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 = 0.0072 μg/L

Where:

A = 52.87 kg (total sold amount API in Sweden year 2023, data from IQVIA).

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) (Reference 1)

D = factor for dilution of wastewater by surface water flow = 10 (ECHA default) (Reference 1)

Predicted No Effect Concentration (PNEC)

Ecotoxicological studies

Algae

No data

Water flea (Daphnia magna):

Acute toxicity

EC50 48 h (immobility) = 240,000 μg/L (OECD 202) (Reference 6)

Water flea (Ceriodaphnia dubia):

Chronic toxicity

NOEC 8 days (reproduction) = 100,000 μg/L (USEPA 1002) (Reference 9)

Fish:

Acute toxicity

No data

Chronic toxicity

NOEC 21 day (biomass) = 8,300 ug/L (OECD 210) (Reference 10)

Microorganisms in activated sludge:

EC50 3 h (inhibition) = 830,000 µg/L (OECD 209) (Reference 5)

PNEC cannot be calculated because data is not available for all three (algae, crustacean and fish) of the toxicity endpoints.

Environmental risk classification (PEC/PNEC ratio)

According to the European Medicines Agency guideline on environmental risk assessment of medicinal products (EMA/CHMP/SWP/4447/00), use of Salbutamol is unlikely to represent a risk for the environment, because the predicted environmental concentration (PEC) at the time of registration was below the action limit 0.01 μg/L.

Degradation

Biotic degradation

Ready degradability:

1% degradation in 28 days (TAD 3.11) (Reference 7)

Inherent degradability:

No Data

Soil Degradation

1.3 to 38.7% degradation in 64d (TAD 3.12) (Reference 8)

Abiotic degradation

Hydrolysis:

DT50 > 1 year (OECD 111) (Reference 4)

Photolysis:

No data

Justification of chosen degradation phrase:

Salbutamol is not readily degradable or inherently degradable. The phrase “Salbutamol is potentially persistent in the environment” is thus chosen.

Bioaccumulation

Partitioning coefficient:

Log Dow = -2.80 at pH 7 (TAD 3.04). (Reference 3)

Log Dow at pH5 = -1.50

Log Dow at pH7 = -2.80

Log Dow at pH9 = -2.80

Justification of chosen bioaccumulation phrase:

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

Excretion (metabolism

The primary route of elimination of hydrofluoroalkane-propelled albuterol (HFA) parent or primary metabolite compound is through the kidney. After an IV dose of racemic albuterol, between 24% to 46% of the R enantiomer is excreted unchanged in the urine (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. Product Information: VENTOLIN(R) HFA inhalation aerosol, albuterol sulfate HFA inhalation aerosol. GlaxoSmithKline, Research Triangle Park, NC, 2008. Prod Info PROAIR HFA(R) inhalation aerosol, 2008

3. Colwyn TC. AH3365F: Determination of Physico-Chemical Properties. Report No. 94/GLX139/0366. Pharmaco Life Science Research Laboratories, November 1994.

4. Colwyn TC. AH3365F: Determination of Hydrolysis as a Function of pH. Report No. 94/GLX140/0202. Pharmaco Life Science Research Laboratories, November 1994.

5. Jenkins WR. AH3365F: Activated Sludge – Respiration Inhibition Test. Report No. 93/GLX141/1050. Pharmaco Life Science Research Laboratories, January 1995.

6. Jenkins CA. AH3365F: Acute Toxicity to Daphnia magna. Report No. 93/GLX142/0028. Pharmaco Life Science Research Laboratories, December 1994.

7. Jenkins WR. AH3365F: Biotic Degradation with Acclimatised Composite Inoculum- Modified Sturm Test. Report No. 93/GLX143/1128. Pharmaco Life Science Research Laboratories, January 1995.

8. O’Connor J. AH3365F: Aerobic Biodegradation in Soil. Report No. 95/GLX145/0118. Pharmaco Life Science Research Laboratories, February 1995.

9. Wetton PM. Salbutamol: Daphnid, Ceriodaphnia dubia Survival and Reproduction Test. Report No. 1127/0952. Safepharm Laboratories Limited, March 2006.

10. Weil M et al. Uptake and Effects of the Beta‐Adrenergic Agonist Salbutamol in Fish: Supporting Evidence for the Fish Plasma Model. Environmental Toxicology and Chemistry 28: 2509-2519, 2019.