September 30th, 2019
Jo Massey, one of PFA’s principal toxicologists, attended the EUROTOX 2019 conference, 8-11th September. The conference was organised by the Finnish Society of Toxicology in the city known to most toxicologists as the host of the European Chemicals Agency, Helsinki. With approximately 1500 participants, the conference hoped to tackle the burning chemical safety challenges of the next decade, with the theme ‘Toxicology – Science Providing Solutions’.
Renowned scientists and invited speakers presented lectures covering a broad spectrum of toxicological areas; with multiple parallel sessions participants were spoilt for choice. Sessions covered everything from adverse outcome pathways (AOPs), in vitro and in silico replacement and screening methods in toxicology, as well as sessions relevant to specific organ systems, such as neurotoxicity, immunotoxicity, gut microbiome toxicity, developmental toxicity and hepatotoxicity. As well as these sessions on toxicology, the conference included sessions on toxicity and risk assessment of nanoparticles, mechanistic risk assessment, challenges in the toxicological evaluation and risk management of substances of unknown or variable composition (UVCBs) and much more.
A highlight of the first day was the annual debate. Representatives of EUROTOX (Martin van den Berg, Utrecht University, Netherlands) and SOT (Paul Foster, NIEHS (retired), Research Triangle, NC, US) presented arguments for and against the motion “Classification of substances as endocrine disruptors has a public health benefit”. Martin van den Berg argued that substances identified as having an endocrine disruptor mode of action should have a new classification with the same regulatory implications as carcinogenic, mutagenic and reproductive toxicants (CMR). He felt it is important to protect against early exposures having effects many years after exposure. Although he acknowledged that this would require an increase in in vivo testing that specifically investigates this endpoint and that there are currently no test systems that cover all endocrine disrupting pathways. However, he had concerns about classifying on hazard alone in cases where endocrine disrupting effects occur only at high exposures that are not relevant to humans, leading to unnecessary classifications.
Paul Foster counterargued that there are many possible ways to affect the endocrine system, but they do not necessarily lead to an adverse outcome, so in terms of an AOP, there is not always an adverse outcome. He explained that classifications should be based on adverse outcomes and not on mechanisms. He considered that where there is an adverse outcome, such as leading to cancer or effects on reproduction or development they are covered by existing classifications. An additional subclassification could be added to the reproductive and development classifications, i.e. a sub-classification to cover ‘may cause harm to children’, to cover exposure during childhood and adolescence that leads to adverse effects later in life. Therefore, when classifying for endocrine effects that do not fit very well in the current system a new subclassification might be useful, but a new stand-alone classification is not necessary. The audience of delegates voted against the proposal, seemingly accepting the argument from Paul Foster that the current classification system already adequately covers endocrine disruption parameters and provides adequate human health protection.
Specific topics were discussed in industry-sponsored lunchtime sessions, for example Charles River ran a session on how to conduct successful Extended One-Generation Reproductive Toxicity (EOGRT) tests, during which specific aspects of the test, such as providing evidence of pup exposure via milk, were highlighted. Another interesting parallel session covered species-specific gastrointestinal toxicity in rabbits. With the increasing number of EOGRT tests and developmental toxicity tests in rabbits being required of our clients under REACH, these two sessions were of particular interest to PFA.