Follow-up actions from positive results of in vitro genetic toxicity testing.
Appropriate follow-up actions and decisions are needed when evaluating and interpreting clear positive results obtained in the in vitro assays used in the initial genotoxicity screening battery (i.e., the battery of tests generally required by regulatory authorities) to assist in overall risk-based decision making concerning the potential effects of human exposure to the agent under test. Over the past few years, the International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) Project Committee on the Relevance and Follow-up of Positive Results in In Vitro Genetic Toxicity (IVGT) Testing developed a decision process flow chart to be applied in case of clear positive results in vitro. It provides for a variety of different possibilities and allows flexibility in choosing follow-up action(s), depending on the results obtained in the initial battery of assays and available information. The intent of the Review Subgroup was not to provide a prescriptive testing strategy, but rather to reinforce the concept of weighing the totality of the evidence. The Review Subgroup of the IVGT committee highlighted the importance of properly analyzing the existing data, and considering potential confounding factors (e.g., possible interactions with the test systems, presence of impurities, irrelevant metabolism), and chemical modes of action when analyzing and interpreting positive results in the in vitro genotoxicity assays and determining appropriate follow-up testing. The Review Subgroup also examined the characteristics, strengths, and limitations of each of the existing in vitro and in vivo genotoxicity assays to determine their usefulness in any follow-up testing.
Dearfield
Kerry L
KL
U.S. Department of Agriculture, Food Safety and Inspection Service, Washington, District of Columbia, USA.
Thybaud
Véronique
V
Cimino
Michael C
MC
Custer
Laura
L
Czich
Andreas
A
Harvey
James S
JS
Hester
Susan
S
Kim
James H
JH
Kirkland
David
D
Levy
Dan D
DD
Lorge
Elisabeth
E
Moore
Martha M
MM
Ouédraogo-Arras
Gladys
G
Schuler
Maik
M
Suter
Willi
W
Sweder
Kevin
K
Tarlo
Kirk
K
van Benthem
Jan
J
van Goethem
Freddy
F
Witt
Kristine L
KL
D000818:Animals; D003661:Decision Support Techniques; D004305:Dose-Response Relationship, Drug; D023381:Endpoint Determination; D015386:Hazardous Substances / Q000592:standards / Q000633:toxicity*; D006801:Humans; D007391:International Cooperation; D009152:Mutagenicity Tests / Q000379:methods* / Q000639:trends; D009153:Mutagens / Q000592:standards / Q000633:toxicity*; D018570:Risk Assessment
D015386:Hazardous Substances; D009153:Mutagens