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:

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

E_rC₅₀ 72 h (growth) = 0.46 mg/L

NOEC_r (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. E_rC₅₀ 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 = 0.00000932854/0.45 = 0.0000207301 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 K_ow = 2.8 using unknown internal method. According to ChemSpider ACD/Percepta the log K_ow = 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

The PBT-criteria are not fulfilled. Therefore, Bortezomib is not considered a PBT-substance.

6. REFERENCES

1. 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.

2. 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.

3. 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. 

4. Grützner I., Bortezomib: Toxicity to Activated Sludge in a Respiration Inhibition Test, OECD 209; RCC Ltd. Study A40015; JnJ Study RMD743; March 28, 2006.

5. 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

6. Bortezomib, ChemSpider, ID # 343402, July 7, 2015, http://www.chemspider.com/Chemical-Structure.343402.html?rid=8f028c39-d830-42ba-a890-e9384a9affab