Detaljerad miljöinformation

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 = 0.0021893285 µg/L

Where:

A = total actual API sales in Sweden for the most recent year 15.9805 kg (total sold amount API in the most recent sales data for Sweden (2022) was distributed by IQVIA in 2023)

R = 0

P = number of inhabitants in Sweden = 10 *10⁶

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

D = factor for dilution of wastewater by surface water flow = 10 (ECHA default) (Reference VII)

Predicted No Effect Concentration (PNEC)

Ecotoxicological studies

Algae (guideline e.g. FDA 4.01):

Algal growth inhibition test with the green alga (Selenastrum capricornutum):

EC₅₀ 10 days > 1000 mg/l (guideline e.g. FDA 4.01) [Reference II]

NOEC = 1000 mg/l (Growth Inhibition)

Blue-green alga (Microcystis aeruginosa):

EC₅₀ 10 days > 1000 mg/l (guideline e.g. FDA 4.01) [Reference III]

NOEC = 1000 mg/l (Growth Inhibition)   

Crustacean (Daphnia magna) (water-flea) (guideline e.g. FDA 4.08) [Reference IV]:

Acute toxicity

EC₅₀ 48 h > 1000 mg/l

NOEC= 1000 mg/l (Survival)

Chronic toxicity

Not available

Fish:

Acute toxicity

Zebra fish (Brachydanio rerio):

LC₅₀ 96 h > 1000 mg/l (guideline e.g. FDA 4.11) [Reference V]

NOEC = 1000 mg/l (Mortality)

Chronic toxicity

Not available

Other ecotoxicity data:

Activated sludge respiration inhibition test (guideline e.g. OECD 209) [Reference I]

EC₅₀ 3h > 2000 mg/L

NOEC 3h ≥ 2000 mg/L

Result: Not readily biodegradable

PNEC (µg/l) = lowest EC50/1000 where 1000 is the assessment factor used. Since for all four species the EC50 > 1000 mg/l, this value was used to calculate the PNEC.

PNEC = 1000 mg/l/1000 = 1000 µg/l

Environmental risk classification (PEC/PNEC ratio)

PEC/PNEC = 0.0021893285/1000 = 0.000002189 i.e. PEC/PNEC ≤ 0.1

Use of Itraconazole has been considered to result in insignificant environmental risk.

Degradation

Biotic degradation

Ready biodegradation

Itraconazole was investigated for its ready biodegradation in a 28-day manometric respirometry test according to FDA 3.11 [Reference VI]:

Intraconazole cannot be regarded as biodegradable since the 60% pass level was not reached within 28 days.

Result: itraconazole is potentially persistent.

Simulation studies: -

Abiotic degradation

Hydrolysis: -

Photolysis: -

Bioaccumulation

Bioconcentration factor (BCF):

BCF: 3338.91 (pH 7,4) (Reference VIII)

Conclusion for bioaccumulation: Itraconazole has high potential for bioaccumulation.

Excretion (metabolism)

-

PBT/vPvB assessment

-

References

1. Buche C., Itraconazole (R051211) Toxicity to Activated Sludge in a Respiration Inhibition Test. RCC Study No. A35098. Janssen Study No. RMD705. May 17, 2006.

2. Vos E., The Effect of Itraconazole on the Growth of the Unicellular Green Algae Selenastrum capricornutum. Sponsor Report No. AASc / 0021. January 4, 1994.

3. Woensel M., The Effect of Itraconazole (R051211) on the Growth of the Unicellular Blue Green Algae Microcytsis aeruginosa. Sponsor Report No. AAMa / 0005. January 20, 1994.

4. Vos E., The Acute Toxicity of Itraconazole (R051211) in the water flea Daphnia magna. Sponsor Report No. ADK6 / 0036. December 9, 1993.

5. Vos E., The Acute Toxicity of Itraconazole (R051211) in the Bluegill Sunfish Lepomis macrochirus. Sponsor Report No. AFLm / 0009. December 9, 1993.

6. Van Ginneken I., The Biodegradability of Itraconazole (R051211) CO₂ Evolution Test. Sponsor Report No. BDAS / 0054. December 22, 1993.

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

8. https://www.chemspider.com/Chemical-Structure.49927.html, 2023.