We are excited to announce new webinars in February and March by Emilie Da Silva “Moving away from animal testing for acute inhalation toxicity testing” and two ASCCT award winners Ignacio J. Tripodi “Toxicological mechanistic inference: Generating mechanistic explanations of adverse outcomes” and Vy Tran “Co-expression Network Analysis to Identify Heterogeneity Between the Breast Cancer Cell Line MCF-7 and Human Breast Cancer Tissues“.
The two ESTIV Award Winner Webinars presented by Laura Escrivá and Lenny Kamelia in January, have been posted online and are now available for viewing at your convenience.
Dr. Laura Escrivá: Role of In Vitro Mechanistic Data for the Assessment of Endocrine Disruptors in the Regulatory Context
Presented by Dr. Laura Escrivá, Assistant Professor, University of Valencia, Spain.
Tuesday, January 21st, 2020 at 4:00 pm CET
ABSTRACT: Scientific EU criteria and guidance from ECHA and EFSA to identify substances with Endocrine Disruptor (ED) properties have recently been implemented for plant protection products and biocidal products. The ECHA/EFSA guidance, mainly addressing EATS (estrogen, androgen, thyroid, steridogenesis) modalities, provides a protocol for ED identification, which includes the evaluation of both the adverse effects and the endocrine activity, by applying weight of evidence analysis.
The assessment of the endocrine activity requires in vitro mechanistic data providing information on the mechanism through which a substance could be considered endocrine active (e.g. by binding to and activating a receptor or interfering with hormone production). Moreover, when potentially endocrine-related adverse effects and endocrine activity are identified, the biological plausibility of the link between endocrine activity and the endocrine mediated adversity should be established by a mode of action analysis. The webinar will focus on the different steps for ED identification according to the ECHA/EFSA guidance illustrating how essential it is the in vitro data for ED assessment under EU regulatory context.
Dr. Lenny Kamelia: A battery of animal-free in vitro assays for evaluating prenatal developmental toxicity potency of highly complex petroleum substances
Presented by Dr. Lenny Kamelia, Division of Toxicology, Wageningen University and Research, The Netherlands.
Tuesday, January 21st, 2020 at 4:00 pm CET
ABSTRACT: REACH legislation requires prenatal developmental toxicity (PDT) testing for substances registered at a volume of >100 tonnes/year, which also applies to petroleum substances (PS). Given that i) PDT testing is one of the most complex, and animal- and resource-intensive regulatory requirements for substances produced at >100 tonnes/year, and ii) PS are highly complex materials (UVCBs), the development of alternative non-animal based testing strategies for PS poses huge challenges. Some PS contain high concentrations of polycyclic aromatic hydrocarbons (PAHs) and we hypothesize that PDT as observed for some PS is caused by certain types of PAH present in these products. To this purpose, DMSO-extracts of 9 PS (varying in PAH content; from 5 different product categories), 1 highly refined base oil (HRBO) (containing no PAHs), and 2 gas-to-liquid (GTL) products (devoid of PAHs) were tested in a battery of in vitro assays, including the embryonic stem cell test (EST), the zebrafish embryotoxicity test (ZET), and the aryl hydrocarbon (AhR) CALUX assay. All DMSO-extracts of the PS, but not of the HRBO and GTL, induced concentration-dependent PDT as quantified in the EST and ZET, with their potency being proportional to their 3- to 7-ring PAH content. Moreover, all PS extracts also showed AhR-mediated activity in the AhR CALUX assay, suggesting a role of the AhR in mediating the observed PDT by these substances. Combining the results of the EST, ZET, AhR CALUX assay, and the PAH content, ranked and clustered the test compounds in line with their in vivo PDT potencies. In conclusion, our battery of in vitro assays, consisting of the EST, ZET and AhR CALUX assay, is able to evaluate and differentiate the PDT potency of highly complex PS, within and among categories. The results are also in concordance with our hypothesis on the role of specific groups of PAHs present in some PS for the observed PDT induced by these substances.