Metabolomics for exposure assessment and toxicity effects of occupational pollutants: current status and future perspectives.

INTRODUCTION: Work-related exposures to harmful agents or factors are associated with an increase in incidence of occupational diseases. These exposures often represent a complex mixture of different stressors, challenging the ability to delineate the mechanisms and risk factors underlying exposure-disease relationships. The use of omics measurement approaches that enable characterization of biological marker patterns provide internal indicators of molecular alterations, which could be used to identify bioeffects following exposure to a toxicant. Metabolomics is the comprehensive analysis of small molecule present in biological samples, and allows identification of potential modes of action and altered pathways by systematic measurement of metabolites. OBJECTIVES: The aim of this study is to review the application of metabolomics studies for use in occupational health, with a focus on applying metabolomics for exposure monitoring and its relationship to occupational diseases. METHODS: PubMed, Web of Science, Embase and Scopus electronic databases were systematically searched for relevant studies published up to 2021. RESULTS: Most of reviewed studies included worker populations exposed to heavy metals such as As, Cd, Pb, Cr, Ni, Mn and organic compounds such as tetrachlorodibenzo-p-dioxin, trichloroethylene, polyfluoroalkyl, acrylamide, polyvinyl chloride. Occupational exposures were associated with changes in metabolites and pathways, and provided novel insight into the relationship between exposure and disease outcomes. The reviewed studies demonstrate that metabolomics provides a powerful ability to identify metabolic phenotypes and bioeffect of occupational exposures. CONCLUSION: Continued application to worker populations has the potential to enable characterization of thousands of chemical signals in biological samples, which could lead to discovery of new biomarkers of exposure for chemicals, identify possible toxicological mechanisms, and improved understanding of biological effects increasing disease risk associated with occupational exposure.

Meta-Analysis of Body Concentration of Polychlorinated Biphenyls and Prostate Cancer.

Prostate Cancer (PCa) is the second most common hormone-sensitive neoplasm among men and the fifth cause of death due to malignancy in developed countries. Moreover, studies have shown the links between polychlorinated biphenyls (PCBs) and hormone-related cancers such as prostate cancer. Hence, we conducted a systematic review and meta-analysis to evaluate the potential relationship between the PCBs and developing PCa. In this meta-analysis study, the relevant databases such as Web of Science, PubMed, and Scopus were studied for English research. The Newcastle-Ottawa Scale was applied to evaluate the quality of the selected publications. The GRADE method was used to assess the risk of bias studies. After reviewing the relevant studies, a cohort and seven case-control studies entered the meta-analysis. These articles were published during 2003-2021 with 2989 participants and 1212 PCa cases. The heterogeneity among the studies was significant (p = 0.001, I2 = 70.61). Using a random-effects model, the association between the serum and plasma levels of PCBs and the risk of PCa was not shown to be significant (OR = 1.12; 95% CI: 0.90-1.39). The results of Egger's test showed no trace of publication bias in the studies (P of bias = 0.573). This systematic review and meta-analysis was presented based on relatively strong evidence and has confirmed negatively significant associations between PCa risk and some PCBs congeners (PCB 44, 52, and 101). This study does not provide strong evidence that total PCB exposure is a risk factor for PCa development in humans.

Probabilistic health risk assessment of occupational exposure to isoflurane and sevoflurane in the operating room.

Risk assessment is an important tool in predicting the possible risk to health. It heightens awareness by estimating the probability of adverse health effects in humans who are exposed to chemicals in the course of their work. Therefore, the present work aims to determine the occupational exposure of operating room staff to the volatile anesthetic gases, isoflurane and sevoflurane, and estimates non-cancer risk using the United States Environmental Protection Agency method. Air samples from the breathing zone of staff members were collected using the Occupational Safety and Health Administration Method 103 and analyzed using gas chromatography-mass spectroscopy. The results indicate that the measured concentrations of isoflurane and sevoflurane are below the National Institute of Occupational Safety and Health standard (2 ppm) for technicians and nurses, but not for anesthesiologists and surgeons. Moreover, the estimated non-cancer risk due to isoflurane is above the acceptable value for anesthesiologists (but acceptable for other occupational categories). A sensitivity analysis indicates that exposure time has the most effect on calculated risk (53.4%). Occupational exposure to anesthetic gases may endanger the health of operating room personnel. Therefore, control measures, such as daily testing of anesthetic devices, ensuring the effectiveness of ventilation systems, advanced scavenging methods, and regular training of staff are highly recommended.

