Detaljerad miljöinformation

Detailed background information

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*394,15*(100-0)

Where:

A = 394,15 kg (total sold amount API in Sweden year 2021, data from IQVIA).

R = 0 % removal rate (due to loss by adsorption to sludge particles, by volatilization, hydrolysis or biodegradation) = 0 if no data is available.

P = number of inhabitants in Sweden = 10*10⁶

V (L/day) = volume of wastewater per capita and day = 200 (ECHA default) (Ref. 1)

D = factor for dilution of waste water by surface water flow = 10 (ECHA default) (Ref. 1)

PEC = 0,054 μg/L

Predicted No Effect Concentration (PNEC)

Ecotoxicological studies (Ref. 3)

Green alga (Pseudokirchneriella subcapitata) growth inhibition test (FDA Technical Assistance Document 4.01)

NOEC 96 h (growth rate) = 0.49 mg/L

EC50 96 h (growth rate) = 11.6 mg/L

Toxicity to blue-green algae, Microcystis aeruginosa, growth inhibition test (FDA Technical Assistance Document 4.01)

NOEC 21 day (growth rate) = 3.0 mg/L

EC50 96 h (growth rate) = 2.66 mg/L

Activated sludge, respiration inhibition test (None Standard Method)

EC50 3 h >100 mg/L

Daphnia magna

Acute toxicity

EC50 48 h (immobility) = 1- 10 mg/L (None Standard Method)

Blue gill sunfish fish, (Lepomis macrochirus), (FDA Technical Assistance Document 4.11)

Acute toxicity

LC50 96 h (mortality) = 0.62 mg/L

Rainbow trout, (Oncorhynchus mykiss), (FDA Technical Assistance Document 4.11)

Acute toxicity

LC50 96 h (mortality) = 0.37 mg/L

Daphnia magna, (FDA Technical Assistance Document 4.11)

Chronic toxicity

NOEC 21 day (survival, reproduction and growth) = 0.23 mg/L

LOEC 21 day (survival, reproduction and growth) = 0.46 mg/L

Based on the most sensitive acute species; rainbow trout 96h LC50 of 0.37 mg/L (equivalent to 370 µg/) and an assessment factor of 1000 in accordance with ECHA guidance (Ref. 3).

PNEC = 370 µg/L /1000 = 0.37 µg/L

Environmental risk classification (PEC/PNEC ratio)

PEC/PNEC = 0,054 / 0,37 = 0,146, i.e. 0,1 < PEC/PNEC ≤ 1 which justifies the phrase “Propofol has been considered to result in low environmental risk.

Biodegradation

Aerobic biodegradation (OECD 301F) (Ref. 4):

Degradation after 28 days= 2,8%

Not readily biodegradable

% removal from aqueous phase after

28 days = 91.1%*

Anaerobic Biodegradation (UK DoE Method,Modified according to ISO 11734) (Ref. 5):

% anaerobic biodegradation after

40 days = 0%

% carbon removal from aqueous phase

after 40 days = 27%*

Soil Adsorption Coefficient (FDA Technical Assistance Document 3.08) (Ref. 6):

Sandy Loam, pH 5.8, 1.6 %OC

Koc = 220 L/Kg

Kd = 4.8 L/Kg

Sandy Loam, pH 7.7, 2.2 %OC

Koc = 310 L/Kg

Kd = 9.7 L/Kg

Silty Clay Loam, pH 4.9, 3.1 %OC

Koc = 310 L/Kg

Kd = 5.0 L/Kg

# Calculated as Biological Oxygen Demand/ Chemical Oxygen Demand

* Anticipated to be due to adsorption to solid phase

%OC Percentage organic carbon

Kd Distribution coefficient for adsorption

Koc Organic carbon normalized adsorption coefficient

According to the above results, Propofol is not readily biodegradable and is not expected to undergo significant biodegradation under aerobic or anaerobic conditions.

Justification of chosen degradation phrase: Based on the data presented above, the phrase,"Propofol is potentially persistent".

Bioaccumulation

LogP = 3,79 (Ref 2)

Since log P < 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. PubChem 2022-01-22, https://pubchem.ncbi.nlm.nih.gov/compound/175805

3. Environmental Risk Assessment Data /Propofol / AstraZeneca.

4. Propofol: Determination of 28 Day Ready Biodegradability. Brixham Environmental, Laboratory, UK, AstraZeneca. Report BL5360. Brown A.R.; Sankey S.A.; Mather J.I.; Johnson P.A. April 1995

5. BL5361 Propofol: Determination of Anaerobic Biodegradability. Brixham Environmental Laboratory, UK, AstraZeneca. Report BL5361. Brown A.R.; Sankey S.A.; Johnson P.A. April

   1995

6. BL5359 Propofol: Soil Sorption and Desorption. Brixham Environmental Laboratory, UK, AstraZeneca. Report BL5359. Woods C.B.; Brown A.R. April 1995