Applying a modified systematic review and integrated assessment framework (SYRINA) - a case study on triphenyl phosphate.

This work presents a case study in applying a systematic review framework (SYRINA) to the identification of chemicals as endocrine disruptors. The suitability and performance of the framework is tested with regard to the widely accepted World Health Organization definition of an endocrine disruptor (ED). The endocrine disrupting potential of triphenyl phosphate (TPP), a well-studied flame retardant reported to exhibit various endocrine related effects was assessed. We followed the 7 steps of the SYRINA framework, articulating the research objective via Populations, Exposures, Comparators, Outcomes (PECO) statements, performed literature search and screening, conducted study evaluation, performed data extraction and summarized and integrated the evidence. Overall, 66 studies, consisting of in vivo, in vitro and epidemiological data, were included. We concluded that triphenyl phosphate could be identified as an ED based on metabolic disruption and reproductive function. We found that the tools used in this case study and the optimizations performed on the framework were suitable to assess properties of EDs. A number of challenges and areas for methodological development in systematic appraisal of evidence relating to endocrine disrupting potential were identified; significant time and effort were needed for the analysis of in vitro mechanistic data in this case study, thus increasing the workload and time needed to perform the systematic review process. Further research and development of this framework with regards to grey literature (non-peer-reviewed literature) search, harmonization of study evaluation methods, more consistent evidence integration approaches and a pre-defined method to assess links between adverse effect and endocrine activity are recommended. It would also be advantageous to conduct more case studies for a chemical with less data than TPP.

Liposome-mediated delivery of challenging chemicals to aid environmental assessment of Bioaccumulative (B) and Toxic (T) properties.

Standard aquatic toxicity tests of chemicals are often limited by the chemicals' water solubility. Liposomes have been widely used in the pharmaceutical industry to overcome poor pharmacokinetics and biodistribution. In this work, liposomes were synthesized and used in an ecotoxicological context, as a tool to assure stable dosing of technically challenging chemicals to zooplankton. Three chemicals with distinctly different characteristics were successfully incorporated into the liposomes: Tetrabromobisphenol A (TBBPA, log Kow 5.9, pKa1 7.5, pKa2 8.5), chlorinated paraffin CP-52 (log Kow 8-12) and perfluorooctanoic acid (PFOA, pKa 2.8). The size, production yield and stability over time was similar for all blank and chemical-loaded liposomes, except for when the liposomes were loaded with 10 or 100 mg g-1 PFOA. PFOA increased the size and decreased the production yield and stability of the liposomes. Daphnia magna were exposed to blank and chemical-loaded liposomes in 48 hour incubation experiments. A dose-dependent increase in body burden in D. magna and increased immobilization (LD50 = 7.6 ng CPs per individual) was observed. This confirms not only the ingestion of the liposomes but also the successful internalization of chemicals. This study shows that liposomes can be a reliable alternative to aid the study of aquatic toxicity of challenging chemicals.