Health risk assessment of occupational exposure to heavy metals in a steel casting unit of a steelmaking plant using Monte-Carlo simulation technique.

The present work aimed to evaluate the health risks of occupational exposure to heavy metals in a steel casting unit of a steel plant. To determine occupational exposure to heavy metals, personal air samples were taken from the workers' breathing zones using the National Institute for Occupational Safety and Health method. Noncancer and cancer risks due to the measured metals were calculated according to the United States Environmental Protection Agency procedures. The results indicated that the noncancer risks owing to occupational exposure to lead (Pb) and manganese were higher than the recommended value in most of the workstations. The estimated cancer risk of Pb was also higher than the allowable value. Moreover, the results of sensitivity analysis indicated that the concentration, inhalation rate, and exposure duration were the most influencing variables contributing to the calculated risks. It was thus concluded that the present control measures were not adequate and further improvements were required for reducing the exposure levels.

Ultrasound-assisted dispersive micro-solid-phase extraction based on N-doped mesoporous carbon and high-performance liquid chromatographic determination of 1-hydroxypyrene in urine samples.

In this research, a new ultrasound-assisted dispersive micro-solid-phase extraction method based on N-doped mesoporous carbon sorbent followed by high-performance liquid chromatography equipped with diode array detector for trace measurement of 1-hydroxypyrene as a metabolite of exposure to polycyclic aromatic hydrocarbons was optimized. Herein, the hard template method was used for the preparation of N-doped mesoporous carbon sorbent. The prepared sorbent was characterized using the Brunauer-Emmett-Teller method, transmission electron microscopy, and elemental analysis. Parameters affecting the extraction of the target metabolite were investigated using the Box-Behnken design method. Considering optimum parameters, the plotted calibration curve for 1-hydroxypyrene was linearly correlated with the concentration span of 0.1-50 µg/L for urine media. The accuracy of the optimized procedure was examined through the relative recovery tests on the fortified urine specimens. The relative recoveries fell between 95 and 101%. The method detection limit of the proposed procedure was also calculated to be 0.03 µg/L.

Probabilistic risk assessment of occupational exposure to volatile organic compounds in the rendering plant of a poultry slaughterhouse.

In this study, occupational exposure to volatile organic compounds (VOCs) in the rendering plant of poultry slaughterhouse was determined and subsequently, carcinogen and non-carcinogenic risks were assessed using the US Environmental Protection Agency (USEPA). National Institute for Occupational Safety and Health (NIOSH) methods of 1501 and 1600 were used to measure VOCs in the breathing zone of the workers. Samples were analyzed by GC/MS. Carcinogenic and non-carcinogenic risks and sensitivity analysis were carried out using Monte Carlo simulations technique. The concentration of benzene and CS2 was higher than the occupational exposure limits (OEL). The hazard quotient (HQ) values for all measured compounds was more than 1, which indicating the high potential for non-carcinogenic risks. Furthermore, the calculated Lifetime Cancer Risks (LCR) for carcinogenic compounds revealed that cancer risk due to benzene is higher than the maximum acceptable level provided by USEPA (10-6). Based on the sensitivity analysis, the concentration and exposure frequency are the most important variable influencing both carcinogen and non-carcinogenic risks. Therefore, the concentration levels of the VOCs and exposure frequency should be controlled using engineering control measures.

Optimization of dispersive liquid-liquid microextraction procedure for detecting chlorpyrifos in human urine samples.

