This summary information about persistence, bioaccumation and toxicity comes from assessment reports and Fass. The conclusion about persistence comes from the assessment reports. The risk comes from the assessment report from 2019.
Persistence. Fluticasone furoate is persistent.
Bioaccumulation. Fluticasone furoate has low potential for bioaccumulation.
Toxicity. Fluticasone furoate has very high chronic toxicity.
Risk. The use of fluticasone furoate has been considered to result in low environmental risk.
General information about assessment reports
Since 2006, an Environmental Risk Assessment (ERA) for the active pharmaceutical substance shall accompany an application for a marketing authorisation in EU for a medicinal product for human use. Parts of environmental data can be found in the public investigation report (PAR/EPAR for medicinal product through a centralized procedure). Since the benefit/risk assessment for human medicinal products at present does not include environmental effects, an update of the environmental risk assessment is not required for renewals of marketing authorizations. There is thus no requirement for companies to stay informed about the development of their substances from an environmental point of view and consequently to update the environmental risk assessment as new data are published.
Assessment report for Elebrato Ellipta, Trelegy Ellipta och Temybric Ellipta (fluticasone furoate/umeclidinium/vilanterol) EMEA/H/C/WS1369, 20 September 2018, EMA/630775/2018 and 26 April 2019, EMA/299628/2019.
Persistence: "OECD 304 A = DT50 > 137 d (12°C). Inherent biodegradability in Soil OECD 304 A = DT50 > 64d 3% mineralization in 64d. Remarks: Reliable Report provided FF (fluticasone furoate, editorial remark) considered as P."
Bioaccumulation: log Kow = 2.61.
Toxicity: There are data for 2 trophic levels, most sensitive fish (Pimephales promelas) NOEC 0.29 microg/L.
"Fluticasone furoate is a glucocorticoid and, as such, is considered a potential endocrine disruptor and therefore the potential endocrine activity of this compound was investigated in an appropriate chronic test system with relevant endpoints."
The risk, PEC/PNEC, calculated from data in the assessment report (2019) from a European perspective:
PEC = 0,0011 microg/L
PNEC = Lowest NOEC, 0.29 microg/L/100 (Assessment Factor (AF) for 1 chronic study) = 0.0029 microg/L
PEC/PNEC = 0.379 which gives the risk low.
Fass environmental information
Fass environmental information for Avamys (fluticasone furoate) from GlaxoSmithKline (downloaded 2022-01-17).
Persistence: "Inherent degradability: 0% degradation in 28 days (OECD 302C). Soil Metabolism: 3% degradation in 64 days (OECD 304). Fluticasone furoate is not readily degradable or inherently degradable but it is slowly degraded in soil. The phrase “fluticasone furoate is potentially persistent” is thus chosen."
Bioaccumulation: Log Kow = 2.61 at pH 7 (OECD 117).
Toxicity: There are data for 2 trophic levels, most sensitive fish (Pimephales promelas) NOEC chronic toxicity = 0.58 microg/L.
PEC/PNEC is based on sales data in Sweden in year 2018. "PNEC (μg/L) = lowest NOEC/10, where 10 is the assessment factor applied for one long-term NOECs but where there is a high degree of confidence that the dataset includes the most sensitive species (fish) and addresses the specific mode of action (endocrine disruption). On this basis the NOEC for fish has been used in the calculation." PEC/PNEC = 1,6 x 10-3 which gives the risk insignificant.
According to ECHA's guidelines for long-term data for one trophic level, AF is 100. This gives PEC/PNEC = 6.75 x 10-5/0.0058 = 0.0116, which gives the risk insignificant.
- European Medicines Agency. European public assessment reports (EPAR) for Elebrato Ellipta and Trelegy Ellipta (flutikasonfuroat/umeklidinium/vilanterol) EMEA/H/C/WS1369, 20 September 2018.
- European Medicines Agency. European public assessment report (EPAR) for Temybric Ellipta 26 April 2019, EMA/299628/2019.Fass.se för vårdpersonal.
- Fass.se för vårdpersonal.
- European Chemicals Agency, ECHA. Guidance on information requirements and chemical safety assessment Chapter R10: Characterisation of dose [concentration]-response for environment. Guidance for the implementation of REACH May 2008.
Author: Health and Medical Care Administration, Region Stockholm