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 = 0.217941134 μg/L

Where:

A = 1590.8112 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)

Predicted No Effect Concentration (PNEC)

Ecotoxicological studies

Algae (Selenastrum capricornutum):

EC₅₀ 72 h (Growth Rate) = > 1030 mg/L (guideline FDA TAD 4.01) (Reference II)

NOEC = ≥ 1030 mg/L (guideline FDA TAD 4.01) (Reference II)

Crustacean (Daphnia magna):

Acute toxicity

EC₅₀ 48h (Immobilization) = > 989 mg/L (guideline FDA TAD 4.08) (Reference III)

Fish (Oncorhynchus mykiss):

Acute toxicity

LC₅₀ 96 h (endpoint) = ≥ 993 mg/L (guideline FDA TAD 4.11)
(Reference IV)

Other ecotoxicity data:

Microorganisms in activated sludge

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

PNEC = 989 μg/L

PNEC (μg/L) = lowest L(E)C₅₀/1000, where 1000 is the assessment factor used. EC₅₀ for daphnia (989 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 = 0.217941134 / 989 = 0.000220365, i.e. PEC/PNEC ≤ 0.1 which justifies the phrase “Use of akamprosat has been considered to result in insignificant environmental risk.”

Degradation

Biotic degradation

Ready degradability:

Test results 5.6 % degradation in 28 days (guideline FDA TAD 3.11).
(Reference VI)

Inherent degradability:

No data available.

Simulation studies:

No data available.

Abiotic degradation

Hydrolysis:

Test results < 10 % degradation in 5 days (guideline FDA TAD 3.09).
(Reference VII)

Photolysis:

No data available.

Justification of chosen degradation phrase:

Akamprosat is not readily biodegradable and undergoes no hydrolysis. The phrase “Akamprosat is potentially persistent” is thus chosen.

Bioaccumulation

Partitioning coefficient:

Log Kow = -2.83 at approx. pH 7 (guideline FDA TAD 3.02). (Reference VIII)

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

I. 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

II. Study report: Toxicity of Acamprosate to the Unicellar Green Alga, Selenastrum capricornutum, Determined Under Static Test Conditions; ABC Laboratories; USA; February 5, 2002

III. Study report: Acute Toxicity of Acamprosate to the Water Flea, Daphnia magna, Determined Under Static Test Conditions (Screening Test); ABC Laboratories; USA; February 4, 2002

IV. Study report: Acute Toxicity of Acamprosate to the Rainbow Trout, Oncorhynchus mykiss, Determined Under Static Test Conditions (Screening Test); ABC Laboratories; USA; February 4, 2002

V. Study report: Activated Sludge, Respiration Inhibition Test of Acamprosate; ABC Laboratories; USA; March 8, 2002

VI. Study report: Determination of the Aerobic Biodegradation in Water for Acamprosate; ABC Laboratories; USA; September 12, 2002

VII. Study report: Hydrolysis Determination of Acamprosate; ABC Laboratories; USA; March 8, 2002

VIII. Study report: Determination of Octanol/Water Partition Coefficient for Acamprosate; ABC Laboratories; USA; May 23, 2