Workgroup Report: Review of Fish Bioaccumulation Databases Used to Identify Persistent, Bioaccumulative, Toxic Substances

Chemical management programs strive to protect human health and the environment by accurately identifying persistent, bioaccumulative, toxic substances and restricting their use in commerce. The advance of these programs is challenged by the reality that few empirical data are available for the tens of thousands of commercial substances that require evaluation. Therefore, most preliminary assessments rely on model predictions and data extrapolation. In November 2005, a workshop was held for experts from governments, industry, and academia to examine the availability and quality of in vivo fish bioconcentration and bioaccumulation data, and to propose steps to improve its prediction. The workshop focused on fish data because regulatory assessments predominantly focus on the bioconcentration of substances from water into fish, as measured using in vivo tests or predicted using computer models. In this article we review of the quantity, features, and public availability of bioconcentration, bioaccumulation, and biota–sediment accumulation data. The workshop revealed that there is significant overlap in the data contained within the various fish bioaccumulation data sources reviewed, and further, that no database contained all of the available fish bioaccumulation data. We believe that a majority of the available bioaccumulation data have been used in the development and testing of quantitative structure–activity relationships and computer models currently in use. Workshop recommendations included the publication of guidance on bioconcentration study quality, the combination of data from various sources to permit better access for modelers and assessors, and the review of chemical domains of existing models to identify areas for expansion

Causative factors behind poloxamer 188 (Pluronic F68, Flocor™)-induced complement activation in human sera A protective role against poloxamer-mediated complement activation by elevated serum lipoprotein levels

AbstractPoloxamer 188 is a complex polydisperse mixture of non-ionic macromolecules. Adverse non-IgE-mediated hypersensitivity reactions occur in some individuals following intravenous injection of poloxamer 188-based pharmaceuticals, presumably via complement activation. Here we have delineated potential causal chemical and biological interactive factors behind poloxamer 188-induced complement activation in human serum specimens. We identified the molecular constituents inherent in poloxamer 188 preparations and studied their effect on generation of the two complement split products, SC5b-9 and Bb. Poloxamer 188 activated complement at sub-micellar concentrations and the results indicated the potential involvement of all three known complement activation pathways. The poloxamer-induced rise of SC5b-9 in human sera was abolished in the presence of a recombinant truncated soluble form of complement receptor type 1, thus confirming the role of C3/C5 convertases in the activation process. Poloxamer 188-mediated complement activation is an intrinsic property of these macromolecules and was independent of the degree of sample polydispersity, as opposed to other non-polymeric constituents. Poloxamer 188 preparations also contained unsaturated chains of diblock copolymers capable of generating SC5b-9 in human sera; this effect was terminated following the removal of double bonds by catalytic hydrogenation. By quasi-elastic light scattering, we established interaction between poloxamer and lipoproteins; interestingly, poloxamer-induced rise in SC5b-9 was significantly suppressed when serum HDL and LDL cholesterol levels were increased above normal to mimic two relevant clinical situations. This observation was consistent with previously reported data from patients with abnormal or elevated lipid profiles where no or poor complement activation by poloxamer 188 occurred. Our findings could provide the basis of novel approaches to the prevention of poloxamer-mediated complement activation

Interdisciplinary progress in approaches to address social-ecological and ecocultural systems

SUMMARYThe emergent human cultures have shaped, and in turn been shaped by, local ecosystems. Yet humanity's intense modification of the environment has resulted in dramatic worldwide declines in natural and cultural capital. Social-ecological systems are becoming more vulnerable through the disruption of livelihoods, governance, institutions, resources and cultural traditions. This paper reviews the environmental sub-disciplines that have emerged to seek solutions for conservation and maintenance of the resilience of social-ecological systems. It shows that a central component is engagement with the knowledges of people within their contexts. Local knowledges of nature (traditional, indigenous, local ecological knowledge and ecoliteracy) are used by place-based cultures to guide actions towards nature. The importance of new engagements between different knowledges is now becoming more widely recognized by scientific institutions. Yet there still exist many false dualisms (for example local knowledge versus science) which tend to emphasize a superiority of one over the other. Ecocultures retain or strive to regain their connections with the environment, and thus improve their own resilience. Revitalization projects offer ways to connect knowledge with action to produce optimal outcomes for both nature and culture, suggesting that systems can be redesigned by emphasis on incorporation of local and traditional knowledge systems.</jats:p

Ventricular Dysrhythmias Associated with Poisoning and Drug Overdose: A 10-Year Review of Statewide Poison Control Center Data from California

