Occurrence, Source and Dietary Exposure of Toxic and Essential Elements in the Indian Food Basket.

In this study, representative urban and peri-urban Indian food baskets have been studied for the presence of toxic and essential elements. The concentration of target toxic and essential elements was used to estimate dietary intakes (EDIs) and health risks. Across all food matrices, toxic elements like Cd and Pb were dominant. The highest concentrations of the target elements were found in vegetables, with Cd, Pb, and Ni being beyond permissible limits of the Food and Agriculture Organization of the United Nations and the World Health organization (0.05 mg/kg, 0.1 mg/kg, and 1.5 mg/kg, respectively) in okra, spinach, and cauliflower. The sum of concentrations of the toxic elements (As, Ni, Hg, Cr, Cd, Pb) in vegetables had a range of 0.54-12.08 mg/kg, the highest sum was found in spinach (median 12.08 mg/kg), followed by okra (median 1.68 mg/kg). The EDI was observed for vegetables with a contribution as high as 92% for Cd. Dairy products were found with the highest loading for Ni with a dietary intake of 3.1 mg/kg/day for adults and twice as much for children. Carcinogenic risk for Ni was the highest and found above the threshold for all food categories, as was the case with As. Cumulative carcinogenic and non-carcinogenic risks were mostly contributed by milk and vegetables, in particular, spinach.

Unlocking India's Potential in Managing Endocrine-Disrupting Chemicals (EDCs): Importance, Challenges, and Opportunities.

Endocrine-disrupting chemicals (EDCs) are a prime concern for the environment and health globally. Research shows that in developing countries such as India both the environment and human populations are severely exposed to EDCs and consequently experience rising incidents of adverse health effects such as diabetes and cancers. In this paper, we discuss the current EDC management approach in India, critically assess its limitations, and describe opportunities for potential improvements. Foremost, current EDC management actions and interventions in India are fragmented and outdated, and far behind the modern and comprehensive approaches adopted in the European Union and other developed countries. Strong and well-planned actions are required on various fronts of science, policy, commerce, and public engagement. These actions include the adoption of a dedicated and modern regulatory framework for managing EDCs, enhancing capacity and infrastructure for EDC monitoring in the environment and human population, employing public-private partnership programs for not only managing EDCs but also in the sectors that indirectly contribute toward the mismanagement of EDCs in the country, and raising awareness on EDCs and promoting health-preserving consumption habits among the public. As India hosts a large proportion of the global human population and biodiversity, the success or failure of its actions will substantially affect the direction of global efforts to manage EDCs and set an example for other developing countries.

Application of a pharmacokinetic model in characterizing sources of polychlorinated biphenyl exposure and determining threshold daily intakes for adverse health effects in infants and toddlers.

Characterization of PCB exposure sources for vulnerable population groups is essential to minimize the health effects of PCB exposure. At the same time, it is important to consolidate the knowledge on threshold intakes of PCBs for infants and toddlers to prevent health effects. We estimated total PCB concentrations from birth to 2 years of age in children from Slovak and Czech populations, which continue to have high PCB concentrations in breast milk. Using a pharmacokinetic (PK) model, we characterized dominant PCB exposure sources and estimated new threshold estimated daily intakes (TEDI) (above which adverse effects cannot be excluded) for postnatal PCB exposure in infants and toddlers. In the PK model, concentrations of seven indicator PCBs in breast milk and cord blood samples from 291 mother-child pairs from the Slovak birth cohort, and 396 breast milk samples from Czech mothers we used, together with their physiological characteristics and PCB concentrations from other exposure sources (food, dust, air). The estimated total PCB concentrations in children's blood at different ages were compared with threshold PCB concentrations of 500, 700 and 1000 ng·glipid-1 in serum proposed by the French Agency for Food, Environmental and Occupational Health & Safety (ANSES) and the German Environment Agency (UBA), above which possible adverse health effects may be expected. We estimated that up to 20.6% of Slovak children and up to 45.7% of Czech children at two years of age exceeded the threshold value of 700 ng·glipid-1 in blood. Mean TEDIs leading to values of 500 ng·glipid-1 in blood for children up to two years ranged between 110 and 220 ng·kg-1·bw·day-1, varying according to breastfeeding duration. Breast milk and prenatal exposure contributed to 71%-85% of PCBs exposure at two years of age. In contrast, the contributions of PCBs from dust and indoor air were negligible.

Efficacy of Ulinastatin and Sulforaphane Alone or in Combination in Rat Model of Streptozotocin Diabetes Induced Vascular Dementia.

