In vitro mutagenicity methodology for nitrosamines (InVitroNAmutagenicity)

Study identification

• PURI:
  https://redirect.ema.europa.eu/resource/49440
• EU PAS number:
  EUPAS49355
• Study ID:
  49440
• Official title and acronym:
  In vitro mutagenicity methodology for nitrosamines (InVitroNAmutagenicity)
• DARWIN EU® study:
  No
• Study countries:
  Germany

  United Kingdom

  United States
• Study description:
  The project “In vitro mutagenicity methodology for nitrosamines” aims at generating a better understanding how the Ames test and the in vitro Comet assay can be methodologically optimized to reliably detect mutagenicity of different nitrosamines (NAs). A carefully selected set of reference NAs, active pharmaceutical ingredient (API)-derived NAs and supporting reference compounds will be used to demonstrate reproducibility, sensitivity (the proportion of genotoxic carcinogens that generate positive results), and specificity (the proportion of non-genotoxic compounds that generate a negative result) of each test model and provide data to estimate and compare the genotoxic potency of test compounds in the two different in vitro assays. One part of the project focuses on evaluation and optimization of the Ames test to improve its sensitivity in detecting the mutagenic potential of NAs with one focus on appropriate solvents and solvent concentrations as well as metabolising systems. The other part is dedicated to evaluation and optimization of the in vitro Comet assay with metabolically competent liver cell models (primary rat and human hepatocytes versus HepG2 cells) as a complementary or alternative assay for detection of potentially mutagenic/carcinogenic NAs and for respective risk assessment. Determination of compound solubility, compound puritiy and determination of metabolic competence of both S9 fractions and cell models will be part of the study.
• Study status:
  Finalised

Research institutions and networks

Institutions

Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM)

Federal Institute for Drugs and Medical Devices (BfArM)

Germany

Swansea University Medical School

United Kingdom

Federal Institute for Drugs and Medical Devices (BfArM) Bonn, Germany, Technical University Kaiserslautern Kaiserslautern, Germany, ICCR-Rossdorf Rossdorf, Germany, Swansea University Medical School Swansea, UK, Leadscope Columbus, Ohio, USA

Study timelines

Date when funding contract was signed

Planned: 09/08/2021

Actual: 09/08/2021

Study start date

Planned: 01/01/2022

Actual: 01/01/2022

Data analysis start date

Planned: 04/10/2022

Date of final study report

Planned: 30/10/2023

Actual: 30/10/2023

Sources of funding

Other

More details on funding

EMA

Study protocol

Initial protocol

D2_Study Protocol_EMA_SC02_in vitro_final

Regulatory

• Was the study required by a regulatory body?:
  Yes
• Is the study required by a Risk Management Plan (RMP)?:
  Not applicable

Other study registration identification numbers and links

SPECIFIC CONTRACT No. 02 implementing framework contract No. EMA/2020/46/L1.02