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  • Vad är miljöinformation?

Miljöinformation

Miljöpåverkan (Läs mer om miljöpåverkan)

Mirtazapin

Miljörisk: Användning av mirtazapin har bedömts medföra försumbar risk för miljöpåverkan.
Nedbrytning: Mirtazapin bryts ned långsamt i miljön.
Bioackumulering: Mirtazapin 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)


PEC = 0.2 μg/L


Where:

A = 1322 kg (total sold amount API in Sweden year 2018, data from IQVIA) (Ref. I)

R = 0 % removal rate (worst case assumption)

P = number of inhabitants in Sweden = 9 *106

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

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


Predicted No Effect Concentration (PNEC)


Ecotoxicological studies

Algae (Pseudokirchneriella subcapitata) (OECD 201) (Reference III):

NOEC (72 hr) (growth rate) = 1.5 mg/L


Crustacean, water flea (Daphnia magna):

Acute toxicity

EC50 48 h (mortality) = 19.5 mg/L (USFDA 4.09) (Ref. IV)


Chronic toxicity

NOEC (21 day) (reproduction and growth) = 0.32 mg/L (OECD 211) (Ref. V)


Fish, fathead minnow (Pimephales promelas):

Acute toxicity

EC50 96 h (mortality) = 6.92 mg/L (USFDA 4.11) (Ref. VI)


Chronic toxicity

NOEC (32 day) (larval survival) = 0.36 mg/L (OECD 210) (Ref. VII)


PNEC = 32 μg/L (320 μg/L/10 based on the most sensitive NOEC for the chronic daphnia and an assessment factor (AF) of 10).


Environmental risk classification (PEC/PNEC ratio)

PEC/PNEC = 0.2/32 = 0.006, i.e. PEC/PNEC ≤ .1 which justifies the phrase "Use of mirtazapine has been considered to result in insignificant environmental risk".


Biotic degradation

Biodegradation Simulation Screening

Test results 4% degradation in 28 days in water (US FDA 3.11) (Ref. VIII)


Biodegradation Simulation Screening

Test results 1% degradation in 28 days in sediment (US FDA 3.11) (Ref. IX)


Sediment Transformation (OECD 308) (Ref. X)

Half-life = 55 days in total water-sediment systems
Half-life = 6 - 7.5 days in water layer


At each sampling interval, samples from each test system were separated into water and sediment phases. The sediment was extracted once with acetonitrile: trifluoroacetic acid 99:1.0 (v:v) and once with acetonitrile:purified reagent water:trifluoroacetic acid 80:20:1.0 (v:v:v). The sediment, with the exception of the Day 0 samples, was then extracted again with acetonitrile:purified reagent water:trifluoroacetic acid 80:20:1.0 (v:v:v) for a maximum of three extractions. The water and sediment extracts were radioassayed by liquid scintillation counting (LSC) and then analyzed by high performance liquid chromatography with radiochemical detection (HPLC/RAM) to quantify [14C]mirtazapine and any degradation products in each phase. Radioactivity in the extracted solids (sediment bound) was quantified by combustion analysis with LSC and the liquid traps for volatile gases were radioassayed by LSC.


Evidence of primary degradation was observed for [14C]mirtazapine in samples from both aerobic water/sediment test systems. One major region (> 10% AR) of radioactivity was observed in the chromatograms for the Weweantic River samples (metabolite identified as Met #4). Several minor regions of radioactivity were observed in some chromatograms for the Taunton River and Weweantic River (including metabolites identified as Met #1, #2, #3 and #5 as well as “Others”). In all cases, the peak averages each represented < 10% AR and Met #1, #2 and #5, and “Others” were not considered further. However, Met #3 (approached 10% AR) and #4 (> 10% AR) were further characterized by LC-MS.


Average material balance (as percent of applied radioactivity) ranged from 92.9 to 97.8% AR for the Taunton River throughout the 100-day study. Average material balance ranged from 93.4 to 98.2% AR for the Weweantic River throughout the 100-day study.

Ultimate biodegradation was observed in the aerobic test systems to be minimal. The cumulative amount of evolved 14CO2 was 0.2% AR for the Taunton River and Weweantic River aerobic test systems at Day 100. The cumulative amounts of volatile organics were < 0.1% AR for the Taunton River and Weweantic River aerobic test systems at Day 100.


Abiotic degradation

Photolysis:

Half-life = 0.35 hours at pH 7 (US FDA 3.10) (Ref. XI)


Justification of chosen degradation phrase:

Mirtazapine does not pass the ready biodegradation test but is inherently degradable in acclimated biological systems. The DT50 ≤ 120 d for the total system, therefore the phrase “Mirtazapine is slowly degraded in the environment” was chosen.


Bioaccumulation

Bioconcentration Factor:

BCF = 334 (OECD 305). (Ref. XII)


Justification of chosen bioaccumulation phrase:

Since BCF < 500, the substance has low potential for bioaccumulation.


References

  1. Data from IQVIA ”Consumption assessment in kg for input to environmental classification - updated 2019 (data 2018)”.

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

    http://guidance.echa.europa.eu/docs/guidance_document/information_requirements_en.htm

  3. Smithers Viscient, 2014. ORG 3770: 72-hour Toxicity Test with the Freshwater Green Alga, Pseudokirchneriella subcapitata, Following OECD Guideline 201, Study No. 359.6780, SV, Wareham, MA, USA, 27 May 2014.

  4. Akzo Research, 1993. "Acute Toxicity of Mirtazapine to Daphnia magna," Study No. CRL F93132, Akzo Research Laboratories, Arnhem, Netherlands, 03 December 1993.

  5. NOTOX B.V., 2012. "Daphnia magna Reproduction Test with Org 3770 (Semi Static)," Study No. 494005, NOTOX B.V., 's-Hertogenbosch, Netherlands, 6 July 2012.

  6. Akzo Research, 1993. "Acute Toxicity of Mirtazapine to Pimephales promelas," Study No. CRL F93192, Akzo Research Laboratories, Arnhem, Netherlands, 10 December 1993.

  7. NOTOX B.V., 2012. "Fish Early Life Stage Toxicity Test with Org 3770 (Semi Static)," Study No. 494003, NOTOX B.V., 's-Hertogenbosch, Netherlands, 24 July 2012.

  8. Akzo Research, 1993. "Aerobic Biodegradation of Mirtazapine in Water," Study No. CRL F93186, Akzo Research Laboratories, Arnhem, Netherlands, 19 November 1993.

  9. Akzo Research, 1993. "Aerobic Biodegradation of Mirtazapine in Sediment," Study No. CRL F93185, Akzo Research Laboratories, Arnhem, Netherlands, 10 December 1993.

  10. Smithers Viscient, 2012. "[14C]ORG 3770: Aerobic Transformation in Aquatic Sediment Systems Based on OECD 308," Study No. 1560.6257, SV, Wareham, MA, USA, 6 Nov 2012.

  11. Akzo Research, 1993. "Aquatic Photodegradation of Mirtazapine," Study No. CRL F93180, Akzo Research Laboratories, Arnhem, Netherlands, 10 December 1993.

  12. NOTOX B.V., 2012. "Bioconcentration Test in Rainbow Trout with [14C]Org 3770 (Flow Through)," Study No. 494006, NOTOX B.V., 's-Hertogenbosch, Netherlands, 8 November 2012.