a global scale, the concentrations generally reached up to micromolar range in environmental media and even in organisms. However, potential adverse effects and toxicity pathways of OPEs have not been systematically assessed. Therefore, it is necessary to review the current situation, formulate the future research priorities, and characterize toxicity mechanisms via data-driven analysis. Results showed that the early toxicity studies focused on neurotoxicity, cytotoxicity, and metabolic disorders. Then the main focus shifted to the mechanisms of cardiotoxicity, endocrine disruption, hepatocytes, reproductive and developmental toxicity to vulnerable sub-populations, such as infants and embryos, affected by OPEs. In addition, several novel OPEs have been emerging, such as bis(2-ethylhexyl)-phenyl phosphate (HDEHP) and oxidation derivatives (OPAsO) generated from organophosphite antioxidants (OPAs), leading to multiple potential ecological and human health risks (neurotoxicity, hepatotoxicity, developmental toxicity, etc.). Notably, in-depth statistical analysis was promising in encapsulating toxicological information to develop adverse outcome pathways (AOPs) frameworks. Subsequently, network-centric analysis and quantitative weight-of-evidence (QWOE) approaches were utilized to construct and evaluate the putative AOPs frameworks of OPEs, showing the moderate confidences of the developed AOPs. In addition, frameworks demonstrated that several events, such as nuclear receptor activation, reactive oxygen species (ROS) production, oxidative stress, and DNA damage, were involved in multiple different adverse outcome (AO), and these AOs had certain degree of connectivity. This study brought new insights into facilitating the complement of AOP efficiently, as well as establishing toxicity pathways framework to inform risk assessment of emerging OPEs.

Non-target screening and risk assessment of organophosphate esters (OPEs) in drinking water resource water, surface water, groundwater, and seawater.

By use of an integrated target, suspect, and non-target screening strategy, we investigated occurrence and spatial distribution of organophosphate esters (OPEs) in four types of water (drinking water resource water, surface water, groundwater, and seawater) collected from Jiangsu Province (China) in 2021 (n = 111). Eighteen out of 23 target OPEs were detectable at least once in these analyzed samples, and the total concentrations (Σ18OPEs) of OPEs in various water samples exhibited a descending order following as: groundwater (67026 ng/L) > surface water (35803 ng/L) > drinking water resource water (21055 ng/L) > seawater (17820 ng/L). The highest concentration detected in groundwater may be ascribed to pollution from surrounding factories. Among the target OPEs, triethyl phosphate (TEP), tris(chloroethyl) phosphate (TCEP), and tris (1-chloro-2-propyl) phosphate (TCIPP) were the most abundant congeners with the average concentrations of 407 ng/L, 143 ng/L, and 475 ng/L, respectively. Besides of 18 target OPEs, we further identified 17 suspect OPEs (3 of them were fully identified by authentic standards) on the basis of in-house suspect screening OPE database, and 2 non-target organophosphates (OPs) on the basis of feature fragments. One of these 2 non-target OPs was fully identified as bis(2-chloroethyl) 2-chloroethylphosphonate (B2CE2CEPP) by matching the retention time and MS/MS data with authentic standard, and the other one was preliminarily identified as 2,4,8,10-tetra-tert-butyl-6-methoxydibenzo[d,f][1,3,2]dioxaphosphepin-6-one (TTBMDBDOPPO). We also observed that B2CE2CEPP shared a similar structure with TCEP, suggesting that they may have similar toxicological characteristics and commercial sources. The ecological and human health risk assessments indicated that all OPEs posed a low or negligible ecological risk to aquatic organisms (algae, crustacean, and fish), and negligible risk to human health except for trimethyl phosphate (TMP) in drinking water resource water.

Organophosphate Esters in Foodstuffs from Multiple Provinces in China: Possible Sources during Food Processing and Implications for Human Exposure.

