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)

PEC = 0.000189745 μg/L

Where:

A = 1.385 kg (total amount API in Sweden (newly introduced product) for 2021 + forecasted sales 2022-2026).

R = 0

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 wastewater by surface water flow = 10 (ECHA default) (Ref. I)

Predicted No Effect Concentration (PNEC)

Ecotoxicological studies

Algae (Raphidocelis subcapitata) (guideline eg OECD 201) (Reference II):

EC₅₀ 72 h (growth rate): > 0.63 mg/L

EC₅₀ 72 h (yield inhibition): > 0.63 mg/L

NOEC (growth and yield): 0.63 mg/L

Due to the low solubility of JNJ-67896153-AAAin test medium, concentration levels that might be toxic for Raphidocelis subcapitata could not be reached.

Crustacean (Daphnia magna):

Acute toxicity

EC₅₀ 48 h (mobility): > 0.74 mg/L (guideline eg OECD 202) (Reference III)

Due to the very low solubility of JNJ-67896153-AAAin test medium, concentration levels that might be toxic for Daphnia magna could not be reached.

Chronic toxicity

NOEC 21 h (growth): 0.10 mg/L (guideline eg OECD 211) (Reference VII)

Fish:

Acute toxicity

Cyprinus carpio

LC₅₀ 96 h (mortality): > 0.91 mg/L (guideline eg OECD 203) (Reference IV)

Due to the very low solubility of JNJ-67896153-AAAin test medium, concentration levels that might be lethal for Cyprinus carpio could not be reached.

Chronic toxicity

Pimephales promelas (fathead minnow)

NOEC 32 d (survival): 0.032 mg/l (guideline eg OECD 210) (Reference VIII)

Other ecotoxicity data:

PNEC (μg/L) = lowest NOEC/10, where 10 is the assessment factor used for three long-term ecotoxicity data endpoints. NOEC = 0.032 mg/L for Fish (Pimephales promelas) has been used, as this was the most sensitive of the three species tested (algae, water flea and fish).

PNEC = lowest NOEC / 10 = 0.032 mg/L / 10 = 3.2 µg/L

Environmental risk classification (PEC/PNEC ratio)

PEC/PNEC = 0.000189745 μg/L / 3.2 µg/L = 0.00005929

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

Degradation

Biotic degradation

Ready degradability:

According to guideline eg OECD 301B (Reference V):

Relative biodegradation values calculated from measurements performed during the test period revealed no biologically relevant biodegradation of JNJ-67896153-AAA (10% and 5%, based on ThCO2).In the toxicity control, more than 25% biodegradation occurred within 14 days (45%, based on ThCO2). Therefore, the test item was considered not to inhibit microbial activity.

Functioning of the test system was checked by testing the procedural control itemsodium acetate, which showed a normal biodegradation curve (93 % within 14 days).

JNJ-67896153-AAA was not readily biodegradable under the conditions of the modified Sturm test.

Ponesimod is potentially persistent.

Inherent degradability:

-

Simulation studies:

-

Abiotic degradation

Hydrolysis:

-

Photolysis:

-

Bioaccumulation

Bioconcentration factor (BCF):

87.9 (guideline eg OECD 305) (Reference IX)

Since BCF < 500, Ponesimod has low potential for bioaccumulation.

Excretion (metabolism)

-

PBT/vPvB assessment

Ponesimod does not fulfils the criteria for PBT and/or vBvP.

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. Wagenaars S.M.A.; Freshwater Algal Growth Inhibition Test with JNJ-67896153-AAA; Test Facility Study No. 20268088; Janssen Study No. RMD1302; September 30, 2020.

3. Wagenaars S.M.A.; Daphnia magna, Acute Toxicity Study with JNJ-67896153-AAA; Test Facility Study No. 20268089; Janssen Study No. RMD1303; September 30, 2020.

4. Wagenaars S.M.A.; Fish, Acute Toxicity Study with JNJ-67896153-AAA; Test Facility Study No. 20268090; Janssen Study No. RMD1304; September 30, 2020.

5. Woutersen J.A.J; Determination of 'Ready' Biodegradability: Carbon Dioxide (CO2) Evolution Test (Modified Sturm Test) of JNJ-67896153-AAA; Test Facility Study No. 20268092; Janssen Study No. RMD1298; September 30, 2020.

6. SDS Ponesimod (ACT-128800) from Patheon Austria GmbH & Co KG, St.Peterstraße 25, A-4020 LINZ (AUSTRIA), Version number 1.15, Revision: 05.05.2021.

7. Bouwman L.; Daphnia Magna, Reporduction Test with JNJ-67896153-AAA; Test Facility Study No. 20270932; Janssen Study No. RMD1305; April 13, 2021.

8. Bouwman L.; Fish Early-Life Stage Toxicity Test with JNJ-67896153-AAA; Test Facility Study No. 20270929; Janssen Study No. RMD1306; January 24, 2022.

9. Gourlay V.; ¹⁴C-Ponesimod: Bioaccumulation in Carp (Cyprinus carpio) – Aqueous Exposure; Test Facility Study No. 159901233; Janssen Study No. RMD1307; January 31, 2022.