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Alecensa

Roche

Kapsel, hård 150 mg
(Vit, 19,2 mm, med "ALE" tryckt med svart bläck på överdelen och "150 mg" tryckt med svart bläck på underdelen.)

antineoplastiska medel, proteinkinashämmare

Aktiv substans:
ATC-kod: L01XE36
Utbytbarhet: Ej utbytbar
Läkemedel från Roche omfattas av Läkemedelsförsäkringen.
  • Vad är miljöinformation?

Miljöinformation

Miljöpåverkan

Alektinib

Miljörisk: Användning av alektinib har bedömts medföra försumbar risk för miljöpåverkan.
Nedbrytning: Alektinib är potentiellt persistent.
Bioackumulering: Alektinib har låg potential att bioackumuleras.


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Detaljerad miljöinformation

Identification and characterisation


Chemical name: Alectinib hydrochloride

CAS number: 1256589-74-8 [1]

Molecular weight: 519.086 [1]

Brand name: Alecensa [1]


Physico-chemical properties

Aqueous solubility: 46 mg/l (37 °C, pH 5) (method not specified) [1]

Dissociation constant, pKa: pKa = 6.7–7.54 QSAR [1], pKa = 11.2–13.7 QSAR [1], pKa = 4.4 QSAR [1]

Melting point: ca. 302 °C (with decomposition) [1]

Vapour pressure: 3.89*E–13 Pa (25 °C) QSAR

KH: 4.634*E–8 Pa*m3/mol QSAR


QSAR = QSAR-modelled (EPISuite, SPARC, ACD Solaris)


Predicted Environmental Concentration (PEC)


PEC is calculated according to the formula:


PEC (μg/L) = (A x 1'000'000'000 x (100-R)) / (365 x P x V x D x 100) = 1.5 x 10-6 x A x (100 - R) = 0.0013 μg/L


Where:

A Sold quantity = 8.63696288 kg/y (total sold amount API in Sweden year 2017, data from IQVIA)

R Removal rate = 0 % Default [2]

P Population of Sweden = 9000000

V Volume of Wastewater = 200 l/day Default [2]

D Factor for Dilution = 10 Default [2]


Predicted No Effect Concentration (PNEC)


Ecotoxicological Studies

Green alga (Raphidocelis subcapitata): [3]

72 h ErC50 (growth rate) >11.7 mg/l (OECD 201)

72 h EyC50 (yield) >11.7 mg/l (OECD 201)

72 h NOEC (overall NOEC) = 11.7 mg/l (OECD 201)


Water-flea (Daphnia magna): [4]

21 d NOEC (overall NOEC) = 0.133 mg/l (OECD 211)


Zebra fish (Danio rerio): [5]

36 d NOEC (overall NOEC) = 10 mg/l (OECD 210)


Micro-organisms (activated sludge): [6]

3 h EC50 (respiration inhibition) >1000 mg/l (OECD 209)

3 h NOEC (respiration inhibition) = 1000 mg/l (OECD 209)


PNEC Derivation

The PNEC is based on the following data:

PNEC (mg/l) = lowest chronic NOEC/10, where 10 is the assessment factor used. A NOEC of 0.133 mg/l (133 μg/l) for daphnids has been used for this calculation.

PNEC = 133 / 10 = 13.3 μg/l


Environmental Risk Classification (PEC/PNEC Ratio)

PEC Predicted Environmental Concentration = 0.0013 μg/l

PNEC Predicted No Effect Concentration = 13.3 μg/l

Ratio PEC/PNEC = 0.0001


PEC/PNEC = 0.0013/13.3 = 0.0001 for Alectinib hydrochloride which justifies the phrase 'Use of Alectinib hydrochloride has been considered to result in insignificant environmental risk.'


Degradation


Biotic Degradation

Ready biodegradability: [7]

0% after 28 days of incubation BOD/ThOD (OECD 301 F)


Inherent biodegradability: ND


Other degradation information: [8]

DT50 (water) = 1.5–2.3 d (OECD 308)

DT50 (total system) = 75–273 d (OECD 308)


Abiotic Degradation

Photodegradation: ND

Hydrolysis: ND


Alectinib hydrochloride is not readily biodegradable; a DT50 (total system) of 75–273 d in water/sediment systems justifies the phrase 'Alectinib hydrochloride is potentially persistent.'


