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.
U.S. Department of Agriculture, Food Safety and Inspection Service, Washington, District of Columbia, USA.
Kerry L
KL
Dearfield
Véronique
V
Thybaud
Michael C
MC
Cimino
Laura
L
Custer
Andreas
A
Czich
James S
JS
Harvey
Susan
S
Hester
James H
JH
Kim
David
D
Kirkland
Dan D
DD
Levy
Elisabeth
E
Lorge
Martha M
MM
Moore
Gladys
G
Ouédraogo-Arras
Maik
M
Schuler
Willi
W
Suter
Kevin
K
Sweder
Kirk
K
Tarlo
Jan
J
van Benthem
Freddy
F
van Goethem
Kristine L
KL
Witt
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