Background: Selecting an effective sample preparation method to measure target pesticides in biological matrices is a serious challenge for researchers. This study aimed to optimize the dispersive liquid-liquid microextraction (DLLME) technique to obtain a simple, valid, and fast method with high efficiency to detect chlorpyrifos in urine samples. Methods: DLLME, coupled with high performance liquid chromatography equipped with ultra violet detector, was used to extract chlorpyrifos pesticide in human urine samples. Different affecting parameters on the efficiency of the method were optimized using one factor at a time method. Results: The limit of detection and enrichment factor of the method was 0.5 and 230 µg L-1, respectively. Linear calibration curve with 1-500 µg L-1 concentration range was used. The relative standard deviation (RSD) for 6 replicate experiments at the concentration of 200 µg L-1 was less than 5%. The relative recoveries of spiked urine samples were 96.3%, 102.3%, and 98.7% at 3 different concentration levels of 50, 200, and 1000 µg L-1, respectively. Conclusion: Compared to other extraction techniques, the optimized DLLME resulted in some advantages such as shorter extraction time, high extraction efficiency, and good enrichment factor for the extraction of chlorpyrifos from human urine samples.

An amino-functionalized mesoporous silica (KIT-6) as a sorbent for dispersive and ultrasonication-assisted micro solid phase extraction of hippuric acid and methylhippuric acid, two biomarkers for toluene and xylene exposure.

The authors described a new application of amino-functionalized KIT-6 for dispersive ultrasonication-assisted micro solid phase extraction of hippuric acid (HA) and methyl hippuric acid (MHA) from human urine and water samples. In the first step, an amino-functionalized mesoporous silica of type KIT-6 was synthesized. It was characterized by field emission scanning electron microscopy, Fourier transform infrared spectrometry, nitrogen adsorption-desorption analysis, thermogravimetry and X-ray diffraction. Following sorption and desorption with 1.0 mL methanol/NH4OH (1%; v/v), HA and MHA were quantified by HPLC with UV detection. Various important parameters were optimized by Box-Behnken design. Under optimized conditions, The limit of detections (LOD) were calculated by a signal-to-noise ratio of 3, which were 0.5 µg L-1 and 0.2 µg L-1 for HA and MHA, respectively, and the calibration plot is linear in the 1-1000 µg L-1 concentration range. Only small matrix effects were found. The method was successfully implemented for the sensitive determination of HA and MHA in (spiked) human urine samples. Graphical abstract Schematic of a sorbent for dispersive micro solid phase extraction coupled with ultrasonic power. It consists of amino functionalized KIT-6 and was used for the simultaneous preconcentration and determination of low levels of hippuric and methyl hippuric acid in urine and water samples.

Trace monitoring of silver ions in food and water samples by flame atomic absorption spectrophotometry after preconcentration with solvent-assisted dispersive solid phase extraction.

In this research, a new sample treatment technique termed solvent-assisted dispersive solid phase extraction (SADSPE) was developed. The new method was based on the dispersion of the sorbent into the sample to maximize the contact surface. In this approach, the dispersion of the sorbent at a very low milligram level was achieved by injecting a mixture solution of the sorbent and disperser solvent into the aqueous sample. Thereby, a cloudy solution formed. The cloudy solution resulted from the dispersion of the fine particles of the sorbent in the bulk aqueous sample. After extraction, the cloudy solution was centrifuged and the enriched analytes in the sediment phase dissolved in ethanol and determined by FAAS. Under the optimized conditions, the detection limit for silver ions was 0.8 µg L(-1). The relative standard deviations for six separate extraction experiments for determination of 5 and 200 µg L(-1) of silver ions was 3.4 and 3.1 %. The preconcentration factor was found to be 61.7. SADSPE was successfully applied for trace determination of silver ions in water and food samples.

Hybrid approaches based on hydrodynamic cavitation, peroxymonosulfate and UVC irradiation for treatment of organic pollutants: fractal like kinetics, modeling and process optimization.

