Detaljerad miljöinformation

Detailed background information

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 = 0.0079 μg/L

Where:

A = 57.8 kg (total sold amount API in Sweden year 2022, data from IQVIA). Reduction of A may be justified based on metabolism data.

R = 0 % removal rate (due to loss by adsorption to sludge particles, by volatilization, hydrolysis or biodegradation) = 0 if no data is available. (If R =/=0 this should be justified under the degradation section) 

P = number of inhabitants in Sweden = 10 *10⁶

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

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

Predicted No Effect Concentration (PNEC)

Ecotoxicological studies*

Green Algae (Pseudokirchneriella subcapitata)) (OECD 201, Study No., 359.6386,):

EC₅₀ 72 h (endpoint) > 3,200 μg/L

NOEC = 3,200μg/L

Water Flea (Daphnia magna):

Acute toxicity

EC₅₀ 72 h (growth) => 5,000 μg L (guideline eg OECD 202)

Chronic toxicity

NOEC 21 days (reproduction) = 340 μg/L (guideline eg OECD 211)

Fish (Pimephales promelas, fathead minnow):

Chronic toxicity

NOEC 32 days (growth) = 0.14 μg/L (guideline eg OECD 210)

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 (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 = 0.0079/0.0003 =  i.e. PEC/PNEC = 26 which justifies the phrase ‘Use of Mometasone has been considered to result in high environmental risk.’

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.

Bioaccumulation

Bioconcentration factor (BCF):

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

Partitioning coefficient:

logKow = 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.

PBT/vPvB assessment

If Substance X fulfils the criteria for PBT and/or vBvP this should be flagged and the following phrase should be added: According to the established EU criteria, the compound should be regarded as a PBT/vPvB substance.

References

1. 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

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

3. 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.

4. 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.

5. 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

6. 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.

7. Smithers Viscient 2010 “Mometasone Furoate - Acute Toxicity to Daphnids, (Daphnia magna) Under Static Conditions following Guideline #202. SV, Wareham, MA, 10 December 2010.

8. 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.

9. 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.

10. 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.

11. 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.

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