Identification and Description of the Uncertainty, Variability, Bias and Influence in Quantitative Structure-Activity Relationships (QSARs) for Toxicity Prediction

Improving regulatory confidence in, and acceptance of, a prediction of toxicity from a quantitative structure-activity relationship (QSAR) requires assessment of its uncertainty and determination of whether the uncertainty is acceptable. Thus, it is crucial to identify potential uncertainties fundamental to QSAR predictions. Based on expert review, sources of uncertainties, variabilities and biases, as well as areas of influence in QSARs for toxicity prediction were established. These were grouped into three thematic areas: uncertainties, variabilities, potential biases and influences associated with 1) the creation of the QSAR, 2) the description of the QSAR, and 3) the application of the QSAR, also showing barriers for their use. Each thematic area was divided into a total of 13 main areas of concern with 49 assessment criteria covering all aspects of QSAR development, documentation and use. Two case studies were undertaken on different types of QSARs that demonstrated the applicability of the assessment criteria to identify potential weaknesses in the use of a QSAR for a specific purpose such that they may be addressed and mitigation strategies can be proposed, as well as enabling an informed decision on the adequacy of the model in the considered context

The Australian Work Exposures Study: Prevalence of Occupational Exposure to Formaldehyde

INTRODUCTION: The aims of this study were to produce a population-based estimate of the prevalence of work-related exposure to formaldehyde, to identify the main circumstances of exposure and to describe the use of workplace control measures designed to decrease those exposures. METHODS: The analysis used data from the Australian Workplace Exposures Study, a nationwide telephone survey, which investigated the current prevalence and exposure circumstances of work-related exposure to 38 known or suspected carcinogens, including formaldehyde, among Australian workers aged 18-65 years. Using the web-based tool OccIDEAS, semi-quantitative information was collected about exposures in the current job held by the respondent. Questions were addressed primarily at tasks undertaken rather than about self-reported exposures. RESULTS: Of the 4993 included respondents, 124 (2.5%) were identified as probably being exposed to formaldehyde in the course of their work [extrapolated to 2.6% of the Australian working population-265 000 (95% confidence interval 221 000-316 000) workers]. Most (87.1%) were male. About half worked in technical and trades occupations. In terms of industry, about half worked in the construction industry. The main circumstances of exposure were working with particle board or plywood typically through carpentry work, building maintenance, or sanding prior to painting; with the more common of other exposures circumstances being firefighters involved in fighting fires, fire overhaul, and clean-up or back-burning; and health workers using formaldehyde when sterilizing equipment or in a pathology laboratory setting. The use of control measures was inconsistent. CONCLUSION: Workers are exposed to formaldehyde in many different occupational circumstances. Information on the exposure circumstances can be used to support decisions on appropriate priorities for intervention and control of occupational exposure to formaldehyde, and estimates of burden of cancer arising from occupational exposure to formaldehyde

A comprehensive list of asthmagens to inform health interventions in the Australian workplace

Objective: To develop a comprehensive list of asthmagens which may occur in occupational settings in Australia. Methods: Potential asthmagens considered for this list were identified through work health and safety classification databases in Australia and through lists developed by professional associations in other countries. Inclusion criteria were: there is evidence that the agent is asthmagenic; it is used in occupational settings; and it is available in Australia. Results: The final list contained 277 asthmagens in 27 groups that may be found in occupational circumstances in Australia. Three other agents that have been documented as asthmagens in Australia were included: almond dust, fluoride (in aluminium pot room fumes); and sawdust from the Australian Blackwood. Conclusions: This is the first comprehensive and inclusive list of Australian occupationally relevant asthmagens to have been compiled. Implications: This list is specific for Australian workplace exposure to asthmagens. It will help focus policy and preventative practices and reduce the burden of occupational asthma. It will also be useful in future studies to identify those who are exposed to the asthmagens and provide information to assist regulators to identify industries, occupations, specific activities and existing exposure standards that can be targeted to improve worker health and welfare

Controlling occupational cancers in Australia

Lin Fritschi, Renae C Fernandez, Deborah A Vallance, Terry J Slevin, Alison Reid, Timothy R Driscoll, Deborah C Glas

A fluorescence approach to investigate repartitioning of coalescing agents in acrylic polymer emulsions

