Miljöpåverkan
Kabazitaxel
Miljörisk:
Användning av cabazitaxel har bedömts medföra försumbar risk för miljöpåverkan.
Nedbrytning:
Cabazitaxel är potentiellt persistent.
Bioackumulering:
Cabazitaxel har låg potential att bioackumuleras.
Läs mer
Detaljerad miljöinformation
Environmental Risk Classification
Predicted Environmental Concentration (PEC)
PEC is calculated according to the following formula:
PEC (µg/L) = (A*109*(100-R))/(365*P*V*D*100) = 1.37*10-6*A*(100-R)
PEC = 1.07*10-5 µg/L
Where:
A = 0.0778 kg (total sold amount API in Sweden year 2022, data from IQVIA)
R = 0% removal rate (due to loss by adsorption to sludge particles, by volatilization, hydrolysis or biodegradation)
P = number of inhabitants in Sweden = 10*106
V (L/day) = volume of wastewater per capita and day = 200 (ECHA default) (Ref I).
D = factor of dilution of waste water by surface water flow = 10 (ECHA default) (Ref I).
Predicted No Effect Concentration (PNEC)
Ecotoxicological studies
Algae (Pseudokirchneriella subcapitata):
EC50 72 h (biomass): 92 μg/L
NOEC 72 h (biomass): 43 μg/L
EC50 72 h (growth inhibition): 130 μg/L
NOEC 72 h (growth inhibition): 64 μg/L
(Protocol: OECD 201)
(Ref II)
Crustacean (Daphnia magna):
EC50 21 days (reproduction): >20 μg/L
NOEC 21 days (survival): 20 μg/l
NOEC 21 days (reproduction): 8.9 μg/L
(Protocol: OECD 211)
(Ref III)
Fish (Pimephales promelas):
NOEC 32 days (survival and growth rate): 110 μg/L
(Protocol: OECD 210)
(Ref IV)
Other ecotoxicity data:
PNEC = 0.89 µg/L
The PNEC (μg/L) = lowest EC50/10 was calculated using results from the most sensitive chronic toxicity endpoint and an assessment factor of 10 (long-term results from at least three species of the base set), to add a safety margin to the toxicity endpoint. The most sensitive species was Daphnia magna for which the NOEC 21 days was 8.9 μg/L.
Environmental Risk Classification (PEC/PNEC ratio)
PEC/PNEC= 1.07*10-5/0.89 = 1.2*10-5
PEC/PNEC ≤ 0.1 which justifies the phrase “Use of cabazitaxel has been considered to result in insignificant environmental risk”.
Degradation
Biotic degradation
Ready degradability:
Test showed 17.76 % degradation in 28 days (guideline OECD 301B)
(Ref V)
Justification of chosen degradation phrase:
Cabazitaxel fails to pass the criteria for ready biodegradability which justifies the phrase “Cabazitaxel is potentially persistent”.
Bioaccumulation
Partitioning coefficient:
Log Pow = 3.78 at pH 7 (guideline OECD 107) (Ref VI)
Justification of chosen bioaccumulation phrase:
Since log Pow < 4 at pH 7, cabazitaxel has low potential for bioaccumulation.
Excretion (metabolism)
Cabazitaxel is excreted to 2.3 % as parent compound and to 76 % as metabolites (Ref VII). Metabolites identified are around 20 (Ref VIII). The pharmacological activity of the metabolites is not known.
References
-
ECHA, European Chemicals Agency, 2008 Guidance on information requirements and chemical safety assessment.
-
Sanofi, internal report: 72-hour acute toxicity test with freshwater green alga, Pseudokirchneriella subcapitata. OECD 201. Report # 13570.6174, March 2010.
-
Sanofi, internal report: Full life-cycle toxicity test with water fleas, Daphnia magna under flow-through conditions. OECD 211. Report # 13570.6177, March 2010.
-
Sanofi, internal report: Early life-stage toxicity test with fathead minnow, Pimephales promelas. OECD 210. Report # 13570.6176, March 2010.
-
Sanofi, internal report: Determination of the biodegradability of a test substance. OECD 301B. Report # 13570.6173, March 2010.
-
Sanofi, internal report: Determinating the partition coefficient (n-Octanol/Water) by the flask-shaking method. OECD 107. Report # 13570.6170, March 2010.
-
Nightingale G, Ryu J. 2012. Cabazitaxel (Jevtana) A novel agent for metastatic castration-resistant prostate cancer. Drug Forecast. 37: 440-448.
-
Jevtana (Cabazitaxel) Injection, prescribing information. Bridgewater, N.J.: Sanofi; Jun, 2010. Available at: http://products.sanofi.us/jevtana/jevtana.html. Accessed February 25, 2014.