Miljöpåverkan
Miljöinformationen för lidokain är framtagen av företaget Roche för Rocephalin® med lidokain
Miljörisk:
Användning av lidokain har bedömts medföra försumbar risk för miljöpåverkan.
Nedbrytning:
Lidokain är potentiellt persistent.
Bioackumulering:
Lidokain har låg potential att bioackumuleras.
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Detaljerad miljöinformation
The assessment for Lidocaine is based on the following entries of sales data fromsales data from IQVIA / LIF - kg consumption 2021:
|
Substance |
CAS no. |
M |
kg (2021) |
|---|---|---|---|
|
Lidocaine |
137-58-6 |
234.3408 |
1237.9284 |
|
Lidocaine hydrochloride (monohydrat) |
6108-05-0 |
288.8165 |
863.4509 |
|
Lidocaine hydrochloride (water free) |
73-78-9 |
270.8017 |
11.2757 |
|
Lidocaine (total) |
|
|
1948.2753 |
Identification and characterisation
Chemical name: Lidocaine
CAS number: 137-58-6
Molecular weight: 234.3408 [1]
Remark: -
Brand name: Rocephalin® med lidokain [1]
Physico-chemical properties
Water solubility:
4000 mg/l as Lidocaine base [10]
680000 mg/l as Lidocaine hydrochloride monohydrate [10]
Dissociation constant, pKa:
8.05 (in 170 mM NaCl at 25 °C, with no added buffers) [9]
7.84 (25 °C) [10]
Melting point:
68–69 °C as Lidocaine base [10]
76–79 °C as Lidocaine hydrochloride monohydrate [10]
Vapour pressure: ND
Boiling point: ND
KH: 8.77*E–09 atm*m3/mol QSAR
QSAR = QSAR-modelled (EPISuite, SPARC, ACD Solaris)
Predicted Environmental Concentration (PEC)
PEC is calculated according to the formula:
PEC (μg/L) = (A x 1'000'000'000 x (100-R)) / (365 x P x V x D x 100) = 1.37 x 10-6 x A x (100 - R) = 0.267 μg/l
Where:
A Sold quantity = 1948.2753 kg/y sales data from IQVIA / LIF - kg consumption 2020
R Removal rate = 0 % Default value [2]
P Population of Sweden = 10 000 000
V Volume of Wastewater = 200 l/day Default value [2]
D Factor for Dilution = 10 Default value [2]
Predicted No Effect Concentration (PNEC)
Ecotoxicological Studies
Green alga (Scenedesmus vacuolatus): [4]
ErC50 24 h (growth rate) at pH 6.5 = 135 mg/l (no standard method)
ErC50 24 h (growth rate) at pH 7.5 = 161 mg/l (no standard method)
ErC50 24 h (growth rate) at pH 8.5 = 142 mg/l (no standard method)
ErC50 24 h (growth rate) at pH 9.0 = 128 mg/l (no standard method)
ErC50 24 h (growth rate) at pH 10.0 = 108 mg/l (no standard method)
(Algae were maintained as batch cultures in Talaquil medium at 25 °C under photosynthetically active radiation (PAR) of 170 ± 20μEm−2 s−1. The buffer constitution of the medium was increased to 20 mM to reach pH-stability over the test period. The buffer constitution was varied with pH as follows: 20mM MES (2-(N morpholino)ethanesulfonic acid, CAS 4432-31-9) was used for pH 6.5, 20 mM MOPS (3-(Nmorpholino) propanesulfonic acid, CAS 1132-61-2) for pH 7.5, 20 mM HEPPS (4 (2-hydroxyethyl)-1-piperazinepropanesulfonic acid, CAS 16052-06-5) for pH 8.5, 20 mM CHES (2-(cyclohexylamino)ethanesulfonic acid, CAS 103-47-9) for pH 9.0, and 20 mM CAPS (3- (cyclohexylamino)-1-propanesulfonic acid, CAS 1135-40-6) for pH 10.0. Algae were grown in medium at the different pH values for at least 3 days before the experiment to allow for adaptation. The test was conducted using OD-readings for the determination of the growth rate μ during 24 h.) [4]
Water-flea (Daphnia magna): cited in: [5]
EC50 48 h (immobilization) = 112 mg/l (OECD 202)
Thamnocephalus platyurus (anostracan crustacean) [8]
LC50 24 h (mortality) = 81.7 mg/l (Thamnotoxkit microbiotest)
Zebra fish (Danio rerio): cited in: [5]
LC50 96 h (mortality) = 106 mg/l (OECD 203)
Zebra fish (Danio rerio) Embryo Test: [11]
LC50 24 h (mortality) = 23 mg/l (OECD 236, adapted)
Micro-organisms:
ND
PNEC Derivation
The PNEC is based on the following data:
PNEC (μg/l) = lowest LC50/1000, where 1000 is the assessment factor used. An LC50 of 23000 μg/l in the Zebra fish (Danio rerio) Embryo Test has been used for this calculation.
