Detaljerad miljöinformation

Physical properties

Molecular weight¹: 411.59 (free base)

Solubility in water¹: Fesoterodine fumurate = 542 x 10⁶ µg/L

Fesoterodine free base = 0.5 x 10⁶ µg/L

pKa¹: 10.3

Vapor pressure (calculated)²: 9.62 x 10^-12 mmHg

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 = 0.000579 μg/L

Where:

A =	4.228 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)4
D =	factor for waste water dilution by surface water flow = 10 (ECHA default)4

Predicted No Effect Concentration (PNEC)

Ecotoxicological studies

Green alga (Scenedesmus subspicatus) (guideline OECD 201)⁵

EC₅₀ 72 h (growth rate, chronic toxicity) = 34 000 μg/L

EC₁₀ 72 h (growth rate, chronic toxicity) = 12 000 μg/L

Daphnids (Daphnia magna) (guideline OECD 211)⁶

LOEC 21 days (reproduction, chronic toxicity) = 10 000 μg/L

NOEC 21 days (reproduction, chronic toxicity) = 3 200 μg/L

Zebra fish (Brachydanio rerio) (guideline OECD 210)⁷

LOEC 35 days (reproduction, chronic toxicity) = 11 500 μg/L

NOEC 35 days (reproduction, chronic toxicity) = 3 900 μg/L

Based on the lowest NOEC for the species Daphnia magna and using the assessment factor⁸ of 10, the PNEC is calculated to 3 200/10 = 320 µg/L.

Environmental risk classification (PEC/PNEC ratio)

PEC/PNEC = 0.000579 / 320 = 1.81 x 10^-6, i.e. PEC/PNEC ≤ 0.1 which justifies the phrase ”Use of fesoterodine has been considered to result in insignificant environmental risk.”

Adsorption (guideline OECD 106)⁹

Soil	Foc (%)	Kd (L/Kg)	KOC (L//kg)
Speyer 2.2	2.29	2.9	127
Mechtildshausen	1.36	5.8	424
Mussig	4.13	9.0	218
Bretagne 1	2.00	3.8	189
Mean		5.4	239

Degradation

Biotic degradation

Water-sediment transformation simulation (guideline OECD 308)¹⁰

Length of study: 102 days

Sediment extraction solvent: Extracted with acetonitrile/water (4:1; v/v; up to three times). From sampling day 7 onwards, Soxhlet extraction using the same solvent mixture was performed for at least 4 hours.

Supplemental extraction solvents: Day 102 supplemetal extraction using acetonitrile / 0.1 M hydrochloric acid (1:1; v,v) under reflux conditions for about 4 hours but due to a low amount of radioactivity, no analysis was performed.

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

Data on day 102 at 20 °C	Rhine river	Möhlin pond
Total system
Half-life (days)	4.91	8.46
Total 14CO2 (% of AR)	67.4	67.2
% Parent (% of AR)	1.6	0.7
Aerobic Water Layer
Half-life (days)	1.5	2.4
Parent (% of AR)	0.0	0.0
Sediment Layer
Half-life (days)	17.7	11.0
Bound/NER (% of AR)	17.1	18.2
Extractables (% of AR)	4.2	7.6
Parent (% of AR)	1.6	0.7

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

Justification of chosen degradation phrase

As the total system DT₅₀ value (water-sediment transformation simulation, OECD 308) was calculated to <32 days, it corresponds to the degradation phrase ”fesoterodine is degraded in the environment.”

Bioaccumulation

Partitioning coefficient (guideline OECD 107)¹¹

pH	Log Kow
5	-3.3
7	0.0
9	1.8

Justification of chosen bioaccumulation phrase

Since log D_ow < 4 at pH 7, fesoterodine has low potential for bioaccumulation.

References

1. Study report A66576: Determination of the partition coefficient (n-octanol/water) of SPM 7605. March 2007.

2. EPI Suite. EPA Office of Pollution Prevention Toxics and Syracuse Research Corporation (SRC).

3. IQVIA KG Consumption 2020 report.

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

5. Study report A66644: SPM 7605: Toxicity to Scenedesmus subspicatus in a 72-hour algal growth inhibition test. December 2006.

6. Study report A66666: SPM 7605: Effect on survival and reproduction of Daphnia magna in a semi-static test over three weeks. March 2007.

7. Study report A66688: SPM 7605: Toxic effects to zebra fish (Brachydanio rerio) in an early‑life stage toxicity test. May 2007.

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

9. Study report A66622: [¹⁴C]-SPM 7605: Adsorption/desorption on soils. June 2007.

10. Study report A66633: [¹⁴C]-SPM 7605: Route and rate of degradation in aerobic aquatic sediment systems. June 2007.

11. Study report A66576: Determination of the partition coefficient (n-octanol/water) of SPM 7605. March 2007.