Miljöpåverkan
Azitromycin (vattenfri)
Miljörisk:
Användning av azitromycin (vattenfri) har bedömts medföra låg risk för miljöpåverkan.
Nedbrytning:
Azitromycin (vattenfri) bryts ned i miljön.
Bioackumulering:
Azitromycin (vattenfri) har låg potential att bioackumuleras.
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Detaljerad miljöinformation
Physical properties
Solubility at pH 7: 5 430 000 µg/L4
pKa: 8.13 for the azalide ring and 9.82 for the desosamine nitrogen5
Vapor pressure: < 1 x 10-7 mmHg
Molecular weight: 785 Da
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 = 0.0095 μg/L
Where:
A = |
69.34 kg (total sold amount API in Sweden year 2020, data from IQVIA)3. |
R = |
0 % removal rate (worst-case scenario) |
P = |
number of inhabitants in Sweden = 10 * 106 |
V (L/day) = |
wastewater volume per capita and day = 200 (ECHA default)1 |
D = |
factor for wastewater dilution by surface water flow = 10 (ECHA default)1 |
Predicted No Effect Concentration (PNEC)
Ecotoxicological studies
Microbial growth inhibition (guideline FDA 4.02)6
Aspergillus niger minimal inhibitory concentration = >1000 000 μg/L
Trichoderma viride minimal inhibitory concentration = >1000 000 μg/L
Clostridium perfringens minimal inhibitory concentration = 2 000 μg/L
Bacillus subtilis minimal inhibitory concentration = 2 000 μg/L
Nostoc sp. minimal inhibitory concentration = 400 μg/L
Activated sludge microorgansims (guideline OECD 209)7
EC10 (respiration inhibition) = 1890 μg/L
EC50 (respiration inhibition) = 269 000 μg/L
Green alga (Pseudokirchneriella subcapitata) (guideline OECD 201)8
NOEC 72 h (growth rate, acute toxicity) = 1.8 μg/L
EC50 72 h (growth rate, acute toxicity) = 8.4 μg/L
Blue-green alga (Microcystis aeruginosa) (guideline OECD 201)9
NOEC 72 h (growth rate, acute toxicity) = 0.19 μg/L
EC50 72 h (growth rate, acute toxicity) = 1.8 μg/L
NOEC 96 h (cell density, acute toxicity) = 0.19 μg/L
EC50 96 h (cell density, acute toxicity) = 0.68 μg/L
Daphnids (Daphnia magna) (guideline OECD 202)10
NOEC 48 hours (immobilization, acute toxicity) = 19 000 μg/L
EC50 48 hours (immobilization, acute toxicity) = 120 000 μg/L
Daphnids (Ceriodaphnia dubia) (guideline EPA 1002.0)11
NOEC 7 days (reproduction, chronic toxicity) = 4.4 μg/L
LOEC 7 days (reproduction, chronic toxicity) = 15 μg/L
EC50 7 days (survival, chronic toxicity) = >1400 μg/L
Rainbow trout (Oncorhynchus mykiss) (guideline OECD 203)12
NOEC 96 hours (mortality, acute toxicity) = 84 000 μg/L
LC50 96 hours (mortality, acute toxicity) = > 84 000 μg/L
Fathead Minnow (Pimephales promelas) (guideline OECD 210)13
NOEC 32 days (early life stage, chronic toxicity) = 4600 μg/L
LOEC 32 days (early life stage, chronic toxicity) = >4600 μg/L
Based on the lowest NOEC for the species Microcystis aeruginosa and using the assessment factor2 of 10, the PNEC is calculated to 0.19/10 = 0.019 µg/L.
Environmental risk classification (PEC/PNEC ratio)
PEC/PNEC = 0.0095/0.019 = 0.50, i.e. PEC/PNEC ≤ 1 which justifies the phrase ”Use of azithromycin has been considered to result in low environmental risk.”
