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 * 0.74 * 100 = 0.0001 μg/L = 0.1 ng/L

Where:

A = 0.7423 kg olopatadin (total sold amount API in Sweden year 2021, data from IQVIA).

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

Algae: no data available

Crustacean (Daphnia magna): no data available

Fish: no data available

Other ecotoxicity data: No data available

PNEC derivation:

No PNEC can be calculated since there is no environmental toxicity data available

Environmental risk classification (PEC/PNEC ratio)

Calculation of a risk ratio is not possible, due to the lack of environmental toxicity data. Therefore, the following phrase is used: "Risk of environmental impact of olopatadine cannot be excluded, since no ecotoxicity data are available."

Degradation

Biotic degradation

Ready degradability: no data available

Justification of chosen degradation phrase:

As no data on biological degradation is available the following phrase is used: ‘The potential for persistence of olopatadine cannot be excluded, due to lack of data.’

Bioaccumulation

Partitioning coefficient:

logK_ow = 0.342 (method unknown) (Alcon Technical Report No. 090:38560:1093)

Justification of chosen bioaccumulation phrase:

As the logK_ow remains below the trigger level for a bioaccumlative substance (logK_ow < 4.0), the following statement is used for olopatadine: ‘Olopatadine has low potential for bioaccumulation.’

Excretion (metabolism)

Following topical application of olopatadine hydrochloride to the eyes, the plasma elimination half-life of the drug is about 3 hours.

Olopatadine is not extensively metabolized. Following oral administration, unchanged olopatadine accounts for 77% of peak plasma total radioactivity, while metabolites (e.g., olopatadine N-oxide, N-desmethyl olopatadine) account for less than 6%. The plasma elimination half-life of olopatadine following oral administration is 8–12 hours.

Olopatadine is eliminated principally by renal excretion; about 60–70% of a systemically absorbed dose of olopatadine is excreted in the urine (86% as unchanged olopatadine), and about 17% is excreted in feces. (AHFS Drug Information, 2017)

PBT/vPvB assessment

Based on screening information, olopatadine cannot be considered a potential PBT substance as the octanol-water partition coefficient remains significantly below the trigger level for a bioaccumulative substance.

References

• ECHA 2008, European Chemicals Agency. 2008 Guidance on information requirements and chemical safety assessment. http://guidance.echa.europa.eu/docs/guidance_document/information_requirements_en.htm

• Alcon Technical Report No. 090:38560:1093

• AHFS Drug Information 2017. Medicines Complete. Pharmaceutical Press. https://www.medicinescomplete.com/mc/ahfs/current/a399006.htm#pkin