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 * 23.7 * 100 = 0.0032 μg/L

Where:

A = 23.6637 kg brinzolamide (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 brinzolamide cannot be ruled out as ecotoxicological data are missing."

According to the European Medicines Agency guideline on environmental risk assessment of medicinal products (EMA/CHMP/SWP/4447/00), use of brinzolamide is unlikely to represent a risk for the environment, because the predicted environmental concentration (PEC) at the time of registration was 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 brinzolamide cannot be excluded, due to lack of data.’

Bioaccumulation

Partitioning coefficient:

logK_ow = 0.817 (method unknown) (Alcon Technical Report No. 136:60:0900)

Justification of chosen bioaccumulation phrase:

As log K_ow < 4, the following statement is used for Brinzolamide: ‘Brinzolamide has low potential for bioaccumulation.’

Excretion (metabolism)

Following topical or systemic administration, brinzolamide undergoes metabolic reactions that include N-dealkylation, O-dealkylation and oxidation of the N-propyl side chain, all CYP-450 catalyzed reactions. N-desethyl brinzolamide is the major metabolite of brinzolamide in primates and human whole blood and is the only quantifiable metabolite in human whole blood. (Alcon Technical Report No. 025:38570:0596, Alcon Technical Report No. 027:38570:0596, Alcon Technical Report No. 029:38570:0596, Alcon Technical Report No. 037:38570:0796) Studies with radioactive ¹⁴C-brinzolamide revealed that after 24 hours following an IV does, that approximately 50-60% of brinzolamide was excreted unchanged from the body and that approximately 42% remained in the blood and the carcass. (Alcon Technical Report No. 014:38570:0496)

PBT/vPvB assessment

Based on screening information, brinzolamide 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

• EMA 2006, European Medicines Agency. European Medicines Agency guideline on environmental risk assessment of medicinal products (EMA/CHMP/SWP/4447/00). https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-environmental-risk-assessment-medicinal-products-human-use-first-version_en.pdf

• Alcon Technical Report No. 136:60:0900

• Alcon Technical Report No. 025:38570:0596

• Alcon Technical Report No. 027:38570:0596

• Alcon Technical Report No. 029:38570:0596

• Alcon Technical Report No. 037:38570:0796

• Alcon Technical Report No. 014:38570:0496