Detaljerad miljöinformation

1. PREDICTED ENVIRONMENTAL CONCENTRATION (PEC):

The Predicted Environmental Concentration is calculated according to the following formula:

2. PREDICTED NO EFFECT CONCENTRATION (PNEC)

2.1. Ecotoxicological studies

2.1.1. Algae

Algal growth inhibition test with the green alga (Selenastrum capricornutum) (OECD 201) [1]:

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

2.1.2. Crustacean

Acute

The Acute Toxicity of risperidone to the Water-flea (Daphnia magna) (FDA 4.08) [2]:

EC₅₀ 48 h = 6 mg/L (Immobilization)

Chronic

Not available

2.1.3. Fish

Acute

The Acute Toxicity of risperidone to the Bluegill sunfish (Lepomis macrochirus) (FDA 4.00) [3]:

LC₅₀ 96 h = 5.8 mg/L (Survival)

Chronic

Not available

2.1.4. Other ecotoxicity data

Toxicity to activated sludge in a respiration inhibition test (OECD 209) [4]:

EC₅₀ 3 h > 1000 mg/L (OECD 209)

NOEC = 47 mg/L

2.2. Calculation of Predicted No Effect Concentration (PNEC)

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

2.3. Environmental risk classification (PEC/PNEC ratio)

PEC/PNEC = 0.0023/5.8 = 0.0004 i.e. PEC/PNEC ≤ 0.1

Conclusion for environmental risk:

The calculated PEC/PNEC ratio is ≤ 1. Hence, risk assessment procedures would indicate that Risperidone would have insignificant long-term risk to the environment. This medicine is potentially persistent and has no significant bioaccumulation potential

3. DEGRADATION

3.1. Biotic degradation

3.1.1. Ready biodegradation

Biodegradability in a CO₂-evolution test (FDA 3.11) [5]:

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.

Conclusion for degradation:

The medicine is potentially persistent.

4. BIOACCUMULATION

4.1. Partition coefficient octanol/water

Partition coefficient octanol/water (shaking flask method) [6]:

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

Conclusion for bioaccumulation:

As log P_ow < 4, risperidone has no significant bioaccumulation potential.

5. REFERENCES

1. 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.

2. 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.

3. 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.

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

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

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

7. 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

8. IMS Health - 2015