Background: Ventricular dysrhythmias are a serious consequence associated with drug overdose and chemical poisoning. The risk factors for the type of ventricular dysrhythmia and the outcomes by drug class are not well documented. Objective: The aim of this study was to determine the most common drugs and chemicals associated with ventricular dysrhythmias and their outcomes. Methods: We reviewed all human exposures reported to a statewide poison control system between 2002 and 2011 that had a documented ventricular dysrhythmia. Cases were differentiated into two groups by type of arrhythmia: (1) ventricular fibrillation and/or tachycardia (VT/VF); and (2) torsade de pointes (TdP). Results: Among the 300 potential cases identified, 148 cases met the inclusion criteria. Of these, 132 cases (89&nbsp;%) experienced an episode of VT or VF, while the remaining 16 cases (11&nbsp;%) had an episode of TdP. The most commonly involved therapeutic classes of drugs associated with VT/VF were antidepressants (33/132, 25&nbsp;%), stimulants (33/132, 25&nbsp;%), and diphenhydramine (16/132, 12.1&nbsp;%). Those associated with TdP were antidepressants (4/16, 25&nbsp;%), methadone (4/16, 25&nbsp;%), and antiarrhythmics (3/16, 18.75&nbsp;%). Drug exposures with the greatest risk of death in association with VT/VF were antidepressant exposure [odds ratio (OR) 1.71; 95&nbsp;% confidence interval (CI) 0.705–4.181] and antiarrhythmic exposure (OR 1.75; 95&nbsp;% CI 0.304–10.05), but neither association was statistically significant. Drug exposures with a statistically significant risk for TdP included methadone and antiarrhythmic drugs. Conclusions: Antidepressants and stimulants were the most common drugs associated with ventricular dysrhythmias. Patients with suspected poisonings by medications with a high risk of ventricular dysrhythmia warrant prompt ECG monitoring

Ventricular dysrhythmias associated with poisoning and drug overdose: a 10-year review of statewide poison control center data from California.

BackgroundVentricular dysrhythmias are a serious consequence associated with drug overdose and chemical poisoning. The risk factors for the type of ventricular dysrhythmia and the outcomes by drug class are not well documented.ObjectiveThe aim of this study was to determine the most common drugs and chemicals associated with ventricular dysrhythmias and their outcomes.MethodsWe reviewed all human exposures reported to a statewide poison control system between 2002 and 2011 that had a documented ventricular dysrhythmia. Cases were differentiated into two groups by type of arrhythmia: (1) ventricular fibrillation and/or tachycardia (VT/VF); and (2) torsade de pointes (TdP).ResultsAmong the 300 potential cases identified, 148 cases met the inclusion criteria. Of these, 132 cases (89%) experienced an episode of VT or VF, while the remaining 16 cases (11%) had an episode of TdP. The most commonly involved therapeutic classes of drugs associated with VT/VF were antidepressants (33/132, 25%), stimulants (33/132, 25%), and diphenhydramine (16/132, 12.1%). Those associated with TdP were antidepressants (4/16, 25%), methadone (4/16, 25%), and antiarrhythmics (3/16, 18.75%). Drug exposures with the greatest risk of death in association with VT/VF were antidepressant exposure [odds ratio (OR) 1.71; 95% confidence interval (CI) 0.705-4.181] and antiarrhythmic exposure (OR 1.75; 95% CI 0.304-10.05), but neither association was statistically significant. Drug exposures with a statistically significant risk for TdP included methadone and antiarrhythmic drugs.ConclusionsAntidepressants and stimulants were the most common drugs associated with ventricular dysrhythmias. Patients with suspected poisonings by medications with a high risk of ventricular dysrhythmia warrant prompt ECG monitoring

Bioconcentration and Aquatic Toxicity of Superhydrophobic Chemicals: A Modeling Case Study of Cyclic Volatile Methyl Siloxanes

Many chemicals in commerce are classified as “superhydrophobic”, having log octanol–water partition coefficients (log <i>K</i>_OW) approaching or exceeding 7. Examples include long-chain alkanes, halogenated aromatics, and cyclic volatile methylsiloxanes (cVMS). We show that superhydrophobic chemicals present unique assessment challenges because of their sparing solubility in water and difficulties in empirical determinations of bioconcentration factors (BCFs) and aquatic toxicity. Using cVMS as an example, BCFs are considerably lower than expected due to biotransformation. Reviewed aquatic toxicity test data for cVMS in a range of aquatic organisms show little or no toxic effects up to solubility limits in water and sediment. Explanations for this apparent lack of toxicity of cVMS, and by extension to other superhydrophobic chemicals, are explored using a conventional one-compartment uptake model to simulate bioconcentration and toxicity tests using an assumed baseline narcotic critical body residue (CBR) and a range of organism sizes. Because of the low aqueous concentrations, equilibration times are very long and BCFs are sensitive to even very slow rates of biotransformation. Most organisms fail to achieve the assumed CBR during feasible test durations even at the solubility limit. Regulatory evaluation of superhydrophobic substances requires specially designed test protocols addressing biotransformation and dietary uptake