Assessment of the Mitigative Capacity of Dietary Zinc on PCB126 Hepatotoxicity and the Contribution of Zinc to Toxicity.

Hepatic levels of the essential micronutrient, zinc, are diminished by several hepatotoxicants, and the dietary supplementation of zinc has proven protective in those cases. 3,3',4,4',5-Pentachlorobiphenyl (PCB126), a liver toxicant, alters hepatic nutrient homeostasis and lowers hepatic zinc levels. The current study was designed to determine the mitigative potential of dietary zinc in the toxicity associated with PCB126 and the role of zinc in that toxicity. Male Sprague-Dawley rats were divided into three dietary groups and fed diets deficient in zinc (7 ppm Zn), adequate in zinc (30 ppm Zn), and supplemented in zinc (300 ppm). The animals were maintained for 3 weeks on these diets, then given a single IP injection of vehicle or 1 or 5 µmol/kg PCB126. After 2 weeks, the animals were euthanized. Dietary zinc increased the level of ROS, the activity of CuZnSOD, and the expression of metallothionein but decreased the levels of hepatic manganese. PCB126 exposed rats exhibited classic signs of exposure, including hepatomegaly, increased hepatic lipids, increased ROS and CYP induction. Liver histology suggests some mild ameliorative properties of both zinc deficiency and zinc supplementation. Other metrics of toxicity (relative liver and thymus weights, hepatic lipids, and hepatic ROS) did not support this trend. Interestingly, the zinc supplemented high dose PCB126 group had mildly improved histology and less efficacious induction of investigated genes than did the low dose PCB126 group. Overall, decreases in zinc caused by PCB126 likely contribute little to the ongoing toxicity, and the mitigative/preventive capacity of zinc against PCB126 exposure seems limited.

Uncontrolled combustion of shredded tires in a landfill - Part 1: Characterization of gaseous and particulate emissions.

In summer 2012, a landfill liner comprising an estimated 1.3 million shredded tires burned in Iowa City, Iowa. During the fire, continuous monitoring and laboratory measurements were used to characterize the gaseous and particulate emissions and to provide new insights into the qualitative nature of the smoke and the quantity of pollutants emitted. Significant enrichments in ambient concentrations of CO, CO2, SO2, particle number (PN), fine particulate (PM2.5) mass, elemental carbon (EC), and polycyclic aromatic hydrocarbons (PAH) were observed. For the first time, PM2.5 from tire combustion was shown to contain PAH with nitrogen heteroatoms (a.k.a. azaarenes) and picene, a compound previously suggested to be unique to coal-burning. Despite prior laboratory studies' findings, metals used in manufacturing tires (i.e. Zn, Pb, Fe) were not detected in coarse particulate matter (PM10) at a distance of 4.2 km downwind. Ambient measurements were used to derive the first in situ fuel-based emission factors (EF) for the uncontrolled open burning of tires, revealing substantial emissions of SO2 (7.1 g kg-1), particle number (3.5×1016 kg-1), PM2.5 (5.3 g kg-1), EC (2.37 g kg-1), and 19 individual PAH (totaling 56 mg kg-1). A large degree of variability was observed in day-to-day EF, reflecting a range of flaming and smoldering conditions of the large-scale fire, for which the modified combustion efficiency ranged from 0.85-0.98. Recommendations for future research on this under-characterized source are also provided.

Does dietary copper supplementation enhance or diminish PCB126 toxicity in the rodent liver?

Copper is essential for the function of the mitochondrial electron transport chain and several antioxidant proteins. However, in its free form copper can participate in Fenton-like reactions that produce reactive hydroxyl radicals. Aryl-hydrocarbon receptor (AhR) agonists, including the most potent polychlorinated biphenyl (PCB) congener, 3,3',4,4',5-pentachlorobiphenyl (PCB126), increase copper levels in rodent livers. This is accompanied by biochemical and toxic changes. To assess the involvement of copper in PCB toxicity, male Sprague-Dawley rats were fed an AIN-93G diet with differing dietary copper levels: low (2 ppm), adequate (6 ppm), and high (10 ppm). After three weeks, rats from each group were given a single ip injection of corn oil (control), 1, or 5 µmol/kg body weight PCB126. Two weeks following injections, biochemical and morphological markers of hepatic toxicity, trace metal status, and hepatic gene expression of metalloproteins were evaluated. Increasing dietary copper was associated with elevated tissue levels of copper and ceruloplasmin. In the livers of PCB126-treated rats, the hallmark signs of AhR activation were present, including increased cytochrome P450 and lipid levels and decreased glutathione. In addition, a doubling of hepatic copper levels was seen, and overall metal homeostasis was disturbed, resulting in decreased hepatic selenium, manganese, zinc, and iron. Expression of key metalloproteins was either decreased (cytochrome c oxidase), unchanged (ceruloplasmin and CuZnSOD), or increased (tyrosinase and metallothioneins 1 and 2) with exposure to PCB126. Increases in metallothionein may contribute/reflect the increased copper seen. Alterations in dietary copper did not amplify or abrogate the hepatic toxicity of PCB126. PCB126 toxicity, i.e., oxidative stress and steatosis, is clearly associated with disturbed metal homeostasis. Understanding the mechanisms of this disturbance may provide tools to prevent liver toxicity by other AhR agonists.

