Kommersiellt obunden läkemedelsinformation riktad till läkare och sjukvårdspersonal

Ethinylestradiol

Information

For this summary, information on bioaccumulation comes from Fass Bayer, persistence and toxicity from Fass MSD and the risk from the Goodpoint report.

Persistence. Ethinylestradiol is slowly degraded in the environment
Bioaccumulation. Ethinylestradiol has high potential for bioaccumulation.
Toxicity. Ethinylestradiol has a very high chronic toxicity.
Risk. See the environmental assessment from Goodpoint below.

Detailed information

Ethinylestradiol and estradiol

The environmental risk of ethinylestradiol is higher than for estradiol. Compared with estradiol, ethinylestradiol is less degraded in the body, in wastewater treatmentplants and in the environment, and ethinylestradiol is also more potent in fish (Friel et al, 2005).

Comment on Fass environmental information

Ethinylestradiol has different classifications on fass.se. According to Lif (the trade association for the research-based pharmaceutical industry in Sweden) the various pharmaceutical companies compile environmental information for their active substances based on internal studies and published data. Based on data, which may thus differ between different pharmaceutical companies, the companies assess the environmental risk with guidance from “Environmental classification of pharmaceuticals at www.fass.se – Guidance for pharmaceutical companies 2012”. The Swedish Environmental Institute (IVL) reviews the assessment but does not have the task of coordinating/harmonizing environmental information from different pharmaceutical companies for the same active substance.

Fass environmental information from Bayer

Fass environmental information for Neovletta 28 (ethinylestradiol, levonorgestrel) from Bayer (downloaded 2021-08-16).

Hazard

Persistence: "In the total water/sediment systems the DT50 of [14C] ethinylestradiol was 24, 36, and 28 days for the 2 systems. [...] Due to the results of the water-sediment study with a total system half-life of < 32d, the use of the phrase “ethinylestradiol is degraded in the environment” is justified."

Bioaccumulation: "Since log Pow was 4,2 and BCF was 371–634 (617–1035 normalized on 6% fat), the trigger of a BCF of 500 was exceeded. Therefore, the substance was considered to have a "high potential for bioaccumulation"."

Chronic toxicity: There are data for 3 trophic levels, most sensitive fish (zebrafish Danio rerio) NOEC 0.0003 microg/L.

Risk

PEC/PNEC is based on sales data in Sweden in year 2019. PEC/PNEC = 14.3, which gives the risk high.

Fass environmental information from MSD

Fass environmental information for Desolett 28 (desogestrel, ethinylestradiol) from MSD (downloaded 2021-08-16).

Hazard

Persistence: "DT50 (total system) = 46 to 75 days (OECD 308). [...] Ethinylestradiol has a DT50 for the total system of ≤120 days. Thus, the phrase “Ethinylestradiol is slowly degraded in the environment” is chosen."

Bioaccumulation: "Log Kow value for ethinylestradiol to range from 3.67 to 4.15. [...] Lipid normalized kinetic BCF = 248 to 264. Since log Kow < 4 and BCF < 500, ethinylestradiol has low potential for bioaccumulation."

Chronic toxicity: There are data for 3 trophic levels, most sensitive fish "(Pimephales promelas) NOEC 301d (increased vitellogenin and lack of sexual differentiation F1 males) = 1 ng/L."

Risk

PEC/PNEC is based on sales data in Sweden in year 2018. PEC/PNEC = 4,1 which gives the risk moderate.

Fass environmental information from Janssen

Fass environmental information for Evra (ethinylestradiol, norelgestromin) from Janssen (downloaded 2021-08-16).

Hazard

Persistence: No data.

Bioaccumulation: Log Dow = 3.67. "Since log Dow < 4, ethinylestradiol has low potential for bioaccumulation."

Toxicity: No data.

Risk

Risk of environmental impact of ethinylestradiol cannot be excluded, since no ecotoxicity data are available.

Manufacturer Janssen has on fass.se stated that that data about the environmental impact is missing for the substance so that the environmental risk cannot be calculated. It is voluntary for manufacturers to provide information on the environmental impact on fass.se.

EU water legislation

Ethinylestradiol has previously been monitored within the framework of EU water legislation. There is now enough data to assess whether ethinylestradiol is to be proposed as a priority substance when the European parliament and the Council next time proposes a revised directive regarding priority substances in the field of water policy.

