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Exposure to heavy metals has been associated with the generation of reactive oxygen species (ROS) among exposed individuals in occupational and environmental settings. Dust is considered a significant contributor to airborne metal exposure, and previous data suggest that their levels in dust may vary based on its particle sizes. However, no biomonitoring study has been reported so far to address the metal-induced oxidative stress using different dust fractions, particularly in occupational settings. We designed a systematic cross-sectional study involving 110 chromite mine workers stratified into loaders (n = 28), extractors (n = 47) and operators (n = 35), and controls (n = 30) to find out the association between dust-bound metal exposure and oxidative stress using urinary creatinine-adjusted metal level as a biomarker of metal exposure. Results suggested elevated urinary levels of Cr 51.34 ± 8.6 along with Pb 34.29 ± 4.39, Cd 21.1 ± 2.6, and Ni 18.98 ± 3.01 µg/g creatinine in exposed (extractor group) workers. Correlating metal levels with oxidative stress revealed elevated malondialdehyde (MDA) levels of 62.28 ± 5.52 nM/dl among the extractors showing high levels of lipid peroxidation. Furthermore, blood superoxide dismutase (SOD) was also found significantly correlated (P = 0.000) with urinary toxic metal levels among exposed workers. We report the association between metal exposure and oxidative stress in exposed mining workers that may give rise to workers' susceptibility towards genetic and non-genetic health implications. The current study emphasized on the need for exposure control measures in the chromite ore mining activity areas.

Increased E-waste generation during recent times has become a global concern, especially for developing countries that are at receiving end from the developed countries. Their improper handling and lacking management practices in developing countries including Pakistan are contributing enormous addition of toxicants into the environment and affecting the health of exposed workers associated with E-waste recycling activities. A systematic cross-sectional study was designed comprising workers associated with E-waste recycling activities in Peshawar city, Pakistan. The study aimed to investigate metal concentrations in dust, particulate matter and urine of exposed workers and correlate with oxidative stress and glutathione S-transferases genotypes (GSTM1 and GSTT1) that play a role in detoxification of metals in humans. A total of 120 blood samples comprising dismantlers (n = 52), repairers (n = 21), smelters (n = 17) and controls (n = 30) were collected. Results showed that metal concentrations were significantly higher in the dust (P = 0.020), particulate matter (P = 0.021) and urine samples (P = 0.00) as compared to controls. We observed significant increase in MDA (P = 0.00) and decrease in SOD (P = 0.00) and CAT (P = 0.00) levels among exposed subjects as compared to controls. Additionally, GSTT1 null genotype was more significantly associated with the dismantlers (P = 0.02). The study shows that E-waste workers are exposed to high level of toxic metals through dust and particulate matter, resulting in significant oxidative stress and related health implications, while GSTT1 null polymorphism is associated with increased susceptibility to these metals and induced health outcomes.

Polycyclic aromatic hydrocarbons (PAHs) are carcinogenic compounds which are emitted through incomplete combustion of organic materials, fossil fuels, consumption of processed meat, smoked food, and from various industrial activities. High molecular mass and mobility make PAHs widespread and lethal for human health. A cellular system in human detoxifies these toxicants through specialized enzymatic machinery called xenobiotic-metabolizing (CYP450) and phase-II (GSTs) enzymes (XMEs). These metabolizing enzymes include cytochromes P450 family (CYP1, CYP2), glutathione s-transferases, and ALDHs. Gene polymorphisms in XMEs encoding genes can compromise their metabolizing capacity to detoxify ingested carcinogens (PAHs etc.) that may lead to prolong and elevated exposure to ingested toxicants and may consequently lead to cancer. Moreover, PAHs can induce cancer through reprograming XMEs' gene functions by altering their epigenetic markers. This review article discusses possible interplay between individual's gene polymorphism in XMEs' genes, their altered epigenetic markers, and exposure to PAHs in cancer susceptibility in Pakistan.

