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) = 1.5^*10^-6*A(100-R)

PEC = 1.5x10^-5 μg/L

Where:

A = 0.1 kg (total sold amount API in Sweden year 2016, QuintilesIMS).

R = 0 % removal rate (worst case assumption)

P = number of inhabitants in Sweden = 9 *10⁶

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

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

Predicted No Effect Concentration (PNEC)

Ecotoxicological studies

Fosaprepitant is a pro-drug of aprepitant and is rapidly converted to aprepitant in the body. Therefore, this environment risk assessment considers the environmental fate and effects of the active moiety, aprepitant.

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

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

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

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. III)

Chronic toxicity

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

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.V)

Chronic toxicity

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

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 = 1.5x10^-5/1.8 = 8.3x10^-6, i.e. PEC/PNEC ≤ .1 which justifies the phrase "Use of fosaprepitant 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 (i.e., no biodegradation) (OECD 314). (Ref. VII)

Justification of chosen degradation phrase:

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

Bioaccumulation

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

Steady state BCF (whole fish) range: 39.2 - 47.9 (Ref.VIII)

Justification of chosen bioaccumulation phrase:

Since measure BCF range < 2000, the substance has low potential for bioaccumulation.

References

I. 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

II. 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.

III. 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.

IV. 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.

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

VI. 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.

VII. 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.

VIII. 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.