title: Degradation and ecotoxicity of the biomedical drug artemisinin in soil.
abstract: The plant Artemisia annua L. is cropped in many countries for production of the antimalarial drug artemisinin. Artemisinin is phytotoxic and has insecticidal activity. Large-scale cultivation of A. annua may cause transfer of artemisinin to soil and, hence, may affect both soil organisms and the aquatic environment if the compound is leachable. In the present study, a new method for extraction of artemisinin from soil was developed, and field concentrations and degradation kinetics of artemisinin in sandy and loamy soils were measured. The soil concentrations in a Danish A. annua field were up to 11.7 mg/kg. The degradation kinetics could be modeled as the sum of two first-order reactions, a fast initial degradation followed by a reaction that was 11- to 25-fold slower. It took at least 35 d before artemisinin could not be detected (<0.36 mg/kg) at 20 degrees C, classifying artemisinin as being relatively persistent in the environment. Combined with its water solubility of 49.7 +/- 3.7 mg/L, this makes it potentially leachable. In soil, artemisinin repelled the earthworm (Eisenia fetida; the 10 and 50% effect concentrations [EC10s and EC50s, respectively] were 5.24 +/- 2.64 and 21.57 +/- 4.73 mg/kg, respectively) and inhibited growth of lettuce (Lactuca sativa L.; EC50, 2.48 mg/kg). Springtails (Folsomia candida) were not affected in the tested concentration range of 1 to 100 mg/kg. Artemisinin had toxicity to the freshwater algae (Pseudokirchneriella subcapitata; EC50, 0.24 +/- 0.01 mg/L) and duckweed (Lemna minor; EC50, 0.19 +/- 0.03 mg/L) similar to that of the commercial herbicide atrazine. Based on the presented data, the risks of adverse environmental effects because of cultivation of A. annua are high and comparable to those when using commercial pesticides.
authors.affiliation: University of Copenhagen, Department of Basic Sciences and Environment, Thorvaldsensvej, Frederiksberg C, Denmark. jessing@life.ku.dk
authors.forename: Karina K
authors.initials: KK
authors.lastname: Jessing
authors.forename: Nina
authors.initials: N
authors.lastname: Cedergreen
authors.forename: John
authors.initials: J
authors.lastname: Jensen
authors.forename: Hans C B
authors.initials: HC
authors.lastname: Hansen
mesh_terms: D000818:Animals; D029064:Araceae / Q000187:drug effects; D037621:Artemisinins / Q000032:analysis / Q000378:metabolism* / Q000633:toxicity*; D054750:Ecotoxicology / Q000379:methods*; D056890:Eukaryota / Q000187:drug effects; D007700:Kinetics; D018545:Lactuca / Q000187:drug effects; D008968:Molecular Conformation; D009835:Oligochaeta / Q000187:drug effects; D012987:Soil / Q000032:analysis*; D012989:Soil Pollutants / Q000032:analysis / Q000378:metabolism* / Q000633:toxicity*; D012995:Solubility; D013997:Time Factors; D018675:Toxicity Tests
chemical_list: D037621:Artemisinins; D012987:Soil; D012989:Soil Pollutants; C031327:artemisinin