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Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - Clarification of some aspects related to genotoxicity assessment
AU - Hardy, Anthony
AU - Benford, Diane
AU - Halldorsson, Thorhallur
AU - Jeger, Michael
AU - Knutsen, Helle Katrine
AU - More, Simon
AU - Naegeli, Hanspeter
AU - Noteborn, Hubert
AU - Ockleford, Colin
AU - Ricci, Antonia
AU - Rychen, Guido
AU - Silano, Vittorio
AU - Solecki, Roland
AU - Turck, Dominique
AU - Younes, Maged
AU - Aquilina, Gabriele
AU - Crebelli, Riccardo
AU - Gürtler, Rainer
AU - Hirsch-Ernst, Karen Ildico
AU - Mosesso, Pasquale
AU - Nielsen, Elsa
AU - van Benthem, Jan
AU - Carfì, Maria
AU - Georgiadis, Nikolaos
AU - Maurici, Daniela
AU - Parra Morte, Juan
AU - Schlatter, Josef
PY - 2017/12
Y1 - 2017/12
N2 - Abstract The European Commission requested EFSA to provide advice on the following: (1) the suitability of the unscheduled DNA synthesis (UDS) in vivo assay to follow-up positive results in in vitro gene mutation tests; (2) the adequacy to demonstrate target tissue exposure in in vivo studies, particularly in the mammalian erythrocyte micronucleus test; (3) the use of data in a weight-of-evidence approach to conclude on the genotoxic potential of substances and the consequent setting of health-based guidance values. The Scientific Committee concluded that the first question should be addressed in both a retrospective and a prospective way: for future assessments, it is recommended no longer performing the UDS test. For re-assessments, if the outcome of the UDS is negative, the reliability and significance of results should be carefully evaluated in a weight-of-evidence approach, before deciding whether more sensitive tests such as transgenic assay or in vivo comet assay would be needed to complete the assessment. Regarding the second question, the Scientific Committee concluded that it should be addressed in lines of evidence of bone marrow exposure: toxicity to the bone marrow in itself provides sufficient evidence to allow concluding on the validity of a negative outcome of a study. All other lines of evidence of target tissue exposure should be assessed within a weight-of-evidence approach. Regarding the third question, the Scientific Committee concluded that any available data that may assist in reducing the uncertainty in the assessment of the genotoxic potential of a substance should be taken into consideration. If the overall evaluation leaves no concerns for genotoxicity, health-based guidance values may be established. However, if concerns for genotoxicity remain, establishing health-based guidance values is not considered appropriate.
AB - Abstract The European Commission requested EFSA to provide advice on the following: (1) the suitability of the unscheduled DNA synthesis (UDS) in vivo assay to follow-up positive results in in vitro gene mutation tests; (2) the adequacy to demonstrate target tissue exposure in in vivo studies, particularly in the mammalian erythrocyte micronucleus test; (3) the use of data in a weight-of-evidence approach to conclude on the genotoxic potential of substances and the consequent setting of health-based guidance values. The Scientific Committee concluded that the first question should be addressed in both a retrospective and a prospective way: for future assessments, it is recommended no longer performing the UDS test. For re-assessments, if the outcome of the UDS is negative, the reliability and significance of results should be carefully evaluated in a weight-of-evidence approach, before deciding whether more sensitive tests such as transgenic assay or in vivo comet assay would be needed to complete the assessment. Regarding the second question, the Scientific Committee concluded that it should be addressed in lines of evidence of bone marrow exposure: toxicity to the bone marrow in itself provides sufficient evidence to allow concluding on the validity of a negative outcome of a study. All other lines of evidence of target tissue exposure should be assessed within a weight-of-evidence approach. Regarding the third question, the Scientific Committee concluded that any available data that may assist in reducing the uncertainty in the assessment of the genotoxic potential of a substance should be taken into consideration. If the overall evaluation leaves no concerns for genotoxicity, health-based guidance values may be established. However, if concerns for genotoxicity remain, establishing health-based guidance values is not considered appropriate.
KW - genotoxicity
KW - in vivo UDS assay
KW - micronucleus test
KW - weight-of-evidence
KW - bone marrow exposure
U2 - 10.2903/j.efsa.2017.5113
DO - 10.2903/j.efsa.2017.5113
M3 - Journal article
VL - 15
JO - EFSA Journal
JF - EFSA Journal
SN - 1831-4732
IS - 12
M1 - 05113
ER -