Repartitioning of co-solvents between particles of latex emulsions was investigated by means of a fluorescence method based on the detection of the amount of co-solvent via the solvatochromic shift of the emission maximum of a fluorescent probe, copolymerized at a low concentration. Complete repartitioning of co-solvents between particles of latex materials with a low Tg (ca. 25 °C) occurred within minutes. For a hydrophilic latex with a Tg of 68 °C, equilibration was achieved within an hour. Repartitioning was faster for more hydrophobic co-solvents. For a hydrophobic latex of similar Tg, co-solvent repartitioning took place on the same time scale, but complete equilibration was not reached. Possibly, there is an additional slow component in the repartitioning, or the prolonged presence of co-solvent causes a structural change in the latex particles that affects the outcome of the experiment

Cross-Sector Review of Drivers and Available 3Rs Approaches for Acute Systemic Toxicity Testing

Acute systemic toxicity studies are carried out in many sectors in which synthetic chemicals are manufactured or used and are among the most criticized of all toxicology tests on both scientific and ethical grounds. A review of the drivers for acute toxicity testing within the pharmaceutical industry led to a paradigm shift whereby in vivo acute toxicity data are no longer routinely required in advance of human clinical trials. Based on this experience, the following review was undertaken to identify (1) regulatory and scientific drivers for acute toxicity testing in other industrial sectors, (2) activities aimed at replacing, reducing, or refining the use of animals, and (3) recommendations for future work in this area

Review and analysis of fire and explosion accidents in maritime transportation

The globally expanding shipping industry has several hazards such as collision, capsizing, foundering, grounding, stranding, fire, and explosion. Accidents are often caused by more than one contributing factor through complex interaction. It is crucial to identify root causes and their interactions to prevent and understand such accidents. This study presents a detailed review and analysis of fire and explosion accidents that occurred in the maritimetransportation industry during 1990–2015. The underlying causes of fire and explosion accidents are identified and analysed. This study also reviewed potential preventative measures to prevent such accidents. Additionally, this study compares properties of alternative fuels and analyses their effectiveness in mitigating fire and explosionhazards. It is observed that Cryogenic Natural Gas (CrNG), Liquefied Natural Gas (LNG) and methanol have properties more suitable than traditional fuels in mitigating fire risk and appropriate management of their hazards could make them a safer option to traditional fuels. However, for commercial use at this stage, there exist several uncertainties due to inadequate studies, and technological immaturity. This study provides an insight into fire and explosion accident causation and prevention, including the prospect of using alternative fuels for mitigating fire and explosion risks in maritime transportation

A 28-day oral dose toxicity study enhanced to detect endocrine effects of hexabromocyclododecane in wistar rats

A 28-day repeated dose study in rats (OECD407) enhanced for endocrine and immune parameters was performed with hexabromocyclododecane (HBCD). Rats were exposed by daily gavage to HBCD dissolved in corn oil in 8 dose groups with doses ranging between 0 and 200 mg/kg bw per day (mkd). Evaluation consisted of dose-response analysis with calculation of a benchmark dose at the lower 95% one-sided confidence bound (BMDL) at predefined critical effect sizes (CESs) of 10-20%. The most remarkable findings were dose-related effects on the thyroid hormone axis, that is, decreased total thyroxin (TT4, BMDL 55.5 mkd at CES--10%), increased pituitary weight (29 mkd at 10%) and increased immunostaining of TSH in the pituitary, increased thyroid weight (1.6 mkd at 10%), and thyroid follicle cell activation. These effects were restricted to females. Female rats also showed increased absolute liver weights (22.9 mkd at 20%) and induction of T4-glucuronyl transferase (4.1 mkd at 10%), suggesting that aberrant metabolization of T4 triggers feedback activation of the thyroid hormone system. These effects were accompanied by possibly secondary effects, including increased cholesterol (7.4 mkd at 10%), increased tibial bone mineral density (> 49 mkd at 10%), both in females, and decreased splenocyte counts (0.3-6.3 mkd at 20%; only evaluated in males). Overall, female rats appeared to be more sensitive to HBCD than male rats, and an overall BMDL is proposed at 1.6 mkd, based on a 10% increase of the thyroid weight, which was the most sensitive parameter in the sequence of events