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 P_ow = 3.78 at pH 7 (guideline OECD 107) (Ref VI)

Justification of chosen bioaccumulation phrase:

Since log P_ow < 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

1. ECHA, European Chemicals Agency, 2008 Guidance on information requirements and chemical safety assessment.

2. Sanofi, internal report: 72-hour acute toxicity test with freshwater green alga, Pseudokirchneriella subcapitata. OECD 201. Report # 13570.6174, March 2010.

3. Sanofi, internal report: Full life-cycle toxicity test with water fleas, Daphnia magna under flow-through conditions. OECD 211. Report # 13570.6177, March 2010.

4. Sanofi, internal report: Early life-stage toxicity test with fathead minnow, Pimephales promelas. OECD 210. Report # 13570.6176, March 2010.

5. Sanofi, internal report: Determination of the biodegradability of a test substance. OECD 301B. Report # 13570.6173, March 2010.

6. Sanofi, internal report: Determinating the partition coefficient (n-Octanol/Water) by the flask-shaking method. OECD 107. Report # 13570.6170, March 2010.

7. Nightingale G, Ryu J. 2012. Cabazitaxel (Jevtana) A novel agent for metastatic castration-resistant prostate cancer. Drug Forecast. 37: 440-448.

8. Jevtana (Cabazitaxel) Injection, prescribing information. Bridgewater, N.J.: Sanofi; Jun, 2010. Available at: http://products.sanofi.us/jevtana/jevtana.html. Accessed February 25, 2014.