Detaljerad miljöinformation

Environmental Risk Classification

Predicted Environmental Concentration (PEC)

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PEC is calculated according to the following formula:

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

PEC = 0,00065305 µg/L

A: 4.7668 kg total sold amount API in Sweden year 2023, data from IQVIA (Ref. I)

R = 0 % removal rate (due to loss by adsorption to sludge particles, by volatilization, hydrolysis or biodegradation)

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)

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

Predicted No Effect Concentration (PNEC)

Ecotoxicological studies*

Algae (Algae, Growth Inhibition):

NOEC = 5820 μg/L. Guideline OECD 201. (Reference III)

Crustacean (Daphnia sp. Reproduction Test):

Chronic toxicity

NOEC = 19600 μg/L. Guideline OECD 211. (Reference III)

Fish (Fish, Early Life Stage Toxicity):

Chronic toxicity

NOEC = 8910 μg/L. Guideline OECD 210. (Reference III)

Microorganisms (Activated Sludge, Respiration Test):

NOEC = 5900 μg/L. Guideline OECD 209. (Reference III)

The PNEC was calculated by division of the lowest NOEC of the most sensitive taxonomic group considering an appropriate assessment factor (AF). The most sensitive taxonomic group were algae, and the lowest effect level was reported as NOEC = 5820 µg/L. The regulatory default standard AF of 10 was used, which is applicable when there are chronic aquatic toxicity studies representing the three trophic levels (algae, crustaceans, and fish).

PNEC = 5820 µg/L / 10 = 582 µg/L

Environmental risk classification (PEC/PNEC ratio)

The risk quotient PEC/PNEC was calculated with 0,00065305 µg/L / 582 µg/L = 0.00000112.

Justification of chosen environmental risk phrase:

A risk quotient < 0.1 qualifies for the phrase “Use of fidaxomicin has been considered to result insignificant environmental risk”.

Degradation

Biotic degradation

Ready degradability:

Ready biodegradability Test (guideline OECD 301). Fidaxomicin is considered to be not readily biodegradable. (Reference III)

Justification of chosen degradation phrase:

Fidaxomicin did not pass the criteria for ready biodegradability. The phrase "Fidaxomicin is potentially persistent" is thus chosen.

Bioaccumulation

Partitioning coefficient:

The log K_ow was reported with 4.4 at pH 7.4. Guideline OECD 107. (Reference III)

Justification of chosen bioaccumulation phrase:

As the log K_ow was > 4 fidaxomicin is considered bioaccumulative which qualifies for the phrase “Fidaxomicin has high potential for bioaccumulation”.

REFERENCES

1. Data from IQVIA ”Consumption assessment in kg for input to environmental classification v1 - updated 2024 (data 2023)”.

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

3. Environmental Risk Assessment, Non-GMO_version_3