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 = 0.05676 μg/L

Where:

A = 414,3148 kg (total sold amount API in Sweden year 2021, 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 (Pseudokirchnerellia subcapitata):

EC₅₀ 72 h (cell density): 52 700 μg/L

EC₅₀ 72 h (area under the growth curve): 46 700 μg/L

EC₅₀ 72h (growth rate): > 76 600 µg/L

NOEC72h (biomass): 17 200 µg/L

NOEC72 (growth rate): 36 300 µg/L

(Protocol: OECD 201)

(Ref II)

Crustacean (Daphnia magna):

EC₅₀ 48 h (acute immobilization): 314 000 μg/L

(Protocol: OECD 202)

(Ref III)

NOEC21d reproduction per introduced adult: 4 000 µg/L

NOEC21d reproduction per surviving adult ≥ 10 000 µg/L

NOEC21d mortality of adults ≥ 10 000 µg/L

(Ref VII)

Fish (Oncorhynchus mykiss):

LC₅₀ 96 h (mortatlity): 1 020 000 μg/L

(Protocol: OECD 203/FDA 4.11)

(Ref IV)

Other ecotoxicity data:

PNEC = 4 000 μg/L /50=80 μg/L

The PNEC (μg/L) was calculated using results from the most sensitive chronic toxicity endpoint and an assessment factor of 50 (two long-term results from species representing two trophic levels). The most sensitive species was Daphnia magna for which the NOEC(21d) was 4 000 μg/L.

Environmental Risk Classification (PEC/PNEC ratio)

PEC/PNEC= 0.05676/80 = 7.1*10^-4

PEC/PNEC ≤ 0.1 which justifies the phrase “Use of alfuzosin has been considered to result in insignificant environmental risk”

Degradation

No data available. Therefore, the summary phrase for degradation should be: "The potential for persistence of alfuzosin cannot be excluded, due to lack of data"

Bioaccumulation

Partition coefficient:

Alfuzosin has low potential for bioaccumulation, as indicated by a log K_ow of 1.51 at pH 7.4 (experimentally determined by HPLC) (Ref V)

Excretion (metabolism)

Alfuzosin is excreted to 10% as parent compound in urine. There are three metabolic pathways: oxidation, O-demethylation and N-dealkylation. Metabolites are mostly excreted in the feces (75 to 91%). The metabolites are pharmacologically inactive. (Ref VI)

References

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

2. Sanofi Internal Report: “Toxicity of Alfuzosin to the unicellular green alga, Pseudokirchneriella subcapitata” (OECD 201) (2006)

3. Sanofi Internal Report: “Acute toxicity of Alfuzosin to the water flea, Daphnia magna, determined under static test conditions” (OECD 202/FDA 4.08) (2006)

4. Sanofi Internal Report: “Acute toxicity of Alfuzosin to the rainbow trout, Oncorhynchus mykiss, determined under static test conditions” (OECD 203/FDA 4.11) (2006)

5. Sanofi Internal Report: "Xatral-product monograph" (Rev 2014)

6. McKeage K. and Plosker G. L. (2002) “Alfuzosin, a review of the therapeutic use of the prolonged-release formulation given once daily in the management of benign prostatic hyperplasia” Drugs 62 (4): 633-653

7. Ref: Sanofi, internal report: Alfuzosine HCL: Effect on Daphnia magna in a Semi-Static Reproduction Test. OECD 211. Report #143662221 August 2022