Nilotinib

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.