In vitro mutagenicity methodology for nitrosamines (InVitroNAmutagenicity)

Study type

• Study type:
  Not applicable
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness

  Other
• If ‘Not applicable’, further details on the study type:
  In vitro study on mutagenicity of nitrosamines
• If ‘other’, further details on the scope of the study:
  Optimization of in vitro mutagenicity/genotoxicity assays for prediction of in vivo mutagenicity and cancerogenicity of nitrosamines

Study drug and medical condition

• Anatomical Therapeutic Chemical (ATC) code:
  (B03BB) Folic acid and derivatives

  Folic acid and derivatives

Population studied

• Age groups:
  Adults (18 to < 46 years)

  Adults (46 to < 65 years)
• Estimated number of subjects:
  0

Study design details

• Main study objective:
  Generating a better understanding on how the Ames test and the in vitro Comet assay can be methodologically optimized to reliably detect mutagenicity of different nitrosamines (NAs) and API-derived nitroso compounds.
• Outcomes:
  Experimental data on mutagenicity of nitrosamines and API-derived nitroso compounds in the Ames test under different conditions, experimental Comet assay data on induction of DNA damage by these compounds using in vitro liver cell models and data on solubility, purity and on metabolic competence of S9 fractions and cell models.
• Data analysis plan:
  A carefully selected set of reference NAs, active pharmaceutical ingredient (API)-derived NAs and supporting reference compounds will be used to finally evaluate 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. The study will be complemented by a small Comet assay round robin study with HepG2 cells to demonstrate reproducibility.

Documents

Study results

EUPAS49355_Abstract_Study Results