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Pulver till koncentrat till infusionsvätska, lösning 600 mg
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Antibakteriella medel för systemiskt bruk, övriga cefalosporiner

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  • Vad är miljöinformation?

Miljöinformation

Miljöpåverkan

Ceftarolinfosamil

Miljörisk: Användning av ceftarolinfosamil har bedömts medföra försumbar risk för miljöpåverkan.
Nedbrytning: Ceftarolinfosamil bryts ned i miljön.
Bioackumulering: Ceftarolinfosamil har låg potential att bioackumuleras.


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Detaljerad miljöinformation


Physical properties4,5


Solubility: 8.6 x 106 µg/L

pKa1 = 1.22, pKa2 = 1.79, pKa3 = 5.1, pKa4 = 10.9

Molecular weight: 604.71 g/mol


Environmental Risk Classification


Predicted Environmental Concentration (PEC)


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 = 1.78 x 10-5 μg/L


Where:

A =

0.13 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


Green alga (Pseudokirchneriella subcapitata) (guideline OECD 201)6

NOEC 72 h (growth rate, chronic toxicity) = 33 000 μg/L

EC50 72 h (growth rate, chronic toxicity) = >330 000 μg/L


Blue-green alga (Anabaena flos-aquae) (guideline OECD 201)7

NOEC 72 h (growth rate, chronic toxicity) = 1.2 μg/L

EC50 72 h (growth rate, chronic toxicity) = 3.8 μg/L


Daphnids (Daphnia magna)

NOEC 48 hours (immobilization, acute toxicity, guideline OECD 202)8 = 100 000 μg/L

LOEC 48 hours (immobilization, acute toxicity, guideline OECD 202)8 = >100 000 μg/L

NOEC 21 days (reproduction, chronic toxicity, guideline OECD 211)9 = 7900 μg/L

LOEC 21 days (reproduction, chronic toxicity, guideline OECD 211)9 = >7900 μg/L


Fathead Minnow (Pimephales promelas) (guideline OECD 210)10

NOEC 32 days (survival, chronic toxicity) = 5000 μg/L

LOEC 32 days (survival, chronic toxicity) = >5000 μg/L


Midge (Chironomus riparius) (guideline OECD 218)11

NOEC 28 days (emergence, chronic toxicity) = 67 000 μg/kg

LOEC 28 days (emergence, chronic toxicity) = >67 000 μg/kg


Based on the lowest NOEC for the species Anabaena flos-aquae and using the assessment factor2 of 10, the PNEC is calculated to 1.2/10 = 0.12 µg/L.


Environmental risk classification (PEC/PNEC ratio)

PEC/PNEC = 1.78 x 10-5 / 0.12 = 1.48 x 10-4, i.e. PEC/PNEC ≤ 0.1 which justifies the phrase ”Use of ceftaroline has been considered to result in insignificant environmental risk.”


Adsorption (guideline US EPA OPPTS 835.1110)12

Activated sludge from Totnes Sewage treatment works was used in the test. There was no significant adsorption of the applied radioactivity (<5%) to activated sludge and therefore, ceftaroline is not predicted to adsorb to solids during wastewater treatment. The Kd was calculated to 8 L/kg.



Degradation


Biotic degradation


Ready degradability (guideline OECD 301F)13


At the end of the 28 day study, <5% of the active substance was degraded. The substance is therefore classified as not readily biodegradable.


Water-sediment transformation simulation (guideline OECD 308)14

Length of study: 98 days

High organic sediment system: Tarnock

Low organic sediment system: Staverton

First sediment extraction solvents: acetonitrile: tetrahydrofuran: isopropyl alcohol (1:1:1 v/v/v) with 5% ammonia

Second sediment extraction solvents: acetonitrile: tetrahydrofuran: isopropyl alcohol (1:1:1 v/v/v) with 5% formic acid


Third sediment extraction solvent: 1M hydrochloric acid


The results from the study are shown in the table below.

Data on day 98 at 20 °C

Tarnock

Staverton

Total system

Half-life (days)

0.8

2.0

Total 14CO2 (% of AR)

10

10

Aerobic Water Layer

Half-life parent substance (days)

0.8

2.0

Parent (% of AR)

<1.2

<1.2

Sediment Layer

Half-life parent substance (days)

ND

ND

Bound/NER (% of AR)

28

18

Extractables (% of AR)

4.4

10.9

ND = not detected, NER = non-extractable residues, AR = applied radioactivity


Abiotic degradation


Hydrolysis (guideline OECD 111)15

pH

Hydrolytic half-life (t1/2) at 25 °C

Hydrolytic half-life (t1/2) at 40 °C

Hydrolytic half-life (t1/2) at 50 °C

5

772 h

160 h

57.3 h

7

341 h

45.3 h

16.3 h

9

12.5 h

2.02 h

0.67 h

Justification of chosen degradation phrase

As the total system DT50 value (water-sediment transformation simulation, OECD 308) was 2 days, it corresponds to the degradation phrase ”ceftaroline is degraded in the environment”.


Bioaccumulation

Partitioning coefficient (guideline OECD 107)16

pH

Log Dow

5

< 0

7

< 0

9

< 0

Justification of chosen bioaccumulation phrase

Since log Dow < 4 at pH 7, ceftaroline has low potential for bioaccumulation.


References

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

  2. ECHA, European Chemicals Agency. 2008 Guidance on information requirements and chemical safety assessment chapter R10.

  3. IQVIA KG Consumption 2020 report.

  4. Zinforo Environmental risk assessment. August 2011.

  5. Ceftaroline fosamil Module 3.2.S.1.3 General properties. February 2019.

  6. Study report BR0170/B: Ceftaroline: Toxicity to the green alga Pseudokirchneriella subcapitata. June 2010.

  7. Study report BR0193/B: Ceftaroline: Determination of toxicity to the blue green-alga Anabaena flos-aquae. July 2010.

  8. Study report BR0158/B: Ceftaroline: Acute toxicity to Daphnia magna. June 2010.

  9. Study report BR0194/B: Ceftaroline: Determination of the effects on the survival and reproduction to Daphnia magna. September 2010.

  10. Study report BR0254B: Ceftaroline: Determination of effects on the early-life stage of the fathead minnow (Pimephales promelas). September 2010.

  11. Study report BR0257/B: [14C] Ceftaroline: Determination of the effects in a water‑sediment system on the emergence of Chironomus riparius using spiked sediment. September 2010.

  12. Study report BR0235/B: [14C] Ceftaroline: Activated sludge sorption isotherm. September 2010.

  13. Study report BR0151/B: Ceftaroline: Determination of ready biodegradability. May 2010.

  14. Study report BR0223/B: [14C] Ceftaroline: Aerobic transformation in aquatic sediment systems. November 2010.

  15. Study report BR0454/B: Hydrolysis as a function of pH test in support of the Environmental Risk Assessment of Ceftaroline. June 2011.

  16. Study report BR0200/B: Partition coefficient (n-octanol/water): HPLC method. September 2010.