Detaljerad miljöinformation

Environmental Risk Classification

Predicted Environmental Concentration (PEC)

PEC is calculated according to the following formula:

PEC (μg/L) = (A^*10^9*(100-R))/(365^*P^*V^*D^*100) = 1.37^*10^-6*A(100-R)

PEC = 0.0005 μg/L

Where:

A = 3.3 kg (total sold amount API in Sweden year 2022, IQVIA) (Ref. I)

R = 0 % removal rate (worst case assumption)

P = number of inhabitants in Sweden = 10 ^*10⁶

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

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

Predicted No Effect Concentration (PNEC)

Ecotoxicological studies

Due to the low solubility, tests were conducted using solvent and solvent control

(approx. 0.55 mg/L in aqueous solution).

Algae, green algae (Pseudokirchneriella subcapitata) OECD 201 (Ref III):

EC₅₀ 72 hr (growth; yield) > 0.184 mg/L; no toxicity up to the limit of solubility

NOEC 72 hr (growth; yield) = 0.184 mg/L; no toxicity up to the limit of solubility

Crustacean, water flea (Daphnia magna):

Acute toxicity

EC₅₀ 48 h (mortality) > 0.345 mg/L; no toxicity up to limit of solubility (OECD 202)

(Ref. IV)

Chronic toxicity

21 day NOEC (growth) = 0.018 mg/L (OECD 211) (Ref. V)

Fish, Fathead minnow (Pimephales promelas):

Acute toxicity

LC₅₀ 96 h (mortality) > 0.462 mg/L (OECD 203) no toxicity up to limit of solubility (Ref.VI)

Chronic toxicity

33 day NOEC (dry weight) = 0.195 mg/L (OECD 210) no toxicity up to the limit of solubility (Rev VII)

PNEC = 1.8 µg/L based on the chronic NOEC for the most sensitive species (D. magna) divided by an assessment factor of 10, per the Guidance.

Environmental risk classification (PEC/PNEC ratio)

PEC/PNEC = 0.0005/1.8 = 0.0003, i.e. PEC/PNEC ≤ 0.1 which justifies the phrase "Use of aprepitant has been considered to result in insignificant environmental risk."

Degradation

Biotic degradation

Biodegradation in sludge:

Test results 50% degradation in 66 days based on CO₂ evolution (not rapidly degradable) (OECD 314) (Ref. VIII)

Justification of chosen degradation phrase:

Based on the data presented above, the phrase, “Aprepitant is potentially persistent” is chosen.

Bioaccumulation

Bioconcentration Factor (BCF), bluegill sunfish, (Lepomis macrochirus)(OECD 305)

Steady state BCF (whole fish) 39.2 - 47.9 (Ref. IX)

Justification of chosen bioaccumulation phrase:

Since measured BCF range < 500, the substance has low potential for bioaccumulation.

References

1. Data from IQVIA ”Consumption assessment in kg for input to environmental classification - updated 2023 (data 2022)”.

2. ECHA, European Chemicals Agency. 2008 Guidance on information requirements and chemical safety assessment. http://guidance.echa.europa.eu/docs/guidance_document/information_requirements_en.htm

3. Smithers Viscient AG, 2011. "Aprepitant: Growth Inhibition Test with Pseudokirchneriella subcapitata (syn. Selenastrum capricornutum) under Static Conditions, Following OECD Guideline 201," Study No. 1115.005.430, SV, Horn, Switzerland, 6 June 2011.

4. Toxikon Corporation 2003. "Aprepitant: Acute Toxicity to the Water Flea, Daphnia magna, Under Static Conditions," Study No., 03J0004a, TOX, Jupiter, FL, USA 10 November 2003.

5. Smithers Viscient AG, 2011. "Aprepitant: Full Life Cycle Toxicity Test with Water Fleas, Daphnia magna, Under Static Renewal Conditions, Following OECD Guideline #211," Study No. 1115.005.230, SV, Horn, Switzerland, 29 June 2011.

6. Toxikon Corporation 2003. "Aprepitant: Acute Toxicity to Fathead Minnow, Pimephales promelas, Under Static Conditions," Study No., 03J0004b, TOX, Jupiter, FL, USA 6 November 2003.

7. Smithers Viscient AG, 2011. "Aprepitant: Early life-stage toxicity test with fathead minnow (Pimephales promelas) Following OECD Guideline #210," Study No. 1115.005.122, SV, Horn, Switzerland, 27 October 2011.

8. Smithers Viscient AG 2011. "Aprepitant: Determination of the Biodegradability in Activated Sludge Based on Procedures of OECD Method 314," Study No., 1115.005.791, SV, Horn, Switzerland 28 January 2011.

9. Smithers Viscient AG, 2011. "Aprepitant: Flow-through Bioconcentration Study with Bluegill Sunfish (Lepomis macrochirus)," Study No. 1115.005.135, SV, Horn, Switzerland, 18 November 2011.