Miljöpåverkan (Läs mer om miljöpåverkan)
Dimetylfumarat
Miljörisk:
Användning av dimetylfumarat har bedömts medföra försumbar risk för miljöpåverkan.
Nedbrytning:
Dimetylfumarat bryts ned i miljön.
Bioackumulering:
Dimetylfumarat har låg potential att bioackumuleras.
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Detaljerad miljöinformation
Detailed background information
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) = 1.5*10-6*A (100-R)
PEC = 0.029 µg/L
Where:
A = 194.8145 kg (total sold amount API in Sweden year 2015, data from IMS Health).
R = 0 % removal rate (due to loss by adsorption to sludge particles, by volatilization, hydrolysis or biodegradation). This is considered a conservative value.
P = number of inhabitants in Sweden = 9*106
V (L/day) = volume of wastewater per capita and day = 200 (ECHA default) (Ref. 1)
D = factor for dilution of waste water by surface water flow = 10 (ECHA default) (Ref. 1)
Predicted No Effect Concentration (PNEC)
Ecotoxicological studies
Algae (Pseudokirchneriella subcapitata) (OECD 201) (Ref. 2):
EC50 72h (growth rate) > 1 800 µg/mL
NOEC (growth rate) = 37 µg/mL
Crustacean (Daphnia magna):
Chronic toxicity (OECD 211) (Ref. 3)
NOEC 21 days (reproduction) = 55.9 µg/mL
Fish (Pimephales promelas):
Chronic toxicity (OECD 210) (Ref. 4)
NOEC 28 days (survival) = 45.7 µg/mL
Other ecotoxicity data:
Calculation of PNEC is obtained by applying assessment factors (AF) to long-term ecotoxicity data (Ref 1):
Lowest NOEC/AF
PNEC = 3.7 μg/L
Where:
Lowest NOEC = 37 µg/mL (Pseudokirchneriella subcapitata, growth inhibition test)
AF = 10 based on the availability of chronic toxicity studies for three trophic levels
Environmental risk classification (PEC/PNEC ratio)
PEC/PNEC = 0.029/3.7 = 0.0078, 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:
Test results showed > 60% degradation within five days (OECD 301) (Ref 5).
Justification of chosen degradation phrase:
Dimethyl fumarate passes the ready degradability test, hence the degradation phrase should be: “Dimethyl fumarate is degraded in the environment.”
Bioaccumulation
Partitioning coefficient: Log Pow= 0.74 at neutral pH (experimentally determined with unknown method) (Ref 6).
Since log Pow < 4 at pH 7, dimethyl fumarate is considered to have “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 7.).
References
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ECHA, European Chemicals Agency. 2008 Guidance on information requirements and chemical safety assessment. http://guidance.echa.europa.eu/docs/guidance_document/information_requirements_en.htm
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Internal document: Smithers Viscient Study No. 3200151. Anderson M. Inhibition of growth to the alga Pseudokirchneriella subcapitata. Report issued April 2013. Smither Viscient (ESG) Ltd., Harrogate, North Yorkshire, United Kingdom.
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Internal document: Covance Study No. 8253806. Last G. Dimethyl fumarate: Chronic effects to Daphnia magna. Report issued January 2012. Covance Laboratories, Harrogate, North Yorkshire, United Kingdom.
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Internal document: Covance Study No. 8253807. Last G. Dimethyl fumarate: Fish early life stage test (Pimephales promelas). Report issued January 2012. Covance Laboratories, Harrogate, North Yorkshire, United Kingdom.
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Environmental risk assessment, CTD module 1.6 of “Tecfidera”
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Hansch C., et al. 1995, Chem ID+, US National Library of Medicine, National Institute of Health, http://chem.sis.nlm.nih.gov https://chem.nlm.nih.gov/chemidplus/name/dimethyl%20fumarate
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Tecfidera SmPC 2016-11-17, http://www.ema.europa.eu