Miljöpåverkan
Anastrozol
Miljörisk:
Användning av anastrozol har bedömts medföra försumbar risk för miljöpåverkan.
Nedbrytning:
Anastrozol är potentiellt persistent.
Bioackumulering:
Anastrozol har låg potential att bioackumuleras.
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Detaljerad miljöinformation
PEC/PNEC = 0.000372 μg/L /1.0 μg/L =0.00037
PEC/PNEC < 0.1
Environmental Risk Classification
Predicted Environmental Concentration (PEC)
PEC is based on following data:
PEC (µg/L) = (A*109*(100-R))/(365*P*V*D*100)
PEC (µg/L) = 1.5*10-6*A*(100-R)
A(kg/year) = total sold amount API in Sweden year 2017, data from IQVIA (former IMS Health and Quintiles).
R (%) = 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 = 9 *106
V (L/day) = volume of wastewater per capita and day = 200 (ECHA default) (Ref.1)
D = factor for dilution of waste water by surface water flow = 10 (ECHA default) (Ref.1)
(Note: The factor 109 converts the quantity used from kg to μg).
A = 2.48 kg.
R = 0
PEC = 1.5 x 10-6 x 2.48 x (100-0) = 0.000372 µg/L
Note: Whilst anastrozole is extensively metabolised in humans, little is known about the ecotoxicity of the metabolites. Hence, as a worst case, for the purpose of this calculation, it is assumed that 100% of excreted metabolites have the same ecotoxicity as parent anastrozole.
Metabolism
Anastrozole is extensively metabolised and less than 10% is excreted as parent via the urine within 72 hours of dosing. The remainder is excreted in the urine as metabolites which are formed via N-dealkylation, hydroxylation and glucuronidation. The main metabolite, triazole, does not exhibit aromatase inhibiting properties (Ref. 2).
Ecotoxicity data
|
Endpoint |
Species |
Common Name |
Method |
Time |
Result |
Ref. |
|---|---|---|---|---|---|---|
|
LOEC - Based on Largest Specific Growth Rates |
Microcystis aeruginosa |
Cyanobacte-rium (Blue-Green Alga) |
US FDA Technical Assistance Document 4.01 |
21 d |
6.0 mg/L |
3 |
|
LOEC - Based on Maximum Standing Crops |
3.0 mg/L |
|||||
|
NOEC - Based on Largest Specific Growth Rates |
3.0 mg/L |
|||||
|
NOEC - Based on Maximum Standing Crops |
1.5 mg/L |
|||||
|
ErC50 - Based on Largest Specific Growth Rates |
96 h |
>48 mg/L |
||||
|
LOEC - Based on Largest Specific Growth Rates |
Pseudokirchne-riella subcapitata (formerly known as Selenastrum capricornutum) |
Green Alga |
US FDA Technical Assistance Document 4.01 |
14 d |
81 mg/L |
4 |
|
LOEC - Based on Maximum Standing Crops |
81 mg/L |
|||||
|
NOEC - Based on Largest Specific Growth Rates |
27 mg/L |
|||||
|
NOEC - Based on Maximum Standing Crops |
27 mg/L |
|||||
|
ErC50 - Based on Largest Specific Growth Rates |
96 h |
31.3 ml/L |
||||
|
LOEC – Based on Reproduction & Length |
Daphnia magna |
Giant Water Flea |
US FDA Technical Assistance Document 4.09 |
21 d |
5.6 mg/L |
5 |
|
NOEC – Based on Reproduction & Length |
3.2 mg/L |
|||||
|
LC50 |
Lepomis macrochirus |
Bluegill Sunfish |
US FDA Technical Assistance Document 4.11 |
96 h |
84 mg/L |
6 |
|
NOEC – Based on Symptoms of Toxicity |
10 mg/L |
|
||||
|
LC50 |
Oncorhynchus mykiss |
Rainbow Trout |
US FDA Technical Assistance Document 4.11 |
96 h |
75 mg/L |
7 |
|
NOEC – Based on Symptoms of Toxicity |
32 mg/L |
|||||
|
NOEC – Based on All Population Relevant Endpoints |
Pimephales promelas |
Fathead Minnow |
Extended OECD 210 Reduced fish full life-cycle, starting with embryos |
104 d |
0.01 mg/L |
8 |
|
LOEC – Based on All Population relevant Endpoints |
>0.01 mg/L |
PNEC (Predicted No Effect Concentration)
Long-term tests have been undertaken for species from three trophic levels, based on internationally accepted guidelines. Therefore, the PNEC is based on toxicity to fathead minnow (Pimephales promelas), the most sensitive species, and an assessment factor of 10 is applied, in accordance with ECHA (Ref. 9).
