Detaljerad miljöinformation

Environmental Risk Classification

Predicted Environmental Concentration (PEC)

Cyproterone acetate consists of the active pharmaceutical moiety cyproterone (base) and acetate (salt), which is not active. For the PEC calculation, the total sale volume in 2022 can be adjusted to the volume of the active moiety. This was done by taking account of the molecular weight of the active moiety: molecular weight of cyproterone acetate is 416.94 g/mol, that of cyproterone is 374.91 g/mol, which equals 89.92 % of the total molecular weight. The sale volume of the active moiety calculates as 16.26 kg x 89.92 % = 14.62 kg.

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) = 0.00000411 µg/L

Where:

A = 14.62 kg (total sold amount API in Sweden year 2022, data from IQVIA / LIF)

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) (Reference I)

D = factor for dilution of wastewater by surface water flow = 10 (ECHA default) (Reference I)

Predicted No Effect Concentration (PNEC)

Ecotoxicological studies*

Algae (green algae, Scenedesmus subspicatus):

E_rC₅₀ 72 hours (growth rate) = 3.4 mg/L. Guideline OECD 201. (Reference II)

Crustacean (waterflea, Daphnia magna):

Acute toxicity

EC₅₀ 48 hours (immobilization) = 2.4 mg/L. Guideline OECD 202. (Reference III)

Environmental risk classification (PEC/PNEC ratio)

Due to insufficient data neither the PNEC nor the PEC/PNEC ratio may be calculated.

Justification of chosen environmental risk phrase:

Insufficient data to calculate the PEC/PNEC ratio qualifies for the phrase “Risk of environmental impact of cyproterone acetate cannot be excluded, since there is not sufficient ecotoxicity data available.”.

Degradation

There is no data on degradation.

Justification of chosen degradation phrase:

The lack of data qualifies for the phrase “The potential for persistence of cyproterone acetate cannot be excluded, due to lack of data.”.

Bioaccumulation

Partitioning coefficient:

The log D_ow was reported as 3.36 at pH 7. Guideline OECD 117. (Reference IV)

Justification of chosen bioaccumulation phrase:

As the log D_ow was < 4 cyproterone acetate is not considered bioaccumulative which qualifies for the phrase “Cyproterone acetate has low potential for bioaccumulation.”.

References

1. Guidance on information requirements and Chemical Safety Assessment Chapter R.16: Environmental exposure assessment. V3.0, Feb. 2016.

2. Growth inhibition test of ZK 5560 on the green algae Scenedesmus subspicatus. Schering AG, Study no. TXST19970157, Report no. A09645.

3. Acute immobilization test of cyproterone acetate with Daphnia magna. Experimental Toxicology, Schering AG, Study no. TXST19970152, Report no. X373.

4. The determination of the n-octanol/water partition coefficient of ZK 9471 and estimation of its acid-base properties (pka value). General Physical Chemistry, Schering AG, study no. 1440, report no. ME47 (1997).