Detaljerad miljöinformation

Carbidopa is given in combination with levodopa used for the treatment of Parkinson's

disease and syndrome. Carbidopa is an inhibitor of aromatic amino acid decarboxylase. It is a white, crystalline compound, slightly soluble in water and very slightly soluble in alcohol.

Carbidopa has a molecular weight of 244.3 g/mole and an empirical formula of

C10H14N2O4·H2O. (Ref II)

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 = 0.056 μg/L

Where:

A = 409.98 kg (total sold amount API in Sweden year 2021, data from IQVIA). Reduction of A may be justified based on metabolism data.

R = 0 % removal rate (due to loss by adsorption to sludge particles, by volatilization, hydrolysis or biodegradation) = 0 if no data is available. (If R not =0 this should be justified under the degradation section) 

P = number of inhabitants in Sweden = 10 *10⁶

V (L/day) = volume of wastewater per capita and day = 200 (ECHA default) (Ref. I)

D = factor for dilution of wastewater by surface water flow = 10 (ECHA default) (Ref. I)

Ecotoxicological studies*

Water Flea (Daphnia magna):

Acute toxicity

EC₅₀ 48 hrs (death) = 35.3 mg/L (guideline eg OECD 202) (Reference III)

Bioaccumulation

Carbidopa has an estimated log Pow of -2.2 and therefore, has no significant bioaccumulation potential. (reference IV)

References

1. 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

2. EPAR for Levodopa/Carbidopa Levodopa/Carbidopa/Entacapone Orion, INN- levodopa, carbidopa, entacapone (europa.eu)

3. ICI Bringham Laboratory, 1989. “Carbidopa: Determination of acute toxicity to Daphania magna” Study No Q1022/A, Brixham, England September 1989

4. HSDB for Carbidopa https://pubchem.ncbi.nlm.nih.gov/compound/34359#section=Computed-Properties

Detaljerad miljöinformation

Levodopa

Environmental risk: Risk of environmental impact of Levodopa cannot be excluded, since there is not sufficient ecotoxicity data available.

Degradation: Levodopa is degraded in the environment.

Bioaccumulation: Levodopa has low potential for bioaccumulation

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 = 0.69 μg/L

Where:

A = 4602 (total sold amount API in Sweden year 2019, data from IQVIA) (Ref I.)

R = 0 % removal rate (worst case assumption)

P = number of inhabitants in Sweden = 9 *10⁶

V (L/day) = volume of wastewater per capita and day = 200 (ECHA default) (Ref. II)

D = factor for dilution of waste water by surface water flow = 10 (ECHA default) (Ref. II)

Predicted No Effect Concentration (PNEC)

Ecotoxicological studies

Crustacean, water flea (Daphnia magna) (OECD 202) (Ref. IV):

Acute toxicity

EC₅₀ 48 h (immobility) = 16 mg/L

Fish, rainbow trout (Oncorhynchus mykiss) (OECD 203) (Ref. III):

Acute toxicity

LC₅₀ 72 h (mortality) > 100 mg/L

Environmental risk classification (PEC/PNEC ratio)

Risk of environmental impact of Levodopa cannot be excluded, since there is not sufficient ecotoxicity data available.

Degradation

Biotic degradation (OECD 301F) (Ref. III)

Biodegradation: 72 %

Exposure time: 28 d

Readily biodegradable

Justification of chosen degradation phrase:

Based on the data presented above, the phrase, “Levodopa is degraded in the environment” is chosen.

Bioaccumulation

Partitioning coefficient (Method unknown) (Ref. V):

Log K_ow = -2.39

Justification of chosen bioaccumulation phrase:

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

References

1. Data from IQVIA ”Consumption assessment in kg for input to environmental classification - updated 2020 (data 2019)”.

2. 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

3. Roche, 2020. “Safety Data Sheet for MADOPAR Tablets 50/12.5 mg”, accessed on 2 Dec 2020 via EHS_L_TEXT(CED-U00 (roche.com)

4. ICI Brixham, 1988. "LEVODOPA: Determination of the Acute Toxicity to Daphnia Magna." Study No. BL/B/3276, Brixham, UK, 27 May 1988.

5. Sangster, J., 1993. “Log Kow Databank”, Sangster Res. Lab. Montreal, Quebec, Canada.