This summary information on persistence and toxicity comes from previous environmental information on fass.se (2011-04-29). Information about bioaccumulation and risk comes from the report from Goodpoint.
Persistence. Donepezil is potentially persistent.
Bioaccumulation. With a log P around 4.7 for donepezil, a strong bioconcentration can be expected.
Toxicity. Acute toxicity data are available only for crustacean. Toxicity data where two levels are missing, is recalculated by a factor of 5. This gives a very high acute toxicity.
Risk. Certain environmental risk from a Swedish perspective.
Persistence: "64 day Screen: Some evidence of biodegradation over 64 days in sludge." The substance is stated to be potentially persistent.
Bioaccumulation: Log D = 2.00 at pH 7.
Acute toxicity: There is data for 1 trophic level, crustacean (Daphnia magna) 48 hr EC50 4300 microg/L.
PEC/PNEC is based on sales data in Sweden. However, it is not clear for which year. PEC/PNEC = 0.016. Available ecotoxicological data do not exclude the risk of environmental impact.
Persistence: It cannot be excluded that donepezil is persistent, due to the lack of data.
Bioaccumulation: It cannot be excluded that donepezil can be bioaccumulated, due to the lack of data.
Toxicity: No data.
Risk of environmental impact of donepezil cannot be excluded, due to the lack of environmental toxicity data.
Donepezil has been measured in treated wastewater and surface water within Region Stockholm but was below the limit of quantification in 2020.
Comparative assessment of environmental risk when using medicinal products in the treatment of Alzheimer's disease/dementia (memantine, donepezil, rivastigmine, galantamine) from a Swedish perspective.
All investigated substances are likely to occur in concentrations close to or below 20 ng/L in Swedish aquatic environments exposed to treated wastewater. The environmental risk is very low for galantamine and rivastigmine, based on expected water exposure in relation to both potential for bioconcentration and potency in humans (fish plasma model) as well as available ecotoxicological data. The environmental risk is also low for memantine, although the ecotoxicity information is more scarce. However, the use of donepezil is associated with a certain environmental risk. The risk is based on the high fat solubility of the substance and thus high potential to bioconcentrate in aquatic biota, together with the high potency of the substance in humans. Based on measured wastewater concentrations and 10 times dilution in recipients, the blood plasma content of exposed fish is estimated to be approximately 4 % of Cmax in blood plasma in treated patients, providing some opportunity for pharmacological effects to occur (Cuklev et al, 2011). Measurements of donepezil in the livers of fish exposed to (foreign) municipal wastewater support this risk picture. Expected effects are primarily on behavior. However, ecotoxicological studies aimed at establishing lowest effect Concentration are lacking.
The use of galantamine, rivastigmine and memantine is not considered to pose an environmental risk. There is an increased risk of donepezil, but due to the lack of ecotoxicity studies, the scientific support is not currently considered strong enough to recommend an exchange. Continued measurements of donepezil in treated wastewater are recommended together with measurements in exposed aquatic biota.
Author: Health and Medical Care Administration, Region Stockholm