Detaljerad miljöinformation

Detailed background information
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) = 1.37*10^-6*A(100-R)

PEC = 7.95 x 10^-6 μg/L

Where:

A = 0.058 kg (total sold amount API free base in Sweden year 2022, data from IQVIA). Total volume of Naratriptan hydrochloride 0.064 = 0.058 Naratriptan free base. Total Naratriptan = 0.058.

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 = 10*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) (Reference 1)

Predicted No Effect Concentration (PNEC)

Ecotoxicological studies

Green Algae (Scenedesmus subspicatus):

IC50 72h (growth) > 100,000 μg/L (OECD 201) (Reference 10)

NOEC = 100,000 μg/L

Water flea (Daphnia magna):

Acute toxicity

EC50 48 h (immobility) = 300,000 μg/L (OECD 202) (Reference 6)

Water flea:

Chronic toxicity

No data

Rainbow Trout (Oncorhyncus mykiss):

Acute toxicity

LC50 96 h (lethality) > 100,000 μg/L (OECD 203) (Reference 11)

Fish:

Chronic toxicity

No Data

Other ecotoxicity data:

Microorganisms in activated sludge:

EC50 3 h (inhibition) > 100,000 μg/L @ 3 hrs (OECD 209) (Reference 5)

PNEC = 100,000/1,000 = 100 μg/L

PNEC (ug/L) = lowest EC50/1000, where 1000 is the assessment factor applied for three acute EC50s. Conservatively, the Alga NOEC (= 100 mg/L) has been used for this calculation as there is uncertainty around the most sensitive EC50 value..

Environmental risk classification (PEC/PNEC ratio)

PEC/PNEC = 7.95 x 10^-6/100 = 7.95 x 10^-8, i.e. PEC/PNEC ≤ 0.1 which justifies the phrase “Use of naratriptan has been considered to result in insignificant environmental risk.”

Degradation

Biotic degradation

Ready degradability:

<1% degradation in 28 days (TAD 3.11). (Reference 8)

Inherent degradability:

3% ultimate (DOC removal) degradation in 28 days (OECD 302). (Reference 9)

27% primary (parent removal) degradation in 28 days (OECD 302).

Soil Degradation

3-36% degradation in 64 days (OECD 304). (Reference 7)

Abiotic degradation

Hydrolysis:

50% degradation @25ºC > 1 year (pH 7) (TAD 3.09). (Reference 4)

Photolysis:

No data

Justification of chosen degradation phrase:

Naratriptan is not readily degradable or inherently degradable. The phrase “Naratriptan is potentially persistent” is thus chosen.

Bioaccumulation

Partitioning coefficient:

Log Dow = -0.62 at pH 7 (TAD 3.02). (Reference 3)

Log Dow at pH 5 = -1.7

Log Dow at pH 7 = -0.62

Log Dow at pH 9 = 1.1

Justification of chosen bioaccumulation phrase:

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

Excretion (metabolism)

Mean clearance after intravenous administration was 470mL/min in men and 380mL/min in women. Renal clearance is similar in men and women at 220mL/min and is higher than the glomerular filtration rate suggesting that naratriptan is actively secreted in the renal tubules. Naratriptan is predominantly excreted in the urine with 50% of the dose recovered as unchanged naratriptan and 30% recovered as inactive metabolites. In vitro naratriptan was metabolised by a wide range of cytochrome P450 isoenzymes. Consequently significant metabolic drug interactions with naratriptan are not anticipated. The mean elimination half-life (t1/2) is 6 hours (Reference 2).

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: Meatbolism and Elimination. Summary of Product Characteristics Naramig (Naratriptan hydrochoride) Tablets. GlaxoSmithKline, July 2013.

3. Stanley RD and Cornish SK. GR85548A: Determination of Octanol-Water partition coefficient. Report No. BL5156/B. Brixham Environmental Laboratory, December 1994.

4. Stanley RD and Cornish SK. GR85548A: Hydrolysis as a Function of pH. Report No. BL5157/B. Brixham Environmental Laboratory, December 1994.

5. Latham M and Croudace CP. GR85548A: Determination of Activated Sludge Respiration Inhibition. Report No. BL5151/B, Brixham Environmental Laboratory, January 1995.

6. Croudace CP, Banner AJ and Stanley RD. GR85548A: Acute Toxicity to Daphnia magna. Report No. BL5117/B. Brixham Environmental Laboratory, January 1995.

7. Long KWJ. GR85548A: Aerobic Biodegradation in Soil. Report No. BL5254/B. Brixham Environmental Laboratory, January 1995.

8. Gillings E. GR85548A: Aerobic Biodegradation in Water. Report No. BL5226/B. Brixham Environmental Laboratory, January 1995.

9. Mead C and McKenzie J. Natripitan hydrochloride: Assessment of Inherent Biodegradability; Modified Zahn-Wellens/EMPA Test. Report No. 1127/538. Safepharm Laboratories Limited, July 2004.

10. Vryhenhoef H and McKenzie J. Natripitan hydrochloride: Algal Inhibition Test. Report No. 1127/537. Safepharm Laboratories Limited, July 2004.

11. Sewell IG and McKenzie J. Natripitan hydrochloride: Acute Toxicity to Rainbow Trout. Report No. 1127/536. Safepharm Laboratories Limited, May 2004.