Nilotinib
Summary
Persistence. Nilotinib is slowly degraded in the environment.
Bioaccumulation. Nilotinib has low potential for bioaccumulation.
Toxicity. Nilotinib has very high chronic toxicity.
Risk. The use of nilotinib (sales data Sweden 2016) has been considered to result in insignificant environmental risk.
Underlying data for P and B are from assessment report and fass.se. T and risk come from Fass.
Detailed information
Assessment report
Assessment report for Tasigna (nilotinib) from 20 December 2010 EMA/CHMP/678167/2010 and from 21 April 2017 EMA/313746/2017.
Hazard
Persistence: "Nilotinib showed a half-life of 179-213 days for the total water-sediment systems (normalized to 12°C) and a half-life of 369 days for soils (normalized to 12°C). Consequently the criteria for a very persistent (vP) substance of 180 days in water-sediment systems and soils defined in the REACH guidance on PBT assessment is exceeded for both compartments."
Bioaccumulation: "Bioconcentration factor of 127. This assessment revealed that nilotinib cannot be considered as a PBT substance based on its low bioconcentration potential in fish."
Toxicity: There are data for 3 trophic levels, most sensitive crustacean (Daphnia magna) NOEC-21 days = 12.7 microg/L. "However algae toxicity and fish chronic toxicity need to be further characterised." No such data are available at the present time, in consultation with the Swedish Medical Products Agency 2018-09-04.
"The active ingredient is not considered as PBT substance. However, the active ingredient and its transformation products are very persistent in soil and sediment."
Risk
The risk, PEC/PNEC, calculated from data in the assessment report from a European perspective:
PEC = 4 microg/L (worst case, there are also data 0,036 och 0,009 "[prevalence and proposal for market data, used in Phase II]") (EMA/313746/2017).
PNEC = NOEC 12.7 microg/L/100 (Assessment Factor (AF) for 1 chronic study) = 0.127 microg/L.
PEC/PNEC = 31.496 which gives the risk high.
According to EMA/CHMP/678167/2010: "Based on data on Daphnia magna, effects on microorganism, sub-chronic effects on fish early life stage, at the predicted environmental concentration (PEC) and calculation of PEC/PNEC ratios, it can be concluded that nilotinib HCl would not represent a relevant risk to surface water and groundwater microorganisms (sewage treatment plant)."
Fass environmental information
Fass environmental information for Tasigna (downloaded 2018-09-05).
Hazard
Persistence: "DT50 (total system) = 84.0–100.0 days. Based on the DT50 for the total system, the phrase 'Nilotinb is slowly degraded in the environment' is chosen.'"
Bioaccumulation: BCFss = 65–75.
Toxicity: There is data for 3 trophic levels, lowest for fish (zebra fish) NOEC 7 days = 2.6 microg/L.
Risk
PEC/PNEC is based on sales data in Sweden in year 2016. PEC = 0.0069 microg/L. PNEC = 0.26 microg/L. PEC/PNEC = 0.027 which gives the risk insignificant.
Author: Health and Medical Care Administration, Region Stockholm