With increasing application of organophosphate esters (OPEs) as flame retardants and plasticizers in the world, the health and ecological risks posed by these chemicals have raised people's concern over the years. Despite the fact that dietary intake is an important pathway for human exposure to OPEs, monitoring on OPEs in foodstuffs is scarce. In this study, we measured 14 OPEs in both packaged (n = 229) and fresh (n = 58) foodstuffs collected across China with a new method that was developed by two-stage solid-phase extraction. The total concentrations of OPEs (ΣOPEs) in 12 categories of packaged foodstuffs and 5 categories of fresh foodstuffs were in the range of 0.212-273 ng/g wet weight (ww) [geometric mean (GM): 5.06 ng/g ww] and 0.189-2.82 ng/g ww (GM: 0.618 ng/g ww), respectively. Significantly higher levels of ΣOPEs were found in packaged food categories of fruits and meat than those in the corresponding fresh ones, implying the extra introduction of OPEs during the processing and storage of foodstuffs. Correlation analysis showed that the GM concentrations of individual OPEs in animal-derived foods with few industrial processing were positively correlated with their annual production volumes in China in 2020, emphasizing the significance of natural sources of OPEs in these food samples. Elevated levels of ΣOPEs (range: 8.94-4120 and GM: 274 ng/g) were found in food-packaging materials, and the predominant OPE analogues were consistent with those found in packaged food samples. The result implies that the food-packaging material can be an important contamination source of OPEs in packaged foodstuffs, which is in particular true for triphenyl phosphate, tris(2-chloroisopropyl) phosphate, tris(2-chloroethyl) phosphate, and 2-ethylhexyl diphenyl phosphate. The median daily intake of ΣOPEs via food was estimated as 65.4 ng/kg bw/day for adults in China, and the category of cereals was the major contributor (72.7%) of the dietary exposure to OPEs. The exposure risk of OPEs via food intake was generally low for the Chinese population. Overall, this study establishes a baseline concentration for OPEs in Chinese foodstuffs and uncovers food contact material as a potential source of OPEs in foods. It is expected that the research in terms of food safety and OPE contamination will benefit from this work.

Spatial distribution and risk assessment of 11 organophosphate flame retardants in soils from different regions of agricultural farmlands in mainland China.

The occurrence and distribution of organophosphate flame retardants (OPFRs) in nationwide farmland soils of mainland China are rarely measured. The current study was the first to collect 325 farmland soil samples from 109 cities throughout mainland China. Ten organophosphate esters (OPEs), including alkyl-OPEs, Cl-OPEs, and aryl-OPEs, together with an organophosphate intermediates (TPPO), were determined. The results indicated that ΣOPFRs ranged from 2.41 ng/g to 35.8 ng/g dry weight (dw), and ΣOPFRs in northeastern and southern China were significantly (p < 0.01) higher than those in northwestern and central China. Alkyl-OPEs and Cl-OPEs served as the main components of OPEs, and the novel aryl-OPEs showed the highest detection frequency (> 92 %). Principal component analysis (PCA) was employed to identify the different sources of OPEs, in which atmospheric deposition, irrigation, or direct release of plastic mulch acted as the main input routes in farmland soils. The potential risks of OPFRs were assessed through soil ingestion exposure and ecotoxicological impacts. Our results showed that direct exposure to farmland soils had no high risks to the human body and ecological environments. This study provides new evidence for further understanding the spatial distributions and contamination status of OPFRs in farmland soils throughout mainland China.

Infants' diminished response to DTaP vaccine is associated with exposure to organophosphate esters.

Organophosphate esters (OPEs) are commonly applied as flame retardants and plasticizers. Toxicological studies suggest exposure effects on immune endpoints, raising concerns as infants' OPE exposures are elevated compared to older children and adults due to hand-to-mouth behavior and breastfeeding. Here, we sought to evaluate the immune responsiveness of infants to a neoantigen (e.g., a newly encountered antigen) in the presence of OPE exposures. As a proxy for immune responsiveness, children were given three doses of the Diphtheria, Tetanus, and Pertussis (DTaP) vaccine as recommended, and diphtheria and tetanus antibodies were evaluated in serum samples collected when children were 12 months old (n = 84). Titers were compared, based on maximum sample overlap, to measurements of OPE metabolites in spot urine samples collected before vaccination (age 2 months, n = 73) and at the time of antibody assessment (12 months of age, n = 46). Metabolites of two chlorinated OPEs were significantly associated with diminished antibodies for diphtheria and tetanus. A metabolite of tris (1,3-dichloroisopropyl)phosphate (TDCIPP) measured at 2 months was associated with decreased diphtheria antibodies (-0.07 IU/mL per log10 increase in metabolite). One metabolite of tris(2-chloroisopropyl)phosphate (TCIPP) measured at 12 months was associated with decreased tetanus antibodies (-0.57 IU/mL per log10 increase in metabolite). These results provide some preliminary insights for OPE exposure impacts on vaccine responses in early life and may have important implications for immune health through childhood and adulthood.