Per- and polyfluoroalkyl substances (PFASs) are a large group of chemicals reported in global environment and are responsible for various adverse impacts on humans and environment. We report a comprehensive study on occurrence of PFASs, including legacy, substitute and emerging ones, from Pakistan. Surface water samples were collected from five ecologically important freshwater reservoirs in Pakistan, namely, Head Panjnad (HP), Head Trimmu (HT), Chashma Barrage (CB), Head Blloki (HB), and Head Qadirabad (HQ). The detection frequencies of PFASs ranged between 37 %-100 %. The highest concentration of ∑

Heavy metals exposure through dust emissions pose a health risk to workers in coal and chromite mines. The processes involved in mining are noteworthy for the generation of heavy metal-contaminated dust which causes human health implications, especially to the workers that are mainly exposed to such toxins. This study determined pollution levels in coal and chromite mines and calculated the health risk of workers being exposed to heavy metal-contaminated dust. We used fractioned dust with particle sizes 75, 75-106, and 107-150 µm to assess the pollution levels, anthropogenic impacts, geo-accumulation index, and enrichment factor for selected coal and chromite mines. Through a probabilistic approach, Monte Carlo simulations were used to determine health risks. The findings revealed that the smallest size dust fraction ( 75 μm) contained the highest metal concentrations. Ingestion was considered a prominent exposure route contributing to health risk. In the dust fraction ( 75 μm), chromite mines exhibited the highest Cr (340.6 mg/kg) and lowest Cd (8.4 mg/kg) concentrations. In coal mines, Mn (284.9 mg/kg) and Cd (2.1 mg/kg) were measured highest and lowest, respectively. Pollution assessment revealed dust to be moderately polluted. Health risk assessment showed that Cr in chromite mines exhibited a mean HI value of 1.16E + 00 that was higher than the safe level (HI 1) having the potential to cause significant health risk to workers. In coal mines, the estimated total HI was 6E-1. Sensitivity analysis revealed concentration and exposure time to be the most influential parameters contributing to risk. Therefore, governmental and nongovernmental organizations must develop dust pollution control guidelines and mitigation measures to safeguard the health of mineworkers by limiting heavy metal exposure.

Arsenic (As) contamination in groundwater is responsible for numerous adverse health outcomes among millions of people. Epigenetic alterations are among the most widely studied mechanisms of As toxicity. To understand how As exposure alters gene expression through epigenetic modifications, a systematic genome-wide study was designed to address the impact of multiple important single nucleotide polymorphisms (SNPs) related to As exposure on the methylome of drinking water As-exposed rural subjects from Pakistan. Urinary As levels were used to stratify subjects into low, medium and high exposure groups. Genome-wide DNA methylation was investigated using MeDIP in combination with NimbleGen 2.1 M Deluxe Promotor arrays. Transcriptome levels were measured using Agilent 8 × 60 K expression arrays. Genotyping of selected SNPs (As3MT, DNMT1a, ERCC2, EGFR and MTHFR) was measured and an integrated genetic risk factor for each respondent was calculated by assigning a specific value to the measured genotypes based on known risk allele numbers. To select a representative model related to As exposure we compared 9 linear mixed models comprising of model 1 (including the genetic risk factor), model 2 (without the genetic risk factor) and models with individual SNPs incorporated into the methylome data. Pathway analysis was performed using ConsensusPathDB. Model 1 comprising the integrated genetic risk factor disclosed biochemical pathways including muscle contraction, cardio-vascular diseases, ATR signaling, GPCR signaling, methionine metabolism and chromatin modification in association with hypo- and hyper-methylated gene targets. A unique pathway (direct P53 effector) was found associated with the individual DNMT1a polymorphism due to hyper-methylation of CSE1L and TRRAP. Most importantly, we provide here the first evidence of As-associated DNA methylation in relation with gene expression of ATR, ATF7IP, TPM3, UBE2J2. We report the first evidence that integrating SNPs data with methylome data generates a more representative epigenome profile and discloses a better insight in disease risks of As-exposed individuals.

