Detaljerad miljöinformation

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	=	0.0020092667 µg/L
Where:
A	=	total actual API sales in Sweden for the most recent year 14.66618 kg (total sold amount API in the most recent sales data for Sweden (2021) was distributed by IQVIA in 2022)
R	=	0
P	=	number of inhabitants in Sweden = 10 *106
V (L/day)	=	volume of wastewater per capita and day = 200 (ECHA default) (Reference I)
D	=	factor for dilution of wastewater by surface water flow = 10 (ECHA default) (Reference I)

Predicted No Effect Concentration (PNEC)

Ecotoxicological studies

Algae (Selenastrum capricornutum) (guideline e.g. OECD 201) [Reference II]

EC₅₀ 72 h (Inhibition of growth) = 26 mg/L

Crustacean (Daphnia magna) (water-flea):

Acute toxicity

EC₅₀ 48 h (Immobilization) = 6 mg/L (FDA 4.08) [Reference III]:

Chronic toxicity

Not available

Fish:

Acute toxicity

Lepomis macrochirus (Bluegill sunfish)

LC₅₀ 96 h (Survival) = 5.8 mg/L (FDA 4.11) [Reference IV]

Chronic toxicity

Not available

Other ecotoxicity data:

Toxicity to activated sludge in a respiration inhibition test according to guideline e.g. OECD 209 [Reference V]:

EC₅₀ 3 h > 1000 mg/L

NOEC = 47 mg/L

PNEC (µg/l) = lowest EC₅₀/1000, where 1000 is the assessment factor used. EC₅₀ for the Bluegill sunfish 5.8 mg/L has been used for this calculation since it is the most sensitive of the three tested species.

PNEC = 5.8 mg/L/1000 = 5.8 µg/L

Environmental risk classification (PEC/PNEC ratio)

PEC/PNEC = 0.0020092667 µg/L /5.8 µg/L = 0.000346425 i.e. PEC/PNEC ≤ 0.1

i.e. PEC/PNEC ≤ 0.1 which justifies the phrase “Use of Risperidone has been considered to result in insignificant environmental risk.

Degradation

Biotic degradation

Ready degradability:

Biodegradability in a CO₂-evolution test according to FDA 3.11 [Reference VI]:

Based on the measurements of CO2 produced and DOC analysis, the percentage biodegradation calculated for Risperidone was 5%.

Based on the measurements of CO₂ produced and DOC analysis, the percentage biodegradation calculated for the reference substance glucose was > 60%. Consequently, it can be concluded that Risperidone is not readily biodegradable.

Result: Risperidone is potentially persistent.

Inherent degradability: -

Simulation studies: -

Abiotic degradation

Hydrolysis: -

Photolysis: -

Bioaccumulation

Partition coefficient octanol/water:

Partition coefficient octanol/water was determined with the shaking flask method [Reference VII]:

The average apparent partition coefficient (total solute measured, regardless of from) of R064766 in 1-octanol/aqueous solution at 25°C as determined by UV spectrometry is:

•           in 1-octanol/buffer pH 5: log P = 0.22

•           in 1-octanol/buffer pH 7: log P = 1.67

•           in 1-octanol/buffer pH 9: log P = 2.91

Bioconcentration factor (BCF): -

Since log Kow (at pH 7) < 4, Risperidone has low potential for bioaccumulation.

Excretion (metabolism)

-

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. Weytjens D.; The effect of risperidone on the growth of the unicellular green alga Selenastrum capricornutum, Janssen Pharmaceutica N.V.; Janssen Study No. AASc/0004; May 14, 1993.

3. Weytjens D.; The acute toxicity of risperidone to the water-flea (Daphnia magna), Janssen Pharmaceutica N.V.; Janssen Study No. ADK6/0017; February 2, 1993.

4. Weytjens D.; The Acute Toxicity of risperidone to the Bluegill sunfish (Lepomis macrochirus), Janssen Pharmaceutica N.V.; Janssen Study No. AFLm/0004; February 2, 1993.

5. Seyfried B.; Toxicity to activated sludge in a respiration inhibition test, RCC Ltd.; RCC Study No. A35087; Janssen Study No. RMD704; April 6, 2006.

6. Weytjens D., Biodegradability in a CO₂-evolution test, Janssen Pharmaceutica N.V.; Janssen Study No. BDAS0036; January 11, 1993.

7. Van Dingenen J.; R064766: Partition coefficient; Janssen Pharmaceutica N.V., Report PC-CHAR 92-59 (921209) – R064766; December 09, 1992.