Detaljerad miljöinformation

Environmental Risk Classification

Predicted Environmental Concentration (PEC)

PEC is calculated according to the following formula:

PEC (μg/L) = (A*10⁹*(100-R))/(365*P*V*D*100) = 1.37*10^-6*A (100-R)

PEC = 0.0214 µg/L

Where:

A = 155.9 kg (sales data for Sweden in 2022).

R = 0% removal rate. In this assessment 0% is used as a conservative value.

P = 10,000,000 (default value for number of inhabitants in Sweden)

V= 200 L/day (wastewater per capita per day, default value)

D = 10 (dilution, default value)

Predicted No Effect Concentration (PNEC)

Ecotoxicological studies

Algae (Raphidocelis subcapitata formally Pseudokirchneriella subcapitata) (OECD 201) (Ref. I):

EC₅₀ 72 h (growth rate) = 1.8 mg/L

NOEC (growth rate) = 0.037 mg/L

Crustacean (Daphnia magna):

Chronic toxicity (OECD 211) (Ref. I)

NOEC 21 days (reproduction) = 0.0559 mg/L

Fish (Pimephales promelas):

Chronic toxicity (OECD 210) (Ref. I)

NOEC 28 days (hatching and post-hatch survival) = 0.0457 mg/L

PNEC = 3.7 μg/L (an assessment factor of 10 is applied to the lowest NOEC from the base set of three long-term toxicity tests. In this case the NOEC of 37 μg/L for growth inhibition of the algae R. subcapitata)

Environmental risk classification (PEC/PNEC ratio)

PEC/PNEC = 0.0214/3.7 = 0.00578, i.e. PEC/PNEC ≤ 0.1 which justifies the phrase "Use of dimethyl fumarate has been considered to result in insignificant environmental risk."

Degradation

Biotic degradation

Ready degradability:

63% degradation in 5 days (OECD 301B CO₂ Evolution Test). (Ref. I)

Justification of chosen degradation phrase:

Since > 60% biodegradation was achieved within five days of test initiation, dimethyl fumarate can be considered readily biodegradable. The degradation phrase should be: “Dimethyl fumarate is degraded in the environment.”

Bioaccumulation

Partitioning coefficient:

Log Kow= 0.77 (Ref I).

Justification of chosen bioaccumulation phrase:

Since log Kow < 4, the substance has low potential for bioaccumulation.

Excretion (metabolism)

In humans, dimethyl fumarate is extensively metabolised with less than 0.1% of the dose excreted as unchanged dimethyl fumarate in urine. Exhalation of CO₂ is the primary route of dimethyl fumarate elimination accounting for 60% of the dose. Renal and faecal elimination are secondary routes of elimination, accounting for 15.5% and 0.9% of the dose respectively. Primary active metabolite is monomethyl fumarate (Ref II).

References

I. WCA (2021) Environmental risk assessment for Tecfidera. Final report.

II. Tecfidera SmPC, http://www.ema.europa.eu

III. ECHA, European Chemicals Agency. 2008 Guidance on information requirements and chemical safety assessment.

http://guidance.echa.europa.eu/docs/guidance_document/information_requirements_en.html.