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Estradiol

Information

This summary information on estradiol comes from Fass Novo Nordisk and Fass Bayer (persistence and bioaccumulation), Fass Bayer (toxicity) and the risk from the report Goodpoint.

Persistence. Estradiol is slowly degraded in the environment.
Bioaccumulation. Estradiol has low potential to bioaccumulate.
Toxicity. Estradiol has very high chronic toxicity.
Risk. See the report from Goodpoint.

Detailed information

Comment on Fass environmental information

Below is environmental information about estradiol from different pharmaceutical companies.The various pharmaceutical companies document environmental effects for their pharmaceuticals with the guidance of “Environmental classification of pharmaceuticals at www.fass.se – Guidance for pharmaceutical companies 2012”. The Swedish Environmental Research Institute (IVL) reviews the information but does not have the task of coordinating/harmonizing environmental information from various pharmaceutical companies for the same active substance.

Fass environmental information Novo Nordisk

Fass environmental information for estradiol, Activelle (estradiol, noretisteron) from Novo Nordisk (downloaded 2020-11-16).

"17β-estradiol is metabolized during human metabolism into the major transformation products estrone, estriol, estrone sulfate and estrone glucoronide. Se vidare Fass-informationen."

Hazard

Persistence: "Activated sludge test according to OECD guideline no. 302A has shown that 17β-estradiol is inherently biodegradable under aerobic conditions in activated sludge. 17β-estradiol is thus slowly degraded in the environment. In a 100 days simulation study of 17β-estradiol (OECD Test Method no. 308), an aerobic mineralisation (marine) of 61±1% respectively 62±3% mineralisation (freswater) was found. Thus, 17β-estradiol is found to be biodegradable in both marine and fresh water. In addition, an activated sludge tests (OECD 302) show that 17β-estradiol is inherently biodegradable under aerobic conditions. Therefore, 17β-estradiol and its metabolites are assessed not to fulfil the criteria of persistence in the aquatic environment."

Bioaccumulation: "Several measured BCFs are available for 17β-estradiol – all well below the cut-off value of 500. Therefore, 17β-estradiol is assessed not to have a high potential for bioaccumulation."

Chronic toxicity: There are data for 3 trophic levels, most sensitive fish. "The lowest no observed effect concentration for 17β-estradiol is a 35–50 d NOEC of 0.5 ng/L for the trout (Onchorhynchus mykiss)."

Risk

PEC/PNEC is based on sales data in Sweden in year 2016. PEC/PNEC = 2.75 which gives the risk moderate.

Fass environmental information Bayer

Fass environmental information for estradiol, Angemin (drospirenone, estradiol) från Bayer (downloaded 2020-11-16).

Hazard

Persistence: "Ready degradability: not readily biodegradable, but significant mineralization. Estradiol was studied for aerobic biodegradability in water in three different CO2 evolution tests. In one test, biodegradation was studied according to OECD method 301B (7). Estradiol was introduced into the test system at concentrations of 10 mg/L. In two other tests, the degradation was studied according to FDA TAD method 3.11(8)(9). In the latter, two concentrations (1 and 10 mg/L) were tested. In all assays, estradiol was degraded to more than 60 % after 28 days. However, degradation proceeded too slowly to formally classify the compound as being readily biodegradable."

Bioaccumulation: "Since log POW was 4.0 but the BCF was 109 (86 normalized on 6 % fat), the trigger of a BCF of 500 was not exceeded. Therefore, the substance was considered to have a low potential for bioaccumulation."

Chronic toxicity: There are data for 3 trophic levels, most sensitive fish (medaka Oryzias latipes) NOEC fertilitet (F0), 59 days = 0.0029 microg/L.

Risk

PEC/PNEC is based on sales data in Sweden in year 2016. PEC/PNEC = 12.4 which gives the risk high.

Fass environmental information Pfizer

Fass environmental information for Oestring (estradiol) from Pfizer (downloaded 2020-11-16).

Hazard

Persistence: No data.

Bioaccumulation: No data.

Toxicity: No data.

