Miljöpåverkan (Läs mer om miljöpåverkan)
Bortezomib
Miljörisk:
Användning av bortezomib har bedömts medföra försumbar risk för miljöpåverkan.
Nedbrytning:
Det kan inte uteslutas att bortezomib är persistent, då data saknas.
Bioackumulering:
Bortezomib har låg potential att bioackumuleras.
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Detaljerad miljöinformation
1. PREDICTED ENVIRONMENTAL CONCENTRATION (PEC):
The Predicted Environmental Concentration is calculated according to the following formula:
PEC (µg/L) = A x 109 x (100-R) / 365 x P x V x D x 100
Where:
|
A (kg/year) |
= |
0.057556941 kg (total sold amount API in the most recent sales data for Sweden (2016) was distributed by QuintilesIMS in summer 2017)) |
|
R (%) |
= |
removal rate (due to loss by adsorption to sludge particles, by volatilization, hydrolysis or biodegradation) |
|
= |
0% (worst-case scenario: no removal) |
|
|
P |
= |
number of inhabitants in Sweden (9 x 106) |
|
V (L/day) |
= |
volume of waste water per capita and day |
|
= |
200 (ECHA default) [5] |
|
|
D |
= |
factor for dilution of waste water by surface water flow |
|
= |
10 (ECHA default) [5] |
|
|
PEC (µg/L) |
= |
0.00000876057 µg/L |
2. PREDICTED NO EFFECT CONCENTRATION (PNEC)
2.1. Ecotoxicological studies
2.1.1. Algae
Algal growth inhibition test with the green alga (Scenedesmus subspicatus) (OECD 201) [1]:
EγC50 72 h (yield) = 0.30 mg/L
NOECγ (yield) = 0.10 mg/L
ErC50 72 h (growth) = 0.46 mg/L
NOECr (growth) = 0.10 mg/L
2.1.2. Crustacean
Acute
Acute toxicity to water-flea (Daphnia magna) (OECD 202) [2]:
EC50 48 h = 0.45 mg/L (Immobility)
NOEC = 0.17 mg/L
Chronic
Not available
2.1.3. Fish
Acute
Acute toxicity to zebra fish (Brachydanio rerio) (OECD 203) [3]:
LC50 96 h (mortality) = 1.1 mg/L
NOEC < 0.46 mg/L
Chronic
Not available
2.1.4. Other ecotoxicity data
Activated sludge respiration inhibition test (OECD 209) [4]
EC50 3 h > 1000 mg/L
NOEC 3 h = 714 mg/L
2.2. Calculation of Predicted No Effect Concentration (PNEC)
PNEC (µg/l) = lowest EC50/1000, where 1000 is the assessment factor used. ErC50 for the alga Scenedesmus subspicatus (0.46 mg/L) and EC50 for Daphnia magna (0.45 mg/L) have been used for this calculation since these two species are the most sensitive of the three tested species and for algae, growth is the most reliable endpoint.
PNEC = 0.45 mg/L/1000 = 0.45 µg/L
2.3. Environmental risk classification (PEC/PNEC ratio)
PEC/PNEC = 0.00000876057/0.45 = 0.0000194679 i.e. PEC/PNEC ≤ 0.1
Conclusion for environmental risk:
The calculated PEC/PNEC ratio is ≤ 0.1.
Use of Bortezomib has been considered to result in insignificant environmental risk.
3. DEGRADATION
Not available.
Conclusion for degradation:
The potential for persistence of Bortezomib cannot be excluded, due to lack of data.
4. BIOACCUMULATION
4.1. Partition coefficient octanol/water
The partition coefficient octanol/water was to determined to be log Kow = 2.8 using unknown internal method. According to ChemSpider ACD/Percepta the log Kow = 2.45. [6].
4.2 Bioconcentration
According to ChemSpider ACD/BCF (pH7.4) = 15.60. [6]
Since BCF < 500, Bortezomib has low potential for bioaccumulation.
Conclusion for bioaccumulation:
Bortezomib has low potential for bioaccumulation.
5. PBT-assessment
|
|
PBT-criteria |
Results for Bortezomib |
|
P |
DT50 freshwater > 40 days or DT50 sediment > 120 days |
No data available |
|
B |
BCF > 2000 |
BCF = 15.60 |
|
T |
Chronic NOEC < 0.01 mg/L or CMR or endocrine disrupting |
NOECalgae = 0.10 mg//L NOECdaphnia = 0.17 mg/L NOECfish = 0.45 mg/L |
The PBT-criteria are not fulfilled. Therefore, Bortezomib is not considered a PBT-substance.
6. REFERENCES
-
Peither A., Bortezomib: Toxicity to Scenedsmus subspicatus in a 72-Hour Algal Growth Inhibition Test, OECD 201; RCC Ltd. Study A39958; JnJ Study RMD740; June 30, 2006.
-
Peither A., Bortezomib: Acute Toxicity to Daphnia Magna in a 48-Hour Immobilization Test, OECD 202; RCC Ltd. Study A39971; JnJ Study RMD741; June 30, 2006.
-
Peither A., Bortezomib: Acute Toxicity to Zebra Fish (Brachydanio rerio) in a 96-Hour Static Test, OECD 203; RCC Ltd. Study A39993; JnJ Study RMD742; June 30, 2006.
-
Grützner I., Bortezomib: Toxicity to Activated Sludge in a Respiration Inhibition Test, OECD 209; RCC Ltd. Study A40015; JnJ Study RMD743; March 28, 2006.
-
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
-
Bortezomib, ChemSpider, ID # 343402, July 7, 2015, http://www.chemspider.com/Chemical-Structure.343402.html?rid=8f028c39-d830-42ba-a890-e9384a9affab