Detaljerad miljöinformation

Identification and characterisation

Chemical name: Baloxavir marboxil (BVM)

CAS number: 1985606-14-1 [1]

Molecular weight: 571,5547 [1]

Chemical name: Baloxavir (BV)

CAS number: 1985605-59-1 [1]

Molecular wight: 483,4931 [1]

Brand name: Xofluza

Physico-chemical properties

Aqueous solubility 5.1 mg/l (20 °C) (OECD 105) (BVM) [1]

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) = 1.37 x 10^-6 x A x (100 - R) = 0.0000008 µg/l

Where: Baloxavir marboxil (BVM) 0.00668 kg/y sales data from IQVIA /LIF - kg consumption 2022

A Sold quantity = 0.00565 kg/y as Baloxavir (BV)

R Removal Rate = 0 % Default [2]

P Population Sweden = 10 000 000

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) >3.2 mg/l mean measured (MMC) (OECD 201) (BV)

72 h EyC50 (yield) = 0.46 mg/l MMC (OECD 201) (BV)

72 h NOEC = 0.092 mg/l MMC (OECD 201) (BV)

Water-flea (Daphnia magna): [4]

21 d NOEC (reproduction) = 44 mg/l MMC (OECD 211) (BV)

Fathead minnow (Pimephales promelas): [5]

35 d NOEC (hatching success) = 0.11 mg/l MMC (OECD 210) (BV)

Micro-organisms (activated sludge): [6]

3 h EC50 = 56 mg/l (OECD 209) (BV)

PNEC Derivation

The PNEC is based on the following data:

PNEC (μg/l) = lowest chronic NOEC, where 10 is the assessment factor used. A NOEC of 0.092 mg/ml (92 μg/l) for algae has been used for this calculation.

PNEC = 92 μg/l / 10 = 9.2 μg/l (BV)

Environmental Risk Classification (PEC/PNEC Ratio)

PEC Predicted Environmental Concentration = 0.0000008 μg/l

PNEC Predicted No Effect Concentration = 9.2 μg/l

Ratio PEC/PNC = 0.00000008

PEC/PNEC = 0.000008/9.2 = 0.00000008 for Baloxavir which justifies the phrase 'Use of Baloxavir marboxil has been considered to result in insignificant environmental risk.'

Degradation

Biotic Degradadation

Ready biodegradability: [7]

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

Fate in sediment/water systems [8]

DT50 (total system) >120 d (OECD 308) (BV)

Abiotic Degradation

Photodegradation: ND

Hydrolysis: ND

Baloxavir marboxil is not readily biodegradable. Baloxavir is persistent in water/sediment systems. This justifies the phrase 'Baloxavir marboxil is potentially persistent.'

Bioaccumulation/Adsorption

logD_OW = 2.0 (pH 5) (OECD 107) (BV) [9]

logD_OW = 2.0 (pH 7) (OECD 107) (BV) [9]

logD_OW = 1.1 (pH 9) (OECD 107) (BV) [9]

K_OC (soils) = 107,000–186,000 l/kg (OECD 106) (BV) [10]

K_OC (sludges) = 16,200–44,000 l/kg (OECD 106) (BV) [10]

Baloxavir has low potential for bioaccumulation since the log D_OW (at pH 7) is <4.

References

1. F. Hoffmann-La Roche Ltd (2022): Environmental Risk Assessment Summary for Baloxavir marboxil. https://www.roche.com/sustainability/environment/environmental-risk-assessment-downloads.htm

2. European Medicines Agency (EMA) (2006/2015): Guideline on the environmental risk assessment of medicinal products for human use. European Medicines Agency, Committee for Medicinal Products for Human Use (CHMP), 01 June 2006, EMA/CHMP/SWP/447/00 corr 2

3. Envigo Research Limited, on behalf of Shionogi & Co., Ltd (2017): Toxicity of Baloxavir to Pseudokirchneriella subcapitata in a 72-hour Algal Growth Inhibition Test; OECD 201. Envigo study no. TC37MV

4. Envigo Research Limited, on behalf of Shionogi & Co., Ltd (2018): Effect of Baloxavir on Survival and Reproduction of Daphnia magna in a Semi-Static Test over Three Weeks; OECD 211. Envigo study no. SG67FT

5. Envigo Research Limited, on behalf of Shionogi & Co., Ltd (2018): Toxic Effects of Baloxavir to Fathead Minnow (Pimephales promelas) in an Early-Life Stage Toxicity Test; OECD 210. Envigo study no. GY73WB

6. Envigo Research Limited, on behalf of Shionogi & Co., Ltd (2017): Toxicity of Baloxavir to Activated Sludge in a Respiration Inhibition Test; OECD 209. Envigo study no. VF05RV

7. Arcadis Schweiz LTD, on behalf of F. Hoffmann-La Roche Ltd (2019): Baloxavir marboxil: Ready biodegradability in an aerobic, aqueous medium: Manometric Respirometry Test; OECD 301 F. ACH study no. A18-02435

8. Envigo Research Limited, on behalf of Shionogi & Co., Ltd (2017): Route and Rate of Degradation of [14C]-Baloxavir in Aerobic Aquatic Sediment Systems; OECD 308. Envigo study no PVO7LY

9. Envigo Research Limited, on behalf of Shionogi & Co., Ltd (2017): Determination of Baloxavir Partition Coefficient (Shake Flask Method); OECD 107. Envigo study no. MS75NV

10. Envigo Research Limited, on behalf of Shionogi & Co., Ltd (2017): Adsorption/Desorption of [14C]-Baloxavir on Three Soils and Two Sludges; OECD 106. Envigo study no NX1OCQ