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) = 1.37*10^-6 * A * (100 - R) = 1.37*10^-6 * 57.249 * (100-45.98) = 0.0042 μg/L = 4.2ng/L

Where:

A = 57.249 kg mometasonfuroat (sum of 39.3068 kg mometasonfuroat and 18.5614 kg mometasonfuroatmonohydrat, equaling 17.94 kg mometasonfuroat) (total sold amount API in Sweden year 2022, data from IQVIA).

R = 45.98 % removal rate (due to loss by adsorption to sludge particles, by volatilization, hydrolysis or biodegradation, as predicted by SimpleTreat 4.0 using a K_d,sludge value of 1937 L/Kg as concluded in Smithers Viscient, Study No., 359.6435, and a first order degradation constant of 0.00094 h^-1 as derived from Smithers Viscient, Study No., 359.6446).

P = number of inhabitants in Sweden = 10 *10⁶

V (L/day) = volume of wastewater per capita and day = 200 (ECHA default) (ECHA 2008)

D = factor for dilution of waste water by surface water flow = 10 (ECHA default) (ECHA 2008).

Predicted No Effect Concentration (PNEC)

Ecotoxicological studies

Algae (Pseudokirchneriella subcapitata) (OECD 201) (Smithers Viscient, Study No., 359.6386)

NOEC 72 h (growth rate) = 3.2 mg/L

Crustacean (Daphnia magna, waterflea):

Chronic toxicity

NOEC 21 d (reproduction) = 0.34 mg/L

LOEC 21 d > 0.34 mg/L (OECD 211) (Smithers Viscient, Study No. 359.6439)

Fish (Pimephales promelas, fathead minnow):

Chronic toxicity

NOEC 32 d (growth) = 0.14 μg/L

LOEC = 0.22 μg/L (OECD 210) (Smithers Viscient, Study No. 359.6440)

Fish (Danio rerio, zebrafish):

Chronic toxicity

NOEC 65 d (slight change in sex ratio) = 0.00313 μg/L = 3.13 ng/L

LOEC = 0.010 μg/L = 10 ng/L (OECD 234) (IES Ltd, Study No. 20210269)

PNEC Derivation:

PNEC = 0.313 ng/L

PNEC (μg/L) = lowest NOEC (3.13 ng/L)/10, where 10 is the assessment factor used when long-term results from at least three species representing three trophic levels are available. The NOEC for the fish sexual development test in zebrafish (Danio rerio) has been used for this calculation.

Environmental risk classification (PEC/PNEC ratio)

PEC/PNEC = 4.2 ng/L / 0.313 ng/L = 13.54, i.e. PEC/PNEC > 10 which justifies the phrase "Use of mometasone has been considered to result in high environmental risk."

Degradation

Biotic degradation

Ready degradability:

<5 % ultimate biodegradation in 28 days, not readily biodegradable. The half-life for primary biodegradation was calculated to be 31 days, and the elimination rate constant was 0.0226 days^-1 (OECD 314B) (Smithers Viscient, Study No. 359.6446).

The fate and degradation of [14C]mometasone in two water-sediment systems was assessed in an OECD 308 study (Smithers Viscient, Study No. 359.6445).

Radioactivity associated with the sediment phase was extracted once with acetonitrile, then 0.1% hydrochloric acid in acetonitrile, and finally with acetonitrile:purified reagent water:hydrochloric acid 80:20:0.1, (v:v:v).

Mometasone rapidly dissipated from the water phase. Evidence of primary degradation was observed. One major peak (>10% AR) was detected in some of the chromatograms as a shoulder of the parent peak. Several minor regions of radioactivity (<10% AR) were observed in some of the chromatograms. The cumulative amount of evolved 14CO2 2.6% and 3.0% AR in the two water-sediment systems at Day 100. The average amount of sediment-bound residue as 10.6% and 11.2% AR in the two water-sediment systems at Day 100. No radioactivity was detected as volatile organic at Day 100. Average material balance ranged from 92.0 to 97.2% AR throughout the 100-day study.

The half-life of [14C]mometasone in the total water-sediment test systems ranged from 81 to 105 days.

