Miljöpåverkan
Atrakurium
Miljörisk:
Risk för miljöpåverkan av atrakurium kan inte uteslutas då ekotoxikologiska data saknas.
Nedbrytning:
Det kan inte uteslutas att atrakurium är persistent, då data saknas.
Bioackumulering:
Atrakurium har låg potential att bioackumuleras.
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Detaljerad miljöinformation
Appendix 1 - Template for environmental information at
Substance atracurium
Miljörisk: Risk för miljöpåverkan av atracurium kan inte uteslutas då ekotoxikologiska data saknas.
Nedbrytning: Det kan inte uteslutas att atracurium är persistent, då data saknas.
Bioackumulering: Atracurium har låg potential att bioackumuleras.
Detailed background information
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 = 2.19*10-4 μg/L
Where:
A = 1.6 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)
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)
No ecotoxicological study results are available, hence the PNEC (μg/L) could not be estimated.
Environmental risk classification (PEC/PNEC ratio)
The PEC/PNEC ratio could not be calculated due to lack of data and therefore justifies the phrase: "Risk of environmental impact of atracurium cannot be excluded, since no ecotoxicity data are available".
However, according to the European Medicines Agency guideline on environmental risk assessment of medicinal products (EMA/CHMP/SWP/4447/00), use of atracurium is unlikely to represent a risk for the environment, because the predicted environmental concentration (PEC) is below the action limit 0.01 μg/L.
Degradation
No degradation data are available, hence justifies the phrase: "The potential for persistence of atracurium cannot be excluded, due to lack of data".
Bioaccumulation
Partitioning coefficient:
Log Pow = 3.34 (predicted) (Ref II)
Log D = -3.98 at pH 7.4 (experimental octanol/phosphate buffer distribution coefficient) (Ref III)
Justification for bioaccumulation phrase:
Since log Log P/D < 4, the substance has low potential for bioaccumulation.
Excretion (metabolism)
Atracurium is eliminated through spontaneous degradation (Hofmann elimination) and hydrolysis via nonspecific esterases. The main metabolite of atracurium is Laudanosine. The metabolites have no effect on the muscle relaxant action (Ref IV).
References
I. 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
II. Drugbank online. https://go.drugbank.com/drugs/DB00732. Retrieved 2022-06-23.
III. Roy JJ, Varin F. Physicochemical properties of neuromuscular blocking agents and their impact on the pharmacokinetic-pharmacodynamic relationship. Br J Anaesth. 2004 Aug;93(2):241-8. doi: 10.1093/bja/aeh181. Epub 2004 May 28. PMID: 15169739.
IV. SmPC Atracurium Besilate 10mg/ml solution for Injection/Infusion PL 25215/0032, hameln pharma gmbh (26/05/2020).