Miljöpåverkan
Rotigotin
Miljörisk:
Användning av rotigotin har bedömts medföra försumbar risk för miljöpåverkan.
Nedbrytning:
Rotigotin är potentiellt persistent.
Bioackumulering:
Rotigotin har låg potential att bioackumuleras.
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Detaljerad miljöinformation
Environmental Risk Classification
Predicted Environmental Concentration (PEC)
PECsurface water is calculated according to the following formula:
PECsurface water (µg/l) = (A*109*(100-R))/(365*P*V*D*100) = 1.5*10-6*A*(100-R)
PEC = 3.5 x 10-4 µg/l
Where:
A = 2.35 kg (total sold amount API in Sweden 2020, data from IQVIA)
R = 0 % removal rate (due to loss by adsorption to sludge particles, by volatilization, hydrolysis or biodegradation)
P = number of inhabitants in Sweden = 10*106
V (l/day) = volume of wastewater per capita and day = 200 (Ref I)
D = factor of dilution of waste water by surface water flow = 10 (Ref I)
Predicted No Effect Concentration (PNEC)
Ecotoxicological studies
Algae (Pseudokirchneriella subcapitata):
EC50 72 h (biomass) = 2 400 µg/l
EC50 72 h (growth inhibition) = 4 530 µg/l
NOEC = 1 230 µg/l
(Protocol: OECD 201)
(Ref II)
Crustacean (Daphnia magna):
EC50 48 h (immobilization) = 14 300 µg/l
(Protocol: OECD 202)
(Ref II)
NOEC 21 days (reduction in reproduction) = 26.5 µg/l
(Protocol: OECD 211)
(Ref II)
Fish (Pimephales promelas):
LC50 96 h (mortality) = 686 µg/l
NOEC 35 days (lethality) = 1.05 µg/l
(Protocol: OECD 210)
(Ref II)
Other ecotoxicity data:
PNECwater = 0.105 µg/l
(The PNECwater [μg/l] = 1.05/10 applying an assessment factor of 10 and using the lowest long-term value when this result was generated for three thropic levels. The result used was for the fish, Pimephales promelas where NOEC was 1.05 μg/l.)
Environmental risk classification (PEC/PNEC ratio)
PECsurface water/PNECwater = 3.5 x 10-4 /0.105 = 0.003 , i.e. PECsurface water/PNECwater ≤ 0.1 which justifies the phrase “Use of rotigotine has been considered to result in insignificant environmental risk”
Degradation
Biotic degradation
Ready degradability: rotigotine showed 8 % degradation over 28 days. (Protocol: OECD 301B) (Ref II)
Hence, rotigotine did not pass the ready degradation test and since there is no information available on grade of mineralisation the phrase: ”rotigotine is potentially persistent.” should be used.
Bioaccumulation
Partitioning coefficient
Log Pow = 3.49 at pH 7 (Protocol: OECD 107) (Ref II)
Justification for chosen bioaccumulation phrase:
Since log Pow < 4 at pH 7, the substance has low potential for bioaccumulation.
Excretion (Metabolism)
More than 60 % of dose delivered to the skin were systemically available within 24 h. Less than 1 % of rotigotine is excreted as parent compound. A number of metabolites have been characterized. The main metabolites have no pharmacological activity. (Ref III).
References
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ECHA, European Chemicals Agency. Guidance on information requirements and chemical safety assessment, version 3.0 Feb 2016.
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Swales. S. Rotigotine: environmental risk assessment for a transdermal patch, Expert report. 2009. (UCB internal reference)
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Cawello W., et al., Absorption, Disposition, Metabolic Fate, and Elimination of the Dopamine Agonist Rotigotine in Man: Administration by Intravenous Infusion or Transdermal Delivery. Drug Metab Dispos. 2009 Oct;37(10):2055-60. http://www.ncbi.nlm.nih.gov/pubmed/19608695