Antibiotics contamination in the water environment is a high priority global concern. Growing levels of antibiotics in freshwater resources, especially groundwater, due to anthropogenic sources such as pharmaceutical and veterinary applications, are alarming. The present study aims to investigate the occurrence, spatial distribution, source apportionment, ecological, and human health risks of antibiotics (n = 23) in groundwater samples (n = 144) of highly populated cities of Pakistan. The elevated level of antibiotics was detected in Faisalabad with the mean concentrations of 13.8 ng/L, followed by Gujrat (7.8 ng/L), Lahore (4.04 ng/L), Quetta 3.9 ng/L, Rawalpindi/Islamabad (2.29 ng/L), and Peshawar (2.03 ng/L), respectively. Out of 23 investigated antibiotics, tigecycline and ciprofloxacin were predominantly present in groundwater with average concentrations of 21.3 ng/L and 18.2 ng/L, respectively. The spatial distribution analyses revealed that among the targeted cities, Faisalabad, an industrial hub of the country, had the most polluted groundwater with dominant classes of antibiotics including quinolones (except flumequine), β-Lactams, tetracyclines, sulfonamides, and amphenicols, implying an elevated consumption of human and veterinary drugs in the city. The occurrence of targeted antibiotics varied greatly among cities (p0.05). PCA-MLR analysis confirmed domestic discharge (31%), animal husbandry (19%), and pharmaceutical/hospital discharge (48%) as the chief contributors to antibiotics contamination in groundwater of Faisalabad. The risk quotient (RQ) values of targeted antibiotics were reported as 1.16E-07 to 1.03E-02, and demonstrated that antibiotics pose no risks to human health, while hazard quotient (HQ) values were observed as 09.5E-05 to 6.6E-01, and only ciprofloxacin, flumequine, oxytetracycline, and sulfamethoxazole revealed moderate to low ecological risks to water species (0.1HQ1). Since, no detailed study has been conducted to evaluate the antibiotics' contamination in groundwater of Pakistan, this robust investigation provides a way forward to further explore the environmental and human health implications of antibiotics in major urban-rural settings in the region.

Arsenic (As), and fluoride (F−) are potent contaminants with established carcinogenic and non-carcinogenic impacts on the exposed populations globally. Despite elevated groundwater As and F− levels being reported from various regions of Pakistan no biomonitoring study has been reported yet to address the co-exposure impact of As and F− among school children. We aimed to investigate the effects of these two contaminants on dental fluorosis and intelligence quotient (IQ) along with the induction of oxidative stress in rural children under co-exposed conditions. A total of 148 children (5 to 16 years old) from the exposed and control group were recruited in the current study from endemic rural areas of Lahore and Kasur districts, Pakistan having elevated As and F− levels in drinking water than permissible limits. We monitored malondialdehyde and its probable association with antioxidants activity (SOD, CAT, and GR) as a biomarker of oxidative stress. GSTM1/T1 polymorphisms were measured to find the impact of As on health parameters. Mean urinary concentrations of As (2.70 vs. 0.016 µg/L, P

BACKGROUND: Pharmaceuticals and personal care products (PPCPs) are emerging contaminants that have been extensively used in present time to improve the living standards. Their persistence in water resources due to various anthropogenic sources such as wastewater treatment plants, pharmaceutical industries, and runoff from agricultural and livestock farms has not only threaten aquatic life but their occurrence in groundwater has also raised concerns related to humans' wellbeing. METHODS: Considering this as a neglected area of research in Pakistan, a systematic monitoring study was designed to investigate their occurrence, sources, and potential environmental and human health risks in groundwater from urban-rural areas of six cities. Ultra-High-Performance Liquid Chromatography-Tandem Mass Spectrometry (UHPLC-MS/MS) was used to analyze the collected samples preceded by solid-phase extraction. RESULTS: Overall, 8 out of 11 selected PPCPs were detected in groundwater samples with detection frequency ranging from 5.5-65%. Their concentrations ranged from below limit of detection (