PNEC = 10 µg/L /10 = 1.0 µg/L
Environmental risk classification (PEC/PNEC ratio)
PEC/PNEC = 0.000372 μg/L /1.0 μg/L =0.00037
i.e., PEC/PNEC ≤ 0.1 which justifies the phrase “Use of anastrozole has been considered to result in insignificant environmental risk.”.
In Swedish: ”Användning av anastrozol har bedömts medföra försumbar risk för miljöpåverkan.” under the heading ”Miljörisk”.
Environmental Fate Data
|
Endpoint |
Method |
Test Substance Concentration |
Time |
Result |
Ref. |
|---|---|---|---|---|---|
|
Biochemical Oxygen Demand |
OECD301F |
50 & 100 mg/L |
28 d |
0 g O2/g |
10 |
|
Percentage Aerobic Biodegradation |
< 5 % by carbon & test substance loss from aqueous phase |
||||
|
Percentage Anaerobic Biodegradation |
DoE 1998 modified according to ISO Committee Draft CD11734 1993 |
25 & 50 mg/L (as Carbon) |
55 d |
0 % by gas production, carbon and test substance loss from aqueous phase |
11 |
Biodegradation
Anastrozole is not readily biodegradable. Based on this data, the phrase "Anastrozole is potentially persistent." is assigned.
In Swedish: “Anastrozol är potentiellt persistent.” under the heading “Nedbrytning”.
Bioaccumulation
Log P (experimental) = 1.58
Anastrozole has no significant bioaccumulation potential, as indicated by the log P. Therefore the statement “Anastrozole has low potential for bioaccumulation.” is assigned.
In Swedish: ”Anastrozole har låg potential att bioackumuleras” under the heading ”Bioackumulering”.
Physical Chemistry Data
|
Endpoint |
Method |
Concentration |
Test Conditions |
Results |
Ref. |
|---|---|---|---|---|---|
|
Soil Adsorption |
US FDA Technical Assistance Document 3.08 |
25 mg/L (Nominal) |
Nebo Soil: 28 % Clay 19 % Sand 53 % Silt pH 5.0 1.45 % organic carbon |
Koc = 1100 |
12 |
|
East Jubilee Soil: 13 % Clay 70 % Sand 17 % Silt pH 5.8 2.2 % organic carbon |
Koc = 180 |
||||
|
Kenny Hill Soil: 14 % Clay 78 % Sand 8 % Silt pH 7.7 3.1 % organic carbon |
Koc = 63 |
||||
|
Water Solubility |
- Method unkown |
- |
25ºC |
500 mg/L |
13 |
|
Dissociation Constant |
- Method unknown |
- |
- |
pKa = 1.4 |
13 |
|
Partition Coefficient Octanol Water |
Method unknown |
- |
- |
Log P= 1.58 |
13 |
References
1. [ECHA] European Chemicals Agency. Guidance on Information Requirements and Chemical Safety Assessment. Chapter R.16: Environmental exposure assessment (Version 3.0). February 2016.
2. Electronic Medicines Compendium, SmPC Anastrozole. https://www.medicines.org.uk/emc(accessed August 2019).
3. Arimidex: Toxicity to the Blue-green alga, Microcystis aeruginosa. Brixham Environmental Laboratory, AstraZeneca, UK, Report BL4897, November 1993.
4. Arimidex: Toxicity to the green alga, Selenastrum capricornutum.
Brixham Environmental Laboratory, AstraZeneca, UK, Report BL4896, November 1993.
5. Arimidex: Chronic toxicity to Daphnia magna. Brixham Environmental Laboratory, AstraZeneca, UK, Report BL4998, November 1993.
6. Arimidex: Acute toxicity to Bluegill sunfish (Lepomis macrochirus). Brixham Environmental Laboratory, AstraZeneca, UK, Report BL5221, December 1994.
7. Arimidex: Acute toxicity to rainbow trout (Oncorhynchus mykiss). Brixham Environmental Laboratory, AstraZeneca, UK, Report BL5220. November 1994.
8. Anastrazole: Determination of the effect on development, growth and spawning ability, of the fathead minnow (Pimephales promelas). Brixham Environmental Laboratory, AstraZeneca, UK, Report BR0180, April 2011.
9. [ECHA] European Chemicals Agency. Guidance on Information Requirements and Chemical Safety Assessment. Chapter R.10: Characterisation of dose [concentration]-response for environment. May 2008.
10. Arimidex: Determination of 28 day ready biodegradability. Brixham Environmental Laboratory, AstraZeneca, UK, Report BL4999, November 1993.
11. Arimidex: Determination of anaerobic biodegradability. Brixham Environmental Laboratory, AstraZeneca, UK, Report BL5020, November 1993.
12. Arimidex: Soil sorption and desorption. Brixham Environmental Laboratory, AstraZeneca, UK, Report BL5014/B, November 1993.
13. Marketing: S.1.3 General Properties. Anastrozole. AstraZeneca, Doc ID-002046669 Version 3.0.