Niladri Basu

The Lancet Commission on pollution and health

Philip J Landrigan, Richard Fuller, Nereus J R Acosta, Olusoji Adeyi, Robert Arnold, Niladri (Nil) Basu, Abdoulaye Bibi Baldé, Roberto Bertollini, Stephan Bose-O’Reilly, Jo Ivey Boufford, Patrick N Breysse, Thomas Chiles, Chulabhorn Mahidol, Awa M Coll-Seck, Maureen L Cropper, Julius Fobil, Valentin Fuster, Michael Greenstone, Andy Haines, David Hanrahan, David Hunter, Mukesh Khare, Alan Krupnick, Bruce Lanphear, Bindu Lohani, Keith Martin, Karen V Mathiasen, Maureen A McTeer, Christopher J L Murray, Johanita D Ndahimananjara, Frederica Perera, Janez Potočnik, Alexander S Preker, Jairam Ramesh, Johan Rockström, Carlos Salinas, Leona D Samson, Karti Sandilya, Peter D Sly, Kirk R Smith, Achim Steiner, Richard B Stewart, William A Suk, Onno C P van Schayck, Gautam N Yadama, Kandeh Yumkella, Ma Zhong

What are the toxicological effects of mercury in Arctic biota

This review critically evaluates the available mercury (Hg) data in Arctic marine biota and the Inuit population against toxicity threshold values. In particular marine top predators exhibit concentrations of mercury in their tissues and organs that are believed to exceed thresholds for biological effects. Species whose concentrations exceed threshold values include the polar bears (Ursus maritimus), beluga whale (Delphinapterus leucas), pilot whale (Globicephala melas), hooded seal (Cystophora cristata), a few seabird species, and landlocked Arctic char (Salvelinus alpinus). Toothed whales appear to be one of the most vulnerable groups, with high concentrations of mercury recorded in brain tissue with associated signs of neurochemical effects. Evidence of increasing concentrations in mercury in some biota in Arctic Canada and Greenland is therefore a concern with respect to ecosystem health.

Is dietary mercury of neurotoxicological concern to wild polar bears (Ursus maritimus)

Polar bears (Ursus maritimus) are exposed to high concentrations of mercury because they are apex predators in the Arctic ecosystem. Although mercury is a potent neurotoxic heavy metal, it is not known whether current exposures are of neurotoxicological concern to polar bears. We tested the hypotheses that polar bears accumulate levels of mercury in their brains that exceed the estimated lowest observable adverse effect level (20 microg/g dry wt) for mammalian wildlife and that such exposures are associated with subtle neurological damage, as determined by measuring neurochemical biomarkers previously shown to be disrupted by mercury in other high-trophic wildlife. Brain stem (medulla oblongata) tissues from 82 polar bears subsistence hunted in East Greenland were studied. Despite surprisingly low levels of mercury in the brain stem region (total mercury = 0.36 +/- 0.12 microg/g dry wt), a significant negative correlation was measured between N-methyl-D-aspartate (NMDA) receptor levels and both total mercury (r = -0.34, p < 0.01) and methylmercury (r = -0.89, p < 0.05). No relationships were observed among mercury, selenium, and several other neurochemical biomarkers (dopamine-2, gamma-aminobutyric acid type A, muscarinic cholinergic, and nicotinic cholinergic receptors; cholinesterase and monoamine oxidase enzymes). These data show that East Greenland polar bears do not accumulate high levels of mercury in their brain stems. However, decreased levels of NMDA receptors could be one of the most sensitive indicators of mercurys subclinical and early effects.

Mercury-associated DNA hypomethylation in polar bear brains via the LUminometric Methylation Assay: a sensitive method to study epigenetics in wildlife.

In this paper we describe a novel approach that may shed light on the genomic DNA methylation of organisms with non‐resolved genomes. The LUminometric Methylation Assay (LUMA) is permissive for genomic DNA methylation studies of any genome as it relies on the use of methyl‐sensitive and ‐insensitive restriction enzymes followed by polymerase extension via Pyrosequencing technology. Here, LUMA was used to characterize genomic DNA methylation in the lower brain stem region from 47 polar bears subsistence hunted in central East Greenland between 1999 and 2001. In these samples, average genomic DNA methylation was 57.9% ± 6.69 (SD; range was 42.0 to 72.4%). When genomic DNA methylation was related to brain mercury (Hg) exposure levels, an inverse association was seen between these two variables for the entire study population (P for trend = 0.17). After dichotomizing animals by gender and controlling for age, a negative trend was seen amongst male animals (P for trend = 0.07) but no associations were found in female bears. Such sexually dimorphic responses have been found in other toxicological studies. Our results show that genomic DNA methylation can be quantitatively studied in a highly reproducible manner in tissue samples from a wild organism with a non‐resolved genome. As such, LUMA holds great promise as a novel method to explore consequential questions across the ecological sciences that may require an epigenetic understanding.