Hydrodynamic cavitation (HC) was emerged as one of the most potential technologies for industrial-scale wastewater or water treatment. In this work, a combined system of HC, peroxymonosulfate (PMS) and UVC irradiation (HC - PMS - UVC) was constructed for effective degradation of carbamazepine. The effect of several experimental parameters and conditions on the carbamazepine degradation was considered. The results show that the degradation and mineralization rates increases with an increase in the inlet pressure from 1.3 to 4.3 bars. The rates of carbamazepine degradation with the combined processes of HC - PMS - UVC, HC - PMS, HC - UVC, and UVC - PMS were 73%, 67%, 40% and 31%, respectively. Under the optimal conditions of reactor, the carbamazepine degradation and mineralization rates were 73% with 59%, respectively. The kinetics of carbamazepine degradation was studied applying a fractal-like approach. So, a new model was proposed by combining first order kinetics model and fractal-like concept. The obtained results show that the proposed fractal-like model gives a better performance compared with traditional first order kinetics model. It has been demonstrated that the HC - PMS - UVC process is a potential treatment method to destroy pharmaceutical pollutants from water and wastewater sources.

Development of a Green Single Drop Microextraction Based on Deep Eutectic Solvent and HPLC-UV for Trace Residue Analysis of Three Frequent-Used Pesticides.

Background: A green sample preparation method named deep eutectic solvent-based single drop microextraction (DES-SDME) was developed and optimized for determining trace metribuzin, dichlorvos, and fenthion. Methods: Two hundred seventy experimental runs were performed, and the optimal values of the five influential factors in the DES-SDME method were determined. The design of the study was based on one factor at a time and the peak area of high-performance liquid chromatography was used as a benchmark for comparing analysis results. Results: After optimizing the effective factors, the linearity range, detection limit and quantification limit of the method were determined by drawing calibration curves for the studied analytes. Conclusion: The results indicated the success of the developed method in obtaining acceptable figures of merit as a green preparation method with accuracy and precision.

The long-term effect of exposure to respirable particulate matter on the incidence of myocardial infarction: a systematic review and meta-analysis study.

Although several studies have investigated the long-term association of respirable particulate matter (PM ≤ 10 µm) with the incidence of myocardial infarction (MI), this association is inconclusive or even contradictory. This systematic review and meta-analysis study aimed to quantify the long-term effect of exposure to respirable PM on the incidence of MI. To find relevant publications, online databases, including Scopus, PubMed, and Web of Science, were searched on October 10, 2021. A random-effect model was used to calculate the pooled hazard ratio (HR) and 95% confidence interval (95% CI) of MI across studies. Heterogeneity was presented with reporting I2 index. Of 4591 records found in the primary searching, the number of 24 prospective cohort studies with more than 70 million participants was included. The pooled HR (95% CI) of MI per 1 µg/m3 increment of respirable PM was estimated as 1.01 (1.00, 1.01). Subgroup analyses according to aerodynamic diameter of PM showed an only significant stronger risk of MI per 1 µg/m3 increase in PM with aerodynamic diameter < 2.5 µm (HR = 1.01, 95% CI = 1.00, 1.01). No sex difference was found in the association of respirable PM with MI incidence. There was only a significant association among studies defined MI as ICD-10: I21 code (HR = 1.01, 95% CI = 1.00, 1.01) and studies defined MI as ICD-10: I21-22 (HR = 1.02, 95% CI = 1.00, 1.04). No significant publication bias was observed across studies. In conclusion, this study confirms a significant association between long-term exposure to respirable PM air pollution and development of MI.

Solidified floating organic droplet microextraction coupled with HPLC for rapid determination of trans, trans muconic acid in benzene biomonitoring.

Benzene is one of the carcinogenic compounds in the work environments. Exposure assessment of benzene through biological monitoring is an acceptable way to accurately measure the real exposure in order to conducting the health risk assessment, but it is always complicated, laborious, time consuming and costly process. A new sensitive, simple, fast and environmental friendly method was developed for the determination of urinary metabolite of benzene, trans trans muconic acid (t,t-MA) by dispersive liquid-liquid micro extraction based on solidification of floating organic droplet coupled with high-performance liquid chromatography with ultra violet detector. Central composite design methodology was utilized to evaluate the effective factors on the extraction output of the target metabolite. The calibration curve was plotted in the concentration ranges of 0.02-5 µg mL-1. The precision and accuracy of the method were assayed via the relative standard deviation (RSD%) and relative recovery (RR%) using spiked samples with three replications. The RR% and RSD% of the optimized method were 86.9-91.3% and 4.3-6.3% respectively. The limit of detection (LOD) of the method was 0.006 µg mL-1. The level of t,t-MA in real samples was ranged from 0.54 to 1.64 mg/g creatinine. We demonstrated that t,t-MA can be extracted and determined by an inexpensive, simple and fast method.

