Rapid seafloor changes associated with the degradation of Arctic submarine permafrost.

SignificanceTemperature increases in Arctic regions have focused attention on permafrost degradation on land, whereas little is known about the dynamics of extensive glacial-age permafrost bodies now submerged under the vast Arctic Continental shelves. Repeated high-resolution bathymetric surveys show that extraordinarily rapid morphologic changes are occurring at the edge of the continental slope of the Canadian Beaufort Sea along what was once the seaward limit of relict Pleistocene permafrost. How widespread similar changes are on the Arctic shelves is unknown, as this is one of the first areas in the Arctic subjected to multiple multibeam bathymetric surveys. Rapid morphologic changes associated with active submarine permafrost thawing may be an important process in sculpturing the seafloor in other submarine permafrost settings.

Powerful turbidity currents driven by dense basal layers.

Seafloor sediment flows (turbidity currents) are among the volumetrically most important yet least documented sediment transport processes on Earth. A scarcity of direct observations means that basic characteristics, such as whether flows are entirely dilute or driven by a dense basal layer, remain equivocal. Here we present the most detailed direct observations yet from oceanic turbidity currents. These powerful events in Monterey Canyon have frontal speeds of up to 7.2 m s-1, and carry heavy (800 kg) objects at speeds of ≥4 m s-1. We infer they consist of fast and dense near-bed layers, caused by remobilization of the seafloor, overlain by dilute clouds that outrun the dense layer. Seabed remobilization probably results from disturbance and liquefaction of loose-packed canyon-floor sand. Surprisingly, not all flows correlate with major perturbations such as storms, floods or earthquakes. We therefore provide a new view of sediment transport through submarine canyons into the deep-sea.

Exposure to Pb, Cd, and As mixtures potentiates the production of oxidative stress precursors: 30-day, 90-day, and 180-day drinking water studies in rats.

Exposure to chemical mixtures is a common and important determinant of toxicity and is of particular concern due to their appearance in sources of drinking water. Despite this, few in vivo mixture studies have been conducted to date to understand the health impact of chemical mixtures compared to single chemicals. Interactive effects of lead (Pb), cadmium (Cd) and arsenic (As) were evaluated in 30-, 90-, and 180-day factorial design drinking water studies in rats designed to test the hypothesis that ingestion of such mixtures at individual component Lowest-Observed-Effect-Levels (LOELs) results in increased levels of the pro-oxidant delta aminolevulinic acid (ALA), iron, and copper. LOEL levels of Pb, Cd, and As mixtures resulted in the increased presence of mediators of oxidative stress such as ALA, copper, and iron. ALA increases were followed by statistically significant increases in kidney copper in the 90- and 180-day studies. Statistical evidence of interaction was identified for six biologically relevant variables: blood delta aminolevulinic acid dehydratase (ALAD), kidney ALAD, urinary ALA, urinary iron, kidney iron, and kidney copper. The current investigations underscore the importance of considering interactive effects that common toxic agents such as Pb, Cd, and As may have upon one another at low-dose levels. The interactions between known toxic trace elements at biologically relevant concentrations shown here demonstrate a clear need to rigorously review methods by which national/international agencies assess health risks of chemicals, since exposures may commonly occur as complex mixtures.

Inhibition of prolyl hydroxylase protects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity: model for the potential involvement of the hypoxia-inducible factor pathway in Parkinson disease.