Bioaccumulation/Adsorption


logDOW = 3.09 (pH 5) (OECD 117) [9]

logDOW = 3.86 (pH 7) (OECD 117) [9]

logPOW = 3.85 (pH 9, non-dissociated state) (OECD 117) [9]

KOC (soils) = 14921–32878 l/kg (OECD 106) [10]

KOC (sludges) = 5707–16634 l/kg (OECD 106) [10]

BCF = 146.8–147.7 l/kg (OECD 305) [11]


Alectinib hydrochloride has low potential for bioaccumulation since the Bioconcentration Factor (BCF) is <500.


Excretion/metabolism

Alectinib hydrochloride is eliminated from human plasma in with a median apparent terminal ranging from 18.2 to 25.3 hours. In massbalance studies, Alectinib hydrochloride was excreted predominantly by faecal pathway. [12]


References


1. F. Hoffmann-La Roche Ltd. 2018. Safety Data Sheet for Alectinib hydrochloride, 17.12.2018; https://www.roche.com/sustainability/what_we_do/for_communities_and_environment/environment/safety_data_sheetsrow. htm.

2. ECHA, European Chemicals Agency. 2008 Guidance on information requirements and chemical safety assessment. http://guidance.echa.europa.eu/docs/guidance_document/information_requirements_en.htm.

3. ECT Oekotoxikologie GmbH, on behalf of F. Hoffmann-La Roche Ltd, Basel, Switzerland (2015). CH5424802-002: A Study on the Toxicity to Algae (Pseudokirchneriella subcapitata) according to OECD Guideline No. 201, 2006 "Freshwater Alga and Cyanobacteria, Growth Inhibition Test". ECT study no. 14AZ3AO.

4. ECT Oekotoxikologie GmbH, on behalf of F. Hoffmann-La Roche Ltd, Basel, Switzerland (2015). CH5424802-002: A Study on the Chronic Toxicity to Daphnia magna according to the OECD Guideline 211 "Daphnia magna, Reproduction Test" adopted 2nd October, 2012. ECT study no. 15AZ7DB .

5. ECT Oekotoxikologie GmbH, on behalf of F. Hoffmann-La Roche Ltd, Basel, Switzerland (2015). CH5424802-002: A Study on the Toxicity to Early-Life Stages of Zebrafish according to OECD Guideline No. 210 "Fish, Early-life Stage Toxicity Test". ECT study no. 14AZ8FV.

6. ECT Oekotoxikologie GmbH, on behalf of F. Hoffmann-La Roche Ltd, Basel, Switzerland (2015). CH5424802-002: A Study on the Respiration Inhibition of Activated Sludge according to OECD Guideline for Testing of Chemicals No. 209. ECT study no. 14AZ6XA.

7. Hydrotox GmbH, on behalf of F. Hoffmann-La Roche Ltd, Basel, Switzerland (2014). AF802, Biodegradability in the Manometric Respirometry Test according to OECD 301 F (July 1992). Hydrotox study no. 888.

8. Battelle UK Ltd, on behalf of F. Hoffmann-La Roche Ltd, Basel, Switzerland (2015). [14C]-RO5424802: Aerobic Aquatic Transformation in Aquatic Sediment Systems. Battelle UK study no. JC/13/014.

9. Battelle UK Ltd, on behalf of F. Hoffmann-La Roche Ltd, Basel, Switzerland (2014). RO5424802: Determination of Octanol/Water Partition Coefficient. Battelle UK study no. JC/13/006.

10. Battelle UK Ltd, on behalf of F. Hoffmann-La Roche Ltd, Basel, Switzerland (2015). [14C]-RO5424802: Adsorption to and Desorption from Three Soils and Two Sludges. Battelle UK study no. JC/13/013.

11. ECT Oekotoxikologie GmbH, on behalf of F. Hoffmann-La Roche Ltd, Basel, Switzerland (2016). [14C]-CH5424802-002: A study on the bioconcentration in zebrafish according to OECD Guideline for Testing of Chemical No. 305. ECT study no. 14AZ3FX.

12. European Medicines Agency (EMA). Committee for Medicinal Products for Human Use (CHMP). Assessment report for Alecensa. EMA/10821/2017, 15 December 2016.