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Magnevist®

Bayer

Injektionsvätska, lösning i förfylld spruta 2 mmol/l
(Klar lösning, fri från partiklar)

Paramagnetiskt kontrastmedel för magnetisk resonanstomografi.

Aktiv substans:
ATC-kod: V08CA01
Utbytbarhet: Ej utbytbar
Läkemedel från Bayer omfattas av Läkemedelsförsäkringen.
  • Vad är miljöinformation?

Miljöinformation

Miljöpåverkan

Gadopentetatdimeglumin

Miljörisk: Användning av gadopentetsyradimegluminat har bedömts medföra försumbar risk för miljöpåverkan.
Nedbrytning: Gadopentetsyradimegluminat är potentiellt persistent.
Bioackumulering: Gadopentetsyradimegluminat har låg potential att bioackumuleras.


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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) = 1.5*10-6*A(100-R)

Where:

A = 13.494842 kg (total sold amount API in Sweden year 2016, data from QuintilesIMS).
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 = 9 *106 

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

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

PEC = 0.002 μg/L


Predicted No Effect Concentration (PNEC)

Ecotoxicological studies

Algae (Desmodesmus subspicatus):

EC50 /72 h (growth inhibition, growth rate) = >100 mg/L
NOEC/72 h = >100 mg/L (guideline OECD 201) (1)

Crustacean (waterflea Daphnia magna):

Acute toxicity

EC50 /48 h (immobilization) = >100 mg/L (guideline OECD 202) (2)

Chronic toxicity

NOEC /21 days (reproduction) = ≥ 10 mg/L (guideline OECD 211) (3)

Fish:

Acute toxicity (Zebrafish Danio rerio)

LC50 /96 h (mortality) = >100 mg/L (guideline OECD 203) (4)

Bacteria (Pseudomonas putida):

EC10/16h (growth) > 1000 mg/L (guideline DIN38412 L8) (5)

PNEC = 200 μg/L (Lowest NOEC Daphnia magna >10000 µg/L; AF 50)


Environmental risk classification (PEC/PNEC ratio)

PEC/PNEC ratio: 0.0079/200 = 0.00004, i.e. PEC/PNEC <0.1 which justifies the phrase Use of Gadopentetsyradimegluminat has been considered to result in insignificant risk.


Degradation

Biotic degradation

Ready degradability: not readily biodegradable

An investigation on the aerobic biodegradability of gadopentetic acid, dimeglumine salt in water was conducted according to OECD 301 E (6). The incubation time was extended to day 62 because of the observation of a slight degradation towards to usual end of the incubation (28 days). Gadopentetic acid, dimeglumine salt was incubated at concentrations of 20 mg C/L given as dissolved organic carbon (DOC), equivalent to 54 mg/L of substance. The results showed that the test solution of gadopentetic acid, dimeglumine salt (containing 407.94 mg gadopentetate and 105.55 mg meglumine) was degraded to approx. 50 % at the end of the incubation period. The degradation started around day 21. However, the elimination of organic carbon in the test solution, as indicated by DOC measurement, was not the result of the degradation of the Gd-DTPA complex, as evidenced by the results of the specific chemical analysis for this complex. Therefore, it is most likely that the loss of DOC is due to the degradation of the dimeglumine component of the salt. Given the fact that dimeglumine consist of two molecules of methylglucamine each contributing 7 carbon atoms to a total number of 28 carbon atoms in the gadopentetic acid, dimeglumine salt it is very likely that the observed 50 % DOC reduction observed at the end of this prolonged study is caused by the degradation of dimeglumine component.


A test on aquatic-sediment distribution was condcted according to OECD 308 (aerobic part) (7). The test substance gadopentetic acid, dimeglumine salt was incubated in an aerated system, which contained intact lake sediment and overlaying lake water. The substance was incubated over a period of 100 days. Because of the high hydrophilicity of the test substance and the expected low adsorption the organic carbon content and the grain size of the sediment were assumed to have no influence on the sorption process. Therefore only one type of sediment was used. The concentration of dimeglumine gadopentetate in the filtered overlaying water was analyzed by HPLC/UV. Additionally, the content of Gd in sediment and the filtrates of the overlaying water, the filtrates of demineralized water and the filtrates of diluted HCl were analyzed by ICP/MS, in order to recover all sediment related, dissolved substance. Dimeglumine gadopentetate was only marginally removed from the overlaying water after 100 days in the aquatic-sediment system. Gd was found to a low extent in the sediment taken at the beginning, after 2, 8 and 15 days. Because Gd was detected also in the non-dosed sediment, it is likely, that the Gd determined in the sediment at day 2, 8 and 15 is of geogenic origin. The test solution was not completely removed during filtration, therefore it is possible that little amounts of Gd in the sediment resulted from that solution. At the end of the incubation, there was a slight increase of the Gd concentration in the sediment that was supposed to be related to the introduced substance.


Justification of chosen bioaccumulation phrase:

Since Gadopentetic acid, dimeglumine salt is not readily degradable, the substance is considered to be potentially persistent in the environment.


Abiotic degradation

Hydrolysis:

Gadopentetic acid, dimeglumine salt is hydrolytically stable (diagnostic product is an aqueous solutuion of gadopentetic acid, dimeglumine salt).


Bioaccumulation

Partitioning coefficient:

Log POW -5.4 (Shake flask method , FDA TAD 3.02) (8)

Justification of chosen bioaccumulation phrase:

Since log POW was -5.4, the substance was considered to have a low potential for bioaccumulation.

Excretion (metabolism)

Gadopentetic acid, dimeglumine salt is introduced unmetabolized as parent compound (contrast agent).


PBT/vPvB assessment

Gadopentetic acid, dimeglumine salt is not PBT/vPvB, because the log POW was lower than 4.5.


References

  1. Growth inhibition test of Magnevist® (Dimeglumine gadopentetate, ZK 93035/dimegl.) on the green algae Desmodesmus subspicatus. Nonclinical Drug Safety, Bayer Schering Pharma AG, Report no. A34544, Study no. TXST20060212 (2006).

  2. Acute immobilization test of Magnevist® (ZK 93035) with Daphnia magna. Nonclinical Drug Safety, Bayer Schering Pharma AG, Report no. A34543, Study no. TXST20060211 (2006).

  3. Reproduction study of Magnevist® (ZK 93035) in Daphnia magna. Nonclinical Drug Safety, Bayer Schering Pharma AG, Report no. A30908, Study no. TXST20050336 (2005).

  4. Acute toxicity of Magnevist ® (dimeglumine gadopentetate, ZK 93035/dimegl.) to the Zebra fish Danio rerio. Nonclinical Drug Safety, Bayer Schering Pharma AG, Report no. A29951, Study no. TXST20050264 (2005).

  5. Growth inhibition test of dimeglumine gadopentetate on the bacterium Pseudomonas putida. Schering AG, Experimental Toxicology, Report no. 9199, Study no. TX19900197 (1991).

  6. Study on the biodegradability of dimeglumine gadopentetate according to the modified OECD screening test. Schering AG, Experimental Toxicology, Report no. A31214, Study no.TXST1990262 (1991).

  7. Aquatic-sediment study (aerobic) with Magnevist® (dimeglumine gadopentetate, ZK 93035/dimegl.). Nonclinical Drug Safety, Bayer Schering Pharma AG, Report no. 37066, Study no. TXST20070034 (2007).

  8. The octanol/water partition coefficient of gadopentatetic acid, dimegl. (ZK 93035) at pH 7 and 25 ºC. Schering AG, General Physical Chemistry, Report no. KS25, Study no.94/137 (1994).