OBJECTIVE: Vascular Dementia (VaD), is associated with metabolic conditions. Diabetes is a major risk factor for the development of VaD. This study investigates the efficacy of ulinastatin (UTI) and sulforaphane (SUL) in streptozotocin (STZ)-diabetes induced vascular endothelium dysfunction and related dementia. METHODS: Single dose STZ (50 mg/kg i.p.) was administered to Albino Wistar rats (male, 200-250 g). Morris water maze and attentional set shifting tests were used to assess the spatial learning, memory, reversal learning, and executive functioning in animals. Body weight, serum glucose, serum nitrite/nitrate, vascular endothelial function, aortic superoxide anion, brains' oxidative markers (thiobarbituric acid reactive species-TBARS, reduced glutathione-GSH, superoxide dismutase-SOD, and catalase-CAT), inflammatory markers (IL-6, IL-10, TNF-α, and myeloperoxidase-MPO), acetylcholinesterase activity-AChE, blood brain barrier (BBB) permeability and histopathological changes were also assessed. UTI (10,000 U/kg) and SUL (25 mg/kg) were used alone as well as in combination, as the treatment drugs. Donepezil (0.5 mg/kg) was used as a positive control. RESULTS: STZ-administered rats showed reduction in body weight, learning, memory, reversal learning, executive functioning, impairment in endothelial function, BBB permeability, increase in serum glucose, brains' oxidative stress, inflammation, AChE-activity, BBB permeability and histopathological changes. Administration of UTI and SUL alone as well as in combination, significantly and dose dependently attenuated the STZ-diabetes-induced impairments in the behavioral, endothelial, and biochemical parameters. CONCLUSION: STZ administration caused diabetes and VaD which was attenuated by the administration of UTI and SUL. Therefore, these agents may be studied further for the assessment of their full potential in diabetes induced VaD.

A comprehensive assessment of endocrine-disrupting chemicals in an Indian food basket: Levels, dietary intakes, and comparison with European data.

Endocrine-disrupting chemicals (EDCs) in diet are a health concern and their monitoring in food has been introduced in the European Union. In developing countries, EDC dietary exposure data are scarce, especially from areas perceived as pollution hotspots, including industrialized countries like India. Several persistent organic pollutants (POPs) act as EDCs and pose a pressure to human health mainly through dietary exposure. In the present study, a range of organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), dioxins and furans were measured in several food items collected from Indian urban (Delhi) and peri-urban (Dehradun) areas. Food basket contamination data were used to estimate EDC dietary exposure and compare it with that of the average European population estimated from available monitoring data. All the target contaminants were found in most food items, especially in dairies and meat products. OCPs were the main contributers to the measured EDC contamination. Food supplied to Delhi's markets had higher EDC contamination than that supplied to the peri-urban market in Dehradun. Despite lax compliance and control measures, Indian dietary exposure of OCPs and PBDEs were comparable with that of Europe and were lower for PCBs and dioxins. Higher meat consumption in Europe only partly explained this pattern which was driven also by the higher EDC residues in some European food items. A substantial part of endocrine disrupting potential in the diet derives from food and animal feeds internationally traded between developed and developing countries. With increasingly globalized food systems, internationally harmonized policies on EDC content in food can lead to better protection of health in both these contexts.

Towards guidelines for time-trend reviews examining temporal variability in human biomonitoring data of pollutants.

In the last few decades, a plethora of studies have focused on human biomonitoring (HBM) of chemical pollutants. Reviewing the copious HBM data reported in these studies is essential for evaluating the effectiveness of pollution management efforts, for example by evaluating time-trends. Nevertheless, guidance to systematically evaluate time trends in published HBM data has never been developed. In this study, we therefore present a proposal for guidelines to conduct "time-trend reviews" (TTRs) that examine time trends in published large HBM datasets of chemical pollutant concentrations. We also demonstrate the applicability of these guidelines through a case study that assesses time-trends in global and regional HBM data on mercury. The recommended TTR guidelines in this study are divided into seven steps: formulating the objective of the TTR, setting up of eligibility criteria, defining search strategy and screening of literature, screening results of search, extracting data, analysing data, and assessing certainty, including the potential for bias in the evidence base. The TTR guidelines proposed in this study are straightforward and less complex than those for conducting systematic reviews assessing datasets on potential human health effects of exposure to pollutants or medical interventions. These proposed guidelines are intended to enable the credible, transparent, and reproducible conduct of TTRs.

An overview of worldwide and regional time trends in total mercury levels in human blood and breast milk from 1966 to 2015 and their associations with health effects.

