Detaljerad miljöinformation

Environmental Risk Classification

Predicted Environmental Concentration (PEC)

PEC is calculated according to the following formula:

PEC (µg/L) = (A*10⁹*(100-R))/(365*P*V*D*100) = 1.37*10^-6*A*(100-R)

PEC = 5.48*10^-6 µg/L

Where:

A = 0.04 kg (total sold amount API in Sweden year 2020, data from IQVIA)

R = 0 % removal rate (due to loss by adsorption to sludge particles, by volatilization, hydrolysis or biodegradation) = 0 if no data is available.

P = number of inhabitants in Sweden = 10*10⁶

V (L/day) = volume of wastewater per capita and day = 200 ECHA default) (Ref. I)

D = factor of dilution of waste water by surface water flow = 10 ECHA default) (Ref. I)

Predicted No Effect Concentration (PNEC)

Ecotoxicological studies

No ecotoxicological test results are available.

Environmental risk classification (PEC/PNEC ratio)

The PEC/PNEC ratio could not be determined since no ecotoxicological test results are available.

According to the European Medicines Agency guideline on environmental risk assessment of medicinal products (EMA/CHMP/SWP/4447/00), use of milrinone is unlikely to represent a risk for the environment, because the predicted environmental concentration (PEC) is below the action limit of 0.01 μg/L.

Justification of chosen summary phrases for the environmental risk:

Risk of environmental impact of milrinone cannot be excluded, since no ecotoxicity data are available.

Degradation

Biotic degradation

Ready degradability:

Milrinone is potentially persistent as indicated by a 2.1 % biodegradation in 28 days. (FDA 3.11)

(Ref. II)

Chosen degradation phrase:
Milrinone is potentially persistent.

Bioaccumulation

Partitioning coefficient:

logP = 1.04; 0.33 (predicted (ALOGPS; ChemAxon, respectively)
(Ref. III)

Justification of chosen bioaccumulation phrase:
Since logP < 4, milrinone has low potential for bioaccumulation.

Excretion (metabolism)

Milrinone is mainly excreted in the urine, mainly in unchanged form (83 %) and to a lesser extent as inactive O-glucuronide (12 %). A small amount is excreted via faeces. In healthy subjects, 60 % of the dose was found in the urine within 2 hours supply and within the first 8 hours 90 % were found.
(Ref. IV)

References

1. ECHA, European Chemicals Agency. 2008 Guidance on information requirements and chemical safety assessment; find here.

2. Internal report, Sterling Winthrop: Milrinone: CO2 Production Test, March 1992. Report number not available.

3. Milrinone at Drug Bank, retrieved 2021-12-13 from Drug Bank.com; find here

4. SmPC of Corotrop, retrieved 2021-12-13 from SE MPA; find here.