Beclomethasone dipropionate

Detailed information

General information about assessment reports

Since 2006, an Environmental Risk Assessment (ERA) for the active pharmaceutical substance shall accompany an application for a marketing authorisation in EU for a medicinal product for human use. Parts of environmental data can be found in the public investigation report (PAR/EPAR for medicinal product through a centralized procedure). The environmental aspect is not considered in the benefit/risk assessments of human medicines. If new data become available after approval that requires an update of the environmental risk assessment, a variation application (“type IB C.I.z variation”) must be submitted to the medicines authority.

The PEC (predicted environmental concentration) values used to calculate risk in the manufacturers' assessment reports are based on the estimated use of the medicinal product to which the assessment report relates, not all medicinal products containing the same active substance.

Focus of this environmental information

Inhalation medicinal products containing beclometasone dipropionate (BDP) act as a prodrug, with the main metabolite beclometasone‑17‑monopropionate (B17MP) providing the anti‑inflammatory effect in the lungs. The focus of this environmental information is on the active metabolite B17MP.

Assessment report Trimbow 2017

Assessment report for B17MP from Trimbow (beclometasone dipropionate, formoterol and glycopyrronium), inhalation medicines, Chiesi Farmaceutici S.p.A., 18 May 2017, EMA/CHMP/289952/2017.

Hazard

Persistence: No data.

Bioaccumulation: Log K_ow = 3.49. "Furthermore, the log K_ow of B17MP is above 3, which requires the consideration of the bioconcentration factor in fish. The Applicant committed also to provide an experimental study of BCF in fish according to TG OECD 305 in the post approval setting."

Chronic toxicity: There is data for 1 trophic level, fish (Pimephales promelas) NOEC 0.13 microg/L.

Risk

The risk, PEC/PNEC, calculated from data in the assessment report from a European perspective:

PEC for B17MP = 0.0018 mikrog/L.

PNEC = NOEC, 0.13 microg/L/10 (Assessment Factor; AF) =  0.013 microg/L. An assessment factor of 10 can be applied according to the guidelines when chronic toxicity data are available for three trophic levels. In the assessment report, however, data are presented only for fish. If chronic data are available for only one trophic level, either fish or Daphnia, the guidelines stipulate the use of AF = 100. NOEC, 0.13 microg/L/100 = 0.0013 microg/L.

PEC/PNEC = 0.14 which gives the risk low if AF = 10. If AF = 100, PEC/PNEC = 1.4, which gives the risk moderate.

"Upon request of CHMP, the Applicant commits to provide the missing data on fate and bioconcentration by the end of the year 2018."

Assessment report Trimbow 2021

Assessment report for B17MP from Trimbow, inhalation medicines, Chiesi Farmaceutici S.p.A., 28 January 2021, EMA/93446/2021.

Hazard

Persistence: OECD 301B: Not readily biodegradable. Conclusion. Additional evaluation required. OECD 308: Emperor Lake. Water: DT₅₀ 3.0 days. Overall system: DT₅₀ 3.9 days. Conclusion. Lower dissipation. Calwich Abbey Lake. Aerobic: DT₅₀ <1 day. Anaerobic: DT₅₀ <1 day. Conclusion. Rapidly dissipated. According to expert B17MP is potentially persistent (C. Coll, Department of Environmental Chemistry, Eawag, 2022-01-28).

Bioaccumulation: Log K_ow 3.49/3.14. Bioaccumulation in fish. OECD 305. No bioconcentration factor calculated. Conclusion. No accumulation occurred.

Chronic toxicity: There is data for one trophic level. "Flow-through life-cycle toxicity test with the fathead minnow (Pimephales Promelas), OECD on fish life-cycle tests, NOEC 0.13 microg/L. Conclusion: B17MP is unlikely to represent a risk. [...] However, due to the potential endocrine disrupting properties of glucocorticoids, a tailored ERA for the active metabolite of beclometasone dipropionate (pro-drug), i.e. beclometasone-17-monopropionate (B17MP), had been performed. On the basis of the tailored ERA it was concluded that beclometasone is not readily biodegradable, not toxic to fish and not expected to bioconcentrate in fish." It is important to note that the final sentence refers to beclometasone and not to B17MP. What significance this has for the interpretation of the results is unclear.

Risk

"B17MP is unlikely to represent a risk"

Article by Carney Almroth BM

The calculated octanol–water partition coefficients for BDP, BMP (= B17MP), and free beclometasone are 4.59, 2.88, and 2.04, respectively (GlaxoSmithKline, 2013), indicating that the metabolites have higher water solubility. The BCF values for the three forms of beclometasone were generally between 2.31 (low dose) and 0.75 (high dose). BDP was taken up by fish, whereas beclometasone was not.

Article by Daley-Yates PT

Administration of BDP by inhalation resulted in measurable plasma concentrations of both unchanged BDP and B17MP in a study with 12 healthy volunteers.

Fass environmental information

Fass environmental information for Oparta (BDP, formoterol), inhalation spray, from Starda Nordic ApS (retrieved on 2025-12-10). The environmental information for beclometasone dipropionate (anhydrous) has been prepared by GlaxoSmithKline for Becotide and Becotide Nasal. Becotide and Becotide Nasal are withdrawn from the Swedish market.

All data in the Fass environmental information refers to BDP unless specified otherwise.

Hazard

Persistence: The substance is not readily biodegradable (3% in 28 days), and no data are available on inherent biodegradability. Soil metabolism shows 21.9–61.5% degradation in 64 days. Hydrolysis results in 50% degradation at pH 7 within 166 hours, while no data are available for photolysis. Overall, BDP is considered potentially persistent.

Bioaccumulation: The partitioning coefficient (log P_ow) is 3.49, indicating that the substance has a low potential for bioaccumulation. The active metabolite, beclomethasone‑17‑monopropionate, likewise shows low potential to bioaccumulate in aquatic organisms, with a calculated log P_ow of 3.5 at pH 7.4.

Acute toxicity: Data are available for two trophic levels, with the most sensitive crustacean showing an EC₅₀ of 3.74 µg/L.

Risk

"PNEC cannot be calculated because data is not available for all three (algae, crustacean and fish) of the toxicity endpoints." Below is the risk calculation based on NOEC for B17MP from assessment reports on Trimbow and PEC from fass.se.

PEC/PNEC is based on sales data in Sweden in year 2023 for the total amount of BDP sold.

PEC = 0.000841 microg/L.

PNEC = NOEC, 0.13 microg/L/100 (Assessment Factor (AF) for 1 chronic studie) = 0.0013 microg/L.

PEC/PNEC = 0.647 which gives the risk low.