The Metabolism And Toxicology Of Manganese

Since manganese (Mn) is both an essential trace metal and, under conditions of excess exposure, a neurotoxic metal, it is important to reach a clearer understanding of how Mn is absorbed, distributed, accumulated, and excreted, as well as to determine the effects of Mn on various metabolic processes, particularly in the brain.;In the present series of studies, Mn was administered to rats via injection (ip or iv), or orally in drinking water.;Mn administered as a single iv dose was recovered primarily from the bile and liver, which together comprised about 80% of the recovered dose, 3 hrs after administration. Mn did not bind to presynthesized hepatic metallothionein. Although the simultaneous administration of Mn + L-dopa caused a significant decrease in the biliary excretion of Mn, no evidence was found to support the contention that the chelation of Mn by L-dopa is a significant factor influencing the distribution and excretion of either Mn or L-dopa.;In plasma, Mn binds extremely poorly to albumin compared to Cd, Zn, and Fe, but binds much better than Cd or Zn to transferrin. The binding of the Mn to plasma proteins is affected by pH, the valence state of Mn (Mn(\u272+) vs Mn(\u273+)), and species differences (human vs rat).;Mn increased in all tissues except liver due to daily ip injections of 3.0 or 3.5 mg Mn/kg for 30 days. Bone and pancreas revealed the largest increases. In blood, increased Mn levels were almost totally accounted for by increases in the erythrocyte fraction. In the brain, certain regions, such as the corpus striatum and midbrain tegmentum, accumulated higher than average levels of Mn compared to other brain regions. Increased Cu concentrations were detected in plasma, pancreas, duodenum, testes, bone, lung, and in several brain regions of the Mn-treated rats. Also, Zn levels in plasma and bone were significantly reduced, as were Mg levels in heart and bone. In the corpus striatum, no changes in the concentrations of any neurotransmitter (DA, NE, 5-HT), nor any of their metabolites (DOPAC, HVA, 5-HIAA) were observed, but in the frontal cortex and pons-medulla, DA levels were significantly elevated over control. There was no change in the concentrations of the DA metabolites, however, indicating that the synthesis of DA may be initially affected by subchronic Mn administration but not the rate of degradation. Levels of NE were also elevated in the pons-medulla of Mn-treated rats. . . . (Author\u27s abstract exceeds stipulated maximum length. Discontinued here with permission of author.) UM

History of Wildlife Toxicology and the Interpretation of Contaminant Concentrations in Tissues

The detection and interpretation of contaminants in tissues of wildlife belongs to the field of toxicology, a scientific discipline with a long, intriguing, and illustrious history (reviewed by Hayes 1991, Gallo 2001, Gilbert and Hayes 2006, Wax 2006). We review its history briefly, to provide a context for understanding the use of tissue residues in toxicology, and to explain how their use has developed over time. Because so much work has been conducted on mercury, and dioxins and polychlorinated biphenyls (PCBs), separate case histories are included that describe the evolution of the use of tissue concentrations to assess exposure and effects of these two groups of contaminants in wildlife. The roots of toxicology date back to early man, who used plant and animal extracts as poisons for hunting and warfare. The Ebers papyrus (Egypt -1550 BC) contains formulations for hemlock, aconite (arrow poison), opium, and various metals used as poisons. Hippocrates (-400 BC) is sometimes credited with proposing the treatment of poisoning by decreasing absorption and using antidotes (Lane and Borzelleca 2007). Chanakya (350-283 BC), Indian advisor of the Maurya Emperor Chandragupta (340-293 BC), urged the use of food tasters as a precaution against poisoning, and the Roman emperor Claudius may have even been poisoned by his taster Halotus in 54 AD. Moses ben Maimon (1135-1204), author of a treatise on poisoning, noted that dairy products could delay absorption of some poisons. Paracelsus (1493-1541) shaped the field of toxicology with his corollaries that experimentation is essential to examining the response, that therapeutic properties should be distinguished from toxic properties, that chemicals have specific modes of action, and that the dose makes the poison. The art of concocting and using poisons reached its zenith during the Italian Renaissance, eventually culminating in its commercialization by Catherine Deshayes (a.k.a., La Voisine, 1640-1680) in France. One of the first to suggest a chemical method for the detection of a poison in modern times was Herman Boerhaave (1668-1738), a physician and botanist, who, according to Jurgen Thorwald (The Century of the Detective), placed the suspected poison on red-hot coals, and tested for odors. The Spanish physician Orfila (1787-1853) served in the French court, and was the first toxicologist to systematically use autopsy and chemical analysis to prove poisoning. He has been credited with developing and refining techniques to detect arsenic poisoning. Other historic accounts include extraction of alkaloids from postmortem specimens (Jean Servais Stas ~1851) as evidence in a nicotine poisoning case (Levine 2003). The chemical analysis of organs and tissues became the basis for establishing poisoning. Much of the early history of toxicology addressed whether someone had been poisoned and how to treat poisoning

