REGULATION & COMPLIANCE
opt-outs . This manual check cannot be simulated in IUCLID .
Registrants adding a weight-ofevidence ( WoE ) adaptation are now prompted to provide arguments for the approach in a more structured format . This is included in the version of IUCLID that was released in May 20233 , so we are all still getting to grips with it . A previous update also included specific templates for nanomaterials , to mirror the specific information requirements for these substances .
New data
Once the existing dossier is as good as possible , the next step is to identify where there are still gaps or weaknesses in the data set . It is good practice to run regular , comprehensive searches of the literature to identify any relevant , newly conducted studies . Remember , a dossier should be a living document and keeping it updated is an important part of your obligations as a registrant .
Equally , it is important to maintain open lines of communication with other companies . Consortium members , downstream users or customers may all identify or generate new data under other regulatory frameworks , and this should be considered if relevant to include in an updated REACH registration submission .
It can also be possible to support older studies , which are perhaps limited compared to modern guidelines , with new ( Q ) SAR predictions . This effectively provides a WoE showing that an older result was valid even if the methodology or reporting detail was deficient .
As a final consideration , it might be necessary or beneficial to generate new data . Remember that new vertebrate animal testing should only be commissioned as a last resort , and all higher tier tests are subject to testing proposals ( i . e . evaluation by ECHA ) prior to being carried out .
If there are gaps or weaknesses in endpoints that would previously have been filled by in vivo tests , can these be filled with new in vitro data ? Several new test methods have been validated and adopted since the original REACH registration deadlines , and even since the final 2018 registration deadline . Indeed , in vitro testing for skin and eye irritation or corrosion is now the default first approach . 4 There is also an approved framework for use of ( Q ) SAR in chemico and in vitro tests for skin sensitisation .
NAMs
Another consideration would be to incorporate new data generated using New Approach Methodologies ( NAMs ). These are novel in vitro methods that consider reactivity at a cellular or genetic level , rather than on an intact organism .
Some are assays in human induced pluripotent stem cells , others are based on high-throughput transcriptomics . These assays are well-established in themselves and are often used as screening assays in the pharmaceutical sector . Some are also starting to be validated as OECD methods , such as the ( anti- ) ERα CALUX bioassay , OECD TG 455.5
The overall approach is known as Next Generation Risk Assessment , which has already been used for some time in the cosmetics sector . 6 Exposure modelling is undertaken to calculate internal human exposures ( i . e . plasma concentrations ). If no bioactivity is seen at these concentrations in the assays , the compound cannot present a toxicity risk . It is still early days with
regard to the acceptance of NAM assays under REACH , but it is a very promising avenue for future work .
Summary
Registration was just the first phase of REACH . Dossiers are living documents and should be kept up to date with any relevant newly identified or generated data .
Studies should be described in as much detail as possible , and documentation in support of adaptations should be as robust as possible . All of this reduces the risk of an evaluation decision that requires action from a registrant – at high cost and with the pressure of a deadline to become compliant .
Many older dossiers are likely to be found non-compliant simply because ECHA ’ s expectations – the level of detail and documentation required – have continually increased over the past few years . There are many options to improve the quality of a dossier , including updating the existing content , conducting searches for studies that are not currently included and generating new data .
Whichever approach you take to update your dossier , the best time to do so is before an evaluation has even started . ●
References : 1 : https :// echa . europa . eu / regulations / reach / evaluation / substance-evaluation / community-rolling-action-plan 2 : Report on the operation of REACH & CLP 2021 : https :// echa . europa . eu / documents / 10162 / 17226 / operation _ reach _ clp _ 2021 _ en . pdf / e271b3c8- 137a-48ad-30ad-499249235ee5 3 : https :// iuclid6 . echa . europa . eu / view-article / - / journal _ content / title / new-iuclid-version-including-format-updates-may23 4 : ECHA Guidance on Information Requirements & Chemical Safety Assessment . Chapter R . 7a : Endpoint-Specific Guidance . Version 6.0 . July 2017 : https :// echa . europa . eu / documents / 10162 / 17224 / information _ requirements _ r7a _ en . pdf / e4a2a18f-a2bd-4a04-ac6d- 0ea425b2567f ? t = 1500275822893 5 : https :// www . oecd-ilibrary . org / environment / test-no-455-performance-based-test-guideline-for-stably-transfected-transactivation-in-vitroassays-to-detect-estrogen-receptor-agonists-and-antagonists _ 9789264265295-en 6 : M . Dent et al ., Computational Toxicology , 2018 , 7 , 20-26 . https :// doi . org / 10.1016 / j . comtox . 2018.06.001
Chris Waine
SENIOR TOXICOLOGIST
BIBRA TOXICOLOGY ADVICE AND CONSULTING
k + 44 20 8619 0770 J chris . waine @ bibratoxadvice . co . uk j www . bibra-information . co . uk
36 SPECIALITY CHEMICALS MAGAZINE ESTABLISHED 1981