Overall, the evidence from this study shows that mometasone is expected to be slowly degraded in the environment.

Justification of chosen degradation phrase:

Based on the half-life in the total water-sediment test system, the phrase “Mometasone is slowly degraded in the environment” is thus chosen.

Bioaccumulation

Bioconcentration factor (BCF):

BCF: 104.9 - 107.1 L/Kg (OECD 305). (Smithers Viscient, Study No. 359.6497)

Partitioning coefficient:

logK_ow = 4.68 (pH 7) (OECD 107) (Smithers Viscient, Study No., 359.6385)

Justification of chosen bioaccumulation phrase:

Since BCF < 500, the following statement is used for mometasone: Mometasone has low potential for bioaccumulation.

Excretion (metabolism)

The portion of an inhaled mometasone furoate dose that is swallowed and absorbed in the gastrointestinal tract undergoes extensive metabolism to multiple metabolites. There are no major metabolites detectable in plasma. In human liver microsomes, mometasone furoate is metabolized by CYP3A4. After intravenous bolus administration, mometasone furoate has a terminal elimination T1/2 of approximately 4.5 hours. A radiolabelled, orally inhaled dose is excreted mainly in the feces (74 %) and to a lesser extent in the urine (8 %) (ATECTURA® BREEZHALER® Novartis CDS 2020).

PBT/vPvB assessment

Mometasone does not fulfil the screening criteria for a bioaccumulative substance and can therefore not be considered a potential PBT substance.

References

• ATECTURA® BREEZHALER® Novartis CDS 2020

• ECHA 2008, European Chemicals Agency. 2008 Guidance on information requirements and chemical safety assessment. http://guidance.echa.europa.eu/docs/guidance_document/information_requirements_en.htm

• Smithers Viscient, 2011. "[14C]Mometasone - Determining the Adsorption Coefficient (Koc) Following OECD Guideline 106," Study No. 359.6435, SV, Wareham, MA, 09 June 2011.

• IES Ltd, 2023. "Mometasone furoate – Fish Sexual Development Test with Zebrafish (Danio rerio)," Study No. 20210269, Switzerland, 25 May 2023.

• Smithers Viscient, 2011. "Mometasone Furoate – Determining the Partition Coefficient (n-Octanol/Water) by the Flask-Shaking Method Following OECD Guideline 107," Study No., 359.6385, SV, Wareham, MA, USA, 10 March 2011.

• Smithers Viscient, 2011. "[14C]Mometasone - Determination of the Biodegradability of a Test Substance in Activated Sludge Based on OECD Method 314B," Study No. 359.6446, SV, Wareham, MA, 01 September 2011.

• Smithers Viscient 2011. "Mometasone Furoate – Activation Sludge Respiration Inhibition Test Following OECD Guideline 209," Study No., 359.6441, SSL, Wareham, MA, USA 25 April 2011

• Smithers Viscient 2011. " Mometasone Furoate - Acute Toxicity to the Freshwater Green Alga, Pseudokirchneriella subcapitata," Study No., 359.6386, SV, Wareham, MA, USA 28 January 2011.

• Smithers Viscient, 2012. "Mometasone Furoate - Full Life-Cycle Toxicity Test with Water Fleas, (Daphnia magna), Under Flow-Through Conditions Following OECD Guideline #211," Study No. 359.6439, SV, Wareham, MA, 1 May 2012.

• Smithers Viscient, 2012. "Mometasone Furoate – Early Life-Stage Toxicity Test with Fathead Minnow, Pimephales promelas, Following OECD Guideline #210," Study No. 359.6440, SV, Wareham, MA, 21 May 2012.

• Smithers Viscient, 2011. “[14C]Mometasone – Aerobic Transformation in Aquatic Sediment Systems Following OECD Guideline 308”. Study No. 359.6445, SV, Wareham, MA, 6 September 2011.

• Smithers Viscient, 2012. "[¹⁴C]Mometasone - Flow-Through Bioconcentration and Metabolism Study with Bluegill Sunfish (Lepomis macrochirus) Following OECD Guideline 305," Study No. 359.6497, SV, Wareham, MA, 21 May 2012.