BACKGROUND: Mercury is a pollutant of global concern. To protect human health and environment from mercury pollution, the Minamata Convention on mercury entered into force in 2017. OBJECTIVES: To support a future effectiveness evaluation of the convention, this study assesses worldwide and regional time trends of total mercury levels in human blood and breast milk across different population sub-groups in the last half-century prior to entry-into-force of the Minamata Convention. This study also provides an overview of the epidemiological literature showing evidence of associations between mercury exposure (in terms of total mercury levels in whole blood, cord blood, and breast milk) and human health. METHODS: We searched electronic databases to identify articles published prior to June 14, 2017 and reported total mercury levels in any of three biological matrices (whole blood, cord blood, or breast milk) and/or associations with human health. Temporal trends of total mercury levels in the selected biological matrices across different population sub-groups were estimated using a linear fit of the log-transformed data. In parallel, statistical methods were employed to assess any possible effect of sources of inhomogeneity (i.e. study and population characteristics such as age, sex, ethnicity, source of exposure, sampling period, and geographical region) in the collected studies. Furthermore, a summary of significant and relevant associations between mercury exposure and human health conditions in children and adults was prepared. FINDINGS: We found significant declines in total mercury levels in whole blood, cord blood, and breast milk between 1966 and 2015. A regional overview of total mercury levels in whole blood, cord blood, and breast milk suggests the highest levels in South America, followed by Africa or Asia whereas the population groups from Europe or North America displayed the lowest levels of total mercury in the selected biological matrices. We observed conclusive consistent associations of mercury exposure with selected health conditions, especially neurodevelopment and neurotoxicity in children and adults. For several other health conditions, reported findings in the collected studies do not support conclusive associations. We also found that several studies demonstrated significant associations between mercury exposure below the USEPA reference level and various health conditions. CONCLUSIONS: This study provides a worldwide and regional overview of trends in total mercury levels in human blood and breast milk and associated health risks prior to entry-into-force of the Minamata Convention and calls for further epidemiological investigations from across the globe to fully understand the health implications of mercury exposure.

Health and ecological risk assessment of emerging contaminants (pharmaceuticals, personal care products, and artificial sweeteners) in surface and groundwater (drinking water) in the Ganges River Basin, India.

Pharmaceuticals, personal care products (PPCPs), and artificial sweeteners (ASWs) are contaminants of emerging concern commonly found in the aquatic environments. In India, studies reporting environmental occurrence of these contaminants are scarce. In this study, we investigated the occurrence and distribution of 15 PPCPs and five ASWs in the river and groundwater (used untreated as drinking water) at several sites along the Ganges River. Based on the measured groundwater concentrations, we estimated the life-long human health risk from exposure to PPCPs through drinking. In addition, we estimated the risk of exposure to PPCPs and ASWs in the river water for aquatic organisms. The sum of detected PPCPs in the river water ranged between 54.7-826 ng/L, with higher concentrations in the severely anthropogenically influenced middle and lower reaches of the Ganges. The highest concentration among the PPCPs in the river water was of caffeine (743 ng/L). The sum of detected ASWs in river water ranged between 0.2-102 ng/L. Similar to PPCPs, the sum of ASWs in the river water was higher in the middle and lower reaches of the Ganges. In groundwater, the sum of detected PPCPs ranged between 34-293 ng/L, whereas of ASWs ranged between 0.5-25 ng/L. Negligible risk for humans was estimated from PPCPs in the drinking groundwater sources along the Ganges River, whereas moderate risks to PPCPs and ASWs (namely: caffeine, sulfamethoxazole, triclocarban, triclosan, and sucralose) were estimated for aquatic organisms in the Ganges River.

Spatial gradients of polycyclic aromatic hydrocarbons (PAHs) in air, atmospheric deposition, and surface water of the Ganges River basin.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous semi-volatile organic pollutants. Their environmental occurrence is of global concern as some of them are carcinogens, mutagens, and teratogens. In this study, concentrations and distributions of 16 priority PAHs (∑PAHs) were measured in air, atmospheric deposition, and surface water at various locations in Himalayan, Middle, and Lower Reaches of the Ganges River, covering a spatial transect of 2500km, during two seasons (pre-monsoon and monsoon). The concentration of ∑PAHs ranged between 2.2 and 182.2ngm-3 in air, between 186 and 8810ngm-2day-1 in atmospheric deposition, and between 0.05 and 65.9ngL-1 in surface water. Air concentrations were strongly correlated with human population density. In the Middle and Lower Reaches of the Ganges River, atmospheric PAHs were mainly attributed to fossil fuel combustion sources. In the Himalayan Reach the influence of forest fire or biomass combustion was evident during the dry pre-monsoon season. Seasonality in concentrations of PAHs in river water was evident in the Himalayan Reach of the river, as a probable consequence of climate-modulated secondary source intensity (i.e. releases from glacier melting). Seasonality faded in the Middle and Lower Reaches of the Ganges where water contamination is expected to mainly reflect anthropogenic primary sources. Ambient air concentrations were used to calculate the probabilistic incremental lifetime cancer risk (ILCR). It was expectedly found to be higher in the Middle and Lower Reaches compared to the Himalayan Reach. The strong correlation between population density and air concentrations suggests population density may be used as a surrogate variable to assess human health risk in data-sparse regions such as the Ganges River basin.

