Miljöpåverkan (Läs mer om miljöpåverkan)
Zolpidem
Miljörisk:
Användning av zolpidem har bedömts medföra försumbar risk för miljöpåverkan.
Nedbrytning:
Zolpidem är potentiellt persistent.
Bioackumulering:
Zolpidem har låg potential att bioackumuleras.
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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) = 1.5*10-6*A*(100-R)
PEC = 0.06 µg/L
Where:
A = 403.154 kg (total sold amount API in Sweden year 2016, data from QuintilesIMS)
R = 0% removal rate (due to loss by adsorption to sludge particles, by volatilization, hydrolysis or biodegradation)
P = number of inhabitants in Sweden = 9×106
V (L/day) = volume of wastewater per capita and day = 200 (ECHA default) (Ref I)
D = factor of dilution of waste water by surface water flow = 10 (ECHA default) (Ref I)
Predicted No Effect Concentration (PNEC)
Ecotoxicological studies
Algae (Selenastrum capricornutum):
EC50 96 h (growth rate) = 2200 μg/L
NOEC = 320 μg/L
(OECD 201) (Ref II))
Crustacean (Daphnia magna):
EC50 48 h (immobilization): 120 000 μg/L
NOEC 48 h (immobilization): 16 000 μg/L
(OECD 202) (Ref III)
Fish (Oncorhyncus mykiss):
EC50 96 h (mortality): 22 000 μg/L
NOEC 96 h (mortality): 6200 μg/L
(OECD 203) (Ref IV)
Other ecotoxicity data:
PNEC = 2.2 µg/L
The PNEC (μg/L) = lowest EC50/1000 was calculated using results from the most sensitive acute toxicity endpoint and an assessment factor of 1000 at least one short-term result from each of the three trophic levels), to add a safety margin to the toxicity endpoint. The most sensitive species was algae Selenastrum capricornutum for which the EC50 was 2200 μg/L.
Environmental Risk Classification (PEC/PNEC ratio)
PEC/PNEC= 0.06 / 2.2 = 0.03, i.e. PEC/PNEC ≤ 0.1 which justifies the phrase "Use of zolpidem has been considered to result in insignificant environmental risk".
Biodegradation
Ready biodegradability:
Test showed 30 % degradation in 28 days (OECD 301) (Ref V)
Justification of chosen degradation phrase:
Zolpidem fails to pass the criteria for ready and inherent biodegradability. The phrase: "Zolpidem is potentially persistent” is thus chosen.
Bioaccumulation
Partition coefficient:
Log Pow =1.2 at neutral pH (estimated) (Ref VI)
Justification of chosen bioaccumulation phrase:
Since log Pow < 4 at pH 7, zolpidem has low potential for bioaccumulation.
Excretion (metabolism)
Zolpidem is extensively metabolized to three major metabolites, with less than 1% of the parent drug excreted unchanged (Ref VII) (Ref VIII). Three major metabolites have been found in humans, but none appears to be pharmacologically active (Ref VIII).
References
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ECHA, European Chemicals Agency, 2008 Guidance on information requirements and chemical safety assessment. https://echa.europa.eu/guidance-documents/guidance-on-information-requirements-and-chemical-safety-assessment
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Sanofi, Internal Report: Zolpidem-Toxicity to the freshwater green alga Selenastrum capricornutum. OECD 201. Report # 91-1-3604, February 1991
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Sanofi, Internal Report: Zolpidem-Acute toxicity to daphnids (Daphnia magna). OECD 202. Report # 90-12-3594, February 1991
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Sanofi, Internal Report: Zolpidem-Acute toxicity to Rainbow Trout (Oncorhyncus mykiss). OECD 203. Report # 90-12-3599, February 1991
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Sanofi, Internal Report: Zolpidem-Ready biodegradability by the closed bottle method. OECD 301D. Report # 90-12-3591, February 1991
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Source Drugbank, assessed as of Sep 11, 2018 http://www.drugbank.ca/drugs/DB00425
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Hempel, G. and Blaschke, G., 1996. Direct determination of zolpidem and its main metabolites in urine using capillary electrophoresis with laser-induced fluorescence detection. Journal of Chromatography B. 675, 131-137.
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Chouinard, G., Lefko-Singh, K., Teboul, E., 1999. Metabolism of anxiolytics and hypnotics: Benzodiazepines, Buspirone, Zopiclone and Zolpidem. Cellular and Molecular Neurobiology. 19, 533-552.