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REACH

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ACC advises firms to improve quality of read-across for REACH

Chemical Watch reports that chemical manufacturers must develop more thorough, scientifically detailed arguments when writing read-across dossiers for upcoming REACH requirements, says the American Chemistry Council (ACC). 

Speaking last week at theGlobalChemconferenceinWashington,DC, ACC senior toxicologist Rick Beckersaidmanufacturersthat provided similarity arguments to the EPAin 2000 should reconsider how they set out read-across arguments in REACH registration dossiers.

Recent technology, such astoxicologicalgenomics,and data streams, such asEPA’shigh-throughputscreeningdata, are now available andindustrymust consult these resources andinclude all relevant information, he said.

“Wehave newtools … tounderstandhow achemicalacts andwe can use that informationto make a betterscienceargumentforread-across that willgiveusgreaterconfidencein using that information,withoutthen having to dotheanimal testing,”MrBecker said.

Read-acrosswas a key component of theEPA’shigh productionvolume challenge programmethatbegan in 2000,MrBecker said. At that time, the agency allowed for groupings across chemical structures with less advanced justification. But “now thatwe havelearned more aboutchemistry, biology and toxicology,I think the expectation is thatindustry will have todo a better job of demonstrating similarity for read-across,” he said.

Given the large number of substances that will have to be registered, under the third REACH deadline in 2018, it is probably not possible for industry to do all of the animal testing that would be needed to fill the data gaps, saidMrBecker. But “aslong as we canestablishenough confidenceusing this information,we seeno reason why we shouldn’t use this approach.”

Industry should use themost recent analyticaltools and data as part of any product stewardship effort,MrBecker added. “We also have tochallenge ourselves, from the standpoint ofproductstewardship. We have to rely on that informationasanindustry to make good decisionsabout product safety as well.”

Professor TerrySchultz, of the UniversityofTennessee,said industry hasanalyseda series of case studies of read-acrossapplicationsfor REACH, butthe analysis didn’t provide clear patterns or illustrate why REACH regulators are accepting one set of chemicals for read-across and rejecting another.

It’sstilldifficult toknowexactly whattheregulatorsarelooking forinaread-acrossREACH dossier, he said.

Last year Echa launched a read-across assessment framework (RAAF) to help experts evaluate consistently human health data for read-across and companies compiling REACH registration dossiers see the aspects of justifications that Echa considers to be crucial.

Later this year, it will be supplemented with information on mixtures and substances of unknown or variable composition (UVCBs).

EU-ToxRisk project underway

Chemical Watch reports that the EU-ToxRisk, a €30m project to develop an animal-free, mechanism-based approach to risk assessment, has started work on a number of case studies, following a kick-off meeting on 13-15 January in Egmond aan Zee, the Netherlands.

The project's ultimate goal is to develop a new way to do risk assessment, Marcel Leist from the University of Konstanz in Germany, a member of EU-ToxRisk's executive office, told Chemical Watch.

Speaking at the meeting, Bennard van Ravenzwaay from German chemical company BASF, one of 39 EU-ToxRisk partners, explained that the aim is to meet regulatory risk assessment needs, rather than focus on pure method development.

The six-year project will focus on repeat-dose systemic toxicity testing in the liver, kidneys, lungs and nervous system, as well as developmental and reproductive toxicity.

Read-across is a central feature. “We really want to focus our resources so that, after three years, we have a new way of doing read-across in Europe, especially for evaluating REACH compounds,” professor Leist told Chemical Watch.

The aim is to build a more “quantitatively structured” system, including a web application, he added. This read-across work will use existing data as well as providing new information, including from high-throughput transcriptomics.

EU-ToxRisk will also build in biological read-across, adding biological descriptors such as gene expression profiles to toxicological and chemical descriptors. “This means that compounds that do not share structural similarity may be used for read-across using biological data,” explained professor Leist.

He described how adverse outcome pathways (AOPs) form the project's backbone.

“We will look at how we can use AOPs practically in risk assessment,” he said. For example, teams will test AOPs using data-rich compounds and optimise or alter them accordingly. Case studies could also look at how they aid risk assessment.

Professor Leist also spoke of developing quantitative AOPs (qAOPs) to predict hazard thresholds from in vitro test system data.

EU-ToxRisk already has about 17 case studies lined up and its partners will soon begin work to test the predictivity of a battery of assays, using data-rich pharmaceutical compounds. Over the course of the project, case studies will progress to less characterised chemicals, including industrial compounds.

A systems evaluation task force, within EU-ToxRisk, will scrutinise any proposed model systems, using a set of criteria. Such criteria are already used widely in industry but less so in academic labs, said professor Leist. “Only models that fit the criteria will be used.” 

The project also has links to the US National Toxicology Programme and EPA. 

“There appear to be multiple points of intersection between the EU-ToxRisk project and the research being undertaken by the US EPA in the National Center for Computational Toxicology,” said Rusty Thomas, director of the EPA's National Center for Computational Toxicology. “I look forward to working with and advising the EU-ToxRisk project. It is poised to have a significant impact on the way we evaluate chemicals for human safety.”

“EU-ToxRisk has really hit the ground running. This was very clear from how focused and productive the kick-off meeting was," said Maurice Whelan, head of the European Union Reference Laboratory for alternatives to animal testing (EURL-Ecvam). 

“I am particularly excited that EU-ToxRisk has fully embraced Adverse Outcome Pathways as a means to manage mechanistic toxicological knowledge and to provide the theoretical basis to design Integrated Approaches to Testing and Assessment (IATA), including a strong emphasis on new ways of incorporating mechanistic toxicity data into grouping and read-across,” he added.

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