Perfluoroalkyl substances (PFAS) in river and ground/drinking water of the Ganges River basin: Emissions and implications for human exposure.

Many perfluoroalkyl substances (PFAS) are ubiquitous environmental contaminants. They have been widely used in production processes and daily-use products or may result from degradation of precursor compounds in products or the environment. India, with its developing industrialization and population moving from traditional to contemporary lifestyles, represents an interesting case study to investigate PFAS emission and exposure along steep environmental and socioeconomic gradients. This study assesses PFAS concentrations in river and groundwater (used in this region as drinking water) from several locations along the Ganges River and estimates direct emissions, specifically for PFOS and PFOA. 15 PFAS were frequently detected in the river with the highest concentrations observed for PFHxA (0.4-4.7 ng L(-1)) and PFBS (

Pharmacological benefits of selective modulation of cannabinoid receptor type 2 (CB2) in experimental Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that pervasively affects the population across the world. Currently, there is no effective treatment available for this and existing drugs merely slow the progression of cognitive function decline. Thus, massive effort is required to find an intended therapeutic target to overcome this condition. The present study has been framed to investigate the ameliorative role of selective modulator of cannabinoid receptor type 2 (CB2), 1-phenylisatin in experimental AD condition. We have induced experimental AD in mice by using two induction models viz., intracerebroventricular (i.c.v.) administration of streptozotocin (STZ) and aluminum trichloride (AlCl3)+d-galactose. Morris water maze (MWM) and attentional set shifting test (ASST) were used to assess learning and memory. Hematoxylin-eosin and Congo red staining were used to examine the structural variation in brain. Brain oxidative stress (thiobarbituric acid reactive substance and glutathione), nitric oxide levels (nitrites/nitrates), acetyl cholinesterase activity, myeloperoxidase and calcium levels were also estimated. i.c.v. STZ as well as AlCl3+d-galactose have impaired spatial and reversal learning with executive functioning, increased brain oxidative and nitrosative stress, cholinergic activity, inflammation and calcium levels. Furthermore, these agents have also enhanced the burden of Aß plaque in the brain. Treatment with 1-phenylisatin and donepezil attenuated i.c.v. STZ as well as AlCl3+d-galactose induced impairment of learning-memory, brain biochemistry and brain damage. Hence, this study concludes that CB2 receptor modulation can be a potential therapeutic target for the management of AD.

Melting Himalayan glaciers contaminated by legacy atmospheric depositions are important sources of PCBs and high-molecular-weight PAHs for the Ganges floodplain during dry periods.

Melting glaciers are natural redistributors of legacy airborne pollutants, affecting exposure of pristine proglacial environments. Our data shows that melting Himalayan glaciers can be major contributors of polychlorinated biphenyls (PCBs) and high-molecular-weight polycyclic aromatic hydrocarbons (PAHs) for surface water in the Gangetic Plain during the dry season. Glacial emissions can exceed in some cases inputs from diffuse sources within the catchment. We analyzed air, deposition and river water in several sections along the Ganges River and its major headwaters. The predominant glacial origin of these contaminants in the Himalayan reach was demonstrated using air-water fugacity ratios and mass balance analysis. The proportion of meltwater emissions compared to pollutant discharge at downstream sections in the central part of the Gangetic Plain was between 2 and 200%. By remobilizing legacy pollutants from melting glaciers, climate change can enhance exposure levels over large and already heavily impacted regions of Northern India.

Neuroprotective Effects of Agomelatine and Vinpocetine Against Chronic Cerebral Hypoperfusion Induced Vascular Dementia.