Contour completion at edge endings

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 1988.Vita.Includes bibliographical references.by Joseph Edward Scheuhammer.Ph.D

Derivation of screening benchmarks for dietary methylmercury exposure for the common loon ( Gavia immer ): Rationale for use in ecological risk assessment

The current understanding of methylmercury (MeHg) toxicity to avian species has improved considerably in recent years and indicates that exposure to environmentally relevant concentrations of MeHg through the diet can adversely affect various aspects of avian health, reproduction, and survival. Because fish‐eating birds are at particular risk for elevated MeHg exposure, the authors surveyed the available primary and secondary literature to summarize the effects of dietary MeHg on the common loon ( Gavia immer ) and to derive ecologically relevant toxic thresholds for dietary exposure to MeHg in fish prey. After considering the available data, the authors propose three screening benchmarks of 0.1, 0.18, and 0.4 µg g −1 wet weight MeHg in prey fish. The lowest benchmark (0.1 µg g −1 wet wt) is the threshold for adverse behavioral impacts in adult loons and is close to the empirically determined no observed adverse effects level for subclinical effects observed in captive loon chicks. The remaining benchmarks (0.18 and 0.4 µg g −1 wet wt) correspond to MeHg levels in prey fish associated with significant reproductive impairment and reproductive failure in wild adult loons. Overall, these benchmarks incorporate recent findings and reviews of MeHg toxicity in aquatic fish‐eating birds and provide the basis for a national ecological risk assessment for Hg and loons in Canada. Environ. Toxicol. Chem. 2012; 31: 2399–2407. © 2012 SETACPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93756/1/1971_ftp.pd

Comparison of intermittent and continuous exposures to inorganic mercury in the mussel, Mytilus edulis: accumulation and sub-lethal physiological effects.

Aquatic organisms are often subject to intermittent exposure to pollutants in real ecosystems. This study aimed to compare mercury accumulation and the physiological responses of mussels, Mytilus edulis during continuous and intermittent exposure to the metal. Mussels were treated in a semi-static, triplicated design to either a control (no added Hg) or 50 µg l(-1) Hg as HgCl2 in continuous (daily) or intermittent (2 day exposure, 2 days in clean seawater alternately) exposure for 14 days. A time-dependent increase in Hg accumulation was observed in the continuous exposure, while the intermittent treatment showed step-wise changes in Hg concentrations with the exposure profile, especially in the gills. At the end of the experiment, tissue Hg concentrations were significantly increased in the continuous compared to the intermittent exposure for digestive gland (4 fold), gonad and remaining soft tissue (>2 fold), but not for the gill and adductor muscle. There was no observed oxidative damage at the end of the experiment as measured by the thiobarbituric acid reactive substances (TBARS) concentrations in tissues from all treatments. However, total glutathione was significantly decreased in the gill and digestive gland of both the continuous and intermittent exposure by the end of the experiment. The neutral red retention ability of the haemocytes was not affected, but total haemocyte counts were significantly decreased (<2 fold) in the intermittent compared to the continuous exposure. Histopathological examinations showed less pathology in the gill, but more inflammation in the digestive gland of mussels for the intermittent compared to the continuous exposure. Overall, the results showed that Hg accumulation from intermittent exposure was less than that of the continuous exposure regime, but the sub-lethal responses are sometimes more severe than expected in the former

Bioaccessibility Tests Accurately Estimate Bioavailability Of Lead To Quail

Hazards of soil-borne lead (Pb) to wild birds may be more accurately quantified if the bioavailability of that Pb is known. To better understand the bioavailability of Pb to birds, the authors measured blood Pb concentrations in Japanese quail (Coturnix japonica) fed diets containing Pb-contaminated soils. Relative bioavailabilities were expressed by comparison with blood Pb concentrations in quail fed a Pb acetate reference diet. Diets containing soil from 5 Pb-contaminated Superfund sites had relative bioavailabilities from 33% to 63%, with a mean of approximately 50%. Treatment of 2 of the soils with phosphorus (P) significantly reduced the bioavailability of Pb. Bioaccessibility of Pb in the test soils was then measured in 6 in vitro tests and regressed on bioavailability: the relative bioavailability leaching procedure at pH 1.5, the same test conducted at pH 2.5, the Ohio State University in vitro gastrointestinal method, the urban soil bioaccessible lead test, the modified physiologically based extraction test, and the waterfowl physiologically based extraction test. All regressions had positive slopes. Based on criteria of slope and coefficient of determination, the relative bioavailability leaching procedure at pH 2.5 and Ohio State University in vitro gastrointestinal tests performed very well. Speciation by X-ray absorption spectroscopy demonstrated that, on average, most of the Pb in the sampled soils was sorbed to minerals (30%), bound to organic matter (24%), or present as Pb sulfate (18%). Additional Pb was associated with P (chloropyromorphite, hydroxypyromorphite, and tertiary Pb phosphate) and with Pb carbonates, leadhillite (a lead sulfate carbonate hydroxide), and Pb sulfide. The formation of chloropyromorphite reduced the bioavailability of Pb, and the amendment of Pb-contaminated soils with P may be a thermodynamically favored means to sequester Pb

