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Filmdragerad tablett 500 mg
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Endokrin terapi, övriga antihormoner och relaterade medel

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Miljöpåverkan (Läs mer om miljöpåverkan)

Abirateron

Miljörisk: Användning av abirateron har bedömts medföra hög risk för miljöpåverkan.
Nedbrytning: Abirateron bryts ned i miljön.
Bioackumulering: Abirateron har hög 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)

=

total actual API sales in Sweden for the most recent year

99.75 (Sales from 2016 – IMS Health)

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) [12]

D

=

factor for dilution of waste water by surface water flow

 

=

10 (ECHA default) [12]

PEC (µg/L)

=

0.0152 µg/L


2. PREDICTED NO EFFECT CONCENTRATION (PNEC)

2.1. Ecotoxicological studies

2.1.1. Algae

Algal growth inhibition test with the green alga (Pseudokirchneriella subcapitata) (OECD 201) [1]:

EγC50 72 h (yield) > 1.0 mg/L

NOECγ (yield) = 1.0 mg/L

ErC50 72 h (growth) > 1.0 mg/L

NOECr (growth) = 1.0 mg/L


2.1.2. Crustacean

Acute

Acute toxicity to water-flea (Daphnia magna) (OECD 202) [2]:

LC50 96 h = 0.25 mg/L

NOEC = < 0.048 mg/L


Chronic

Reproduction test with water-flea (Daphnia magna) (OECD 211) [3]:

NOEC 21 days = 0.47 µg/L (Reproduction and Growth)


2.1.3. Fish

Acute

Acute toxicity to rainbow trout (Oncorhynchuss mykiss) (OECD 203) [4]:

LC50 96 h = 0.13 mg/L

NOEC = 0.065 mg/L


Chronic

Fish early life stage test with fathead minnow (Pimephales promelas) (OECD 210) [5]:

NOEC 35 days = 1.1 µg/L (Total body length)


Fish partial life cycle study with fathead minnow (Pimephales promelas) (OECD 229) [11]:

NOEC 119 days = 13 ηg/L (Number of spawns per female)


2.1.4. Other ecotoxicity data

Activated sludge respiration inhibition test (OECD 209) [6]

EC50 3h > 1000 mg/L

NOEC 3h ≥ 1000 mg/L


2.2. Calculation of Predicted No Effect Concentration (PNEC)

PNEC (µg/l) = lowest NOEC/10, where 10 is the assessment factor used. NOEC for fathead minnow Pimephales promelas of 13 ηg/L has been used for this calculation since it is the most sensitive of the three tested species.


PNEC = 13 ηg/L/10 = 1.3 ηg/L = 0.0013 µg/L


2.3. Environmental risk classification (PEC/PNEC ratio)

PEC/PNEC = 0.0152/0.0013 = 11.7


Conclusion for environmental risk:

The calculated PEC/PNEC ratio is > 10. This indicated that the use of Abiraterone acetate has been considered to result in high environmental risk.


3. DEGRADATION

3.1. Biotic degradation

3.1.1. Ready biodegradation

Abiraterone acetate was investigated for its ready biodegradation in a 28-day CO2-evolution test according to OECD 301B [7]:

Result: Not readily biodegradable.


3.1.2. Simulation study: Aerobic degradation in aquatic sediment systems:

Abiraterone acetate was investigated for its aerobic degradation in a 101-day aquatic sediment test, according to OECD 308 [8].


For analysis the sediment was extracted once with acetonitrile, once with acetonitrile:trifluoroacetic acid 100:0.5 (v:v) and once (twice

on Day 101) with acetonitrile:water:trifluoroacetic acid 80:20:0.5, (v:v:v) for a maximum of four extractions. The water and sediment extracts were radioassayed by LSC and then analyzed by HPLC/RAM to quantify [14C]abiraterone

acetate and degradation products in the fractions. The radioactivity in the post extracted solids (sediment bound) were quantified by combustion analysis. The volatile organic traps were radioassayed by LSC.


The rates of dissipation (DT50 and DT90) of Abiraterone acetate from the water phase and the entire system were calculated using first order kinetics:

System

Water

Total system

 

DT50

(Days)

DT90

(Days)

DT50

(Days)

DT90

(Days)

Taunton River Aerobic

2.3

7.7

4.9

16

Weweantic River Aerobic

2.3

7.6

3.3

11

In aerobic aquatic sediment systems, Abiraterone acetate rapidly dissipated from the water phase by adsorption to the sediment.


