Treosulfan

Detailed information

Treosulfan is a prodrug that is converted into the active epoxide metabolites EBDM (monoepoxide) and DEB (diepoxide).

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 are available in the public assessment report (PAR/EPAR for centrally approved medicines). Environmental considerations are not included in the benefit-risk assessment for human medicines. If new data emerge after approval that necessitate an update of the environmental risk assessment, a variation application (“type IB C.I.z variation”) must be submitted to the regulatory authority.

Assessment report Trecondi 2018

Assessment report for Trecondi (treosulfan), medac Gesellschaft fur klinische Spezialpraparate, 13 December 2018, EMA/903773/2019.

Table 1. Summary of main study results contains no data. It is therefore not possible to verify from the report the ecotoxicological effect data, the number of trophic levels assessed, or other underlying effect endpoints. Although the results are described and discussed in the text, the summary that the table appears intended to provide is not included.

Hazard

Persistence: Treosulfan is not readily biodegradable. Approximately 25 to 40% of the administered dose treosulfan is excreted unchanged in urine and is therefore expected to enter wastewater treatment plants via domestic sewage. Wastewater treatment plants remove approximately 30 to 40% of the substance, indicating that a proportion of unchanged treosulfan may reach the aquatic environment. However, environmental exposure is expected to be low.

Bioaccumulation: The log K_ow values for treosulfan and its metabolites are ≤ 4.5, indicating a low potential for bioaccumulation.

Toxicity: No data.

Risk

A refined PEC _surfacewater value was calculated for treosulfan and its metabolites and was found to be below the action limit of 0.01 microg/L. An environmental risk assessment (ERA) was performed for both treosulfan and its active metabolites. Considering the low PEC value, the available pharmacokinetic data and the environmental minimisation measures included in the SmPC, the ERA was accepted. The applicant concluded that treosulfan and its metabolites are unlikely to represent a risk to the environment. However, no detailed data or documentation underlying the environmental risk assessment (e.g. exposure calculations, ecotoxicity data, or PNEC derivation) have been presented.

Assessment report Trecondi 2023

Assessment report for Trecondi, medac Gesellschaft fur klinische Spezialpraparate, type II variation, 26 January 2023, EMA/CHMP/117245/2023.

Hazard

Persistence: No data.

Bioaccumulation: The experimentally determined log K_ow values for treosulfan and its active epoxide metabolites (EBDM and DEB) were -1.58, -1.18 and -0.40, respectively, indicating low lipophilicity and a low potential for bioaccumulation.

Toxicity: No data.

Risk

PEC_surfacewater = 0.003 microg/L.

According to EMA guidelines, a medicinal product is considered unlikely to pose an environmental risk when the PEC_surfacewater is below 0.01 microg/L and no other environmental concerns are identified. The low log K_ow values further indicate a low bioaccumulation potential; therefore, a Phase II ERA was not considered necessary.

Comment

Treosulfan has only undergone a phase I study in accordance with regulatory requirements for environmental risk assessments (Guideline on the environmental risk assessment of medicinal products for human use, EMEA/CHMP/SWP/4447/00 Rev. 1- Corr.) A phase I study includes data on bioaccumulation and an estimation of the environmental concentration of treosulfan (PEC_Surfacewater). If the specified threshold values are not exceeded, the company is not required to conduct a Phase II study, which includes data on toxicity, persistence, and risk assessment based on PEC/PNEC.

Fass environmental information

Fass environmental information for Trecondi from Medac (retrieved on 2026-09-18).

Hazard

Persistence: No data.

Bioaccumulation: Log P = -1.58 (treosulfan)
Log P = -1.18 (metabolite EBDM = monoepoxide)
Log P = -0.40 (metabolite DEB = diepoxide)

Toxicity: No data.

Risk

PEC is based on total sold amount API (active pharmaceutical ingredient) in Sweden year 2025.

PEC = 0.00184 microg/L.

Risk of environmental impact of treosulfan cannot be excluded, since no ecotoxicity data are available. "According to the European Medicines Agency Guideline on environmental risk assessment of medicinal products (EMA/CHMP/SWP/4447/00 Rev. 1), use of treosulfan is unlikely to represent a risk for the environment, because the predicted environmental concentration (PEC) at the time of registration was below the action limit 0.01 microg/L."