Multiple metals exposure and neurotoxic risk in bald eagles ( Haliaeetus leucocephalus ) from two Great Lakes states

In the present study, the authors determined concentrations of several elements (As, Cd, Co, Cu, Cr, Mn, Pb, Sb, Zn) in the brains and livers of 46 bald eagles ( Haliaeetus leucocephalus ) from two Great Lakes states, Michigan and Minnesota. To explore whether exposures are of neurological concern, the authors assessed their associations with neurochemical receptors ( N ‐methyl‐ D ‐aspartate [NMDA] and γ‐aminobutyric acid A [GABA(A)]) and enzymes (glutamine synthetase [GS] and glutamic acid decarboxylase [GAD]) that play critical roles in vertebrate neurobehavior and reproduction. For most elements, levels in the livers and brains did not differ between region and gender. Hepatic Pb levels averaged 33.1 ppm (dry wt), 30.4% of all carcasses exceeded proposed avian Pb thresholds (>26.4 ppm), and in 30.8% of the birds examined evidence of Pb pellets or fragments was found. Significant changes in the activities of GS and GAD were related to brain concentrations of several metals (Pb, Cd, Co, Cu, Zn). No relationships were found among any of the nine elements and NMDA or GABA(A) receptor levels. When combined with the authors' previous study on these same eagles that showed Hg‐associated alterations in GS, GAD, and NMDA receptor levels, the present research suggests that bald eagles are exposed to various elements, especially Pb and Hg, that are capable of causing changes in GABAergic and glutamatergic neurotransmission. The functional significance of these neurochemical changes warrants attention. Environ. Toxicol. Chem. 2012;31:623–631. © 2011 SETACPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90053/1/1712_ftp.pd

Net methylmercury production in 2 contrasting stream sediments and associated accumulation and toxicity to periphyton

Periphyton uptake of bioaccumulative methylmercury (MeHg) may be an important entryway into the food web of many stream ecosystems where periphyton can be dominant primary producers. The net production of MeHg in stream sediment, its bioaccumulation in periphyton, and the potential toxicity of divalent Hg (Hg[II]) and MeHg in sediment to periphyton were investigated with a 67‐d in situ incubation experiment using chemical exposure substrates containing either a fine‐grained, organic‐rich or a sandy, low‐organic sediment, each amended with varying concentrations of mercuric chloride. Methylmercury was produced in sediment, and concentrations increased with greater amounts of added Hg(II); however, the net production of MeHg was inhibited in the highest Hg(II) treatments of both sediments. The range of total Hg concentrations that inhibited MeHg production was between approximately 80 000 ng Hg and 350 000 ng Hg per gram of organic matter for both sediments. Periphyton colonizing substrates accumulated MeHg in proportion to the concentration in sediment, but periphyton exposed to the sandy sediment accumulated approximately 20‐fold more than those exposed to the organic‐rich sediment relative to sediment MeHg concentrations. Toxicity of either Hg(II) or MeHg to periphyton was not observed with either periphyton organic content, net primary production, or respiration as endpoints. These results suggest that in situ production and bioaccumulation of MeHg in stream ecosystems can vary as a function of sediment characteristics and Hg(II) loadings to the sediment. Environ Toxicol Chem 2016;35:1759–1765. © 2015 SETACPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134236/1/etc3324_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134236/2/etc3324.pd

Rapid methods to detect organic mercury and total selenium in biological samples

<p>Abstract</p> <p>Background</p> <p>Organic mercury (Hg) is a global pollutant of concern and selenium is believed to afford protection against mercury risk though few approaches exist to rapidly assess both chemicals in biological samples. Here, micro-scale and rapid methods to detect organic mercury (< 1.5 ml total sample volume, < 1.5 hour) and total selenium (Se; < 3.0 ml total volume, < 3 hour) from a range of biological samples (10-50 mg) are described.</p> <p>Results</p> <p>For organic Hg, samples are digested using Tris-HCl buffer (with sequential additions of protease, NaOH, cysteine, CuSO₄, acidic NaBr) followed by extraction with toluene and Na₂S₂O₃. The final product is analyzed via commercially available direct/total mercury analyzers. For Se, a fluorometric assay has been developed for microplate readers that involves digestion (HNO₃-HClO₄and HCl), conjugation (2,3-diaminonaphthalene), and cyclohexane extraction. Recovery of organic Hg (86-107%) and Se (85-121%) were determined through use of Standard Reference Materials and lemon shark kidney tissues.</p> <p>Conclusions</p> <p>The approaches outlined provide an easy, rapid, reproducible, and cost-effective platform for monitoring organic Hg and total Se in biological samples. Owing to the importance of organic Hg and Se in the pathophysiology of Hg, integration of such methods into established research monitoring efforts (that largely focus on screening total Hg only) will help increase understanding of Hg's true risks.</p