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Trobalt

MiljöinformationReceptstatusFörmånsstatus
GlaxoSmithKline

Filmdragerad tablett 50 mg
Avregistreringsdatum: 2018-07-19 (Tillhandahålls ej) (Lila, runda, filmdragerade tabletter, 5,6 mm, med "RTG 50" präglat på ena sidan.)

Antiepileptika

Aktiv substans:
ATC-kod: N03AX21
För information om det avregistrerade läkemedlet omfattas av Läkemedelsförsäkringen, kontakta Läkemedelsförsäkringen.
Läs mer om avregistrerade läkemedel

Miljöpåverkan (Läs mer om miljöpåverkan)

Retigabin

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


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Detaljerad miljöinformation


Environmental Risk Classification


Predicted Environmental Concentration (PEC)


PEC is calculated according to the following formula:

PEC (μg/L) = (A*109*(100-R))/(365*P*V*D*100) = 1.5*10-6*A(100-R)

PEC = 0.00028 μg/L


Where:

A = 1.848 kg (total sold amount API in Sweden year 2014, data from IMS Health). Reduction of A may be justified based on metabolism data.


R = 0% removal rate (conservatively, it has been assumed there is no loss by adsorption to sludge particles, by volatilization, hydrolysis or biodegradation)


P = number of inhabitants in Sweden = 9 *106


V (L/day) = volume of wastewater per capita and day = 200 (ECHA default) (Ref. I)


D = factor for dilution of waste water by surface water flow = 10 (ECHA default) (Ref. I)


Predicted No Effect Concentration (PNEC)


Ecotoxicological Studies


Green Algae (Scenedesmus subspicatus):

IC50 96h (growth) = 130 μg/L (OECD 201) (Reference 4)

NOEC = 37 μg/L


Water flea (Daphnia magna):

Acute toxicity

No data


Water flea (Daphnia magna):

Chronic toxicity

NOEC 21 days (reproduction) = 900 μg/L (OECD 211) (Reference 5)


Rainbow Trout (Oncorhyncus mykiss):

Acute toxicity

No data


Fathead minnow (Pimephales promelas):

Chronic toxicity

NOEC 28 days (growth) = 32 μg/L (OECD 210) (Reference 6)


Other ecotoxicity data:


Chironomid (Chironomus riparius)

NOEC 28 days (reproduction) = 32,000 μg/kg (OECD 218) (Reference 11)


Microorganisms in activated sludge:

EC50 3 h (inhibition) > 100,000 μg/L @ 3 hrs (OECD 209) (Reference 7)

NOEC = 100 000 μg/L


PNEC = 32/10 = 3.20 μg/L


PNEC (μg/L) = lowest NOEC/10, where 10 is the assessment factor applied for three long-term NOECs. NOEC for fathead minnow (= 32 ug/L) has been used for this calculation since it is the most sensitive of the three tested species.


Environmental risk classification (PEC/PNEC ratio)

PEC/PNEC = 0.00028/3.2= 0.000088, i.e. PEC/PNEC ≤ 0.1 which justifies the phrase “Use of retigabine has been considered to result in insignificant environmental risk.”


Degradation


Biotic degradation


Ready degradability:

<5% degradation in 28 days (OECD 301) (Reference 3)


Inherent degradability:

0% degradation in 28 days (OECD 302) (Reference 10)

46%-69% primary degradation

This may be regarded as evidence for inherent primary biodegradation. This substance is not inherently biodegradable.


Simulation studies:

Water-sediment study:

50% (DT50) dissipation in 2.5 – 4.3 days (OECD 308) (Reference 8)

Ultimate biodegradation = 5-10% in 99 days


Abiotic degradation


Hydrolysis:

No data


Photolysis:

No data


Justification of chosen degradation phrase:

Retigabine is not readily biodegradable nor inherently biodegradable. This substance is predicted to degrade in water sediment systems ≥ 120 days. The phrase “Retigabine is potentially persistent” is thus chosen.


Bioaccumulation


Partitioning coefficient:


Log Dow at pH 5 = 2.09 (OECD 107) (Reference 9)
Log Dow at pH 7 = 2.14
Log Dow at pH 9 = 2.12


Justification of chosen bioaccumulation phrase:

Since log Dow < 4 at pH 7, the substance has low potential for bioaccumulation.


Excretion (metabolism)

In Elimination of retigabine occurs via a combination of hepatic metabolism and renal excretion. A total of approximately 84% of the dose is recovered in the urine, including the N-acetyl metabolite (18%), N-glucuronides of the parent active substance and of the N-acetyl metabolite (24%), or parent active substance (36%). Only 14% of retigabine is excreted in the faeces (Reference 2).

PBT/vPvB assessment

Retigabine does not fulfil the criteria for PBT and/or vBvP.


All three properties, i.e. ‘P’, ‘B’ and ‘T’ are required in order to classify a compound as PBT (Reference 1). Retigabine does not fulfil the criteria for PBT and/or vBvP based on log Pow < 4.


Please, also see Safety data sheets on http://www.msds-gsk.com/ExtMSDSlist.asp


References

  1. ECHA, European Chemicals Agency. 2008 Guidance on information requirements and chemical safety assessment.


  2. Pharmacokinetic properties: Elimination. Summary of Product Characteristics Trobalt (Retigabine). GlaxoSmithKline, April 2015.


  3. RETIGABINE: Determination of 28 day ready biodegradability. Report No. BL8545/B. Brixham Environmental Laboratory, January 2008.


  4. RETIGABINE: Toxicity to the green alga Pseudokirchneriella subcapitata. Report No. BL8549/B. Brixham Environmental Laboratory, March 2008.


  5. RETIGABINE: Chronic toxicity to Daphnia magna. Report No. BL8540/B. Brixham Environmental Laboratory, March 2008.


  6. RETIGABINE: Determination of effects on the Early-Life Stage of the fathead minnow (Pimephales promelas). Report No. BL8539/B. Brixham Environmental Laboratory, March 2008.


  7. RETIGABINE: Effect on the respiration rate of activated sludge. Report No. BL8538/B. Brixham Environmental Laboratory, January 2008.


  8. RETIGABINE: Aerobic transformation in aquatic sediment systems. Report No. BL8589/B. Brixham Environmental Laboratory, August 2008.


  9. Walker J and White DF. Retigabine: Determination of Partition Coefficient (n-Octanol/Water). Report No. 41100025. Harlan Laboratories Limited, June 2011.


  10. Clarke N and Mullee D. Retigabine: Assessment of Inherent Biodegradability; Modified MITI (II) Test. Report No. 1127/1796. Harlan Laboratories Limited, November 2009.


  11. Goodband TJ and Mullee DM. Retigabine: Sediment-Water Chironomid Toxicity Test Using Spiked Sediment. Report No. 41100026. Harlan Laboratories Limited, October 2011.