Fluticasone furoate

Detailed information

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 reports

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.

Hazard

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 K_ow = 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."

Risk

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).

Hazard

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 K_ow = 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.

Risk

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.