Nintedanib

Assessment report

Assessment report for Ofev (nintedanib) 20 November 2014, EMA/76777/2015.

Hazard

Persistence: "DT50 or ready biodegradability. DT50 or ready biodegradability. Conclusion P. OECD 301B; Not ready biodegradable. Study report No U09-0242-01. OECD 308; River (r), pond (p). DT50, water = 0.56 (r) and 0.43 (p). DT50, sediment = not calculated as no or very low degradation was observed. DT50, whole system = 1.28 (r) and 0.47 (p). Kd values = 1.28 (r) and 0.47 (p). Conclusion: Nintedanib is rapidly dissipated from the water phase, and adsorbs to the sediment. Once in the sediment, the degradation process is slow, mainly via formation of bound residues and minor metabolites."

Bioaccumulation: "pH 5: log D = 0.93, pH 7: log D = 2.7, pH 9: log D = 3.34, log P = 3.4." Conclusion not B.

Toxicity: There are data for 3 trophic levels, most sensitive fish (Brachydanio rerio) NOEC 38 microg/L.

Risk

The risk, PEC/PNEC, calculated from data in the assessment report from a European perspective:

PEC = 2.5 microg/L

PNEC = Lowest NOEC, 38 microg/L/10 (Assessment Factor (AF) for 3 chronic studies) = 3.8 microg/L

PEC/PNEC = 0.658 which gives the risk low.

Fass environmental information

Fass environmental information for Ofev (nintedanib) (downloaded 2019-04-24).

Hazard

Persistence: "Nintedanib did not pass the ready degradation test (OECD 301B). In a tranformation study (OECD 308) it was degraded in sediment although more than 15% of the parent compound remained at the end of the study. Based on these data Nintedanib is considered to be “slowly degraded in the enviroment”."

Bioaccumulation: "pH 5: log D = 0.93, pH 7: log D = 2.7, pH 9: log D = 3.34, log P = 3.4. Based on the data from the OECD Guideline 122 study showing an n-octanol/water partition coefficient of < 4 at pH 7, Nintedanib is considered to have “low potential for bioaccumulation”."

Toxicity: There are data for 3 trophic levels, most sensitive fish NOEC (Danio rerio, 21 days, lethality) 38 microg/L.

Risk

PEC/PNEC is based on sales data in Sweden in year 2018. PEC/PNEC = 0.00076 which gives the risk insignificant.