Chronic cerebral hypoperfusion (CCH) has been considered as a critical cause for the development of cognitive decline and dementia of vascular origin. Melatonin receptors have been reported to be beneficial in improving memory deterioration. Phosphodiesterase-1 (PDE1) enzyme offers protection against cognitive impairments and cerebrovascular disorders. Aim of this study is to explore the role of agomelatine (a dual MT1 and MT2 melatonin receptor agonist) and vinpocetine (selective PDE1 inhibitor) in CCH induced vascular dementia (VaD). Two vessel occlusion (2VO) or bilateral common carotid arteries ligation method was performed to initiate a phase of chronic hypoperfusion in mice. 2VO animals have shown significant cognitive deficits (Morris water maze), cholinergic dysfunction (increased acetyl cholinesterase -AChE) activity alongwith increased brain oxidative stress (decreased brain catalase, glutathione, as well as superoxide dismutase with an increase in malondialdehyde levels), and significant increase in brain infarct size (2,3,5- triphenylterazolium chloride-TTC staining). Treatment of agomelatine and vinpocetine reduced CCH induced learning and memory deficits and limited cholinergic dysfunction, oxidative stress, and tissue damage, suggesting that agomelatine and vinpocetine may provide benefits in CCH induced VaD.

The legal framework to manage chemical pollution in India and the lesson from the Persistent Organic Pollutants (POPs).

India's rapid agro-economic growth has resulted into many environmental issues, especially related to chemical pollution. Environmental management and control of toxic chemicals have gained significant attention from policy makers, researchers, and enterprises in India. The present study reviews the policy and legal and non-regulatory schemes set in place in this country during the last decades to manage chemical risk and compares them with those in developed nations. India has a large and fragmented body of regulation to control and manage chemical pollution which appears to be ineffective in protecting environment and human health. The example of POPs contamination in India is proposed to support such a theory. Overlapping of jurisdictions and retrospectively approached environmental policy and risk management currently adopted in India are out of date and excluding Indian economy from the process of building and participating into new, environmentally-sustainable market spaces for chemical products. To address these issues, the introduction of a new integrated and scientifically-informed regulation and management scheme is recommended. Such scheme should acknowledge the principle of risk management rather than the current one based on risk acceptance. To this end, India should take advantage of the experience of recently introduced chemical management regulation in some developed nations.

Modulation of transient receptor potential vanilloid subtype 1 (TRPV1) and norepinephrine transporters (NET) protect against oxidative stress, cellular injury, and vascular dementia.

Chronic cerebral hypoperfusion (CCH) is a risk factor for the development of vascular dementia (VaD). CCH participates in a negative role in cognitive impairments. Transient receptor potential vanilloid subtype 1 (TRPV1) participates in cognition, ischemic damage and neuroprotection. Selective norepinephrine transporter (NET) inhibitors have a role in cognitive dysfunction and oxidative stress. The role of TRPV1 and NET in CCH induced VaD is still unknown. The present study has been structured to investigate the role of vanillin; a selective agonist of TRPV1 as well as atomoxetine; a selective NET inhibitor in CCH induced VaD in mice. Permanent bilateral common carotid arteries ligation or two vessel occlusion (2VO) technique was used to induce a stage of chronic cerebral hypoperfusion in mice. 2VO animals have shown significant impairment of locomotion (Actophotometer), motor coordination (Rota rod), learning and memory (Morris water maze). 2VO animals have shown significant reduction in brain catalase, glutathione, and superoxide dismutase, with significant increase in brain infarct size (TTC staining), malondialdehyde and acetyl cholinesterase-AChE activity. Whereas, administration of vanillin as well as atomoxetine has significantly attenuated 2VO induced impaired locomotion, motor coordination, learning and memory, brain damage, brain oxidative stress and higher AChE activity. It may be concluded that 2VO induced CCH has elicited VaD, which was attenuated by vanillin and atomoxetine. Thus, modulators of vanilloid receptors and norepinephrine transporter may be explored further for their benefits in CCH induced VaD.

Environment and human exposure to persistent organic pollutants (POPs) in India: a systematic review of recent and historical data.

Persistent organic pollutants (POPs) have been used in a wide range of agricultural and industrial commodities, resulting in vigorous deterioration of environment and human health. A number of studies on the occurrence of POPs confirm their presence in various environmental compartments and human body. In order to deal with this global concern, India has recently prepared the National Implementation Plan (NIP) of the Stockholm Convention. Common beliefs point at India as a hot spot of POP contamination and human exposure; however no systematic analysis was ever performed so far considering all available past data on POP occurrence. This review aims to examine the distribution pattern of POPs in multicompartment environment and human samples, meta-analysis of time trends in exposure levels to environment and humans, and cross country comparison of POP contamination with China. Based on this review, it can be concluded that the Indian environment and human population are highly contaminated by DDTs and HCHs; however scarcity of data on other POPs makes it challenging to assess their nationwide human and environmental exposure. No evidence of a general decline in DDT and HCH residues in the environment and human body come out from the meta-analysis of time trend. While comparing contamination levels between India and China, tendency towards decline in POP contamination is visible in China, unlike India.