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) = 0.000029 μg/L

PEC = 0.000029 μg/L

Where:

A = 0.2121 kg (total amount of API sold in Sweden year 2023, 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 wastewater 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)

The calculation of a risk ratio is not possible, due to the lack of environmental toxicity data. Therefore, the following phrase is used: “Risk of the environmental impact of Emedastine cannot be excluded, since no ecotoxicity data are available.”

However, according to the European Medicines Agency guideline on environmental risk assessment of medicinal products (EMA/CHMP/SWP/44447/00 corr2), the use of Emedastine is unlikely to represent a risk for the environment, given that its predicted environmental concentration (PEC) is below the action limit 0.01 μg/L.

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 emedastine cannot be excluded, due to lack of data.’

Bioaccumulation

Partitioning coefficient:

LogK_ow = 2.03 (method unknown) (Clarke’s Analysis of Drugs and Poisons, 2017)

Justification of chosen bioaccumulation phrase:

As the LogK_ow remains below the trigger level for a bioaccumulative substance of 4.0, the following statement is used for emedastine: ‘Emedastine has a low potential for bioaccumulation.’

Excretion (metabolism)

Following oral administration of emedastine, the drug is metabolized in the liver principally to 5- and 6-hydroxyemedastine, metabolites that appear to undergo further oxidation to form 5′-oxo analogs.112 Emedastine N-oxide also is formed as a minor metabolite.

In adults, about 44% of an oral dose is recovered in the urine within 24 hours.1 About 3.6% of an orally administered dose is excreted in urine as parent drug; 5- and 6-hydroxyemedastine and their conjugates also are recovered in urine. (AHFS Drug Information, 2017).

PBT/vPvB assessment

Emedastine has a low potential for bioaccumulation given that its octanol-water partition coefficient is below the trigger value for a bioaccumulative substance. Nevertheless, given that data is not available for the other two “PBT” properties of persistence and toxicity, an absolute PBT assessment is not possible.

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

• Clarke’s Analysis of Drugs and Poisons. Pharmaceutical Press 2017. MedicinesComplete. Royal Pharmaceutical Press. https://www.medicinescomplete.com/mc/clarke/current/CLK-TD-c58-mn0001.htm?q=emedastine&t=search&ss=text&tot=7&p=1#_hit

• AHFS Drug Information, 2017. Pharmaceutical Press 2017. https://www.medicinescomplete.com/mc/ahfs/current/a399007.htm#chem-stab