Temozolomide

Detailed information

Fass environmental information

Fass environmental information for Temodal (temozolomide) from Merck Sharp & Dohme AB (retrieved on 2026-04-10).

Hazard

Persistence: In a biotic degradation study, temozolomide showed 61% elimination of the parent compound at Day 21 and 83% mineralization to CO₂ at Day 35 (OECD 301B).

For abiotic degradation via hydrolysis, the half‑life was 69 days at pH 4 and less than 1 day at pH 7 and pH 9 (OECD 111).

Since 83% of temozolomide mineralizes to the non‑hazardous end product CO₂ within 35 days, significant mineralization is expected in the environment. Therefore, the phrase "Temozolomide is slowly degraded in the environment" has been selected.

Bioaccumulation: Log K_ow = 1.35 at pH 7.

Acute toxicity: There are data for 3 trophic levels, most sensitive green algae EC₅₀ 72 h (growth rate) > 90000 microg/L. Comment: Values reported as greater than are not according to the guidelines. The actual value may be lower.

Risk

PEC/PNEC is based on sales data in Sweden in year 2022.

PEC = 0.0015 microg/L.

PNEC = Lowest EC₅₀, 90000 microg/L/1000 (Assessment Factor (AF) for 3 acute studies) = 90 microg/L.

PEC/PNEC = 0.000017 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 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.

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, as well as possibly other products from the same company, not all medicinal products containing the same active substance.

EMA’s scientific discussion for Temodal

EMA’s scientific discussion for Temodal, 2005-12-13.

"An estimate of the maximum environmental concentration resulting from the use of the product was developed based on projections of sales and flows to sewer systems. The environmental impact is not expected to be significant."

Assessment report for generics

There are assessment reports for several generics containing similar information. Here, the report for Temozolomide Sun is presented, 19 May 2011, EMA/CHMP/197697/2011.

No Environmental Risk Assessment was submitted. This is justified as the introduction of Temozolomide Sun by Sun Pharmaceutical Industries Europe B.V. is not expected to increase the overall sales volume of temozolomide products or the environmental exposure to the active substance. The environmental risk is therefore considered unchanged.

Comment on generics

After the implementation of the latest European Medicines Agency (EMA) ERA guideline (1 September 2024), a generic company has the following options for Article 10 procedures under Directive 2001/83/EC:

i) to argue that a full ERA is not required because the pharmaceutical substance belongs to certain substance groups (e.g., so-called natural substances);

ii) to identify an official ERA from a previously accepted product and use it; or

iii) to develop its own ERA according to the latest EMA ERA guideline.

Arguments for not submitting an Environmental Risk Assessment (ERA) based on the claim that total environmental exposure has not increased (via total sales volumes) belong to the previous ERA guideline system (2006–2024) and are no longer applicable. Regarding option ii), it should be noted that if a reference ERA exists, the generic company must demonstrate that its conclusions remain technically relevant (since the latest ERA guideline introduced several new technical requirements absent in the previous ERA guideline) and in terms of exposure (showing that the estimated exposure used in the reference ERA remains reasonable). Regulatory authorities (national and EMA) recommend that generic companies attempt to obtain reference ERA documentation from other companies via a so-called Letter of Access (LoA). However, if this is not possible, it remains feasible to argue that the conclusions of an existing reference ERA are still relevant based on information gathered from public assessment reports (summarized descriptions of environmental risk assessments) and product information (to confirm that dosages, indications, etc., have not changed). It should be noted that in some cases, reference ERAs approved between 2006 and 2024 may need to be modified (e.g., with additional experimental studies). If no previous reference ERA can be identified or used, the generic company must commit to developing its own ERA.