Risk

Risk of environmental impact of estradiol cannot be excluded, since no ecotoxicity data are available. It is voluntary for manufacturers to provide information about environmental impact on fass.se.

Assessment report Zoely

Assessment report for estradiol, Zoely (nomegestrol, estradiol) from 2011, procedure No. EMEA/H/C/001213.

Hazard

Persistence: No data.

Bioaccumulation: "The results of the bioconcentration studies in fish indicate that bioconcentration is not a significant environmental concern for these species. In most of the non-fish species a similar conclusion can be reached based on relatively low BCFs. The results from the studies in zebra mussels are interesting, but seem to indicate that E2 (estradiol, ed. remark) is taken up by these organisms and stored in an inactive form. There is less data available concerning the effect of E2 on sediment organisms. However, based on analogy to EE2 (etinylestradiol, ed. remark), a much more potent estrogen, it is not expected to have significant effects on sediment species."

Chronic toxicity: Data for 3 trophy levels are not reported, but it is interpreted as based on used AF 10. Fish "the lowest NOEC (2.6 ng/L)."

Risk

"In conclusion, based on the above results, NOMAC (nomegestrol, ed. remark)-E2 does not appear to present a specific risk to the aquatic environment. However, given the hormonal activity of both components, nomegestrol acetate and estradiol, a warning has been included in the relevant section of the product SmPC and in the package leaflet as follows: Zoely tablets no longer required should not be disposed via wastewater or the municipal drainage system. The hormonal active compounds in the tablet may have harmful effects if reaching the aquatic environment. Return them to a pharmacy or dispose them in another safe way according to local requirements. These measures will help to protect the environment.”

Report Goopoint

Estradiol is on the EU list of substances whose concentrations in surface waters should be monitored in the Member States for environmental reasons. In addition to e.g., ethinyl estradiol and endogenous estrogen, estradiol contributes to the amount of estrogens in the environment. See also ethinyl estradiol.

Estradiol is included in Region Stockholm's table of pharmaceuticals with a negative environmental impact according to the environmental programme 2017–2021.

Estradiol is more easily degraded than ethinyl estradiol in the body, in the wastwater treatment plant, in the environment and is less potent in fish. An oral dose of 1.5 mg estradiol gives an excreeted dose in the urine of only 100 micrograms. Therefore, the risk is probably lower with estradiol despite the often higher dosage.

The Wise list

Estradiol is recommended in the Wise list. The Wise list is the drug formulary of essential medicines for common diseases in Region Stockholm from the Drug and Therapeutics Committee. Environmental classification of pharmaceuticals is taken into consideration, sometimes with other environmental aspects, when selecting pharmaceuticals for the Wise list. When comparable pharmaceuticals are equivalent to medical effects, safety and pharmaceutical efficacy, environmental impact and price are considered.

Suggestions on how to reduce emissions of estradiol

Concrete proposals on how to work to reduce emissions of environmentally harmful pharmaceuticals on the list have been developed in close cooperation with the Stockholm Drug and Therapeutics Committee's expert groups. The action proposals were developed from an environmental perspective. The patient's best always goes first and several pharmaceuticals on the list are also included in the Wise list. However, for such pharmaceuticals, there may be measures that could reduce the environmental impact.

Concrete proposal for estradiol

  • Estradiol is recommended in the Wise list.
  • Individual adaptation of contraceptives as well as pharmaceuticals for treatment of menopausal symptoms and symptomatic vaginal atrophy is important in order to optimize treatment and avoid side effects.
  • For topical application of patches with estradiol (Estradot, recommended in the Wise list) for menopausal symptoms, the amount of pharmaceutical administered to an individual is significantly lower than the dose required to give the corresponding effect with estradiol tablets.
  • Ensure that you, in your own business, discard leftover pharmaceuticals and used patches and vaginal inserts correctly.  
  • Inform the patient about the importance of discarding leftover pharmaceuticals, as well as used patches and vaginal inserts, correctly. Order the folder for patients "Protect the Environment – Throw in the Right Way".

Author: Health and Medical Care Administration, Region Stockholm