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Tablett 100 mg
(Odragerad, vit till nästan vit, rund, bikonvex tablett, 11 mm i diameter, präglad "T" ovanför "207" på ena sidan och "100" på den andra sidan)

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  • Vad är miljöinformation?

Miljöinformation

Miljöpåverkan (Läs mer om miljöpåverkan)

Bedakilin

Miljörisk: Särskilt miljöfarliga egenskaper
PBT/vPvB-klass: I enlighet med EU:s fastställda kriterier ska substansen betraktas som en PBT/vPvB-substans


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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)

=

0.3008 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) [9]

D

=

factor for dilution of waste water by surface water flow


=

10 (ECHA default) [9]

PEC (µg/L)

=

0.0000457839 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) [2]:

EγC50 72 h (yield) > 0.77 µg/L

NOECγ (yield) ≥ 0.77 µg/L

ErC50 72 h (growth) > 0.77 µg/L

NOECr (growth) ≥ 0.77 µg/L


2.1.2. Crustacean

Acute

Not available.


Chronic

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

NOEC 21 days (endpoint: mortality) ≥ 4.7 µg/L


2.1.3. Fish

Acute

Not available.


Chronic

Fish early life stage test with zebra fish (Brachydanio rerio) (OECD 210) [4]:

NOEC 28 days (endpoint: mortality) ≥ 4.1 µg/L


2.1.4. Other ecotoxicity data

Activated sludge respiration inhibition test (OECD 209) [1]

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 the green alga Pseudokirchneriella subcapitata of 0.77 µg/L has been used for this calculation since it is the most sensitive of the three tested species.


PNEC = 0.77 µg/L/10 = 0.077 µg/L


2.3. Environmental risk classification (PEC/PNEC ratio)

PEC/PNEC = 0.0000457839/0.077 = 0.000594596 i.e. PEC/PNEC ≤ 0.1


Conclusion for environmental risk:

The calculated PEC/PNEC ratio is ≤ 0.1. Hence, risk assessment procedures would indicate that bedaquiline would have insignificant long-term risk to the environment. However, the half-life in the environment is > 120 days, the BCF is > 2000 and the chronic toxicity is < 0.01 mg/L (NOEC).
Bedaquiline should therefore be regarded as a PBT substance, according to ECHA Guidance criteria, and as such the current PEC/PNEC ratio may underestimate the potential for long-term risk to aquatic organisms.


3. DEGRADATION

3.1. Biotic degradation

3.1.1. Ready biodegradation

Bedaquiline was investigated for its ready biodegradation in a 28-day manometric respirometry test according to OECD 301F [5]:

Result: Not readily biodegradable.


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

Bedaquiline was investigated for its aerobic degradation in a 100-day aquatic sediment test, according to OECD 308 [6]:

The rates of dissipation (DT50 and DT90) of bedaquiline 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)

River

2.7

9.0

257

>1 year

Pond

2.3

7.7

163

>1 year


In aerobic aquatic sediment systems, bedaquiline rapidly dissipated from the water phase by adsorption to the sediment. Once in the sediment, bedaquiline was slowly degraded and formation of bound residues was observed.


Conclusion for degradation:

Bedaquiline is potentially persistent.


4. BIOACCUMULATION

4.1. Partition coefficient octanol/water

The partition coefficient octanol/water was determined using the shaking flask method. [7]
log Dow = 2.93 (pH = 3)


4.2. Bioconcentration

The bioconcentration and depuration characteristics of bedaquiline in the rainbow trout in a flow through system were examined according to OECD 305 [8].


BCFlow dose = 1433

BCFhigh dose = 2049

The BCF value of the high dose indicates that bedaquiline bioconcentrates in the rainbow trout.


Conclusion for bioaccumulation:

Bedaquiline 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 = 2.7 days
DT50,system = 257 days

Bioaccumulation

BCF > 2000

BCF = 1433 (low dose) and 2049 (high dose)

Toxicity

Chronic NOEC < 10 µg/L

NOECalgae = 0.77 µg/L
NOECdaphnia = 4.7 µg/L
NOECfish = 4.1 µg/L


Conclusion for PBT-assessment:

According to the established EU-criteria bedaquiline should be regarded as a PBT substance.


6. REFERENCES

  1. Memmert U., Toxicity of TMC207 (R403323) to activated sludge in a respiration inhibition test; Harlan Laboratories Study C29658; TMC207-TiDP13-NC213; June 19, 2009.

  2. Peither A., TMC207 (R403323) – Toxicity to Pseudokirchneriella subcapitata in a 72-hour algal growth inhibition test; Harlan Laboratories Study C29660; TMC207-TiDP13-NC214; December 14, 2010.

  3. Peither A., Effect of TMC207 (R403323) on survival and reproduction of Daphnia magna in a semi-static test over three weeks; Harlan Laboratories Study C29682; TMC207-TiDP13-NC215; December 14, 2010.

  4. Peither A., Toxic effects of TMC207 (R403323) to zebra fish (Brachydanio rerio) in an early-life stage toxicity test; Harlan Laboratories Study C29693; TMC207-TiDP13-NC216; December 14, 2010.

  5. Memmert U., Ready biodegradability of TMC207 (R403323) in a manometric respirometry test; Harlan Laboratories Study C29750; TMC207-TiDP13-NC219; July 7, 2009.

  6. Mégel V., 14C-TMC207 – Route and rate of degradation in aerobic aquatic sediment systems; Harlan Laboratories Study C29636; TMC207-TiDP13-NC211; May 11, 2010.

  7. Habeck C., TMC207 (R403323) – Determination of the partition coefficient (n-octanol/water); Harlan Laboratories Study C29748; TMC207-TiDP13-NC218; November 3, 2009.

  8. Kenner O., Bioconcentration of 14C-TMC207 – Flow-through test in the rainbow trout (Onchorhynchus mykiss); Harlan Laboratories Study C29704; TMC207-TiDP13-NC217; August 17, 2010.

  9. 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