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 = 2 E-04 μg/L

Where:

A = 1.1 kg (total sold amount API in Sweden year 2021, data from 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

Green Algae (Selenastrum capricornutum)) (U.S. EPA “Short-Term Methods for Estimating Chronic Toxicity of Effluents and Receiving Water to Freshwater Organisms”, 1994 (Ref. III):

EC₅₀ 96 h (growth rate) = 0.1 mg/L

NOEC = 0.05 mg/L

Crustacean, water flea (Daphnia magna) (U.S. EPA “Methods for Measuring the Acute Toxicity of Effluents and Receiving Waters to Fresh Water and Marine Organisms”, 1993) (Ref. III)

Acute toxicity

LC₅₀ 48 h (mortality) = 22.6 mg/L

NOEC = 15 mg/L

Fish, fathead minnow (Pimephales promelas) U.S. EPA “Methods for Measuring the Acute Toxicity of Effluents and Receiving Waters to Fresh Water and Marine Organisms”, 1993) (Ref. III):

Acute toxicity

LC₅₀ 96 h (mortality) = 2.4 mg/L

NOEC = 0.3 mg/L

Fish, fathead minnow (Pimephales promelas) (OECD 210) (Ref. IV):

Chronic toxicity

NOEC 32d (total length and dry weight) = 0.084 mg/L

LOEC 32d (total length and dry weight) = 0.16 mg/L

Crustacean, water flea (Daphnia magna) (OECD 211) (Ref. V):

Chronic toxicity

NOEC 21d = 0.67 mg/L

LOEC 21d = 1.4 mg/L

PNEC = 5 μg/L (50 μg/L / 10 based on the most sensitive acute NOEC for the green algae with an assessment factor (AF) of 10)

Environmental risk classification (PEC/PNEC ratio)

PEC/PNEC = 2 E-04/5 = 3 E-05 i.e. PEC/PNEC ≤ 0.1 which justifies the phrase "Use of caspofungin has been considered to result in insignificant environmental risk."

Biotic degradation

Biodegradation (OECD 302B)

71.9% degradation in 7 days (Ref. VI)

Elimination of caspofungin acetate from the activated sludge test solutions occurred steadily over the 28-day test. Test substance concentrations decreased by 70% within 7 days and indicates that caspofungin acetate undergoes inherent primary biodegradation (as defined by the OECD guidelines for inherent biodegradability testing). Additionally, the 20% decline of TOC in the activated sludge indicates that caspofungin acetate also undergoes some ultimate biodegradation by converting to CO2. Therefore, caspofungin acetate can be classified as inherently, primarily biodegradable, without pre-adaption to the inoculum according to the OECD Guidelines and is not expected to persist in the environment.

Abiotic degradation

Hydrolysis:

Half life = 2.8 hr at pH 7, 60 ºC (Ref. III)

Photolysis:

Half life = 24.5 days at pH 8.3 (Ref. III)

Justification of chosen degradation phrase:

Since caspofungin passes the criteria for inherent biodegradability, the phrase “Caspofungin is slowly degraded in the environment” was chosen.

Bioaccumulation

Partitioning coefficient:

Measured Log K_ow = - 1.6 at neutral pH (method unknown) (Ref. VII)

Justification of chosen bioaccumulation phrase:

Since log K_ow < 4, the substance has low potential for bioaccumulation

References

1. Data from IQVIA ”Consumption assessment in kg for input to environmental classification - updated 2022 (data 2021)”.

   
   

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. Merck, 2021. “Environmental Quality Criteria Monograph for Caspofungin”, 25 Oct 2021.

   
   

4. Smithers Viscient, 2015. "Caspofungin Acetate – Early Life-Stage Toxicity Test with Fathead Minnow (Pimephales promelas)", Test No., 359.6826, Wareham, MA, USA, 09 July 2015.

   
   

5. Smithers Viscient, 2015. "Caspofungin Acetate – Full Life-Cycle Toxicity Test with Water Fleas, Daphnia magna, Under Flow-Through Conditions Following OECD Guideline #211", Test No., 359.6827, Wareham, MA, USA, 27 May 2015.

   
   

6. Smithers Viscient, 2015. "Caspofungin Acetate – Determination of the Biodegradability of a Test Substance Based on OECD Method 302B (Zahn-Wellens/EMPA Test)", Test No., 359.6828, Wareham, MA, USA, 20 Jan 2015.

   
   

7. Merck, 2000. “Caspofungin Chemical and Pharmaceutical Manufacturing and Controls Documentation Summary”, 02 March, 2000.