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) = 0.0018 μg/L

Where:

A = 13.03 kg (total sold amount API in Sweden year 2021, 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, Desmodesmus subspicatus):

NOEC 72 hours (growth rate) = 0.013 mg/L, E_rC₅₀ 72 hours (growth rate) = 0.51 mg/L. Guideline OECD 201. (Reference II)

Crustacean (waterflea, Daphnia magna):

Acute toxicity

EC₅₀ 48 hours (immobilization) > 4.6 mg/L. Guideline OECD 202. (Reference III)

Fish (zebrafish, Danio rerio):

Acute toxicity

LC₅₀ 96 hours (survival) > 5.03 mg/L. Guideline OECD 203. (Reference IV)

Chronic toxicity

NOEC 28 days (reproduction) = 0.005 μg/L. Non-standard test method. (Reference V)

The PNEC was calculated by division of the lowest effect level (NOEC) of the most sensitive taxonomic group considering an appropriate assessment factor (AF). There is no chronic study with daphnids but as norethisterone (acetate) is a hormone fish can be expected to be the most sensitive taxonomic group and the respective NOEC = 0.005 µg/L. The regulatory default standard AF of 10 was used, which is applicable when there are chronic aquatic toxicity studies representing the three trophic levels (algae, crustaceans, and fish).

PNEC = 0.005 µg/L / 10 = 0.0005 µg/L

Environmental risk classification (PEC/PNEC ratio)

The risk quotient PEC/PNEC was calculated with 0.0018 µg/L / 0.0005 µg/L = 3.57.

Justification of chosen environmental risk phrase:

A risk quotient between 1 and 10 qualifies for the phrase “Use of Norethisterone (acetate) has been considered to result in moderate environmental risk.”.

Degradation

Biotic degradation

Ready degradability:

The test substance was incubated in an aqueous solution including nutrients with activated sludge form a municipal sewage treatment plant for 30 days in a concentration of 10 mg carbon/L in triplicates. Additionally, sodium acetate as reference substance, a blank control and sodium acetate plus norethisterone e as toxicity control were tested. CO₂ formation was measured on day 4, 7, 11, 14, 17, 23, 28 and 30. The study reported 0 % biodegradation of Norethisterone (acetate) in 28 days. Guideline OECD 301. (Reference VI)

Abiotic degradation

Hydrolysis:

Norethisterone (acetate) was determined to be stable at pH 5, 7, and 9. Guideline EEC, C.7. (Reference VII)

Justification of chosen degradation phrase:

Norethisterone (acetate) was not readily biodegradable, is hydrolytically stable and as there is no higher tier transformation study the half-life is considered to be DT₅₀ > 120 d, which qualifies for the phrase “Norethisterone (acetate) is potentially persistent.”.

Bioaccumulation

Partitioning coefficient:

The log D_ow was reported with 2.7 at pH 7. Guideline OECD 117. (Reference VIII)

Justification of chosen bioaccumulation phrase:

As the log D_ow was < 4 Norethisterone (acetate) is not considered bioaccumulative which qualifies for the phrase “Norethisterone (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. Alga, growth inhibition test with norethisterone, Currenta GmbH & Co OHG, ownership: Bayer AG, report no. 2015/0057/04 (2016)

3. Acute immobilization of norethisterone e with Daphnia magna. Experimental Toxicology, Schering AG, study no. TX96099, report no. X211 (1997)

4. Fish, acute toxicity with norethisterone, Currenta GmbH & Co OHG, ownership: Bayer AG, report no. 2015/0057/03 (2016)

5. Paulos P, Runnalls TJ, Nallani G, La Point T, Scott AP, Sumpter JP, Huggett DB. (2010). Reproductive responses in fathead minnow and Japanese medaka following exposure to a synthetic progestin, norethindrone. Aquat Toxicol 99:256–262.

6. Study on the biodegradability of norethisterone in the CO2- evolution test (modified Sturm-test). Experimental Toxicology, Schering AG, study no. TX96088, report no. X128 (1996)

7. Norethisterone/ZK5378/Report on physicochemical properties/estimation of the hydrolytic stability on the basis of hydrolytic behavior of structurally similar compounds. General Physical Chemistry, Schering AG, study no. APC194/00 (2000)

8. Norethisterone/ZK5378/Report on the partition coefficient. General Physical Chemistry, Schering AG, study no. APC132/95, report no. LJ0 (1995)