We studied cancer patients for possible PAH exposure, using urinary concentration of 1-hydroxypyrene (1-OHP) as a biomarker of internal dose of polycyclic aromatic hydrocarbons (PAHs). The subjects included in this study belonged to various socio-demographic backgrounds, and were diagnosed with cancer (i.e. lung, head and neck or digestive tract cancer). In general, we observed high concentration of urinary 1-OHP among digestive tract cancer patients, compared with the controls (CN) (mean 1.06, median 1.03 and mean 0.62, median 0.63 μmol/mol-Cr in digestive tract cancer patients and controls respectively). The concentrations of urinary 1-OHP were higher than the background level of PAHs; therefore, these groups could have been exposed to PAHs. Highest urinary 1-OHP concentration was observed in digestive tract cancer patients (median 1.25 μmol/mol-Cr) with GSTM-1 genotype. The results of PCA were consistent with qualitative and quantitative data analysis. The contribution of urinary 1-OHP eigenvector revealed a relatively high PAH-exposure among cancer patients compared with CN, while diet and age were influential parameters among cancer patients, which could have a strong link in cancer etiology in the selected exposure groups.

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Pharmaceutically active compounds are newly recognized micropollutants which are ubiquitous in aquatic environment mainly due to direct discharge of treated and untreated wastewater from wastewater treatment plants. These contaminants have attracted mounted attention due to their toxic effects on aquatic life. They disrupt biological processes in non-target lower organisms upon exposure. Biodegradation, photo-degradation, and sorption are key processes which determine their fate in the environment. A variety of conventional and advanced treatment processes had been extensively investigated for the removal of pharmaceuticals from wastewater. However, due to structural complexity and varying operating parameters, complete removal seems ideal. Generally, due to high energy requirement of advanced treatment technology, it is considered cost ineffective. Transport of pharmaceutical compounds occurs via aquatic channels whereas sediments and aquatic colloids play a significant role as sinks for these contaminants. The current review provides a critical understanding of fate and toxicity of pharmaceutical compounds and highlights their vulnerability and occurrence in South Asia. Antibiotics, analgesics, and psychiatric drugs were found predominantly in the water environment of South Asian regions. Despite significant advances in understanding pharmaceuticals fate, toxicity, and associated risks since the 1990s, still substantial data gaps in terms of monitoring, human health risks, and legislation exist which presses the need to develop a more in-depth and interdisciplinary understanding of the subject.

Present study aimed to evaluate the contamination status of organochlorine pesticides (OCPs) and their associated potential for air–soil exchange and health risks from ecologically important sites of the Indus Basin, Pakistan. Among different OCPs investigated, ΣDDTs and ΣHCHs were more prevalent compounds in the agricultural soils and ambient air samples of the study area. The average concentrations for DDTs were found higher at downstream agricultural sites, particularly at Head Panjnad (Soil: 320 ng/g; Air: 743 pg/m 3 ) and acting as an ultimate sink of ΣOCP burden in soils. Spatial distribution patterns inferred ubiquitous distribution of ΣDDTs in soils and air of the study area. Source diagnostic ratios demonstrated that studied OCPs either are illegally being used in agricultural practices or/and they are residues of past use in the environment. Fugacity fraction model revealed wide variations (ff = 0.12–0.94) with 20% of OCPs above equilibrium range and net volatilization of α -endosulfan, β -HCH and o , p ′-DDD. Assessment of cancer risks for OCPs indicated a higher cancer risk (CR > 1 × 10 − 6 ) for the residents of the Indus Basin. According to the available soil quality guidelines, DDTs and HCHs were above the permissible limits and pose a threat to natural habitat and biodiversity of the Indus Basin.

This study reports the first investigation of polychlorinated naphthalenes (PCNs) in air and soil samples from ecologically important sites of the Indus River Basin, Pakistan. The concentrations of ∑39-PCNs in air and soil were found in a range between 1-1588 pg m(-3) and 0.02-23 ng g(-1) while the mean TEQ values were calculated to be 5.4E(-04) pg TEQ m(-3) and 1.6E(+01) pg TEQ g(-1), respectively. Spatially, air and soil PCN concentrations were found to be high at Rahim Yar Khan (agricultural region). Lower-medium chlorinated PCNs (sum of tri-, tetra- and penta-CNs) predominated in both air and soil, altogether constituting 87 and 86% of total PCNs in the two environmental matrices, respectively. According to the data, soil-air partitioning of PCNs was interpreted to be similarly controlled by the combined effect of black carbon and organic matter in the Indus River Basin, with no preferential implication of the recalcitrant organic form.