Conclusion for degradation:

Abiraterone acetate is degraded in the environment.


4. BIOACCUMULATION

4.1. Partition coefficient octanol/water

The partition coefficient octanol/water was determined according to OECD 117 [9]

Log Dow >6.20 (pH = 6.10)


4.2. Bioconcentration

The bioconcentration and depuration characteristics of Abiraterone acetate in the rainbow trout in a flow through system were examined according to OECD 305 [10].


BCFlow dose = 625

BCFhigh dose = 576

The BCF value of the low and high dose indicates that Abiraterone acetate has high potential to bioconcentrate in the rainbow trout.


Conclusion for bioaccumulation:

Abiraterone acetate has high potential for bioaccumulation


5. PBT-ASSESSMENT

 

PBT-criteria

Results for BDQ

Persistence

Half-life in freshwater: DT50 > 40 days

Half-life in sediment: DT50 > 120 days

DT50,river = 2.3 days

DT50,system = 4.9 days

Bioaccumulation

BCF > 2000

BCF = 625 (low dose) and 576 (high dose)

Toxicity

Chronic NOEC < 10 µg/L

NOECalgae = 1.0 mg/L

NOECdaphnia = 0.47 µg/L

NOECfish = 13 ηg/L

Conclusion for PBT-assessment:

According to the established EU-criteria Abiraterone acetate should not be regarded as a PBT substance.


6. REFERENCES

  1. Softcheck K., Abiraterone Acetate – Acute Toxicity to the Freshwater Green Alga, Pseudokirchneriella subcapitata Following OECD Guideline #201; Springborn Smithers Laboratories Study No. 13674.6187; JNJ Study No. RMD 1073; May 27, 2010.

  2. Fournier A.; Abiraterone Acetate – Acute toxicity to water fleas (Daphnia magna) under static conditions, following OECD Guideline No. 202; Springborn Smithers Study No. 13674.6188; JNJ Study No. RMD1074; June 14, 2010.

  3. Sayers L., Abiraterone Acetate – Full Life-Cycle Toxicity Test with Water Fleas, Daphnia magna, Under Static-Renewal Conditions, Following OECD Guidelines #211; Springborn Smithers Laboratories Study No. 13674.6210; JNJ Study No. RMD 1079; October 6, 2010.

  4. Fournier A.; Abiraterone acetate – Acute toxicity to rainbow trout (Oncorhynchus mykiss) under static-renewal conditions, following OECD Guideline No. 13674.6189; JNJ Study No. RMD1075; June 9, 2010.

  5. Lee M., Abiraterone Acetate – Early Life Stage Toxicity Test with Fathead Minnow, Pimephales promelas, Following OECD Guideline #210; Springborn Smithers Laboratories Study No. 13674.6211; JNJ Study No. RMD 1080; October 8, 2010.

  6. Turk R., Abiraterone Acetate – Activated Sludge Respiration Inhibition Test Following OECD Guideline 209; Springborn Smithers Laboratories Study No. 13674.6190; JNJ Study No. RMD 1076; January 28, 2010.

  7. McLaughlin S.; Abiraterone acetate – Determination of the biodegradability of a test substance based on OECD Method 301B (CO2-evolution test); Springborn Smithers Study No. 13674.6191; JNJ Study No. RMD1077; January 6, 2010.

  8. Turk R., Lentz N., [14C] Abiraterone Acetate – Aerobic Transformation in Aquatic Sediment Systems Following OECD Guideline 308; Springborn Smithers Study No. 13674.6195; JNJ Study No. RMD 1078; September 14, 2010.

  9. Van Meter D., Abiraterone Acetate – Determination of n-Octanol/Water Partition Coefiecent Following OECD Guidelines, Section 117; Springborn Smithers Study No. 13674.6186; JNJ Study No. RMD 1072; March 15, 2010.

  10. Lentz N., Abiraterone Acetate - Flow-Through Bioconcentration and Metabolism Study with Rainbow Trout (Oncorhnychus mykiss) Following OECD Guideline 305; Springborn Smith Study No. 13674.6215; JNJ Study No. RMD 1082; November 10, 2010.

  11. York D., Abiraterone Acetate – Modified Partial Life-Cycle Exposure with Fathead Minnow (Pimephales promelas) Following OECD Guideline 229; Springborn Smithers Study No. 13674.6239; August 7, 2012.

  12. 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

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