Hypoxia-inducible factor (HIF) plays an important role in cell survival by regulating iron, antioxidant defense, and mitochondrial function. Pharmacological inhibitors of the iron-dependent enzyme class prolyl hydroxylases (PHD), which target alpha subunits of HIF proteins for degradation, have recently been demonstrated to alleviate neurodegeneration associated with stroke and hypoxic-ischemic injuries. Here we report that inhibition of PHD by 3,4-dihydroxybenzoate (DHB) protects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced nigral dopaminergic cell loss and up-regulates HIF-1alpha within these neurons. Elevations in mRNA and protein levels of HIF-dependent genes heme oxygenase-1 (Ho-1) and manganese superoxide dismutase (Mnsod) following DHB pretreatment alone are also maintained in the presence of MPTP. MPTP-induced reductions in ferroportin and elevations in nigral and striatal iron levels were reverted to levels comparable with that of untreated controls with DHB pretreatment. Reductions in pyruvate dehydrogenase mRNA and activity resulting from MPTP were also found to be attenuated by DHB. In vitro, the HIF pathway was activated in N27 cells grown at 3% oxygen treated with either PHD inhibitors or an iron chelator. Concordant with our in vivo data, the MPP(+)-elicited increase in total iron as well as decreases in cell viability were attenuated in the presence of DHB. Taken together, these data suggest that protection against MPTP neurotoxicity may be mediated by alterations in iron homeostasis and defense against oxidative stress and mitochondrial dysfunction brought about by cellular HIF-1alpha induction. This study provides novel data extending the possible therapeutic utility of HIF induction to a Parkinson disease model of neurodegeneration, which may prove beneficial not only in this disorder itself but also in other diseases associated with metal-induced oxidative stress.

Biomarkers of Mn exposure in humans.

BACKGROUND: Studies have reported associations between manganese (Mn) exposures and Mn levels in blood and urine, though the suitability of these biological measures as biomarkers of exposure is not well known. METHODS: We evaluated whether whole blood, plasma, and urine Mn levels reflect exposures in occupationally exposed humans. RESULTS: In active ferroalloy workers, blood Mn was associated with total air Mn levels in subjects currently exposed to low (median = 0.42 microg/m(3), P = 0.009) and moderate (median = 4.2 microg/m(3), P = 0.007) air Mn levels, but not in workers exposed to the highest Mn levels (median = 292 microg/m(3), P = 0.31). In bridge welders blood Mn (P < 0.01), but not plasma or urine Mn was significantly associated with their cumulative respiratory exposure index. In welders, approximately 6% (range approximately 3-9%) of whole blood Mn was contained in the plasma fraction, though there was no association between whole blood and plasma Mn levels (Pearson's R = 0.258, P = 0.12). In contrast, in fresh whole blood samples spiked with Mn ex vivo approximately 80% or more of added Mn partitioned in the plasma, while only approximately 20% or less partitioned in the cellular fraction. CONCLUSIONS: These data suggest a complex and limited relationship between exposure and blood Mn levels that may depend upon exposure attributes and the latency of blood sampling relative to exposure; plasma and urine Mn appear to be of little utility as exposure biomarkers. This underscores the need to fully characterize and validate these or other biomarkers for use in constructing appropriate exposure metrics and determining exposure-effect relationships.

Adequacy and consistency of animal studies to evaluate the neurotoxicity of chronic low-level manganese exposure in humans.

The adequacy of existing animal studies to understand the effects of chronic low-level manganese exposures in humans is unclear. Here, a collection of subchronic to chronic rodent and nonhuman primate studies was evaluated to determine whether there is a consistent dose-response relationship among studies, whether there is a progression of effects with increasing dose, and whether these studies are adequate for evaluating the neurotoxicity of chronic low-level manganese exposures in humans. Neurochemical and behavioral effects were compared along the axis of estimated internal cumulative manganese dose, independent of the route of exposure. In rodents, motor effects emerged at cumulative doses below those where occupationally exposed humans start to show motor deficits. The main neurochemical effects in rodents were an increase in striatal gamma-aminobutyric acid (GABA) concentration throughout the internal cumulative dose range of 18 to 5300 mg Mn/kg but a variable effect on striatal dopamine concentration emerging at internal cumulative doses above approximately 200 mg Mn/kg. Monkey studies showed motor deficits and effects on the globus pallidus at relatively low doses and consistent harmful effects on both the globus pallidus and the caudate and putamen at higher doses (> 260 mg Mn/kg). Internal cumulative manganese doses of animal studies extend more than two orders of magnitude (< 1 to 5300 mg Mn/kg) above the doses at which occupationally exposed humans show neurological dysfunction (10-15 mg Mn/kg). Since the animal data indicate that manganese neurotoxicity may be different at low compared to elevated exposures, most existing animal model studies might be of limited relevance for the risk assessment of chronic low-level manganese exposure to humans.

