Detaljerad miljöinformation

Physical properties⁴

Solubility: 14 000 000 µg/L

pKa: Carboxylic acid = 2.9 & pyrrolondinylamine = 7.4

Vapor pressure: 6.85 x 10^-18 mmHg

Molecular weight: 383.46 Da

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 = 0.0382 μg/L

Where:

A =	278.67 kg (total sold amount API in Sweden year 2020, data from IQVIA)3.
R =	0 % removal rate (worst-case scenario)
P =	number of inhabitants in Sweden = 10 * 106
V (L/day) =	wastewater volume per capita and day = 200 (ECHA default)1
D =	factor for wastewater dilution by surface water flow = 10 (ECHA default)1

Predicted No Effect Concentration (PNEC)

Ecotoxicological studies

Activated sludge microorgansims (guideline OECD 209)⁵

EC₁₀ (NOEC) (respiration inhibition) = >100 000 μg/L

EC₅₀ (respiration inhibition) = >100 000 μg/L

Blue-green alga (Anabaena flos-aquae) (guideline OECD 201)⁶

NOEC 72 h (growth rate, chronic toxicity) = 15 μg/L

EC₅₀ 72 h (growth rate, chronic toxicity) = 26 μg/L

Daphnids (Daphnia magna) (guideline FDA 4.08)⁷

NOEC 48 hours (immobilisation, acute toxicity) = ≥900 000 µg/L

EC₅₀ 48 hours (immobilisation, acute toxicity) = >900 000 µg/L

Based on the lowest NOEC for the species Anabaena flos-aquae and using the assessment factor² of 10, the PNEC is calculated to 15/10 = 1.5 µg/L.

Environmental risk classification (PEC/PNEC ratio)

PEC/PNEC = 0.0382 / 1.5 = 0.025, i.e. PEC/PNEC ≤ 0.1 which justifies the phrase ”Use of meropenem has been considered to result in insignificant environmental risk.”

Adsorption (guideline FDA 3.08)⁸

Solid	Kd (L/Kg)	Koc (L/Kg)
Nebo soil (1.45% organic carbon)	315	21724
East Jubilee soil (2.2% organic carbon)	25	1121
Kenny Hill soil (3.1% organic carbon)	7	220

Degradation

Biotic degradation

Ready degradability (guideline OECD 301C)⁹

Not readily biodegradable.

Justification of chosen degradation phrase

Meropenem did not pass the ready biodegradability test. Therefore, meropenem has received the FASS degradation phrase ”Meropenem is potentially persistent.”

Bioaccumulation

Partitioning coefficient (shake flask method, 24 °C)⁴

pH	Log Pow
5	< -3
7	< -3
9	< -3

Justification of chosen bioaccumulation phrase

Since log P_ow < 4 at pH 7, meropenem has low potential for bioaccumulation.

References

1. ECHA, European Chemicals Agency. 2016 Guidance on information requirements and chemical safety assessment chapter R16.

2. EMA, Guideline on the environmental risk assessment of medicinal products for human use.
   

3. IQVIA KG Consumption 2020 report.

4. Module 3.2.S.1.3 General Properties. March 2010.
   

5. Study report BL5373/B: MERREM: Determination of respiration inhibition. March 1992.
   

6. Study report BR0530/B: Meropenem: Determination of toxicity to the blue-green alga, Anabaena flos-aquae. November 2011.

7. Study report BL4430/B: MERREM: Acute toxicity to Dapnia magna. July 1992.

8. Study report BL4513/B: MERREM: Soil sorption and desorption. July 1992.

9. Study report BL4445/B: MERREM: Determination of 28 day ready biodegradability. July 1992.