Toxicity of dietary methylmercury to fish: Derivation of ecologically meaningful threshold concentrations

Threshold concentrations associated with adverse effects of dietary exposure to methylmercury (MeHg) were derived from published results of laboratory studies on a variety of fish species. Adverse effects related to mortality were uncommon, whereas adverse effects related to growth occurred only at dietary MeHg concentrations exceeding 2.5 µg g(-1) wet weight. Adverse effects on behavior of fish had a wide range of effective dietary concentrations, but generally occurred above 0.5 µg g(-1) wet weight. In contrast, effects on reproduction and other subclinical endpoints occurred at dietary concentrations that were much lower (<0.2 µg g(-1) wet wt). Field studies generally lack information on dietary MeHg exposure, yet available data indicate that comparable adverse effects have been observed in wild fish in environments corresponding to high and low MeHg contamination of food webs and are in agreement with the threshold concentrations derived here from laboratory studies. These thresholds indicate that while differences in species sensitivity to MeHg exposure appear considerable, chronic dietary exposure to low concentrations of MeHg may have significant adverse effects on wild fish populations but remain little studied compared to concentrations in mammals or birds.

Occupational and environmental mercury exposure among small-scale gold miners in the Talensi-Nabdam District of Ghana's Upper East region.

Mercury use in small-scale gold mining is ubiquitous across Ghana but little is known about the extent to which such activities have contaminated community residents and miners. Here, occupational exposures to elemental mercury (via urine sampling) and dietary exposures to methylmercury (via hair sampling) were assessed among 120 participants recruited from a mining community located in the Talensi-Nabdam District of Ghanas Upper East region during summer 2009. More than one-fifth of the participants had moderately high levels of urinary mercury (>10μg/L) and 5% had urine mercury levels that exceeded the WHO guideline value of 50μg/L. When participants were stratified according to occupation, those active in the mining industry had the highest mercury levels. Specifically, individuals that burned amalgam had urine mercury levels (median: 43.8μg/L; mean ± SD: 171.1±296.5μg/L; n=5) significantly higher than median values measured in mechanical operators (11.6μg/L, n=4), concession managers/owners (5.6μg/L, n=11), excavators that blast and chisel ore (4.9μg/L, n=33), individuals that sift and grind crushed ore (2.2μg/L, n=47), support workers (0.5μg/L, n=14), and those with no role in the mining sector (2.5μg/L, n=6). There was a significant positive Spearman correlation between fish consumption and hair mercury levels (r=0.30) but not with urine mercury (r=0.18) though further studies are needed to document which types of fish are consumed as well as portion sizes. Given that 200,000 people in Ghana are involved in the small-scale gold mining industry and that the numbers are expected to grow in Ghana and many other regions of the world, elucidating mercury exposure pathways in such communities is important to help shape policies and behaviors that may minimize health risks.

Absence of fractionation of mercury isotopes during trophic transfer of methylmercury to freshwater fish in captivity

We performed two controlled experiments to determine the amount of mass-dependent and mass-independent fractionation (MDF and MIF) of methylmercury (MeHg) during trophic transfer into fish. In experiment 1, juvenile yellow perch (Perca flavescens) were raised in captivity on commercial food pellets and then their diet was either maintained on unamended food pellets (0.1 μg/g MeHg) or was switched to food pellets with 1.0 μg/g or 4.0 μg/g of added MeHg, for a period of 2 months. The difference in δ(202)Hg (MDF) and Δ(199)Hg (MIF) between fish tissues and food pellets with added MeHg was within the analytical uncertainty (δ(202)Hg, 0.07 ‰; Δ(199)Hg, 0.06 ‰), indicating no isotope fractionation. In experiment 2, lake trout (Salvelinus namaycush) were raised in captivity on food pellets and then shifted to a diet of bloater (Coregonus hoyi) for 6 months. The δ(202)Hg and Δ(199)Hg of the lake trout equaled the isotopic composition of the bloater after 6 months, reflecting reequilibration of the Hg isotopic composition of the fish to new food sources and a lack of isotope fractionation during trophic transfer. We suggest that the stable Hg isotope ratios in fish can be used to trace environmental sources of Hg in aquatic ecosystems.

