Budesonide

Detailed information

Comment on Fass environmental information

Budesonide 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 Pulmicort

Fass environmental information for Pulmicort (budesonide) from AstraZeneca (downloaded 2024-10-18).

Hazard

Persistence: "Total system DT₅₀ of 18.1 days. As the highest DT₅₀ values reported passes the criteria of DT₅₀ ≤ 32d for the total system, and less than 15% budesonide was remaining as the parent compound at the end of the study the following phrase is therefore assigned: Budesonide is degraded in the environment."

Bioaccumulation: OECD305: BCF_L at 3μg/L = 9 ± 3. Not bioaccumulative in fish

Toxicity: There are data for 3 trophic levels, most sensitive fish (Danio rerio) NOEC 0,9 microg/L.

Risk

PEC/PNEC is based on sales data in Sweden in year 2023. PEC/PNEC = 0.1004 which gives the risk low.

Fass environmental information for Budenofalk

Fass environmental information for Budenofalk (budesonide) from Vifor Pharma (downloaded 2024-10-18).

Hazard

Persistence: OECD301E: "Degradation after 7 days < 8%. Not readily biodegradable. Since data from further degradation tests is lacking, the phrase ‘Budesonide is potentially persistent’ is used under the heading Biodegradation."

Bioaccumulation: Log K_ow = 3.3.

Acute toxicity: There are data for 3 trophic levels, most sensitive alg EC₅₀ 8,6 mg/L.

Risk

PEC/PNEC is based on sales data in Sweden in year 2023. PEC/PNEC = 0.0011 which gives the risk insignificant.

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). Since the benefit/risk assessment for human medicinal products at present does not include environmental effects, an update of the environmental risk assessment is not required for renewals of marketing authorizations. There is thus no requirement for companies to stay informed about the development of their substances from an environmental point of view and consequently to update the environmental risk assessment as new data are published.

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.

Assessment report for Jorveza (budesonide) 09 November 2017 EMA/774645/2017

Hazard

Persistence: "OECD 301: not readily biodegradable. OECD 308: Pending, expected end 2018."

Bioaccumulation: log K_ow = 3.23. "OECD 305: Pending, expected end 2018."

Toxicity: No data.

Risk

PEC_surfacewater 0.00008 microg/L. Conclusion: "> 0.01 threshold: N"

"The environmental risk assessment for budesonide can however not be finished until the ongoing test on transformation in aquatic sediment systems (OECD 308), bioaccumulation study (OECD 305) and fish full life-cycle Test (OPPTS 850.1500) are completed by end of 2018."

Other information

"Budesonid is a glucocorticoid and, as such, is considered a potential endocrine disruptor and therefore the potential endocrine activity of this compound was investigated in an appropriate chronic test system with relevant endpoints."

Assessment report for Jorveza 26 March 2020, EMA/199925/2020

Hazard

Persistence according to OECD 308: DT_{50, 12 °C water} = 14.7 d.
DT_{50, 12 °C sediment} = 62.6 d.
DT_{50, 12 °C whole system} = 38.6 d. 

Bioaccumulation: Log K_ow 3.23. BCF = 9.

Chronic toxicity: There are data for 3 trophic levels, most sensitive fish (Danio rerio) NOEC 0.032 microg/L.

Risk

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

PEC_{surfacewater, refined} = 0.00017 microg/L.

PNEC = Lowest NOEC, 0.032 microg/L/10 (Assessment Factor (AF) for 3 chronic studies) = 0.0032 microg/L

PEC/PNEC = 0.053125 which gives the risk insignificant.

Assessment report for Trixeo Aerosphere

Assessment report for Trixeo Aerosphere (formoterol, glycopyrronium bromide, budesonide) about budesonide 15 October 2020, EMA/582495/2020.

Hazard

Persistence according to OECD 308: DT_{50, whole system} = 12.5 days (River); 18.1 (Pond).
DT_{50, aqueous phase} = 6.45 days (River); 6.9 (Pond).
DT_{50, sediment system} = 22.7 days (River); not calculable (Pond).

Bioaccumulation: Log K_ow = 3.45.

Chronic toxicity: There are data for 2 trophic levels, most sensitive crustacean (Daphnia sp.) NOEC 3400 microg/L.

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

PEC_surfacewater = 0.0032 microg/L.

PNEC = Lowest NOEC 3400 microg/L/50 (ssessment Factor (AF) for 2 chronic studies) = 68 microg/L

PEC/PNEC = 0.000047 which gives the risk insignificant.

Comment on persistence

Based on the assessment reports from 2020, budesonide is likely non-persistent according to an expert (C. Coll, Department of Environmental Chemistry, Eawag, 2021-05-03).

Assessment report for Kinpeygo

Assessment report for Kinpeygo (budesonide), 19 May 2022, EMA/570757/2022.

Hazard

Persistence according to OECD 308: DT₅₀, _{12 °C water} = 13.7/14.7 d.
DT_{50, 12 °C sediment} = 48.4/62.6 d.
DT_{50, 12 °C whole system} = 26.6/37.1 d.
% shifting to sediment = 49.0/68.6 % (both @ 30 d)
Mineralisation: 86.2/68.6 %.

Bioaccumulation: BCF = 9.

Chronic toxicity: There are data for 3 trophic levels, most sensitive fish (Danio rerio) NOEC 0.032 microg/L.

Risk

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

PEC = 0.0016 microg/L.

PNEC = Lowest NOEC, 0.032 microg/L/10 (Assessment Factor (AF) for 3 chronic studies) = 0.0032 microg/L.

PEC/PNEC = 0.5 which gives the risk low.

Assessment report type II group of variations

DuoResp Spiromax (budesonide, formoterol) 22 April 2021, EMA/CHMP/310290/2021 and BiResp Spiromax (budesonide, formoterol) 22 April 2021, EMA/CHMP/310289/2021.

"In accordance with the Guideline on the Environmental Risk Assessment of Medicinal Products for Human use (EMEA/CHMP/SWP/4447/00 corr 2), a justification for the absence of an environmental risk assessment (ERA) has been provided. The applicant states that the proposed budesonide/formoterol Spiromax 80/4.5, 160/4.5, 320/9 µg per dose, inhalation powder products would replace the currently marketed medicinal products and hence the exposure of the environment to budesonide and formoterol is not likely to increase. Therefore, the absence of ERA is considered acceptable."

Report Goodpoint 2020

Comparative assessment of environmental risk when using the corticosteroids betamethasone, budesonide, hydrocortisone and prednisolone from a Swedish perspective.

The use of both betamethasone and budesonide poses an environmental risk, and exchange with synthetic glucocorticoids with a lower environmental risk is to be advocated in cases where it is possible from a clinical perspective. Hydrocortisone and prednisolone have a lower environmental risk but are rarely medically interchangeable alternatives to betamethasone and budesonide. Note that corresponding environmental risk assessments have not been made for other synthetic glucocorticoids that are available on the Swedish market, and which could possibly constitute exchange alternatives. No actions are recommended with regard to replacement of hydrocortisone and prednisolone as their use poses a low environmental risk given the current state of knowledge.