Global event-based surveillance of chemical incidents.

BACKGROUND: The number of chemicals in our society and in our daily lives continues to increase. Accompanying this is an increasing risk of human exposure to and injury from hazardous substances. Performing regular, structured surveillance of chemical incidents allows a greater awareness of the types of chemical hazards causing injury and the frequency of their occurrence, as well as providing a better understanding of exposures. OBJECTIVE: The objective of performing event-based surveillance (EBS) and capturing chemical incidents is to use this information to increase the situational awareness of chemical incidents, improve the management of these incidents and to inform measures to protect public health. METHODS: This paper describes a method for EBS for chemical incidents, including the sources used, storing the gathered information and subsequent analysis of potential trends in the data. RESULTS: We describe trends in the type of incidents that have been detected, the chemicals involved in these incidents and the health effects caused, in different geographic regions of the world. SIGNIFICANCE: The methodology presented here provides a rapid and simple means of identifying chemical incidents that can be set up rapidly and with minimal cost, the outputs of which can be used to identify emerging risks and inform preparedness planning, response and training for chemical incidents.

Development of a mechanism for the rapid risk assessment of cross-border chemical health threats.

BACKGROUND: Chemical incidents can result in harm to public health and the environment. Although most are localised and have little impact, some affect wide areas, a range of sectors and may lead to many casualties. A public health response to assess the risks and provide advice to authorities and the public is usually required. In some cases, incidents may affect more than one country and require effective cross-border communication and coordination. OBJECTIVE: We describe tools and mechanisms to improve health security from cross-border chemical health threats and to support the implementation of the Decision of the European Parliament and the Council of the European Union (EU) on serious cross-border threats to health (Decision 1082/2013/EU). METHODS: Experts were recruited to a network and their suitability was assessed by using a skills framework. Input by relevant stakeholders such as the World Health Organisation and the European Centre for Disease Prevention and Control, followed by EU-wide exercises, ensured that tools developed were fit for purpose. RESULTS: A network of public health risk assessors and a methodology for providing rapid independent expert public health advice during a chemical emergency have been developed. SIGNIFICANCE: We discuss the legacy of these mechanisms including their incorporation into the working arrangements for the EU Scientific Committee for Health, Environment and Emerging Risks and future developments in the field.

Development of a new categorization system for pesticides exposure to support harmonized reporting between EU Member States.

OBJECTIVES: European legislation requires reporting from Member States on acute poisoning incidents involving pesticides. However, standard rules for data collection and reporting have not yet been set out. The new categorization system presented in this paper is aimed at enabling Member States to gather comparable data and provide standard reporting on pesticide poisoning exposures. MATERIALS AND METHODS: European Regulations providing separate official categorization of biocidal and plant protection pesticides, were used as a basis to build up a unified pesticide categorization and coding system. Data on selected pesticide exposures collected by Poison Control Centres in six EU countries were reviewed, categorized and reported according to the proposed system. RESULTS: The resulting pesticide categorization system has two dimensions. The first part identifies the main category of use, i.e. biocide/plant protection pesticide/unknown, and the secondary category of use, e.g. Rodenticides, Insecticides and acaricides. The second part of the system is organized into two levels: level one identifies chemical grouping, e.g. Coumarins, Pyrethrins/pyrethroids, while level two identifies the active compound by using its Chemical Abstract Service Registry Number. The system was used to provide a unified categorization to compare exposures to plant protection and biocidal Rodenticides and Pyrethrins/pyrethroids Insecticides and acaricides identified by six EU member states. CONCLUSION: The developed pesticide categorization system was successfully applied to data extracted from different databases and was able to make the required information comparable. The data reported filling in common templates containing a pre-ordinate list of active compounds categorized according the proposed system, highlighted different capabilities in data collection and recording, showing that some of the collaborating centres were not able to distinguish between main categories of pesticide products or provide information on active compounds. The results indicate that a special effort should be dedicated to support detailed data recording at national level. Providing common tools to systematically report to the EU Commission hazardous exposures to pesticides, as well as to other selected categories of products, could allow for data comparability between Member States and greatly improve post marketing surveillance and alerting systems in Europe.