PNEC = 23000 / 1000 = 23 μg/l
Environmental Risk Classification (PEC/PNEC Ratio)
PEC Predicted Environmental Concentration = 0.267 μg/L
PNEC Predicted No Effect Concentration = 23 μg/L
Ratio PEC/PNEC = 0.012
PEC/PNEC = 0.267/23 = 0.012 for Lidocaine which justifies the phrase 'Use of Lidocaine has been considered to result in insignificant environmental risk.'
Degradation
Biotic Degradation
Ready biodegradability: ND
Inherent biodegradability: ND
Other degradation information: [6]
Degradation in surface water t½ = 92 d (laboratory, 23 °C, in the dark), t½ = 110 d (field, 2-28 °C, in the dark)
Abiotic Degradation
Photodegradation: t½ = 0.4 d (laboratory, light), t½ = 1.3 d (field, light) [6]
Hydrolysis: ND
Lidocaine is neither readily, nor inherently biodegradable. This justifies the phrase 'Lidocaine is potentially persistent.'
Bioaccumulation/Adsorption
logPOW 1.66 QSAR [3]
logPOW 2.44 method unknown, cited in: [3]
logDOW 1.63 (pH 7.4, 25 °C) [9]
logDOW 1.66 (phosphate buffer, pH 7.4, 25 °C) [10]
KOC ≤420 QSAR [3]
BCF <20 QSAR [3]
Lidocaine has low potential for bioaccumulation (log DOW <4 at pH 7.4).
Excretion/metabolism
Lidocaine is metabolized chiefly by the liver. Its major degradative pathway is conversion to monoethylglycinexylidide by oxidative N-deethylation followed by hydrolysis to 2,6-xylidine. Further conversion of 2,6-xylidine to 4-hydroxy-2,6-xylidine appears to occur in man, since the latter compound excreted in urine over a 24-hour period has accounted for over 70% of an orally administered dose of lidocaine. No more than 10% of the dose is excreted as parent lidocaine. [7]
References
1. F. Hoffmann-La Roche Ltd (2021): Environmental Risk Assessment Summary for Lidocaine. https://www.roche.com/sustainability/environment/environmental-risk-assessment-downloads.htm.
2. European Medicines Agency (EMA) (2006/2015): Guideline on the environmental risk assessment of medicinal products for human use. European Medicines Agency, Committee for Medicinal Products for Human Use (CHMP), 01 June 2006, EMA/CHMP/SWP/447/00 corr 2.
3. US Environmental Protection Agency, EPI (Estimation Programs Interface) Suite™ v4.11.
4. Neuwoehner J, Escher BI. 2011. The pH-dependent toxicity of basic pharmaceuticals in the green algae. Aquatic Toxicology 101:266-275.
5. Landesumweltamt Brandenburg (LUA). 2002. Ökotoxikologische Bewertung von Humanarzneimitteln in aquatischen Ökosystemen, Band 39, Studien und Tagungsberichte (ISSN 0948-0838).
6. Rúa-Gómez PC, Püttmann W. 2013. Degradation of lidocaine, tramadol, venlafaxine and the metabolites O-desmethyltramadol and O-desmethylvenlafaxine in surface waters. Chemosphere 90:1952–1959.
7. Collinsworth KA, Kalman SM, Harrison DC. 1974. The clinical pharmacology of lidocaine as an antiarrhythymic drug. Circulation. 50(6):1217-30.
8. Nałecz-Jawecki G, Persoone G. 2006. Toxicity of selected pharmaceuticals to the anostracan crustacean Thamnocephalus platyurus: comparison of sublethal and lethal effect levels with the 1h Rapidtoxkit and the 24h Thamnotoxkit microbiotests. Environ Sci Pollut Res Int. 13(1):22-7.
9. Strichartz GR, Sanchez V, Arthur GR, Chafetz R, Martin D. 1990. Fundamental properties of local anesthetics. II. Measured octanol:buffer partition coefficients and pKa values of clinically used drugs. Anesth Analg. 71(2):158-70.
10. Gröningsson K, Lindgren J-E, Lundberg E, Sandberg R, Wahlén A. 1985. Lidocaine Base and Hydrochloride. Analytical Profiles of Drug Substances. 14:207-243.
11. Lomba L, Ribate MP, Zuriaga E, García CB, Giner B. 2019. Acute and subacute effects of drugs in embryos of Danio rerio . QSAR grouping and modelling. Ecotoxicol Environ Saf. 172:232-239.