This summary information about persistence and bioaccumulation for metformin is from the assessment report Segluromet (ertugliflozin/metformin hydrochloride) 25 January 2018, EMA/86928/2018 and Fass. Information about toxicity comes from Fass environmental information for Komboglyze. The risk comes from the report of Goodpoint.
Persistence. Metformin is slowly degraded in the environment.
Bioaccumulation. Metformin has low potential for bioaccumulation.
Toxicity. Metformin has moderate chronic toxicity.
Risk. The use of metformin in Sweden has been considered to result in low environmental risk.
Below is Hazard and Risk according to data from the assessment report for Segluromet (ertugliflozin/metformin hydrochloride) 25 January 2018, EMA / 86928/2018.
Persistence: "DT50, sediment (20C) = 14d, DT50, water (12C) = 12–43.3d, DT50, sediment (12C) = 38.8d, % shifting to sediment = 50.8–59.5% AR after 17d. TG218 test. Metformin can be considered persistent in water according to PBT criteria (DT50 > 40d)."
Bioaccumulation: log Kow -2, "Not B".
Chronic toxicity: There is NOEC for three trophic levels, lowest NOEC for fish 10 mg/L.
The risk, PEC/PNEC, calculated from data in the assessment report from a European perspective:
PEC = 5.0 mikrog/L
PNEC = Lowest NOEC, 10000 microg/L/10 (Assessment Factor (AF) for three chronic studies) = 1000 microg/L
PEC/PNEC = 0.005 which gives the risk insignificant.
"Disclaimer: With the exception of the literature studies and the Novartis Core data sheet, all studies used in this Environmental Assessment are the property of Janssen. Novartis has been authorised by Janssen to use the study reports for the purpose of contributing to the Swedish www.fass.se database."
Persistence: DT50 (total system) = 43.0–53.0 days (OECD 308, 101 days). [...] According to the pass criteria for OECD308 studies, metformin can be classified as ‘Metformin is slowly degraded in the environment' (DT50 for total system ≤ 120 days).
Bioaccumulation: Log P = -2.48 (OECD107).
Toxicity: There are data for 3 trophic levels, most sensitive fish (Pimephales promelas, fathead minnow) NOEC 32 days = 10300 microg/L.
PEC/PNEC is based on sales data in Sweden in year 2018. PEC/PNEC = 0.024 which gives the risk insignificant.
Persistence: Percentage Aerobic Biodegradation (FDA 3.11) 10 mg/L 28 d 0.6%: Not readily biodegradeable. OECD 308: 102 d. 1.0 mg/L (High Organic Matter Sediment) DT50 = 6.59 days (Total System) 1.0 mg/L (Low Organic Matter Sediment) DT50 = 55.0 days (Total System). Results from the aerobic biodegradation test, showed that metformin hydrochloride is not readily biodegradable. Evidence from the OECD 308 study is that metfromin hydrochloride is likley to dissipate from the aqueous phase and partition into the sediment phase. [...] The phrase “Metformin hydrochloride is slowly degraded in the environment.” has been assigned.
Bioaccumulation: Log Kow = -1.43.
Toxicity: There are data for 3 trophic levels, most sensitive crustaceans (Ceriodaphnia dubia) NOEC 1000 microg/L.
PEC/PNEC is based on sales data in Sweden in year 2017. PEC/PNEC = 0.23 which gives the risk low.
Measured levels in Sweden are far below reported concentration of environmental impact. Abroad significant higher levels in wastewater are reported.
Author: Health and Medical Care Administration, Region Stockholm