N-doped mesoporous carbon as a new sorbent for ultrasonic-assisted dispersive micro-solid-phase extraction of 1-naphthol and 2-naphthol, the biomarkers of exposure to naphthalene, from urine samples.

This study aimed to optimize a new sample preparation method using N-doped mesoporous carbon sorbent for simultaneous measurement of 1-naphthol and 2-naphthol, the biomarkers of exposure to naphthalene. The samples were analyzed using high-performance liquid chromatography supplied with ultraviolet detector (HPLC-UV). N-doped mesoporous carbon sorbent was obtained via the hard template procedure. The synthesized nanosorbent was then characterized by transmission electron microscopy (TEM), Brunauer-Emmett-Teller (BET), and elemental analysis (CHN). The effective factors in the extraction of the studied biomarkers were examined by the Box-Behnken (BBD) methodology. Regarding the optimum conditions, the sketched calibration curve for naphthols was linear in the concentration levels of 1-600 µg L-1 for human urine samples. The accuracy and reproducibility of the introduced method were determined using the relative recovery (RR %) and relative standard deviation (RSD %) tests on the fortified urine samples. RR% and RSD% were found to be 97.0-101.2% and 3.1-9.0%, respectively. The calculated method detection limit of the optimized procedure was 0.3 µg L-1 and 0.5 µg L-1 for 1-naphthol and 2-naphthol, respectively.

The hierarchy of preventive measures to protect workers against the COVID-19 pandemic: A review.

BACKGROUND: The high spread rate of coronaviruses, specifically severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has raised concerns about the spread of the disease in crowded occupational environments. The risk of occupational exposure to coronavirus depends on the type of industry and the nature of work. Currently, most countries are working for reactivating their economies and need to improve working conditions for a safe situation during the COVID-19 pandemic. OBJECTIVE: The present work aimed to investigate the current engineering and administrative control measures, which are necessary to protect workers against COVID-19 in workplaces. METHODS: The current strategies, including engineering control, administrative control, personal protective equipment, and their efficiencies, were reviewed and discussed. RESULTS: Reviewing the literature indicated that a collection of control approaches should be implemented for an effective control of the virus. Control measures could be selected based on the risk of exposure to COVID-19. The results also revealed that relying solely on a specific control measure could not effectively control the outbreak. CONCLUSION: In conclusion, employers and health professionals must continually monitor international and local guidelines to identify changes in recommendations to make their workplaces safer. Establishment of an expert team in any workplace for the implementation of more effective control measures is warranted, as well.

Occupational health risk assessment of volatile organic compounds emitted from the coke production unit of a steel plant.

In this study, cancer and non-cancer risks of exposure to volatile organic compounds in the coke production unit of a steel plant were evaluated. To determine individual exposure to benzene, toluene, xylene and ethylbenzene, personal samples were taken from the breathing zone of workers according to National Institute for Occupational Safety and Health (NIOSH) method 1501. Cancer and non-cancer risk assessment was performed, using US Environmental Protection Agency (US EPA) methods. Samples analysis showed that the concentration of benzene in the energy and biochemistry and the benzol refinement sections was higher than occupational exposure limits. The cancer risk for benzene in all sections was significantly higher than allowable limit; the non-cancer risk for benzene in all sections and toluene in the benzol refinement section was also higher than 1.0. In conclusion, the current control measures are not sufficient and should be improved for efficient control of occupational exposures.

