Knowns and unknowns on burden of disease due to chemicals: a systematic review.

BACKGROUND: Continuous exposure to many chemicals, including through air, water, food, or other media and products results in health impacts which have been well assessed, however little is known about the total disease burden related to chemicals. This is important to know for overall policy actions and priorities. In this article the known burden related to selected chemicals or their mixtures, main data gaps, and the link to public health policy are reviewed. METHODS: A systematic review of the literature for global burden of disease estimates from chemicals was conducted. Global disease due to chemicals was estimated using standard methodology of the Global Burden of Disease. RESULTS: In total, 4.9 million deaths (8.3% of total) and 86 million Disability-Adjusted Life Years (DALYs) (5.7% of total) were attributable to environmental exposure and management of selected chemicals in 2004. The largest contributors include indoor smoke from solid fuel use, outdoor air pollution and second-hand smoke, with 2.0, 1.2 and 0.6 million deaths annually. These are followed by occupational particulates, chemicals involved in acute poisonings, and pesticides involved in self-poisonings, with 375,000, 240,000 and 186,000 annual deaths, respectively. CONCLUSIONS: The known burden due to chemicals is considerable. This information supports decision-making in programmes having a role to play in reducing human exposure to toxic chemicals. These figures present only a number of chemicals for which data are available, therefore, they are more likely an underestimate of the actual burden. Chemicals with known health effects, such as dioxins, cadmium, mercury or chronic exposure to pesticides could not be included in this article due to incomplete data and information. Effective public health interventions are known to manage chemicals and limit their public health impacts and should be implemented at national and international levels.

Mass lead intoxication from informal used lead-acid battery recycling in dakar, senegal.

BACKGROUND AND OBJECTIVES: Between November 2007 and March 2008, 18 children died from a rapidly progressive central nervous system disease of unexplained origin in a community involved in the recycling of used lead-acid batteries (ULAB) in the suburbs of Dakar, Senegal. We investigated the cause of these deaths. METHODS: Because autopsies were not possible, the investigation centered on clinical and laboratory assessments performed on 32 siblings of deceased children and 23 mothers and on 18 children and 8 adults living in the same area, complemented by environmental health investigations. RESULTS: All 81 individuals investigated were poisoned with lead, some of them severely. The blood lead level of the 50 children tested ranged from 39.8 to 613.9 microg/dL with a mean of 129.5 microg/dL. Seventeen children showed severe neurologic features of toxicity. Homes and soil in surrounding areas were heavily contaminated with lead (indoors, up to 14,000 mg/kg; outdoors, up to 302,000 mg/kg) as a result of informal ULAB recycling. CONCLUSIONS: Our investigations revealed a mass lead intoxication that occurred through inhalation and ingestion of soil and dust heavily contaminated with lead as a result of informal and unsafe ULAB recycling. Circumstantial evidence suggested that most or all of the 18 deaths were due to encephalopathy resulting from severe lead intoxication. Findings also suggest that most habitants of the contaminated area, estimated at 950, are also likely to be poisoned. This highlights the severe health risks posed by informal ULAB recycling, in particular in developing countries, and emphasizes the need to strengthen national and international efforts to address this global public health problem.

Cell uptake and radiotoxicity studies of an nuclear localization signal peptide-intercalator conjugate labeled with [99mTc(CO)3]+.

A trifunctional bioconjugate consisting of the SV40 nuclear localization signal (NLS) peptide, an aliphatic triamine ligand, and the DNA intercalating pyrene has been synthesized and quantitatively labeled with [(99m)Tc(OH(2))(3)(CO)(3)](+). The radiotoxicity of the resulting nucleus-targeting radiopharmaceutical on B16F1 mouse melanoma cells has been investigated to evaluate the activity of Auger and Coster-Kronig electrons on the viability of cells. We found a dose-dependent significant radiotoxicity of the nucleus-targeting radiopharmaceutical clearly related to the low energy decay of (99m)Tc. These principal results imply a possible therapeutic strategy based on the use of the low-energy Auger electron-emitting (99m)Tc radionuclide attached to nucleus-targeting molecules and comprising an intercalator. Highly efficient DNA targeting vectors could complement the usual role of (99m)Tc in diagnostic applications. The Auger electrons emitted by the (99m)Tc nuclide induce DNA damage leading ultimately, through a mitotic catastrophe pathway, to necrotic cell death. Non-DNA-targeting (99m)Tc complexes display much lower radiotoxicity.