Kommersiellt obunden läkemedelsinformation riktad till läkare och sjukvårdspersonal

Norethisterone

Hazard 6 P 3 B 0 T 3 Risk See below

Information

The T-value in the score for hazard refers to chronic toxicity. Underlying data for P, B, T and risk are from Fass.

Fass environmental information Primolut-Nor

Fass environmental information for Primolut-Nor (norethisterone) (downloaded 2019-01-24).

Hazard

Persistence: "The biodegradability was studied in a CO2 evolution test (OECD 301B) (7). The test substance was incubated in an aqueous solution including nutrients with microorganisms 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 as toxicity control were tested. CO2 production was measured/calculated on day 4, 7, 11, 14, 17, 23, 28 and 30. No degradation was observed within 28 days of incubation. Norethisterone/norethisterone acetate is potentially persistent."

Bioaccumulation: "Log POW 2.7 at pH 7 and 25 °C (Shake flask method, OECD 117). [...] Since Log POW (at pH 7) < 4, the phrase norethisterone/norethisterone acetate has a low potential for bioaccumulation is justified."

Toxicity: There are data for 3 trophic levels, most sensitive fish (Danio rerio) NOEC 0.005 microg/L.

Risk

PEC/PNEC is based on sales data in Sweden in year 2016. PEC/PNEC = 4.4 wich gives the risk moderate.

Fass environmental information Activelle

Fass environmental information for norethisterone from Activelle (estradiol, norethisterone) (downloaded 2019-01-24).

Hazard

Persistence: "Norethisterone and NETA (norethisterone acetate, editoral note) are not readily biodegradable under “modified Sturm test” conditions since less than 10% of the substance was biodegraded within 28 days."

Bioaccumulation: Log Pow = 3.7. "Since LogPow < 4 it indicates that NETA has low potential for bioaccumulation."

Toxicity: There are data for 2 trophic levels, most sensitive green alga 600 microg/L.

Risk

Risk of environmental impact of norethisterone cannot be excluded due to lack of eco-toxicity data.

Concentrations in the aquatic environment and impact on fish

In various international studies, the reported level of norethisterone in purified wastewater ranges from undetectable to 188 ng/L (the latter appears to be unreasonably high) and in surface water from 1 to 7.5 ng/L.

Effects on fish has been shown in various studies at levels from 1 ng/L. Based on prescribing data, expected levels downstream Swedish watewater treatment plants could be around 2.6 ng/L.

Comparisons with other substances

A substance's ability to activate the androgen receptor in fish is believed to also contribute to increased risk of environmental impact. Norethisterone, levonogestrel and etonogestrel activate the androgen receptor in fish at very low concentrations, whereas, for example, drospirenone is a much less potent androgen receptor agonist. The risk is likely to be lower for norethisterone than for levonorgestrel seen from the risk of affecting fish via the androgen receptor.

Based on binding to the androgen receptor, binding to SHBG (Sex Hormone Binding Globulin) and studies on fish, norethisterone and levonogestrel are a higher environmental risk than medroxyprogesterone. Binding to SHBG is believed to contribute to increased bioconcentration (and thus potency) in fish.

Author: Health and Medical Care Administration, Region Stockholm