Estimation of TD50 and Acceptable Intake (AI) values of nitrosamines

Estimation of TD50 and Acceptable Intake (AI) values of nitrosamines

According to the ICH M7(R1) guideline, a preliminary analysis of actual and potential impurities should be done by searching the database and literature on bacteria’s carcinogenicity and mutagenicity.

The QSAR Lab offer includes read-across and determination of TD50 and AI values ​​for the substance defined by a client (compound name/compound CAS number).

The report includes:

  • detailed documentation on the methodology of searching for analogs for a defined compound,
  • SAR similarity analysis for selected analogs and a defined compound,
  • the estimated TD50 value for the defined compound based on the selected analog(s),
  • assessment of source publications on the carcinogenicity of analogs used to determine the TD50 value in terms of the quality of each of the studies performed and its results (e.g., compliance with OECD guidelines, GLP system, etc.)

The analyses are based on the expert knowledge and the results of in silico research according to:

  • EMA/454576/2016,
  • ICH guideline Q3A (R2) Impurities in New Drug Substances CPMP/ICH 2737/99 was last updated by EMA in October 2006,
  • M7(R1) Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk, which was first issued in 2014 with the most recent revision adopted by CHMP in February 2018,
  • Questions and answers for marketing authorisation holders/applicants on the CHMP Opinion for the Article 5(3) of Regulation (EC) No 726/2004 referral on nitrosamine impurities in human medicinal products EMA/409815/2020,
  • Read-across Assessment Framework.

The results of the analyses are compiled in the report.


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