Detaljerad miljöinformation

Atorvastatin is synthetic lip-lowering agent used for treatment of high cholesterol. Studies of at atorvastatin indicate it is soluble in water (327 mg/l) at 20 C. (Ref II)

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 = 0.0011 mg/L

Where:

A = 8141.9479 kg (total sold amount API in Sweden year 2022, data from IQVIA).

Reduction of A may be justified based on metabolism data.

R = 0 % removal rate (due to loss by adsorption to sludge particles, by volatilization, hydrolysis or biodegradation) = 0 if no data is available. (If R not = 0 this should be justified under the degradation section) 

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*

Algae (Pseudokirchneriella subcapitataa) (guideline eg OECD 201) (Reference VI):

NOEC (growth) = 14 mg/L

Crustacean (Daphania magna):

Acute toxicity

EC₅₀ 48 h (immobility) = 200 mg/L (guideline eg OECD 202) (Reference IX)

Chronic toxicity

NOEC 21 days (growth) = 0.20 mg/L (guideline eg OECD 211) (Reference XI)

Fish (Pimephalse promelas):

Acute toxicity

LC₅₀ 96 h (mortality) = <92 mg/L (guideline eg OECD 203) (Reference IX)

Chronic toxicity

NOEC 33 days (growth) = 0.49 g/L (guideline eg OECD 210) (Reference X)

An PNEC of 0.02 mg/L was determined for atorvastatin based on the results of the chronic water flea study, the most sensitive species tested (NOEC = 0.2 mg/L) An assessment (safety) factor of 10 (AF = 10) was applied since sufficient chronic toxicity data is available forspecies from three trophic levels.

Environmental risk classification (PEC/PNEC ratio)

PEC/PNEC = 0.0011/0.02 = 0.055, i.e.

‘Use of atorvastatin has been considered to result in insignificant environmental risk.’

Degradation*

Studies of atorvastatin indicate it is soluble in water (327 mg/L) at 20ºC. Studies of the octanol-water partition coefficient (Kow) indicate that atorvastatin does not have the potential to bioaccumulate in organisms (log Kow = 1.62 at pH 7). The log Koc values indicate it is mobile in soil and sludge (log Koc < 3). A biodegradation study indicates that atorvastatin is rapidly biodegradable in sludge. (Ref. III-IV, VI)

Primary degradation (Loss of parent):

Half-life (DT50) in water = 19.9 to 21.9 days

DT50 in total system = 26.4 to 32.4 days. (Ref. V)

The amounts of Atorvastatin in the total test systems (i.e. water layers plus sediment extracts) at the end of the test were 7.8% and 3.3%, respectively. The DT50 values for parent Atorvastatin in the total test systems were 32.4 and 26.4 days.

A measured portion (25 mL) of extraction solvent was added to each vial. The extraction solvent was acetone/tetrahydrofuran (1:1), the same solvent used to extract sediment samples. Sediment samples were fortified with [14C]Atorvastatin and extracted using a variety of solvents. The extraction solvent that provided the best results was a mixture of acetone and tetrahydrofuran (ACE/THF 1:1).

Bioaccumulation

Partitioning coefficient:

log Kow          pH 5 = 3.38

pH 7 = 1.62

pH 9 = 0.745 (guideline eg OECD 107). (Reference IV)

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

References

1. 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

2. Wildlife International, 2010. "Determination of water solubility of Atorvastatin by the Shake Flask Method" OECD 105, Project number 105C-142. 14 January 2010.

3. Wildlife International, 2011. "Atorvastatin: Adsorption/Desorption Characteristics in Representative Soils and Sludge Solids," Project No., 105E-153, 25 April 2011.

4. Wildlife International, 2010. "Determination n-octanol/water partition coefficient by the shake flask method" OECD 107, Project number 105C-143. 1 March 2010.

5. Wildlife International, 2011. " Atorvastatin: Aerobic Transformation in Aquatic

   Sediment Systems," OECD 308 Project No., 105E-154, 2 September 2011.

6. Wildlife International, 2011. "Atorvastatin: Biodegradation in Activated Sludge: OECD 314B, Project number 105E-155. 11 March 2011.

7. Wildlife International, 2010. "Atorvastatin: A 96-hr toxicity test with the freshwater alga (Pseudokirchneriella subcapitata)", OECD 201, Project No. 105A-194, 9 April 2010.

8. Wildlife International, 2010. "Atorvastatin: An Activated Sludge, Respiration

   Inhibition Test" OECD 209, Project number 105E-151. 13 January 2010.

9. Pfizer, 2013. LIPITOR Safety Data Sheet, accessed from

   http://www.pfizer.com/sites/default/files/products/material_safety_data/PD009.pdf on 22 August 2014.

10. Wildlife International, 2010. "Atorvastatin: An early life-stage toxicity test with the

    fathead minnow (Pimephales promelas)", OECD 210, Project No. 105A-196, 7

    September 2010.

11. Wildlife International, 2010. "Atorvastatin: A semi-static life-cycle toxicity test with the cladoceran (Daphnia magna)", OECD 211, Project No. 105A-195, 8 July 2010.

12. Wildlife International, 2012. "14C-Atorvastatin: A Prolonged Sediment Toxicity Test with Chironomus riparius using spiked sediment" Project No., 105A-202A, 13 July 2012.