Detaljerad miljöinformation

Detailed background information

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 = 1.25 * 10^-3 μg/L

Where:

A = 9.139 kg (total amount API of azelastine hydrochloride in Sweden year 2022, data from IQVIA) (Ref. 1).

R = removal rate = 0% (no data available)

P = number of inhabitants in Sweden = 10*10⁶

V (L/day) = volume of waste water per capita and day = 200 (ECHA default) (Ref.2 chapter R.2)

D = factor for dilution of waste water by surface water flow = 10 (ECHA default) (Ref.2 chapter R.2)

According to the European Medicines Agency guideline on environmental risk assessment of medicinal products (EMA/CHMP/SWP/4447/00), use of Azelastine 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.

Predicted No Effect Concentration (PNEC)

Ecotoxicological studies

Desmodesmus subspicatus (green algae) (OECD 201) (ref. 3)

NOEC 72 hours (growth rate) = 0.37 mg/L

NOEC 72 hours (AUC) = 0.37 mg/L

NOEC 72 hours (yield) = 0.37 mg/L

E_rC₅₀ 72 hours = 4.9 mg/L

E_bC₅₀ 72 hours = 1.5 mg/L

E_yC₅₀ 72 hours = 1.2 mg/L

Daphnia magna (crustacea) (ref. 4)

NOEC 21 days (reproduction) = 0.29 mg/L (OECD 211)

Danio rerio (zebra fish) (ref. 5)

NOEC 30 days (mortality) = 0.11 mg/L (OECD 210)

NOEC 30 days (hatching phase) = 0.11 mg/L (OECD 210)

Respiration inhibition test in aerobic bacteria (OECD 209) (ref. 6)

NOEC 3 hours = 10 mg/L

EC₅₀ 3 hours = 53 mg/L

For the calculation of PNEC, long-term NOEC for the most sensitive species is used. Fish obtained the lowest value of NOEC and is thus considered to be the most sensitive species.

Long-term toxicity results for three species across three trophic levels (fish, crustacean and algae) justifies an assessment factor (AF) of 10 according to ECHA guideline (Ref.2 chapter R.10).

PNEC is calculated as NOEC (fish)/10 (AF)

PNEC = 11 μg/L

Environmental risk classification (PEC/PNEC ratio)

PEC/PNEC = 1.25 * 10^-3 / 11 = 11.4 * 10^-5 μg/L

PEC/PNEC < 0.1 which justifies the phrase “Use of Azelastine has been considered to result in insignificant environmental risk”.

Degradation

Azelastine is not ready biodegradable, <60% biotic degradation in 28 days, no abiotic degradation observed during study period. (OECD 301B) (Ref. 7)

Azelastine fails to meet the criteria for ready biodegradability and no abiotic degradation is observed. No data regarding inherent biodegradability or simulation studies are available.

The substance is assigned the phrase ”Azelastine is potentially persistent”.

Bioaccumulation

Experimentally derived Log K_ow values for Azelastine range from 1.00 to 3.85 depending on pH and initial concentration (shake flask method, FDA technical assistance handbook, section §3.02) (Ref. 8).

Log K_ow < 4 which justifies use of the phrase “Azelastine has low potential for bioaccumulation”.

References:

1. Data from IQVIA ”Consumption assessment in kg for input to environmental classification – updated 2021 (data 2022)

2. ECHA, European Chemicals Agency. Guidance on information requirements and chemical safety assessment. Ver 2.1, 2011

3. Determination of 72h-EC50 of Azelastine hydrochloride in Desmodesmus subspicatus according to OECD 201 resp. EU C.3, Meda internal document 2011

4. Determination of the effects on reproduction of Daphnia magna after exposition to Azelastine hydrochloride according to OECD 211 resp. EU C.20, Meda internal document 2011

5. Determination of the toxicity in the early-life stage toxicity test of Azelastine hydrochloride against Danio rerio Hamilton-Buchanan following OECD Guideline 210, Meda internal document 2011

6. Determination of the inhibition of the respiration of activated sludge when exposed to Azelastine hydrochloride according to OECD 209 resp. EU C.11, Meda internal document 2011

7. Determination of the aerobe ready biodegradability of Azelastine hydrochloride in the CO₂ evolution test following OECD 301B resp. EU C.4.C, Meda internal document 2011

8. Environmental risk assessment (Non-GMO) on Azelastine hydrochloride, Meda internal document 2011