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 = 0.0033 μg/L

Where:

A = 23,86 kg (total sold amount API in Sweden year 2021, data from IQVIA.)

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

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)

Metabolism

Bupivacaine is extensively and rapidly metabolised in the liver in humans, followed by excretion via urine. Less than 10% of the dose is excreted as parent bupivacaine. There is no excretion via faeces. (Ref. 2).

Ecotoxicological data

Endpoint	Species	Common Name	Method	Time	Result	Reference
EC50 - Based on Immobilisation	Daphnia magna	Giant Water Flea	OECD 202	48 h	39 mg/L Note 1	3
NOEC - Based on Immobilisation	Daphnia magna	Giant Water Flea	OECD 202	48 h	7.5 mg/L Note 1	3

Environmental risk classification (PEC/PNEC ratio)

Since no long term effect data are available, and only short term effect data from one species, the water flea, is available, it is not possible to calculate the PNEC and hence not the PEC/PNEC ratio. Therefore the statement "Risk of environmental impact of bupivacaine cannot be excluded, since there is not sufficient ecotoxicity data available" is assigned.

In Swedish: ” Risk för miljöpåverkan av bupivakain kan inte uteslutas då det inte finns tillräckliga ekotoxikologiska data.” under the heading ”Miljörisk”.

Environmental Fate Data

Endpoint	Method	Test Conditions	Result	Reference
Solubility Water	Non-standard method	pH 1.8 – 6 pH 8 – 12	40000 - 50000 mg/L 150 - 250 mg/L	4
Dissociation Constant	Method unknown	25°C	pKa = 8.21	5
Distribution Coefficient Octanol Water	Method unknown	25°C	Log D = 2.54 @ pH 7.4	5

Note 1: Concentrations were confirmed by analysis, and results expressed as nominal.

Biodegradation

No information on biodegradation is available. Therefore the statement "The potential for persistence of bupivacaine cannot be excluded, due to lack of data" is assigned.

In Swedish: ”Det kan inte uteslutas att bupivakain är persistent, då data saknas” under the heading ”Nedbrytning”.

Bioaccumulation

Log D = 2.54 at pH 7.4. (Ref. 5)

Bupivacaine has no significant bioaccumulation potential, as indicated by the experimental log D. Therefore the statement "Bupivacaine has low potential for bioaccumulation" is assigned.

In Swedish: ”Bupivakain har låg potential att bioackumuleras” under the heading ”Bioackumulering”.

References

1. [ECHA] European Chemicals Agency. December 2021. Guidance on Information Requirements and Chemical Safety Assessment. Chapter R.16: Environmental exposure assessment (version 3.0)Substance Information - ECHA (europa.eu)

   
   

2. Panter G H, Hutchinson T H, Bamforth J E. 2003. AstraZeneca Pain Management Active Pharmaceutical Ingredients: Mode of Action Literature Review for Potential Ecotoxicity. AstraZeneca Global Health & Environment Report No BL 7521/B.
   
   

3. Bupivacaine hydrochloride: Acute toxicity to Daphnia magna.
   Brixham Environmental Laboratory Report BL7890. July 2004.
   
   

4. Shah J.C., Maniar M. J. 1993. pH-Dependent Solubility & Dissolution of Bupivacaine & Its Relevance To The Formulation of A Controlled Release System.
   Controlled Release v23 n3 p261-270.
   
   

5. Strichartz G.R. Sanchez V. ; Arthur G.R. ; Chafetz R.; Martin D., 1990. Fundamental Properties of Local Anesthetics. 2. Measured Octanol: Buffer Partition Coefficients and pKa Values of Clinically Used Drugs. Anesth. Analg. v71 n2 p158-170.