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.
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).
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 for Neovletta 28 (ethinylestradiol, levonorgestrel) from Bayer (downloaded 2021-08-16).
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.
PEC/PNEC is based on sales data in Sweden in year 2019. PEC/PNEC = 14.3, which gives the risk high.
Fass environmental information for Desolett 28 (desogestrel, ethinylestradiol) from MSD (downloaded 2021-08-16).
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."
PEC/PNEC is based on sales data in Sweden in year 2018. PEC/PNEC = 4,1 which gives the risk moderate.
Fass environmental information for Evra (ethinylestradiol, norelgestromin) from Janssen (downloaded 2021-08-16).
Persistence: No data.
Bioaccumulation: Log Dow = 3.67. "Since log Dow < 4, ethinylestradiol has low potential for bioaccumulation."
Toxicity: No data.
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.
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.
Ethinylestradiol is among special pollutants in the Swedish Agency for Marine and Water Management regulation HVMFS 2019:25.
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.
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).
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
Author: Health and Medical Care Administration, Region Stockholm