Modulation of triglyceride and cholesterol ester synthesis impairs assembly of infectious hepatitis C virus.

In hepatitis C virus infection, replication of the viral genome and virion assembly are linked to cellular metabolic processes. In particular, lipid droplets, which store principally triacylglycerides (TAGs) and cholesterol esters (CEs), have been implicated in production of infectious virus. Here, we examine the effect on productive infection of triacsin C and YIC-C8-434, which inhibit synthesis of TAGs and CEs by targeting long-chain acyl-CoA synthetase and acyl-CoA:cholesterol acyltransferase, respectively. Our results present high resolution data on the acylglycerol and cholesterol ester species that were affected by the compounds. Moreover, triacsin C, which blocks both triglyceride and cholesterol ester synthesis, cleared most of the lipid droplets in cells. By contrast, YIC-C8-434, which only abrogates production of cholesterol esters, induced an increase in size of droplets. Although both compounds slightly reduced viral RNA synthesis, they significantly impaired assembly of infectious virions in infected cells. In the case of triacsin C, reduced stability of the viral core protein, which forms the virion nucleocapsid and is targeted to the surface of lipid droplets, correlated with lower virion assembly. In addition, the virus particles that were released from cells had reduced specific infectivity. YIC-C8-434 did not alter the association of core with lipid droplets but appeared to decrease production of infectious virus particles, suggesting a block in virion assembly. Thus, the compounds have antiviral properties, indicating that targeting synthesis of lipids stored in lipid droplets might be an option for therapeutic intervention in treating chronic hepatitis C virus infection.

Cell cycle dependent changes in membrane stored curvature elastic energy: evidence from lipidomic studies.

One of the most developed theories of phospholipid homeostasis is the intrinsic curvature hypothesis, which, in broad terms, postulates that cells regulate their lipid composition so as to keep constant the membrane stored curvature elastic energy. The implication of this hypothesis is that lipid composition is determined by a ratio control function consisting of the weighted sum of concentrations of type II lipids in the numerator and the weighted sum of concentrations of Type 0 lipids in the denominator. In previous work we used a data-driven approach, based on lipidomic data from asynchronous cell cultures, to determine a criterion that allows the different lipid species to be assigned to the set of type 0 or of type II lipids, and hence construct a ratio control function that serves as a proxy for the lipid contribution to total membrane stored curvature elastic energy in vivo. Here we apply the curvature elastic energy proxy to the analysis of lipid composition data from synchronous HeLa cells as they traverse the cell cycle. Our analysis suggests HeLa cells modify their membrane stored elastic energy through the cell cycle. In S-phase type 0 lipids are the most abundant, whilst in G2 type II lipids are most abundant. Changes in our proxy for membrane stored elastic energy correlate with membrane curvature dependent processes in the HeLa cell around division, providing some insights into the interplay between the individual lipid and protein contributions to membrane free energy.

An in vivo ratio control mechanism for phospholipid homeostasis: evidence from lipidomic studies.

While it is widely accepted that the lipid composition of eukaryotic membranes is under homeostatic control, the mechanisms through which cells sense lipid composition are still the subject of debate. It has been postulated that membrane curvature elastic energy is the membrane property that is regulated by cells, and that lipid composition is maintained by a ratio control function derived from the concentrations of type II and type 0 lipids, weighted appropriately. We assess this proposal by seeking a signature of ratio control in quantified lipid composition data obtained by electrospray ionization mass spectrometry from over 40 independent asynchronous cell populations. Our approach revealed the existence of a universal 'pivot' lipid, which marks the boundary between type 0 lipids and type II lipids, and which is invariant between different cell types or cells grown under different conditions. The presence of such a pivot species is a distinctive signature of the operation in vivo, in human cell lines, of a control function that is consistent with the hypothesis that membrane elastic energy is homeostatically controlled.