Adsorption (guideline OECD 106)14
Solid |
Kd (L/Kg) |
Koc (L/Kg) |
Activated sludge (dewatered cationic polymer) |
14.5-29.1 |
55.8-112 |
Activated sludge (not dewatered cationic polymer) |
59.6-59.8 |
378-379 |
2.7% organic matter soil (California clay) – Aqueous phase 0.01 M CaCl2 |
948 |
59 600 |
2.7% organic matter soil (California clay) – Aqueous phase distilled, deionized water |
585 |
36 800 |
2.7% organic matter soil (Kansas silt loam) – Aqueous phase 0.01 M CaCl2 |
660 |
41 500 |
2.7% organic matter soil (Kansas silt loam) – Aqueous phase distilled, deionized water |
362 |
22 800 |
1.9% organic matter soil (Texas silt loam) – Aqueous phase 0.01 M CaCl2 |
526 |
47 100 |
1.9% organic matter soil (Texas silt loam) – Aqueous phase distilled, deionized water |
444 |
39 600 |
HOM = high organic matter, LOM = low organic matter
Degradation
Biotic degradation
Ready degradability (guideline OECD 301D)7
18.8% degradation after 28 days. Azithromycin is therefore considered to be not readily biodegradable.
Water-sediment transformation simulation (guideline OECD 308)14
Length of study: 102 days
High organic sediment system: Turkey creek
Low organic sediment system: Choptank river
Sediment extraction solvent: Acetonitrile
Supplemental extraction solvents: Methyl alcohol and 10% methyl alcohol : 90% dichloromethane (v/v)
The results from the study are shown in the table below.
Data on day 102 at 20 °C |
Turkey Creek |
Choptank River |
|
Total system |
|||
Half-life (days) |
20.8 |
22.0 |
|
Total 14CO2 (% of AR) |
0.5 |
0.3 |
|
Aerobic Water Layer |
|||
Extractables (% of AR) |
4.8 |
5.1 |
|
Sediment Layer |
|||
Bound/NER (% of AR) |
91.7 |
82.8 |
|
Extractables (% of AR) |
2.6 |
6.5 |
ND = not detected, NER = non-extractable residues, AR = applied radioactivity
Justification of chosen degradation phrase
The DT50 value (water-sediment transformation simulation, OECD 308) was calculated to 22 days, corresponding to the degradation phrase ”Azithromycin is degraded in the environment.”
Bioaccumulation
Partitioning coefficient (guideline OECD 107)15
pH |
Log Kow |
5 |
0.14 |
7 |
0.48 |
9 |
1.56 |
Justification of chosen bioaccumulation phrase
Since log Dow < 4 at pH 7, azithromycin has low potential for bioaccumulation.
References
-
ECHA, European Chemicals Agency. 2016 Guidance on information requirements and chemical safety assessment chapter R16.
-
ECHA, European Chemicals Agency. 2008 Guidance on information requirements and chemical safety assessment chapter R10.
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IQVIA KG Consumption 2020 report.
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Study report 2438.6151: Azithromycin – Determination of the Water Solubility Following FDA TAD 3.01. August 1991.
-
Study report 2438.6153: Azithromycin – Determination f the Dissociation Constant Following FDA TAD 3.04. September 1991
-
Study report 2438.6155: Azithromycin – Determination of microbial growth inhibition. FDA TAD 4.02. July 1991.
-
Study report 2438.6159: Azithromycin – Ready biodegradability by the closed bottle method. September 1991.
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Study report 2438.6338: Azithromycin (CP-62,993-3) – Acute toxicity to the freshwater green alga (Pseudokirchneriella subcapitata). Aug 2004.
-
Study report 2438.6421: Azithromycin (CP-62,993-3) – Acute toxicity to the freshwater blue‑green alga, Microcystis aeruginosa. October 2005.
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Study report 2438.6158.: Azithromycin – Acute toxicity to daphnids (Daphnia magna) under static conditions. July 1991.
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Study report 2438.6419: Azithromycin (CP-62,993-3) – The life cycle toxicity test with daphnids, Ceriodaphnia dubia, under static renewl conditions. Aug 2004.
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Study report 2438.6339: Azithromycin (CP-62,993-3) – Acute toxicity to rainbow trout (Oncorhynchus mykiss) under static conditions. November 2002.
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Study report 2438.6420: Azithromycin (CP-62,993-3) – Early life-stage toxicity test with fathead minnow (Pimephales promelas). August 2004.
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Study report 2438.6154: Azithromycin – Determination of the sorption and desorption properties following FDA technical assistance document 3.08. August 1991.
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Study report 260E-134: Azithromycin: Aerobic and anaerobic transformation in aquatic sediment systems. September 2005.
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Study report 2468.6152: Azithromycin – Determination of the n-octanol/water partition coefficient following FDA technical assistance document 3.02. August 1991.