REGULATION & COMPLIANCE
• Estrogen receptor transactivation assay ( OECD 455 )
• Androgen receptor transactivation assay ( OECD 458 )
• H295R steroidogenesis assay ( OECD 456 )
• Aromatase assay ( OPPTS 890.1200 ) For substances raising concerns , testing for repeated dose toxicity , screening for reproductive or developmental toxicity , and in vivo tests on ED are being considered even at low tonnages . Two options for triggers are under discussion : biological half-life predicted from log Kow (> 3 ) and in vitro TK data
Additional requirements for potential ED properties are the uterotrophic bioassay in rodents ( OECD 440 ) and the Hershberger bioassay in rats ( OECD 441 ). To account for the increased data requirements , several in vivo studies are proposed to be deleted or replaced , such as prenatal developmental toxicity in second species and long-term repeated dose toxicity studies .
The expected changes in environmental health data requirements include :
• Replacement of the short-term fish toxicity test with in vitro tests OECD 249 or OECD 236
• Replacement of the bioaccumulation test in fish by either in vitro tests ( OECD 319 A / B ) or alternative test methods ( Hyalella Azteca bioconcentration test )
• Long-term toxicity testing on invertebrates ( Daphnia ) to be moved from Annex IX to Annex VII Additional requirements for potential ED to include the amphibian metamorphosis assay ( OECD 231 ), the fish sexual development test ( OECD 234 ), the Medaka extended onegeneration reproduction test ( OECD 240 ) or the larval amphibian growth & and development assay ( OECD 241 ).
Carcinogenicity
A carcinogenicity study may be required for substances manufactured or imported into the EEA in amounts of 1,000 tonnes / year or more . REACH Annex X stipulates that the study may be proposed by the registrant or required by ECHA if : the substance has widespread dispersive use ; there is evidence of frequent or long-term human exposure ; the substance is classified as a germ cell mutagen category 2 ; or there is evidence from the repeated dose data that the substance can induce hyperplasia and / or preneoplastic lesions . If the substance is classified as a category 1A or 1B germ cell mutagen , a carcinogenicity study will not normally be required .
A requirement for mutagenicity data is included for substances in amounts of more than 1 tonne / year and can give some indication of the genotoxic carcinogenicity potential for substances in lower tonnage bands .
In the context of the CSS , the EC submitted a formal support request to ECHA in 2021 . The list of priorities for reviewing the chemicals policy and legislation included revising REACH , speeding up the evaluation of substances and prioritising the ( re- ) evaluation of chemicals based on their hazard classes .
ECHA has since then prepared a restrictions roadmap to prioritise substances , including carcinogenic substances , for ( group ) restrictions . It was published in 2022 and can be used as an indication of the
( groups of ) chemicals targeted as known carcinogens .
The EC further proposed in the CSS to amend REACH data requirements to enable the identification of all carcinogenic substances manufactured or imported in the EEA , irrespective of volume . However , this is one of many proposals included in the CSS and it has not been mentioned in subsequent documents published by the EC and ECHA .
The registration procedure , as well as the restriction and authorisation of chemicals , will remain the key tools to regulate the identification and use of carcinogen substances in the EEA in the short term .
Conclusion
Some major changes in the registration requirements of chemicals in the EEA are expected . Although it remains to be seen which options and additional concepts will be included in the final proposal for the revision of REACH , it is already certain that the new regulatory and data requirements will pose some additional challenges which require expert knowledge for manufacturers and importers alike .
For companies based outside the EEA , keeping an overview of the most current developments , and identifying the new requirements applying to their substances and products may be especially difficult . Companies should check well ahead whether they can cope with the new challenges on their own or whether they need external help . Despite the remaining uncertainties about the implementation of the changes , it is advisable to start preparing in time to ensure compliance in the future . ●
Dr Minetta Wunderskirchner
SENIOR REGULATORY AFFAIRS MANAGER
KNOELL GERMANY GMBH k Tel : + 49 214 20658 127 J mwunderskirchner @ knoell . com j www . knoell . com
32 SPECIALITY CHEMICALS MAGAZINE ESTABLISHED 1981