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 = 0.00096 µg/L

Where:

A = 6,996025 kg (total sold amount API in Sweden year 2021, data from IQVIA)

R = 0 % removal rate (due to loss by adsorption to sludge particles, by volatilization, hydrolysis or biodegradation) = 0 if no data is available.

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 waste water by surface water flow = 10 (ECHA default) (Ref. I)

According to the European Medicines Agency guideline on environmental risk assessment of medicinal products (EMA/CHMP/SWP/4447/00), use of gadobenat is unlikely to represent a risk for the environment, because the predicted environmental concentration (PEC) is below the action limit of 0.01 μg/L.

Predicted No Effect Concentration (PNEC)

Ecotoxicological studies

Algae (Selenastrum capricornutum):

Acute toxicity:

EC₅₀ 72 h (growth inhibition): > 111 000 μg/L

Protocol: OECD 201

(Ref. II)

Water flea (Daphnia magna):

Acute toxicity:

EC₅₀ 48 h (immobilization) > 961 000 μg/L

Protocol: OECD 202

(Ref. III)

Rainbow trout (Oncorhynchus mykiss):

Acute toxicity:

LC₅₀ 96 h (mortality) > 875 000 μg/L.

Protocol: OECD 203

(Ref. IV)

Other ecotoxicity data:

PNEC = 111 μg/L

PNEC (μg/L) = lowest EC₅₀ /1 000 = 111 000/1 000, where 1 000 is the assessment factor used (acute toxicity data only). EC₅₀ for algae, Selenastrum capricornutum has been used for this calculation since it is the most sensitive of the three tested species.

Environmental Risk Classification (PEC/PNEC ratio)

PEC/PNEC = 0.00096/111 = 8,65*10^-6

PEC/PNEC ≤ 0.1 which justifies the phrase “use of gadobenat has been considered to result in insignificant environmental risk".

Degradation

Gadobenate and meglumine moieties of gadobenate dimeglumine were shown to be inherently biodegradable in a test for 'ready' biodegradability, with the meglumine moiety achieving 61 % degradation after 18 days and gadobenate dimeglumine a level of 51 % degradation after 76 days.

Protocol: OECD 301B

(Ref. V)

No other data is avaiable.

Justification of chosen degradation phrase:

The potential for bioaccumulation of gadobenate cannot be excluded, due to lack of data.

Bioaccumulation

Partitioning coefficient

Log P = - 4.1 at pH 7 (estimated with ChemAxon)
(Ref. VI)

Justification for chosen bioaccumulation phrase: 

Since log P < 4 at pH 7, the substance has low potential for bioaccumulation.

Excretion (metabolism)

Gadobenate ion is rapidly cleared from plasma and is eliminated mainly in urine and to a lesser extent in bile.
(Ref. VII)

References

1. ECHA, European Chemicals Agency. 2008 Guidance on information requirements and chemical safety assessment - find here.

2. Internal document: Gadobenate Dimeglumine: determination of 72-hour EC₅₀ to selenastrum capricornutum. HLS Report No. 95/BCC005/1384. June 26, 1996.

3. Internal document: Gadobenate Dimeglumine: acute toxicity on Daphnia magna. HLS Report No. 95/BCC00/1383. June 12, 1996.

4. Internal document, ERA, module 1.6. October 2015.

5. Internal document: HLS Report No. 96/BCC007/0176. June 26, 1996.

6. Drug Bank. Retrieved from DrugBank 2023-04-17 - find here.

7. SmPC of MultiHance. Retrieved from MPA 2023-04-17 - find here.