Miljöpåverkan
Fezolinetant
Miljörisk:
Risk för miljöpåverkan av fezolinetant kan inte uteslutas då ekotoxikologiska data saknas.
Nedbrytning:
Det kan inte uteslutas att fezolinetant är persistent, då data saknas.
Bioackumulering:
Fezolinetant har låg potential att bioackumuleras.
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Detaljerad miljöinformation
Environmental Risk Classification
Predicted Environmental Concentration (PEC)
PEC in water is calculated according to the following formula:
PEC [µg/L] = (A*109*(100-R))/(365*P*V*D*100) = 1.37 x 10-6 x A x (100-R)PEC = 0.00137 μg/L
Where:
A: 10 kg (forcasted sales data five years after launch).R: 0 % removal rate (due to loss by adsorption to sludge particles, by volatilization, hydrolysis or biodegradation) = 0 since no data is available.
P: number of inhabitants in Sweden = 10 x 106
V: 200 L/day (volume of wastewater per capita and day) (ECHA default) (Ref.1)
D: 10 (factor for dilution of wastewater by surface water flow) (ECHA default) (Ref.1)
According to the European Medicines Agency guideline on environmental risk assessment of medicinal products (EMA/CHMP/SWP/4447/00), use of fezolinetant is unlikely to represent a risk for the environment, because the predicted environmental concentration (PEC) is below the action limit 0.01 μg/L.
Predicted No Effect Concentration (PNEC):
No data available
Environmental risk classification (PEC/PNEC ratio)
The PEC/PNEC ratio could not be determined because there are not sufficient ecotoxicological test results. This justifies the use of the environmental risk standard phrase: "Risk of environmental impact of fezolinetant cannot be excluded, since there is not sufficient ecotoxicity data available"/"Risk för miljöpåverkan av fezolinetant kan inte uteslutas då ekotoxikologiska data saknas."
Degradation
No data available. This justifies use of the degradation standard phrase: "The potential for persistence of fezolinetant cannot be excluded, due to lack of data" / "Nedbrytning: Det kan inte uteslutas att fezolinetant är persistent, då data saknas."
Bioaccumulation
A GLP compliant study was conducted according to OECD 107 test guideline (Ref. 4) to determine the logKow of fezolinetant over a range of environmentally relevant pH values (Ref. 5). The Partition coefficient in octanol/water (logKow) was found to be 1.4 at pH 7 (Ref. 5)
Since log Pow < 4 at neutral pH, the substance has low potential for bioaccumulation.
Also, LogP for fezolinetant is reported as 1.57 or 1.78 (Ref. 2) and fezolinetant is therefore concluded to have a low potential to bioaccumulate (Ref.3). This justifies the use of the bioaccumulation standard phrase: “Fezolinetant has low potential for bioaccumulation” / “Fezolinetant har låg potential att bioackumuleras.”
Excretion (Metabolism)
No data available
References
1. ECHA, European Chemicals Agency. 2008 Guidance on information requirements and chemical safety assessment.http://guidance.echa.europa.eu/docs/guidance_document/information_requirements_en
2. Fezolinetant: Uses, Interactions, Mechanism of Action | DrugBank Online
3. Guidance to regulation (EC) No1272/2008 on classification, labelling and packaging (CLP) of substances and mixtures. European Chemical Agency, http://guidance.echa.europa.eu/docs/guidance_document/clp_en.pdf
5. Volic N., 2021. Determination of Physico-Chemical Properties of Fezolinetant (ESN-364).Charles River Laboratories Den Bosch BV, Study No. 20213092