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 P_ow = 3.49 at pH 7 (Protocol: OECD 107) (Ref II)

Justification for chosen bioaccumulation phrase: 

Since log P_ow < 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

1. ECHA, European Chemicals Agency. Guidance on information requirements and chemical safety assessment, version 3.0 Feb 2016.

2. Swales. S. Rotigotine: environmental risk assessment for a transdermal patch, Expert report. 2009. (UCB internal reference)

3. 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