Sacubitril

Detailed information

Fass environmental information

Fass environmental information for sakubitril from Entresto (sacubitril, valsartan) from Novartis (downloaded 2023-09-28).

Hazard

Persistence: "DT50_{total system} = 6.5 – 11.2 days; DT90_{total system} = 21.7 – 37.2 days (OECD 308). [---] According to the criteria prescribed for OECD 308 studies and given that the DT50 of sacubitrat is < 32 days for the total system. Sacubitril can be classified as “Sacubitril is degraded in the environment.”"

Bioaccumulation: "LogD pH 2 = 2.9; LogD pH 5 = 1.7; LogD pH 7 = -0.66 (OECD107). ... Justification of chosen bioaccumulation phrase: Since log P < 4, Sacubitril has a low potential for bioaccumulation."

Toxicity: There are data for 3 trophic levels, most sensitive fish NOEC (Pimephales promelas, fathead minnow) NOEC 10 000 microg/L.

Risk

PEC/PNEC is based on sales data in Sweden in year 2021. PEC/PNEC = 0.00008 which gives the risk insignificant.

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.

The PEC values used to calculate risk in the manufacturers' assessment reports are based on the estimated use of the medicinal product to which the assessment report relates, not all medicinal products containing the same active substance.

Assessment report

Assessment report for Entresto, 24 September 2015, EMA/671279/2015. Sacubitril is metabolised to LBQ657 which the environmental risk assessment is about.

Hazard

Persistence: "OECD 308: DissT_{50, water} = 6.0 and 6.5 d. DegT_{50, system} = 11 and 11 d. % shifting to sediment: 36% and 56% at day 14, increasing thereafter."

Bioaccumulation: Log K_ow = 2.9.

Chronic toxicity: There are data for 3 trophic levels, most sensitive fish NOEC ≥ 10 000 microg/L.

Comment: Values reported as greater than or greater than/equal to are not according to the guidelines. The actual value may be lower.

Risk

The risk, PEC/PNEC, calculated from data in the assessment report from a European perspective:

PEC = 0.97 microg/L.

PNEC = Lowest NOEC, 10 000 microg/L/10 (Assessment Factor (AF) for 3 chronic studies) = 1 000 microg/L

PEC/PNEC = 0.00097 which gives the risk insignificant.