Dose-effect relationships between manganese exposure and neurological, neuropsychological and pulmonary function in confined space bridge welders.

BACKGROUND: Although adverse neuropsychological and neurological health effects are well known among workers with high manganese (Mn) exposures in mining, ore-processing and ferroalloy production, the risks among welders with lower exposures are less well understood. METHODS: Confined space welding in construction of a new span of the San Francisco-Oakland Bay Bridge without adequate protection was studied using a multidisciplinary method to identify the dose-effect relationship between adverse health effects and Mn in air or whole blood. Bridge welders (n = 43) with little or no personal protection equipment and exposed to a welding fume containing Mn, were administered neurological, neuropsychological, neurophysiological and pulmonary tests. Outcome variables were analysed in relation to whole blood Mn (MnB) and a Cumulative Exposure Index (CEI) based on Mn-air, duration and type of welding. Welders performed a mean of 16.5 months of welding on the bridge, were on average 43.8 years of age and had on average 12.6 years of education. RESULTS: The mean time weighted average of Mn-air ranged from 0.11-0.46 mg/m(3) (55% >0.20 mg/m(3)). MnB >10 microg/l was found in 43% of the workers, but the concentrations of Mn in urine, lead in blood and copper and iron in plasma were normal. Forced expiratory volume at 1s: forced vital capacity ratios (FEV(1)/FVC) were found to be abnormal in 33.3% of the welders after about 1.5 years of welding at the bridge. Mean scores of bradykinesia and Unified Parkinson Disease Rating Scale exceeded 4 and 6, respectively. Computer assisted tremor analysis system hand tremor and body sway tests, and University of Pennsylvania Smell Identification Test showed impairment in 38.5/61.5, 51.4 and 88% of the welders, respectively. Significant inverse dose-effect relationships with CEI and/or MnB were found for IQ (p

Ammunition is the principal source of lead accumulated by California condors re-introduced to the wild.

The endangered California Condor (Gymnogyps californianus) was reduced to a total population of 22 birds by the end of 1982. Their captive-bred descendants are now being released back into the wild in California, Arizona, and Baja California, where monitoring indicates they may accumulate lead to toxic levels. Fragments of ammunition in the carcasses of game animals such as deer, elk, and feral pigs not retrieved by hunters or in gut piles left in the field have been considered a plausible source of the lead, though little direct evidence is available to support this hypothesis. Here, we measured lead concentrations and isotope ratios in blood from 18 condors living in the wild in central California, in 8 pre-release birds, and in diet and ammunition samples to determine the importance of ammunition as a source of exposure. Blood lead levels in pre-release condors were low (average 27.7 ng/mL, SD 4.9 ng/ mL) and isotopically similar to dietary and background environmental lead in California. In contrast, blood lead levels in free-flying condors were substantially higher (average 246 ng/mL, SD 229 ng/mL) with lead isotopic compositions that approached or matched those of the lead ammunition. A two-endmember mixing model defined by the background 207Pb/206Pb ratio of representative condor diet samples (0.8346) and the upper 207Pb/206Pb ratio of the ammunition samples (0.8184) was able to account for the blood lead isotopic compositions in 20 out of the 26 live condors sampled in this study (i.e., 77%). Finally, lead in tissues and in a serially sampled growing feather recovered postmortem from a lead-poisoned condor in Arizona evidence acute exposure from an isotopically distinct lead source. Together, these data indicate that incidental ingestion of ammunition in carcasses of animals killed by hunters is the principal source of elevated lead exposure that threatens the recovery in the wild of this endangered species.

Issues in neurological risk assessment for occupational exposures: the Bay Bridge welders.

