FASS logotyp
Receptbelagd

Peka på symbolerna och beteckningarna till vänster för en förklaring.

Kontakt

Sök apotek med läkemedlet i lager

Sök lagerstatus

INTELENCE

Janssen

Tablett 200 mg
(Vit till benvit, bikonvex, avlång tablett med "T200" präglat på ena sidan.)

Antivirala läkemedel för systemiskt bruk, icke-nukleosidanaloger, omvänt transkriptas-hämmare

Aktiv substans:
ATC-kod: J05AG04
Läkemedel från Janssen omfattas av Läkemedelsförsäkringen.
  • Vad är miljöinformation?

Miljöinformation

Miljöpåverkan

Etravirin

Miljörisk: Användning av etravirin har bedömts medföra försumbar risk för miljöpåverkan.
Nedbrytning: Etravirin är potentiellt persistent.
Bioackumulering: Etravirin har låg potential att bioackumuleras.


Läs mer

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)

=

16.572 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) [10]

D

=

factor for dilution of waste water by surface water flow

 

=

10 (ECHA default) [10]

PEC (µg/L)

=

0.002522374 µg/L


2. PREDICTED NO EFFECT CONCENTRATION (PNEC)

2.1 Ecotoxilogical studies

2.1.1. Algae

Green algae (Scenedesmus subspicatus) (OECD 201): [1]

EC50 72 h > 4.9 µg/L

NOEC = 4.9 µg/L (inhibition of growth)


2.1.2. Crustacean


Acute

Not available


Chronic

Water-flea (Daphnia magna) reproduction test (OECD 211): [2]

NOEC 21 days = 9.1 µg/L (Survival)


2.1.3. Fish


Acute

Not available.


Chronic

Zebra fish (Brachydanio rerio) early life stage test (OECD 210) [3]

NOEC 35 days = 10 µg/L


2.1.4. Other ecotoxicity data

Activated sludge respiration inhibition test (OECD 209) [4]

EC50 3h > 1000 mg/kg


NOEC 3h ≥ 1000 mg/L


Earthworm Acute Toxicity (Eisenia fetida) in a 14-day test (OECD 207) [8]

NOEC 14 days >1000 mg/kg dry soil


Sediment-dwelling larva of Chironomus riparius in a water-sediment system (OECD 219) [9]

NOEC 28 days > 20 µg/L


2.2. Calculation of Predicted No Effect Concentration (PNEC)

PNEC (µg/L) = lowest NOEC from long-term ecotoxicity/10, where 10 is the assessment factor used. NOEC for algae (4.9 µg/L) has been used for this calculation since it is the most sensitive of the three tested species.


PNEC = 4.9 µg/L/10 = 0.49 µg/L


2.3. Environmental risk classification (PEC/PNEC ratio)

PEC/PNEC = 0.002522374 µg/L / 0.49 µg/L = 0.005147702 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 use of the medicine has been considered to result in insignificant environmental risk.


3. DEGRADATION

3.1. Biotic degradation

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

Etravirine was investigated for its aerobic degradation in a 100-day aquatic sediment test, according to OECD 308 [5].The rates of dissipation (DT50 and DT90) of Etravirine from the water phase were calculated using first order kinetics:


System

Water


DT50

(Days)

DT90

(Days)

River

0.6

2.0

Pond

1.1

3.6


Etravirine is slowly degraded to form four minor degradation products in an aerobic transformation test in aquatic sediment systems (OECD 308). Consequently, Etravirine is not considered as readily biodegradable. The medicine is considered as potentially persistent.


Conclusion for degradation:

Etravirine is potentially persistent.


4. BIOACCUMULATION

4.1. Partition coefficient octanol/water

The partition coefficient octanol/water was determined according to OECD 117
log Dow = 3.4 [6]


4.2. Bioconcentration

The bioconcentration and depuration characteristics of Etravirine in the rainbow trout (Oncorhynchus mykiss) in a flow through system were examined according to OECD 305. [7]


BCFlow dose = 370.3

BCFhigh dose = 476.9

These BCF values indicate that Etravirine does not have a significant bioaccumulation potential.


Conclusion for bioaccumulation:

Etravirine has no significant bioaccumulation potential


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 = 0.6 days
DT50,system = slowly degraded

Bioaccumulation

BCF > 2000

BCF = 370.3 (low dose) and476.9 (high dose)

Toxicity

Chronic NOEC < 10 µg/L

NOECalgae = 4.9 µg/L
NOECdaphnia = 9.1 µg/L
NOECfish = 10 µg/L


Conclusion for PBT-assessment:

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


6. REFERENCES

  1. Peither A., TMC 125 (R165335): Toxicity to Scenedesmus subspicatus in a 72-Hour Algal Growth Inhibition Test (OECD 201); RCC Ltd Study A59231; JNJ Study RMD771; March 20, 2007.

  2. Peither A., TMC 125 (R165335): Effect on Survival and Reproduction of Daphnia Magne in a Semi-Static Test Over Three Weeks (OECD 211); RCC Ltd study A59253; JNJ Study RMD772; March 20, 2007.

  3. Peither A., TMC 125 (R165335): Toxic Effects of Zebra Fish (Brachydanio rerio) in an Early-Life Stage Toxicity Test (OECD 210); RCC Ltd study A59275; JNJ Study RMD773; April 19, 2007.

  4. Seyfried B., TMC 125 (R165335): Toxicity to activated Sludge in a Respiration Inhibition test (OECD 209); RCC Ltd study A59297; JNJ Study RMD774; December 19, 2006.

  5. Völkel W., TMC 125 (R165335): Route and Rate of Degradation in aerobic Aquatic Sediment Systems (OECD 308); RCC Ltd study A59365; JNJ Study RMD778; February 15, 2007.

  6. Weiseenfeld M., Partition Coefficent (n-octanol/water) of TMC 125 (R165335) RCC study A59308; March 10, 2006.

  7. Burri R., Bioconcentration: Flow-Through Fish Test with [3H] –TMC125 in Rainbow Trout (Oncorhynchus mykiss); RCC Ltd Study A59332; JNJ Study RMD777; September 29, 2006.

  8. Schmidt T., TMC 125 (R165335): Acute Toxicity of the Earthworm Eisenia fetida in a 14 day test (OECD 207); RCC Study Number B14973; JNJ Study RMD905; July 4, 2007.

  9. Memmert U., Effects on the Development of Sediment-Dwelling Larvae of Chironomus riparius in a Water-Sediment System (OECD 219): RCC Study Number B67511: JNJ Study RMD983; August 4, 2008.

  10. 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