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Regorafenib

Hazard 9 P 3 B 3 T 3 Risk See below

Information

The T-value in the score for hazard refers to chronic toxicity.

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.

Assessment report

Assessment report for Stivarga (regarofenib) 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: The Pharmaceutical unit of Region Stockholm