Mercury contamination in spotted seatrout, Cynoscion nebulosus: An assessment of liver, kidney, blood, and nervous system health

Marine fishes in South Florida (Florida Keys-Florida Bay-Everglades region) accumulate higher concentrations of mercury (Hg) in their tissues than similar fishes from other areas of the southeastern U.S., though it is not known whether these elevated levels affect fish health. In this study, we used quantifiable pathological and biochemical indicators to explore Hg-associated differences in marine fish from South Florida, where Hg contamination is high, and from Indian River Lagoon, Florida, which served as a reference area. Hg concentrations in all tissues of mature spotted seatrout (Cynoscion nebulosus) from South Florida were significantly higher than those from Indian River Lagoon and were within the threshold range of those in studies where effects of Hg exposure have been observed. The distribution of Hg among tissues followed the same trend in both areas, with the greatest concentration in kidney tissue, followed by liver, muscle, brain, gonad, and red blood cells. Blood-plasma biochemistry showed that concentrations of iron, inorganic phosphate, lactate dehydrogenase, and aspartate aminotransferase were significantly less in South Florida. Also, fructosamine and alkaline phosphatase were significantly less in South Florida. Liver histology revealed that pyknosis/necrosis, interstitial inflammation, and bile duct hyperplasia were found only in seatrout from South Florida, and steatosis/glycogen was more frequently found in Indian River Lagoon specimens. In renal tissue, interstitial inflammation, glomerular dilatation and thickening, and tubular degeneration and necrosis were more frequently found in South Florida specimens. Changes in the liver cytoskeleton and morphology may explain some of the differences in blood parameters between study areas. Neurochemical analyses showed that brain N-methyl-d-aspartic acid (NMDA) receptors (but not those of muscarinic cholinergic receptors, monoamine oxidase, or acetylcholinesterase) were significantly less in fish from South Florida than from Indian River Lagoon. These findings provide compelling evidence that elevated Hg could cause quantifiable pathological and biochemical changes that might influence the health of spotted seatrout and could also affect other marine fish species.

Effects of mercury on neurochemical receptor-binding characteristics in wild mink.

Piscivorous wildlife, such as mink (Mustela vison), routinely are exposed to mercury (Hg) in their natural environment at levels that may cause adverse behavioral outcomes. The purpose of this study was to determine if a correlation exists between neurochemical receptors and concentrations of Hg in the brains of wild mink. Specifically, receptor-binding assays were conducted to characterize the muscarinic cholinergic (mACh) and dopaminergic-2 (D2) systems in brain tissues collected from mink trapped in the Yukon Territory, Ontario, and Nova Scotia (Canada), and values were correlated with total Hg and methyl Hg (MeHg) concentrations in the brains. A significant correlation was found between Hg (total Hg and MeHg) and mACh receptor density (r = 0.546; r = 0.596, respectively) or ligand affinity (r = 0.413; r = 0.474, respectively). A significant negative correlation was found between total Hg and D2 receptor density (r = -0.340) or ligand affinity (r = -0.346). These correlations suggest that environmentally relevant concentrations of Hg may alter neurochemical function in wild mink, and that neurochemical receptor-binding characteristics can be used as a novel biomarker to assess Hgs effects on wildlife. Given the importance of the muscarinic cholinergic and dopaminergic pathways in animal behavior, further studies are required to explore the physiological and ecological significance of these findings.

New insight into biomarkers of human mercury exposure using naturally occurring mercury stable isotopes.

Human exposure to methylmercury (MeHg) and elemental mercury vapor (Hg(0)(g)) are often estimated using total Hg concentrations in hair and urine, respectively. We investigated whether Hg stable isotopes could be used to better distinguish between exposure to Hg(0)(g) versus MeHg. We found that hair from North American dental professionals was characterized by high positive Δ(199)Hg values (mean = 1.86‰, 1 SD = 0.12‰, n = 11). This confirms that among people who regularly consume fish, total Hg concentrations in hair reflect exposure to MeHg. In contrast, we found that urine from the same individuals was characterized by a range of Δ(199)Hg values (0.29 to 1.77‰, 2 SD = 0.06‰, n = 12) that were significantly correlated to the number of dental amalgams in each individuals mouth. We hypothesize that fish-derived MeHg is demethylated within the body, causing mass-dependent fractionation and the excretion of inorganic Hg in urine. Mercury in urine therefore represents a mixture of demethylated fish-derived MeHg and amalgam-derived inorganic Hg. We estimate that the majority (>70%) of Hg in urine from individuals with <10 dental amalgams is derived from ingestion of MeHg in fish. These data suggest that within populations that consume fish, urine total Hg concentrations may overestimate Hg exposure from personal dental amalgams.