Evaluating Evidence for Association of Human Bladder Cancer with Drinking-Water Chlorination Disinfection By-Products

Exposure to chlorination disinfection by-products (CxDBPs) is prevalent in populations using chlorination-based methods to disinfect public water supplies. Multifaceted research has been directed for decades to identify, characterize, and understand the toxicology of these compounds, control and minimize their formation, and conduct epidemiologic studies related to exposure. Urinary bladder cancer has been the health risk most consistently associated with CxDBPs in epidemiologic studies. An international workshop was held to (1) discuss the qualitative strengths and limitations that inform the association between bladder cancer and CxDBPs in the context of possible causation, (2) identify knowledge gaps for this topic in relation to chlorine/chloramine-based disinfection practice(s) in the United States, and (3) assess the evidence for informing risk management. Epidemiological evidence linking exposures to CxDBPs in drinking water to human bladder cancer risk provides insight into causality. However, because of imprecise, inaccurate, or incomplete estimation of CxDBPs levels in epidemiologic studies, translation from hazard identification directly to risk management and regulatory policy for CxDBPs can be challenging. Quantitative risk estimates derived from toxicological risk assessment for CxDBPs currently cannot be reconciled with those from epidemiologic studies, notwithstanding the complexities involved, making regulatory interpretation difficult. Evidence presented here has both strengths and limitations that require additional studies to resolve and improve the understanding of exposure response relationships. Replication of epidemiologic findings in independent populations with further elaboration of exposure assessment is needed to strengthen the knowledge base needed to better inform effective regulatory approaches

Novel toxicity associated with a Limnothrix-like species : mouse bioassay results

Background & Aims: A search for novel cylindrospermopsin (CYN) producers found a Limnothrix strain that inhibited protein synthesis but did not contain detectable CYN or analogues (HPLC, LC-MS, ELISA), nor the CYN gene (Bernard et al 2010). Methods: Mouse bioassays (time-course up to seven days, and set times up to 24h) were performed followed by detailed post-mortem (PM) dissections and histopathology. By 3h, these reduced but clear mucoid diarrhoea (containing sloughed endothelium and blood cells) was observed. Body weights were reduced by 24h and remained below controls for 7d. Liver and spleen weights (% body weight) increased by 4h and remained high until at least 24h. Histopathology (10-24h) indicated cell death in the small intestine (widespread), liver and kidneys. White blood cell numbers increased in the circulation, spleen and lungs. Conclusions: Limnothrix produces a potent in vivo cytotoxin. It is water-extractable and produced by a commonly occurring genus. Hence it is a potential risk to drinking water sources. We are currently (1) clarifying the genetic identity of the toxic strain, (2) determining its Australian distribution, (3) purifying and characterising the active compound, and (4) investigating its mechanism of action post-mortem (PM) dissections and histopathology. Results: By 0.5h post-injection, signs included extreme sensitivity to touch and sudden noises, and hind limb weakness

Humpage, “Bacterial degradation of microcystin toxins in drinking water eliminates their toxicity

Abstract Microcystin-LR and -LA were readily biodegraded by a bacterium, Sphingpoyxis sp. LH21, in a treated reservoir water. Detection of the microcystins was conducted using high-performance liquid chromatography (HPLC), protein phosphatase 2A (PP2A) inhibition assay and a cell-based cytotoxicity assay. The HPLC results correlated well with the two assays. The decrease in cytotoxicity, coupled with the associated decrease in microcystin concentrations, indicated that no cytotoxic by-products were being generated, highlighting the applicability of biodegradation as a feasible treatment option for effective microcystin removal.

Cyanotoxins are not implicated in the etiology of coral black band disease outbreaks on Pelorus Island, Great Barrier Reef

Cyanobacterial toxins (i.e. microcystins) produced within the microbial mat of coral black band disease (BBD) have been implicated in disease pathogenicity. This study investigated the presence of toxins within BBD lesions and other cyanobacterial patch (CP) lesions, which, in some instances (∼19%), facilitated the onset of BBD, from an outbreak site at Pelorus Island on the inshore, central Great Barrier Reef (GBR). Cyanobacterial species that dominated the biomass of CP and BBD lesions were cultivated and identified, based on morphology and 16S rRNA gene sequences, as Blennothrix- and Oscillatoria-affiliated species, respectively, and identical to cyanobacterial sequences retrieved from previous molecular studies from this site. The presence of the cyanotoxins microcystin, cylindrospermopsin, saxitoxin, nodularin and anatoxin and their respective gene operons in field samples of CP and BBD lesions and their respective culture isolations was tested using genetic (PCR-based screenings), chemical (HPLC-UV, FTICR-MS and LC/MSn) and biochemical (PP2A) methods. Cyanotoxins and cyanotoxin synthetase genes were not detected in any of the samples. Cyanobacterial species dominant within CP and BBD lesions were phylogenetically distinct from species previously shown to produce cyanotoxins and isolated from BBD lesions. The results from this study demonstrate that cyanobacterial toxins appear to play no role in the pathogenicity of CP and BBD at this site on the GBR