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 = 0.00880 kg (total sold amount API in Sweden year 2019, data from IQVIA/LIF).
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 = 0.0000013 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: 0.0000013/200 =6.5 * 10^-9, i.e. PEC/PNEC <0.1 which justifies the phrase "Use of gadoliniumpentetat dimeglumin has been considered to result in insignificant risk."

Degradation

Biotic degradation

Ready degradability: not readily biodegradable

An investigation on the aerobic biodegradability of gadoliniumpentetat dimeglumin 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). Gadoliniumpentetat dimeglumin 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 gadoliniumpentetat dimeglumin (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 gadoliniumpentetat dimeglumin 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 gadoliniumpentetat dimeglumin 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 gadoliniumpentetat dimeglumin 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. Gadoliniumpentetat dimeglumin 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 gadoliniumpentetat dimeglumin is not readily degradable, the substance is considered to be potentially persistent in the environment.

Abiotic degradation

Hydrolysis:

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

Bioaccumulation

Partitioning coefficient:

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

Justification of chosen bioaccumulation phrase:

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

Excretion (metabolism)

Gadoliniumpentetat dimeglumin is introduced unmetabolized as parent compound (contrast agent).

PBT/vPvB assessment

Gadoliniumpentetat dimeglumin is not PBT/vPvB, because the log P_OW 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).