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

PEC = 1.00 x 10^-4 μg/L

Where:

A = 0.73 kg (total sold amount API in Sweden year 2023, data from IQVIA). 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 = 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) (Ref. I)

Predicted No Effect Concentration (PNEC)

Ecotoxicological studies

Green Algae (Scenedesmus subspicatus):

IC50 96h (inhibition) = 2,800 μg/L (OECD 201) (Reference 3)

NOEC = 1,300 μg/L

Water flea (Daphnia magna):

Acute toxicity

EC50 48 h (immobility) = 13,800 μg/L (OECD 202) (Reference 10)

Water flea (Ceriodaphnia dubia):

Chronic toxicity

NOEC 8 days (reproduction) = 1,100 μg/L (USEPA 1002) (Reference 6)

Rainbow Trout (Oncorhyncus mykiss):

Acute toxicity

LC50 96 h (lethality) = 24,000 μg/L (OECD 203) (Reference 5)

Fathead minnow, Pimephales promelas:

Chronic toxicity

No data

Other ecotoxicity data:

Microorganisms in activated sludge:

EC50 3 h (inhibition) > 688,000 μg/L (OECD 209) (Reference 10)

Terrestrial toxicity

Manure worm (Eisenia foetida):

LC50 28d = 230,000 μg/kg (TAD 4.12) (Reference 8)

PNEC = 1,100/50 = 22 μg/L

PNEC (μg/L) = lowest NOEC/50, where 50 is the assessment factor applied for two long-term NOECs. NOEC for water flea (= 1,100 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 = 1.00 x 10^-4/22 = 4.55 x 10^-6, i.e. PEC/PNEC ≤ 0.1 which justifies the phrase “Use of salmeterol has been considered to result in insignificant environmental risk.”

Degradation

Biotic degradation

Ready degradability:

No data

Inherent degradability:

50% degradation in 12.80 days (TAD 3.11). (Reference 10)

Soil metabolism:

29.9 to 49.9% degradation in 64 days (OECD 304) (Reference 9)

Abiotic degradation

Hydrolysis:

50% degradation > 1 year (TAD 3.09). (Reference 10)

Photolysis:

No data

Justification of chosen degradation phrase:

Salmeterol is not readily degradable but it is inherently primarily degradable in that removal of the parent API in the Sewage Treatment Plant is expected to a significant extent. The phrase “Salmeterol is potentially persistent” is thus chosen.

Bioaccumulation

Partitioning coefficient:

Log Dow = 1.71 at pH 7 (TAD 3.02). (Reference 4)

Log Dow at pH 5 = 2.06

Log Dow at pH 7 = 1.71

Log Dow at pH 9 = 1.32

Justification of chosen bioaccumulation phrase:

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

Excretion (metabolism)

Salmeterol is extensively metabolised to a pharmacologically inactive 17 metabolite 1-hydroxy-2-naphthoic acid (xinafoate). The major route of excretion of drug related material is via the faeces, 25-60%. (Reference 2).

PBT/vPvB assessment

Salmeterol 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). Salmeterol does not fulfil the criteria for PBT and/or vBvP based on log Dow < 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. Product Information: Serevent(R) Diskus(R), Salmeterol inhalation powder. GlaxoSmithKline, Research Triangle Park, NC, 2003a.

3. Vryenhoef V and McKenzie J. Salmeterol Xinafoate: Algal Inhibition Test. Report No. 1127/547. Safepharm Laboratories Limited, April 2005.

4. Hartley DR. Salmeterol hydroxynapththoate: Determination of the n-Octanol/Water Partition Coefficient following FDA Technical Assisstance Document 3.02. Report No. 92-2-4102. Springborn laboratories, Inc, April 1992.

5. Sewell IG and McKenzie J. Salmeterol Xinafoate: Acute Toxicity to Rainbow Trout. Report No. 1127/546. Safepharm Laboratories Limited, April 2005.

6. Wetton PM Salmeterol Xinafoate: Daphnid, Ceriodaphnia Dubia Survival and Reproduction Test. Report No. 1127/949. Safepharm Laboratories Limited, March 2006.

7. Sewell IG and McKenzie J. Salmeterol Xinafoate: Acute Toxicity to Rainbow Trout. Report No. 1127/546. Safepharm Laboratories Limited, April 2005.

8. Handley JW, Sewell IG and Bartlett AJ. GR33343G: Earthworm Subacute Toxicty Test. Report No. 303/678. Safepharm Laboratories Limited, May 1995.

9. Secker, RC. GR33343G: Biodegradation in Soil. Report No. WPT/94/243. Pharmaco LSR Ltd, February1995.

10. Material Safety Data Sheet for Advair HFA. SDS number 126599. GlaxoSmithKline plc, November 2008.