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)

PEC = 1.13 µg/L

Where:

A = 7506.77 kg (total sold amount API in Sweden year 2018, 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 = 9*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 (Selenastrum capricornutum)

Acute toxicity:

EC₅₀ 14 d (growth inhibition) > 1000 mg/L
Protocol: OECD 201
(Ref II)

Water flea (Daphnia magna)

Acute toxicity:

LC₅₀ (acute immobilization) > 1000 mg/L
Protocol: OECD 202
(Ref III)

Fish (Bluegill, Lepomis macrochirus)

Acute toxicity:

LC₅₀ > 1000 mg/L
Protocol: OECD 203
(Ref IV)

Other ecotoxicity data:

PNEC = 1000 μg/L

PNEC (μg/L) = lowest LC/EC₅₀ 1000 mg/L/1 000, where 1 000 is the assessment factor used (acute toxicity data only). The most sensitive of the three tested species is unknown since LC/EC₅₀ were the same for all three species. This value has been used for this calculation.

Environmental Risk Classification (PEC/PNEC ratio)

PEC/PNEC= 1.13/1000 = 0.0013

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

Degradation

Abiotic and biotic degradation

Iomeprol had no inhibitory effect on the respiration rate of activated sludge up to a concentration of 100 mg/L . (Protocol: OECD 209). (Ref V).

Degradation of iomeprol was established over a period of 28 days. The COD value was 0.858 mg O₂/mg. The BOD value at 4, 8, and 24 h and on days 7, 14, 21 and 28 was 0, 0.035, 0.040, 0.060, 0.085, 0.120 and 0.130 mg O₂/mg.

The results given by HPLC determinations shown that the alteration in the chemical structure of iomeprol (primary biodegradation) did not exceed 15%.

On the basis of the biodegradability values found: 0, 4.1, 4.7, 7.0, 9.9, 14.0 and 15.2% respectively at 4, 8, 24 h and on days 7, 14, 21, and 28, it can be concluded that iomeprol is not readily biodegradable⁷. (Protocol: OECD 301). (Ref VI).

Environmental Risk Classification

Hence, iomeprol did not pass the ready degradation test and since there is no information available on grade of mineralisation the phrase: ”iomeprol is potentially persistent.” should be used.

Bioaccumulation

Partition coefficient

An estimation of the partition coefficient of iomeprol between n-octanol and aqueous media was made by adding suitable volumes of a water solution of iomeprol (40350 mg/L) to known volumes of a pre-saturated mixture of n-octanol-water. The K_owvalue (n-octanol solubility/aqueous solubility) was 0.0021 (log₁₀K_ow = -2,68) .

Non-clinical data on iomeprol (Iomeron) reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, toxicity to reproduction. Pre-clinical effects were observed only at exposures considered sufficiently in excess of the maximum human exposure indicating little relevance to clinical use.

Results from studies in rats, mice and dogs demonstrate that iomeprol has an acute intravenous or intraarterial toxicity similar to that of the other non-ionic contrast media, as well as a good systemic tolerability after repeated intravenous administrations in rats and dogs. (Method unknown). (Ref VII)

Environmental Risk Classification
Justification for chosen bioaccumulation phrase:

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

Excretion (metabolism)

There is no significant serum protein binding and iomeprol is not metabolized.

Elimination is almost exclusively through the kidneys and is rapid.

(Ref VIII)

References

1. ECHA, European Chemicals Agency. Guidance on information requirements and chemical safety assessment, version 3.0 Dec 2015.

2. Iomeprol. Algal growth inhibition study. RBM Study No. 950109, 1996

3. Iomeprol. Acute immobilization study in Daphnia magna. RBM Study No. 940841, 1996

4. Iomeprol. Acute toxicity study in fish (semi-static test). RBM Study No. 940740, 1996

5. Iomeprol. Activated sludge, respiration inhibition test. RBM Study No. 940742, 1995

6. Iomeprol. Ready biodegradability (closed bottle test). RBM Study No. 940743, 1995.

7. Physical and chemical characterization of iomeprol. Enichem Study No. 02095, 1995.

8. Iomeron SmPC, retrived from https://www.medicines.org.uk/emc/product/3892/smpc