The goal of occupational risk assessment is often to estimate excess lifetime risk for some disabling or fatal health outcome in relation to a fixed workplace exposure lasting a working lifetime. For sub-chronic or sub-clinical health effects measured as continuous variables, the benchmark dose method can be applied, but poses issues in defining impairment and in specifying acceptable levels of excess risk. Such risks may also exhibit a dose-rate effect and partial reversibility such that effects depend on how the dose is distributed over time. Neurological deficits as measured by a variety of increasingly sensitive neurobehavioral tests represent one such outcome, and the development of a parkinsonian syndrome among welders exposed to manganese fume presents a specific instance. Welders employed in the construction of piers for a new San Francisco-Oakland Bay Bridge in San Francisco were previously evaluated using a broad spectrum of tests. Results for four of those tests (Rey-Osterrieth Complex Figure Test, Working Memory Index, Stroop Color Word Test and Auditory Consonant Trigrams Test) were used in the benchmark dose procedure. Across the four outcomes analyzed, benchmark dose estimates were generally within a factor of 2.0, and decreased as the percentile of normal performance defining impairment increased. Estimated excess prevalence of impairment, defined as performance below the 5th percentile of normal, after 2 years of exposure at the current California standard (0.2 mg/m3, 8 h TWA), ranged 15-32% for the outcomes studied. Because these exposures occurred over a 1-2-year period, generalization to lifetime excess risk requires further consideration of the form of the exposure response and whether short-term responses can be generalized to equivalent 45-year period. These results indicate unacceptable risks at the current OSHA PEL for manganese (5.0 mg/m3, 15 min) and likely at the Cal OSHA PEL as well.

A noninvasive isotopic approach to estimate the bone lead contribution to blood in children: implications for assessing the efficacy of lead abatement.

Lead hazard control measures to reduce children's exposure to household lead sources often result in only limited reductions in blood lead levels. This may be due to incomplete remediation of lead sources and/or to the remobilization of lead stores from bone, which may act as an endogenous lead source that buffers reductions in blood lead levels. Here we present a noninvasive isotopic approach to estimate the magnitude of the bone lead contribution to blood in children following household lead remediation. In this approach, lead isotopic ratios of a child's blood and 5-day fecal samples are determined before and after a household intervention aimed at reducing the child's lead intake. The bone lead contribution to blood is estimated from a system of mass balance equations of lead concentrations and isotopic compositions in blood at the different times of sample collection. The utility of this method is illustrated with three cases of children with blood lead levels in the range of 18-29 microg/dL. In all three cases, the release of lead from bone supported a substantial fraction of the measured blood lead level postintervention, up to 96% in one case. In general, the lead isotopic compositions of feces matched or were within the range of the lead isotopic compositions of the household dusts with lead loadings exceeding U.S. Environmental Protection Agency action levels. This isotopic agreement underscores the utility of lead isotopic measurements of feces to identify household sources of lead exposure. Results from this limited number of cases support the hypothesis that the release of bone lead into blood may substantially buffer the decrease in blood lead levels expected from the reduction in lead intake.

Lead poisoning of seabirds: environmental risks from leaded paint at a decommissioned military base.

The sources and risk factors for lead exposure to humans are relatively well recognized, yet much less is known about lead exposure risks and effects to wildlife. Here we utilized lead isotopic fingerprinting to investigate sources of elevated lead exposure to Laysan albatross (Phoebastria immutabilis) chicks in the Midway Island National Wildlife Refuge, which was established on the site of a decommissioned military base that previously had undergone lead remediation. Whole blood from chicks as well as soil and paint chips from the chicks' nests were collected from birds nesting close to (<5 m, building site) and distant from (>100 m, reference site) buildings and analyzed for lead levels and isotopic compositions using magnetic sector ICP-MS. Blood lead levels of chicks from the building site had a geometric mean of 190 microg/dL (average = 320 +/- 310 SD, range = 6.8-1400, n = 21) as compared to 4.5 microg/dL (average = 6.0 +/- 4.2 SD, range = 1.2-13, n = 15) in chicks from the reference site. Nest soil lead levels from both sites were similar and relatively low (0.05-11 microg/g) unless visibly contaminated with paint chips (building site). Isotopic analyses confirmed that leaded paint was the source of lead poisoning in these chicks and showed that the pathway of exposure was via direct ingestion of paint chips and not through contaminated soil. This study found continued risk to wildlife and possibly humans from lead hazards in a wildlife refuge established on a decommissioned military base. In addition, this study demonstrates the utility of lead isotopes to identify environmental lead hazards and exposure pathways to wildlife.