The Swedish Agency for Marine and Water Management

Ethinylestradiol is among special pollutants in the Swedish Agency for Marine and Water Management regulation HVMFS 2019:25.

Report Goodpoint

Estimated levels in Swedish waters are in some cases sufficiently high to affect reproduction and gender development in fish.

Ethinylestradiol is included in Region Stockholm's table of pharmaceuticals with a negative environmental impact according to the environmental programme 2017–2021 based on lowest effect concentration, LOEC = 0.32 nanog/L, and concentrations found in treated wastewater.

The Wise list

Ethinylestradiol is recommended in the Wise list in Region Stockholm. 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.

When using combination preparations with estrogen and gestagen, the gestagen component must also be considered. In particular, levonogestrel stands out as a drug with increased environmental risk. Environmental risk assessment is therefore relevant for both the gestagen and the estrogenic component.

In total, levonorgestrel + ethinylestradiol and etonogestrel + ethinylestradiol are considered to be the highest environmental risk, drospirenone + ethinylestradiol lower risk (based on gestagen component) and nomegestrol and estradiol lowest risk (based primarily on the gestagen component but also the estrogen component).

Suggestions on how to reduce the emissions of ethinylestradiol

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 ethinylestradiol

  • Ethinylestradiol (combined contraceptives) is recommended in the Wise list.
  • Individual adjustment of  contraceptives is important  in order to optimize treatment and avoid side effects.
  • Ensure that you, in your own business, discard leftover pharmaceuticals and used rings and patches correctly.
  • Inform the patient about the importance of discarding leftover pharmaceuticals, as well as used P-rings and patches, correctly.
  • Order the folder for patients "Protect the Environment – Throw in the Right Way".

References

  1. Fass för vårdpersonal.
  2. Goodpoint. Prioritering av läkemedel med miljörisk inom SLL. Stockholm: Goodpoint; 2016. Rapport LS 2016–0634.
  3. Parrott JL, Blunt BR. Life-cycle exposure of fathead minnows (Pimephales promelas) to an ethinylestradiol concentration below 1 ng/L reduces egg fertilization success and demasculinizes males. Environ Toxicol. 2005;20:131-41.
  4. D.G.J Larsson, M Adolfsson-Erici, J Parkkonen, M Pettersson, A.H Berg, P.-E Olsson et al. Ethinyloestradiol — an undesired fish contraceptive? Aquatic Toxicology 1999; 45 (2-3): 91-97.
  5. Kidd KA, Blanchfield PJ, Mills KH, Palace VP, Evans RE, Lazorchak JM et al. Collapse of a fish population after exposure to a synthetic estrogen. Proc Natl Acad Sci U S A. 2007;104:8897-901.
  6. Zeilinger J, Steger-Hartmann T, Maser E, Goller S, Vonk R, Länge R. Effects of synthetic gestagens on fish reproduction. Environ Toxicol Chem. 2009;28:2663-70.
  7. Friel PN, Hinchcliffe C, Wright JV. Hormone replacement with estradiol: conventional oral doses result in excessive exposure to estrone. Altern Med Rev. 2005;10:36-41.
  8. Runnalls TJ, Beresford N, Kugathas S, Margiotta-Casaluci L, Scholze M, Scott AP et al. From single chemicals to mixtures--reproductive effects of levonorgestrel and ethinylestradiol on the fathead minnow. Aquat Toxicol. 2015;169:152-67.
  9. Provtagningar av läkemedelsrester i vatten, sediment och fisk för Region Stockholm.
  10. IVL Swedish Environmental Research Institute Ltd Fick J, Lindberg RH, Fång J, Magnér J, Kaj L, Brorström-Lundén E. Screening 2014. Analysis of pharmaceuticals and hormones in samples from WWTPs and receiving waters. Rapport C 135.
  11. Havs- och vattenmyndighetens föreskrift HVMFS 2019:25.
  12. Region Stockholm. Förteckning över miljöbelastande läkemedel med åtgärdsförslag framtagen inom ramen för Region Stockholms miljöprogram 2017–2021.
  13. Region Stockholms läkemedelskommitté. Kloka listan.
  14. Region Stockholm's Drug and Therapeutics Committee. The Wise list 2015.

Author: Health and Medical Care Administration, Region Stockholm