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Aluminum (Al) is a ubiquitous substance encountered both naturally (as the third most abundant element) and intentionally (used in water, foods, pharmaceuticals, and vaccines); it is also present in ambient and occupational airborne particulates. Existing data underscore the importance of Al physical and chemical forms in relation to its uptake, accumulation, and systemic bioavailability.Address for correspondence: Calvin C. Willhite, Risk Sciences International, 55 Metcalfe Street, Suite 700, Ottawa, ON, Canada. calvinwillhite@hotmail.com. Declaration of interestPartial funding for this work was provided by a contract to review the recent scientific literature on health effects of aluminum between the International Aluminium Institute (IAI, www.world-aluminium.org), the Aluminium Reach Consortium (ARC, www.aluminium-reach-consortium.eu), and Risk Sciences International (RSI, www.risksciences.com), a Canadian company established in 2006 in partnership with the University of Ottawa. Additional financial support was provided by the Natural Sciences and Engineering Research Council of Canada (NSERC) to D. Krewski, who holds the NSERC Chair in Risk Science at the University of Ottawa. C.C. Willhite, N.A. Karyakina, F. Momoli, and N. Yenugadhati were compensated by RSI for their contributions to the review. I. Arnold, T. Wisniewski and R. Yokel received no compensation from RSI for their contributions to this work. The authors, whose affiliations are shown on the title page, had sole responsibility for preparation of this paper, including determining the strategy for reviewing the scientific literature summarized in this article, synthesizing the findings, and drawing conclusions. Scientists associated with IAI/ARC were given the opportunity to review and offer technical comments on the paper, prior to submission to Critical Reviews in Toxicology. I. Arnold serves as a consultant to the International Aluminium Institute. None of the authors have appeared before regulatory agencies on behalf of the sponsors, or appeared as experts in legal proceedings concerning matters reviewed in this paper. The scientific opinions and conclusions expressed in the paper are exclusively those of the authors, and are independent of the sources of financial support. HHS Public Access Author Manuscript Author ManuscriptAuthor Manuscript Author ManuscriptThe present review represents a systematic examination of the peer-reviewed literature on the adverse health effects of Al materials published since a previous critical evaluation compiled by Krewski et al. (2007). The scientific literature on the adverse health effects of Al is extensive. Health risk assessments for Al must take into account individual co-factors (e.g., age, renal function, diet, gastric pH). Conclusions from the current review point to the need for refinement of the PTWI, reduction of Al contamination in PN solutions, justification for routine addition of Al to vaccines, and harmonization of OELs for Al substances.

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Rats learned to press a lever for intravenous injections of amphetamine or apomorphine. They also learned to avoid the taste of saccharin which was associated with experimenter-administered amphetamine or with self-administered apomorphine. Thus these, and presumably other, self-administered drugs serve as compound pharmacological stimuli, having both positively reinforcing and aversive properties.

Nanoceria is used as a catalyst in diesel fuel, as an abrasive in printed circuit manufacture, and is being pursued as an antioxidant therapeutic. Our objective is to extend previous findings showing that there were no reductions of cerium in organs of the mononuclear phagocyte (reticuloendothelial) system up to 30 days after a single nanoscale ceria administration. An ~5% aqueous dispersion of citrate-stabilized 30 nm ceria, synthesized and characterized in-house, or vehicle, was iv infused into rats terminated 1, 7, 30, or 90 days later. Cageside observations were obtained daily, body weight weekly. Daily urinary and fecal cerium outputs were quantified for 2 weeks. Nine organs were weighed and samples collected from 14 tissues/organs/systems, blood and cerebrospinal fluid for cerium determination. Histology and oxidative stress were assessed. Less than 1% of the nanoceria was excreted in the first 2 weeks, 98% in feces. Body weight gain was initially impaired. Spleen weight was significantly increased in some ceria-treated groups, associated with abnormalities. Ceria was primarily retained in the spleen, liver, and bone marrow. There was little decrease of ceria in any tissue over the 90 days. Granulomas were observed in the liver. Time-dependent oxidative stress changes were seen in the liver and spleen. Nanoscale ceria was persistently retained by organs of the mononuclear phagocyte system, associated with adverse changes. The results support concern about the long-term fate and adverse effects of inert nanoscale metal oxides that distribute throughout the body, are persistently retained, and produce adverse changes.