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 = 0.000004439 μg/L

Where:

A = 0.0324 kg (total sold amount API in Sweden year 2022, data from IQVIA). No metabolism has been assumed in the PEC calculation and it has been assumed that 100% is excreted as the active parent molecule.

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 for dilution of wastewater by surface water flow = 10 (ECHA default) (Ref. I)

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

Predicted No Effect Concentration (PNEC)

Ecotoxicological studies:

• Algae (Pseudokirchneriella subcapitata):

EC₅₀ 72 h (Growth Rate) = 1.1 mg/L (guideline OECD 201) (Reference II)

NOEC 72 h = 0.056 mg/L (guideline OECD 201) (Reference II)

• Crustacean (Daphnia magna):

Acute toxicity

EC₅₀ 48 h (Immobilisation) = 233 mg/L (guideline FDA TAD 4.08) (Reference III)

Chronic toxicity

No test results are available.

• Fish (Lepomis macrochirus):

Acute toxicity

LC₅₀ 96 h (Mortality) = 225 mg/L (guideline FDA TAD 4.11)
(Reference IV)

Chronic toxicity

No test results are available.

• Other ecotoxicity data:

Microorganisms in activated sludge

EC₅₀ 3 hours (Inhibition) > 1000 mg/L (OECD 209) (Reference V)

PNEC = 1.1 μg/L

PNEC (μg/L) = lowest L(E)C₅₀/1000, where 1000 is the assessment factor used. EC₅₀ for algae (1.1 mg/L) has been used for this calculation since it is the most sensitive of the three tested species.

Environmental risk classification (PEC/PNEC ratio)

PEC/PNEC = 0.000004439 / 1.1 = 0.000004035, i.e. PEC/PNEC ≤ 0.1 which justifies the phrase “Use of kladribin has been considered to result in insignificant environmental risk.”

Degradation

Biotic degradation

No test results are available.

Abiotic degradation

No test results are available.

Bioaccumulation

Partitioning coefficient:

Log Kow = 0.0595 at pH 7 (guideline OECD 107) (Reference VI)

Justification of chosen bioaccumulation phrase:

Since log Kow < 4 at pH 7, the substance has low potential for bioaccumulation.

Excretion (metabolism)

No data available.

References

1. 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

2. Study report: Cladribine – Acute toxicity to the freshwater green alga, Pseudokirchneriella subcapitata. Springborn Smithers Laboratories, Wareham, USA (2007)

3. Federal Drug Agency Center for Drug Evaluation and Research. 1996. Retrospective review of ecotoxicity data submitted in environmental assessments. Docket 96N-0057. Rockville, MD, USA.

4. Study report: The acute toxicity of 2-CdA in the bluegill sunfish Lepomis macrochirus. Janssen Biotech N.V. Olen, Belgium (1992)

5. Study report: Cladribine – Activated Sludge Respiration Inhibition. Springborn Smithers Laboratories, Wareham, USA (2007)

6. Study report: Cladribine - Partition Coefficient (n-octanol / water): Shake Flask Method. DR. U. NOACK-LABORATORIEN, Sarstedt, Germany (2009)