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) = 1.37*10^-6 * 19.0023 * 100 = 0,002603 μg/L = 2.6 ng/L

Where:

A = 19.0023 kg deferoxamine mesylate (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) = 0, if no data is available.

P = number of inhabitants in Sweden = 10 * 10⁶

V (L/day) = volume of wastewater per capita and day = 200 (ECHA default) (ECHA 2008)

D = factor for dilution of waste water by surface water flow = 10 (ECHA default) (ECHA 2008).

Predicted No Effect Concentration (PNEC)

Ecotoxicological studies

Algae (Selenastrum capricornutum): no data available

Crustacean (Daphnia magna, waterflea):

Acute toxicity

EC50 48 h (immobilisation) > 100.0 mg/L (OECD 202) (Ciba-Geigy Project No. 95N021)

Fish (Danio rerio, zebrafish):

Acute toxicity

LC50 96 h (mortality) > 1000.0 mg/L (OECD 203) (Ciba-Geigy Ecotoxicology department Project No. 821478)

Other ecotoxicity data:

Bacterial Respiration Inhibition:

IC20 3 h > 100.0 mg/L (activated sludge respiration inhibition, OECD209) (Ciba-Geigy Project No.95G037)

PNEC Derivation:

No PNEC can be calculated since there is only environmental toxicity data from two trophic levels available.

Environmental risk classification (PEC/PNEC ratio)

No PNEC can be calculated since there is not sufficient environmental toxicity data available. Therefore, the following phrase is used: "Risk of environmental impact of deferoxamine cannot be excluded, since there is not sufficient ecotoxicity data available."

However, according to the European Medicines Agency guideline on environmental risk assessment of medicinal products (EMA/CHMP/SWP/44447/00 corr2), the use of deferoxamine is unlikely to represent a risk for the environment, because the predicted environmental concentration (PEC) is below the action limit 0.01 μg/L.

Degradation

Biotic degradation

Ready degradability:

69 % degradation in 28 days, readily biodegradable (OECD 301B) (Ciba-Geigy Project No. 90.2349)

Justification of chosen degradation phrase:

Deferoxamine passes the criteria for ready biodegradation. The phrase Deferoxamine is degraded in the environment is thus chosen.

Bioaccumulation

Partitioning coefficient:

Log K_ow < -3.0 (20 °C, method unknown).

Justification of chosen bioaccumulation phrase:

Since log Kow < 4, deferoxamine has low potential for bioaccumulation.

Partitioning coefficient:

Log K_ow = 2.62 (shake flask method) (Gotsbacher et al. 2017)

Justification of chosen bioaccumulation phrase:

Since log Kow < 4, deferoxamine has low potential for bioaccumulation.

Excretion (metabolism)

Both desferrioxamine DFO and ferrioxamine (FO) have biphasic elimination after intramuscular injection in healthy volunteers; for DFO the apparent distribution half-life is 1 hour, and for FO 2.4 hours. The apparent terminal half-life is 6 hours for both. Within six hours of injection, 22 % of the dose appears in the urine as DFO and 1 % as FO. (DESFERAL® (desferrioxamine) Core Data Sheet).

References

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

• EMA 2006, European Medicines Agency. European Medicines Agency guideline on environmental risk assessment of medicinal products (EMA/CHMP/SWP/4447/00). https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-environmental-risk-assessment-medicinal-products-human-use-first-version_en.pdf

• Ciba-Geigy Project No. 95N021. No full reference available.

• Ciba-Geigy Ecotoxicology department Project No. 821478. No full reference available.

• Ciba-Geigy Project No.95G037. No full reference available.

• Ciba-Geigy Project No. 90.2349, 21.11.1990. No full reference available.

• Gotsbacher Michael P, Telfer Thomas J, Witting Paul K, Double Kay L, Finkelstein David I, Codd Rachel, Analogues of desferrioxamine B designed to attenuate iron-mediated neurodegeneration: synthesis, characterisation and activity in the MPTP-mouse model of Parkinson’s disease, Metallomics, Volume 9, Issue 7, July 2017, Pages 852–864, https://doi.org/10.1039/c7mt00039a