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 = 0.592 µg/L

Where:
A = 4323.375 kg (total sold amount API in Sweden year 2022, data from IQVIA)
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 I)
D = factor of dilution of waste water by surface water flow = 10 (ECHA default) (Ref I)

Predicted No Effect Concentration (PNEC)

Ecotoxicological studies

Algae (Desmodesmus subspicatus):
EC₁₀ 72 h (growth rate) = 43 640 µg/L
EC₅₀ 72 h (growth rate) = 428 670 µg/L
NOEC 72 h (growth rate) = 3 230 µg/L

(OECD 201)
(Ref II)

Crustacean (Daphnia magna):

EC₅₀ 48 h (immobilization) = > 100 000 μg/L

(OECD 202)

(Ref III)

Chronic toxicity Crustacean (Daphnia magna):

NOEC 21 days (reduction in reproduction) = 3 090 µg/L

EC₁₀ 21 days (reduction in reproduction) = 2 010 µg/L
(OECD 211)
(Ref IV)

Fish (Leuciscus idus f. melanotus):
LC₅₀ 96 h (mortality) = > 500 000 µg/L

(Protocol: non-standard. Additional information: static test. 5 test concentrations. 10 fish/test concentration. pH 8, oxygen content 7 mg/l, temperature 20 °C)

(Ref V)

Other ecotoxicity data:

PNEC = 40.2 μg/L

The PNEC (μg/L) = lowest EC₁₀/50 (assessment factor of 50 due to two long term toxicity endpoints available for two trophic levels (algae, daphnia))

The most sensitive species was Daphnia magna for which the EC₁₀ was used.

Environmental Risk Classification (PEC/PNEC ratio)

PEC/PNEC = 0.592 µg/L/40.2 μg/L = 0.015, i.e. PEC/PNEC ≤ 0.1, which justifies the phrase: Use of furosemide has been considered to result in insignificant environmental risk.

Degradation

No degradation data is available, hence justifying the degradation phrase:
"The potential for persistence of furosemid cannot be excluded, due to lack of data".

Bioaccumulation

Partitioning coefficient

Log K_ow = 2.03 at neutral pH (experimentally derived, method unknown)
(Ref VI)

Justification of chosen bioaccumulation phrase:

Since log K_ow < 4 at pH 7, furosemide has low potential for bioaccumulation.

Excretion (metabolism)

The metabolism of furosemide occurs mainly in the kidneys and the liver, to a smaller extent. The kidneys are responsible for about 85 % of total furosemide total clearance, where about 40 % involves biotransformation. Two major metabolites of furosemide are furosemide glucuronide, which is pharmacologically active, and saluamine (CSA) or 4-chloro-5-sulfamoylanthranilic acid.

The kidneys are responsible for 85 % of total furosemide total clearance, where about 43 % of the drug undergoes renal excretion. Significantly more furosemide is excreted in urine following the I.V. injection than after the tablet or oral solution. Approximately 50 % of the furosemide load is excreted unchanged in urine, and the rest is metabolized into glucuronide in the kidney.
(Ref VII)

References

1. ECHA, European Chemicals Agency. 2008 Guidance on information requirements and chemical safety assessment. https://echa.europa.eu/guidance-documents/guidance-on-information-requirements-and-chemical-safety-assessment

2. Aventis, 2002a, Study report: Furosemide - Growth Inhibition Test with freshwater algae

3. Aventis, 2002b, Study report: Furosemide – 48 h acute toxicity study in Daphnia magna

4. Sanofi, Internal Report: Furosemide: Influence to Daphnia magna in a Semi-Static Reproduction Test. Report # 117661221.2017

5. Hoechst, 1980, Study report: Furosemide – acute toxicity to Leuciscus idus f. melatonus

6. Source: DrugBank, Human Metabolome Database (HMDB). Sangster J; LOGKOW Databank. Sangster Res. Lab., Montreal Quebec, Canada (1994).

7. DrugBank - Furosemide, retrieved from Drug Bank 2021-06-04; find here.