Regorafenib
Summary
Risk. Regorafenib is considered to have particularly hazardous properties. According to EU established criteria, regorafenib is considered a PBT/vPvB substance. The toxicity of aquatic organisms is very high, the substance is capable of bioaccumulation and degradation is slowly in the environment.
This summary information comes from assessment report and fass.se.
Detailed information
Assessment report
Assessment report for Stivarga (regorafenib) 4 July 2017, EMA / 467788/2017.
Hazard
Persistence: DT50water = <1 day, DT50system = >> 100 days at 22–24 degrees Celsius and DT50soil = 181 days at 20 +/- 2 degrees Celsius.
Bioaccumulation: BCF = 3 241 L/kg.
Chronic toxicity: There is NOEC for three trophic levels, lowest NOEC for fish 0.007 microg/L.
"PBT-statement: regorafenib is considered PBT, not vPvB."
Risk
The risk, PEC/PNEC, calculated from data in the assessment report from a European perspective:
PEC = 0.6 microg/L.
PNEC = Lowest NOEC, 0.007 microg/L/10 (Assessment Factor (AF) chronic studies with three species) = 0.0007 microg/L.
PEC/PNEC = 857.
Fass environmental information
Fass environmental information for Stivarga (downloaded 2018-05-03).
PEC/PNEC is based on sales data in Sweden in 2015. PEC / PNEC = 0.08
"The calculated PEC/PNEC value is <0.1. Hence, risk assessment procedures would indicate that regorafenib has insignificant long-term risk to the environment. However, the half-life in freshwater sediment is >120d, the BCF is >2000, and the chronic toxicity is <0.01 mg/L (NOEC). Regorafenib should therefore be regarded as PBT substance, according to the ECHA guidance criteria, and as such the current PEC/PNEC ratio may underestimate the potential for long-term risks to aquatic organisms."
Author: Health and Medical Care Administration, Region Stockholm