Development of Dispersive Liquid-Liquid Microextraction Procedure for Trace Determination of Malathion Pesticide in Urine Samples.

BACKGROUND: Measurement of pesticides in biological matrices is become a serious challenge for researches because of their very low concentration in different matrices. The aim of this study was to develop a new sample preparation method with high accuracy and validity, simplicity and short retention time for determination of malathion. METHODS: Dispersive liquid-liquid micro-extraction (DLLME) technique coupled with high-performance liquid chromatography equipped with ultraviolet detector (HPLC-UV) developed for trace extraction and determination of malathion pesticide in human urine samples. This study was done in 2017 at Tehran University of Medical Sciences, Tehran, Iran. One variable at a time (OVAT) method was used to optimize parameters affecting the malathion extraction. Different parameters such as extraction solvent, disperser solvent, and volume of the extraction solvent, volume of the disperser solvent, centrifugation time and speed, salt addition, and sample pH were studied and optimized. RESULTS: Under the optimized conditions, the limit of detection and enrichment factor of the method were 0.5 µg L-1 and 200, respectively. The calibration curve was linear in the concentration range of 2-250 µg L-1. The relative standard deviation for six replicate experiments at 200 µg L-1 concentration was less than 3%. The relative recoveries of spiked urine samples were 96.3%, 101.7% and 97.3% at three different concentration levels of 50, 200 and 1000 µg L-1, respectively. CONCLUSION: DLLME procedure was successfully developed for the extraction of malathion from human urine samples. Compared to other extraction techniques, the proposed procedure had some advantages such as shorter extraction time, better reproducibility, and higher enrichment factor.

Spatial distribution variation and probabilistic risk assessment of exposure to chromium in ground water supplies; a case study in the east of Iran.

A high concentration of chromium (VI) in groundwater can threaten the health of consumers. In this study, the concentration of chromium (VI) in 18 drinking water wells in Birjand, Iran, s was investigated over a period of two yearsNon-carcinogenic risk assessment, sensitivity, and uncertainty analysis as well as the most important variables in determining the non-carcinogenic risk for three age groups including children, teens, and adults, were performed using the Monte Carlo simulations technique. The northern and southern regions of the study area had the highest and lowest chromium concentrations, respectively. The chromium concentrations in 16.66% of the samples in an area of 604.79 km2 were more than World Health Organization (WHO) guideline (0.05 mg/L). The Moran's index analysis showed that the distribution of contamination is a cluster. The Hazard Index (HI) values for the children and teens groups were 1.02 and 2.02, respectively, which was more than 1. A sensitivity analysis indicated that the most important factor in calculating the HQ was the concentration of chromium in the consumed water. HQ values higher than 1 represent a high risk for the children group, which should be controlled by removing the chromium concentration of the drinking water.

Application of mercapto ordered carbohydrate-derived porous carbons for trace detection of cadmium and copper ions in agricultural products.

In this paper, we have introduced nanoporous carbon modified with mercapto groups as a new solid-phase method for extraction of cadmium(II) and copper(II) ions. The modified nanoporous carbon sorbent was characterised by thermogravimetric analysis, differential thermal analysis, transmission electron microscopy, Fourier transform infrared spectrometry, X-ray diffraction, and nitrogen adsorption surface area (BET) measurements. Effects of pH value, flow rates, type, concentration and volume of the eluent, breakthrough volume, and effect of other ions were studied. The experimental results show that simultaneous trace cadmium(II) and copper(II) ions can be quantitatively preconcentrated at pH 6.0 with recoveries >97%. Under optimised conditions, limits of detection are 0.04 and 0.09 ng mL(-1) for the ions of cadmium and copper respectively, and the precision of the method for analysis of cadmium and copper ions (5.0 µg of each target ions, N=8) are 2.4% and 2.1%, respectively. The obtained capacities of mercapto-nanoporous carbon were found to be 145 and 95 mg g(-1) for cadmium and copper ions, respectively. The accuracy of the proposed procedure was verified by analysing standard reference material. Finally, the introduced sorbent was successfully applied for trace determination of cadmium and copper ions in food samples.