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) = 1.37*10^-6 * 18.14 * 100 = 0.025 μg/L

Where:

A = 18.14 kg ondansetron (total sold amount API in Sweden year 2021, data from IQVIA)

Total sold amount API in Sweden year 2021 is based on sum of sold ondansetronhydrokloriddihydrat (20.64 kg; molecular weight (MW): 365.9 g/mol ~ 16.55 kg free base) and ondansetron free base (1.5882 kg; MW: 293.4 g/mol), expressed as free base.

• 16.55 kg + 1.5882 kg = 18.14 kg ondansetron free base

R = 0 % removal rate (due to loss by adsorption to sludge particles, by volatilization, hydrolysis or biodegradation) = 0, if no data is available.

P = number of inhabitants in Sweden = 10 * 10⁶

V (L/day) = volume of wastewater per capita and day = 200 (ECHA default) (ECHA 2008)

D = factor for dilution of waste water by surface water flow = 10 (ECHA default) (ECHA 2008)

Predicted No Effect Concentration (PNEC)

Ecotoxicological studies

Green Algae (Selenastrum capricornutum):

IC50 96 h (growth rate inhibition) > 3,100 μg/L (OECD 201) (Reference 8)

NOEC = 620 μg/L

Water flea (Daphnia magna)

Acute toxicity

EC50 48 h (immobility) = 28,000 μg/L (OECD 202) (Reference 5)

NOEC = 14,000 μg/L

Water flea (Ceriodaphnia dubia)

Chronic toxicity

NOEC 7 d (reproduction) = 320 μg/L (USEPA 1002) (Reference 11)

Rainbow Trout (Oncorhyncus mykiss):

Acute toxicity

LC50 96 h (lethality) = 6,500 μg/L (OECD 203) (Reference 9)

NOEL = 2,600 μg/L

Fathead minnow (Pimephales promelas):

Chronic toxicity

No data

Other ecotoxicity data:

Microorganisms in activated sludge:

EC50 3 h (inhibition) > 1,000,000 μg/L @ 3 hrs (OECD 209) (Reference 4)

NOEC = 100,000 μg/L

PNEC = 320/100 = 3.20 μg/L

PNEC (μg/L) = lowest NOEC/100, where 100 is the assessment factor applied for two long-term NOECs when such results have not been generated from that showing the lowest L(E)C50 of the short-term tests. The lowest NOEC for water flea (= 320 µg/L) has been used for this calculation since it is the most sensitive of the two tested species.

Environmental risk classification (PEC/PNEC ratio)

PEC/PNEC = 0.025 μg/L / 3.20 μg/L = 0.0008, i.e. PEC/PNEC ≤ 0.1 which justifies the phrase “Use of Ondansetron has been considered to result in insignificant environmental risk.”

Degradation

Biotic degradation

Ready degradability:

No data

Inherent degradability:

19% degradation in 28 days (OECD 302). (Reference 10)

Soil Metabolism:

20-99.9% degradation in 64 days (TAD 3.12) (Reference 7)

Abiotic degradation

Hydrolysis:

50% degradation (pH 7) > 1 year (TAD 3.09) (Reference 3)

Photolysis:

No data

Justification of chosen degradation phrase:

Ondansetron is not readily degradable nor inherently biodegradable. The phrase “Ondansetron is potentially persistent” is thus chosen.

Bioaccumulation

Partitioning coefficient:

Log Dow = 1.00 (TAD 3.02) (Reference 6)

Log Dow at pH 5 = 0.23

Log Dow at pH 7 = 1.00

Log Dow at pH 9 = 1.26

Justification of chosen bioaccumulation phrase:

Since log Dow < 4 at pH 7, the substance has low potential for bioaccumulation.

Excretion (metabolism)

Ondansetron is cleared from the systemic circulation predominantly by hepatic metabolism. Less than 5% of the absorbed dose is excreted unchanged in the urine. (Reference 2).

PBT/vPvB assessment

Ondansetron does not fulfil the criteria for PBT and/or vBvP.

All three properties, i.e. ‘P’, ‘B’ and ‘T’ are required in order to classify a compound as PBT (Reference 1). Ondansetron does not fulfil the criteria for PBT and/or vBvP based on log Dow < 4.

References

1. ECHA, European Chemicals Agency. 2008 Guidance on information requirements and chemical safety assessment.

2. Global Datasheet Ondansetron. Version 39. 01 May 2015.

3. Mao J. Ondansetron hydrochloride – Determination of Aqueous Hydrolysis Rate Constant and Half-Life.. Report No. 91-8-3891. Springborn Laboratories, inc. November 1991

4. Hartley DA. Ondansetron hydrochloride – Activated Sludge Respiration Inhibition. Report No. 91-8-3870. Springborn Laboratories, inc. November 1991.

5. LeLievre MK. Ondansetron hydrochloride – Acute Toxicity to Daphnids (Daphnia pulex) under Static Conditions. Report No. 91-8-3882. Springborn Laboratories, inc, November 1991.

6. Colwyn TC. GR38032X: Determination of Physico-Chemical Properties. Report No. 94/GLX171/1157. Pharmaco LSR Ltd, February 1995.

7. Morgan P. GR38032X: Biodegradation in Soil. Report No. 94/GLX172/0783. Pharmaco LSR Ltd, February 1995.

8. Desjardins D, Kendall T, Krueger HR. Ondansetron hydrochloride: A 96-hour Toxicity Test with the Freshwater Alga  (Selenastratum capricornutum). Report No. 374A-121. Wildlife International Limited, July 2004.

9. Palmer SJ, Kendall TZ, Krueger HR. Ondansetron hydrochloride: A 96-hour Static Acute Toxicity Test with the Rainbow Trout (Oncoryhynchus mykiss). Report No. 374A-120. Wildlife International Limited, July 2004.

10. Shaefer EC. Ondansetron hydrochloride: An Evaluation of Inherent Biodegradability Using the Zahn-Wellens Test. Report No. 374E-122A. Wildlife International Limited, March 2005.

11. Goodband TJ: Ondansetron hydrochloride: Daphnid, Ceriodaphnia Dubia Survival and Reproduction Test. Report No. 1127/01213. Safepharm Laboratories Limited, July 2007.