Correction: High prevalence of elevated blood lead levels in both rural and urban Iowa newborns: Spatial patterns and area-level covariates.

[This corrects the article DOI: 10.1371/journal.pone.0177930.].

Toxic metals in ayurvedic preparations from a public health lead poisoning cluster investigation.

Background Herbal formulations, traditional medicine, and complementary and alternative medicine are used by the majority of the world's population. Toxicity associated with use of Ayurvedic products due to metal content is an increasingly recognized potential public health problem. Objectives Report on toxic metals content of Ayurvedic products obtained during an investigation of lead poisoning among users of Ayurvedic medicine. Methods Samples of Ayurvedic formulations were analyzed for metals and metalloids following established US. Environmental Protection Agency methods. Results Lead was found in 65% of 252 Ayurvedic medicine samples with mercury and arsenic found in 38 and 32% of samples, respectively. Almost half of samples containing mercury, 36% of samples containing lead and 39% of samples containing arsenic had concentrations of those metals per pill that exceeded, up to several thousand times, the recommended daily intake values for pharmaceutical impurities. Conclusions Lack of regulations regarding manufacturing and content or purity of Ayurvedic and other herbal formulations poses a significant global public health problem.

High prevalence of elevated blood lead levels in both rural and urban Iowa newborns: Spatial patterns and area-level covariates.

Lead in maternal blood can cross the placenta and result in elevated blood lead levels in newborns, potentially producing negative effects on neurocognitive function, particularly if combined with childhood lead exposure. Little research exists, however, into the burden of elevated blood lead levels in newborns, or the places and populations in which elevated lead levels are observed in newborns, particularly in rural settings. Using ~2300 dried bloods spots collected within 1-3 days of birth among Iowa newborns, linked with the area of mother's residence at the time of birth, we examine the spatial patterns of elevated (>5 µg/dL) blood lead levels and the ecological-level predictors of elevated blood lead levels. We find that one in five newborns exceed the 5 µg/dL action level set by the US Centers for Disease Control & Prevention (CDC). Bayesian spatial zero inflated regression indicates that elevated blood lead in newborns is associated with areas of increased pre-1940s housing and childbearing-age women with low educational status in both rural and urban settings. No differences in blood lead levels or the proportion of children exceeding 5 µg/dL are observed between urban and rural maternal residence, though a spatial cluster of elevated blood lead is observed in rural counties. These characteristics can guide the recommendation for testing of infants at well-baby appointments in places where risk factors are present, potentially leading to earlier initiation of case management. The findings also suggest that rural populations are at as great of risk of elevated blood lead levels as are urban populations. Analysis of newborn dried blood spots is an important tool for lead poisoning surveillance in newborns and can direct public health efforts towards specific places and populations where lead testing and case management will have the greatest impact.

Dietary Manganese Modulates PCB126 Toxicity, Metal Status, and MnSOD in the Rat.

PCB126 (3,3',4,4',5-pentachlorobiphenyl) is a potent aryl hydrocarbon receptor agonist and induces oxidative stress. Because liver manganese (Mn) levels decrease in response to PCB126, a Mn dietary study was designed to investigate the role of Mn in PCB126 toxicity. Male Sprague Dawley rats received diets containing 0, 10, or 150 ppm added Mn for 3 weeks, followed by a single ip injection of corn oil or PCB126 (5 µmol/kg body weight). After 2 weeks, Mn, Cu, Zn, and Fe levels in the heart, liver, and liver mitochondria, and Mn-containing superoxide dismutase (MnSOD) and metallothionein mRNA, MnSOD protein, and MnSOD activity were determined. Mn levels in liver, heart, and liver mitochondria were strongly decreased by the Mn-deficient diet. Small effects on Fe levels and a stepwise increase in MnSOD activity with dietary Mn were also visible. PCB126 caused profound changes in Cu (up), Zn, Fe, and Mn (down) in liver, but not in heart, and differing effects (Cu, Zn, and Fe up, Mn down) in liver mitochondria. Liver MnSOD and metallothionein mRNA levels and MnSOD protein were increased but MnSOD activity was decreased by PCB126. PCB126-induced liver enlargement was dose-dependently reduced with increasing dietary Mn. These changes in metals homeostasis and MnSOD activity in liver but not heart may be a/the mechanism of PCB126 liver-specific toxicity. Specifically, transport of Fenton metals (Cu, Fe) into and Mn out of the mitochondria, a probable mechanism for lower MnSOD activity, may be a/the cause of PCB126-induced oxidative stress. The role of metallothioneins needs further evaluation. Dietary Mn slightly alleviated PCB126-induced toxicities.