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) = 0.0000206 μg/L

Where:

A = 0.15 kg indacaterol maleate (total sold amount API in Sweden year 2020, data from IQVIA).

R = 0 % removal rate.

P = number of inhabitants in Sweden = 10 *10⁶

V (L/day) = volume of wastewater per capita and day = 200 (ECHA default) (ECHA 2008)

D = factor for dilution of waste water by surface water flow = 10 (ECHA default) (ECHA 2008).

Predicted No Effect Concentration (PNEC)

Ecotoxicological studies

Algae (Desmodesmus subspicatus) (92/69/EC (L383) C.3) (CETA Study Nr.: 37/02/23, Report Nr. 1803/L):

EC50 72 h (growth rate) > 100.0 mg/L

Crustacean (Daphnia magna, waterflea):

Acute toxicity

EC50 48 h (immobilisation) > 100.0 mg/L (92/69/EEC (L.383) C.2) (CETA Study Nr.: 1/03/22, Report Nr. 2066/L)

Fish:

Acute toxicity (Poecilia reticulata, guppy)

LC50 96 h (mortality) > 100.0 mg/L (OECD203) (CETA Study Nr: 37/02/21, Report Nr. 1807/L)

Other ecotoxicity data:

Bacterial respiration inhibition

EC₅₀ 3 h > 300.0 mg/L (activated sludge respiration inhibition) (87/302/EEC Part C) (ARC Study No.: NOV30)

PNEC derivation:

PNEC = 100.0 μg/L

PNEC (μg/L) = lowest EC₅₀/1000, where 1000 is the assessment factor used, based on the fact that three acute toxicity studies are available, covering three trophic levels. An EC₅₀ of 100 mg/L is used for this calculation, based on the fact that no acute toxic effects were observed in fish, Daphnia and algae at the highest tested concentration of 100.0 mg/L.

Environmental risk classification (PEC/PNEC ratio)

PEC/PNEC = 0.0000206 μg/L / 100.0 μg/L = 0.000000206, i.e. PEC/PNEC ≤ 0.1 which justifies the phrase "Use of indacaterol has been considered to result in insignificant environmental risk."

Degradation

Biotic degradation

Ready degradability:

0 % degradation in 28 days, not readily biodegradable (OECD301D). (CETA Study Nr.: 37/02/25, Report Nr.: 1811/L)

Justification of chosen degradation phrase:

Indacaterol is not readily biodegradable. Therefore, the phrase “Indacaterol is potentially persistent” is chosen.

Bioaccumulation

Partitioning coefficient:

Log P = -0.74 at 20.1°C (EC440/2008 A.8 8). (NOTOX Project 491643)

Justification of chosen bioaccumulation phrase:

Since log P < 4, indacaterol has low potential for bioaccumulation.

Excretion (metabolism)

In clinical studies which included urine collection, the amount of indacaterol excreted unchanged via urine was generally lower than 2% of the dose. In a human ADME study where indacaterol was given orally, the fecal route of excretion was dominant over the urinary route. Indacaterol was excreted into human feces primarily as unchanged parent drug (54% of the dose) and, to a lesser extent, hydroxylated indacaterol metabolites (23% of the dose). (Novartis Core Data Sheet Onbrez® Breezhaler®).

References

ECHA 2008, European Chemicals Agency. 2008 Guidance on information requirements and chemical safety assessment.

CETA Study Nr.:37/02/23, Report Nr. 1803/L. QAB149 Alga, growth inhibition test. Final report: 15.09.2004                                                                                                                                            Study No.: 1/03/22, Report No.: 2066/L. QAB149 Daphnia, acute immobilisation test. Final report: 15.09.2004                                                                                                                                                                                                                     

CETA Study Nr: 1807/L, Report Nr.: 37/02/21. QAB149 Fish, acute toxicity test. Final report: 15.09.2004                                                                                                                                                                                                      

Study project Nr.: NOV30, Report No: ARC- -UL-0561. QAB149 Activated sludge respiration inhibition test. Final report: November 2002.          

                             

CETA Study Nr.: 37/02/25, Report Nr.: 1811/L. QAB149 Determination of ready biological degradability - closed bottle test. Final report:15.09.2004.      

                                                                             

NOTOX Project 491643. Determination of physico-chemical properties of QAB149 DS / indacatarol maleate. Final report: 21.08.2009.   

Novartis Core Data Sheet Onbrez® Breezhaler® and related products (indacaterol maleate). Version 2.1. 30. September 2013.