The effect of chloroquine, quinacrine, and metronidazole on both soybean plants and soil microbiota
Introduction
The fate of medical and metabolic effects of antimicrobial agents on humans and animals has been widely researched. However, limited assessment of the environmental risks involved in exposing the medical substances to the environment has been conducted. A variety of these medical agents may pass through the systems of the target organisms, spreading into the environment (Halling-Sørensen et al., 1998). Once in the environment, these compounds may persist for some duration depending on the chemical structure, temperature, and a variety of environmental factors (Gavalchin and Katz, 1994). Chloroquine, metronidazole and quinacrine are extensively used therapeutically against protozoa infections such as Giardia sp., Plasmodium sp., Trichomonas sp., and in the case of metronidazole, against some anaerobic bacteria pathogens. Anti-protozoan agents and their metabolites have been detected in urine and feces of patients in therapeutic treatment (Connor et al., 1977; Maschke et al., 1997), a major route through which they can be exposed to the environment where their fate and effects remain unknown. There is a need for ecotoxicological evaluation of drugs (Lanzky and Halling-Sørensen, 1997).
Some anti-microbial compounds negatively affected the growth and development of plants, the effect varying between plant species (Batchelder, 1981, Batchelder, 1982). Information about how chloroquine, metronidazole and quinacrine might affect the soil biota and plants is lacking. These compounds can be introduced into soil when manure, wastewater, and treated sludge are applied to agricultural fields. The biodegradability of these compounds during the waste treatment process is unknown (Lanzky and Halling-Sørensen, 1997). Since chloroquine, metronidazole and quinacrine are designed to control protozoa in humans and other animals, they are likely to be potentially hazardous to protozoa in soil when manure, sludge or wastewater that contains their residues is applied to soil. Thus, it is likely that soil protozoa would serve as a reasonable bio-indicator of the effects of any of these compounds on the environment.
Considering the wide use of these compounds for therapeutic reasons and in veterinary medicine (Halling-Sørensen et al., 1998; Spikes, 1998; Sørensen and Hansen, 2000), it is necessary to accumulate information about their potential effects on soil microorganisms and plants. Preliminary studies were conducted to determine the potential effects of chloroquine, metronidazole and quinacrine on both soil microbiota (bacteria and protozoa) and on soybean (Glycine max) plants.
Section snippets
Anti-microbial agents
Chloroquine, metronidazole and quinacrine dihydrochloride were obtained from Sigma Chemical Company, St. Louis, Missouri, USA. The molecular structures are shown in Fig. 1. All of the compounds are readily soluble in water. Prior to use, stock solutions of chloroquine, quinacrine dihydrochloride and metronidazole were prepared by dissolving 60, 20 and 7.5 mg ml−1, respectively, in deionized water.
Soil
A sample of Palmyra gravelly silt loam (pH 6.6% and 4.9% organic matter) was collected from the top
Effectiveness of the test compounds
In the absence of an anti-protozoan compound, T. pyriformis populations attained a population of in axenic culture after 20 h (Fig. 2). However, with increasing concentrations of chloroquine or metronidazole, these T. pyriformis decreased. As much as 32 mg chloroquine ml−1 were required to dramatically decrease the protozoa populations to below the detection limit of 1×104 protozoa ml−1 in less than 18 h. A metronidazole concentration of 5.7 mg ml−1 depressed the numbers of T.
Discussion
The soybean plants were sensitive to all of the three anti-microbial agents tested but the sensitivity greatly differed between compounds. Most detrimental to the soybean plants is metronidazole since concentrations as low as 0.5 mg metronidazole g−1 soil adversely affected the plants. Metronidazole is weakly adsorbed to soils (Rablølle and Spliid, 2000) and this could have enabled most of the added compound to remain in the soil solution, making it readily available for uptake by the plants.
Acknowledgements
This study was funded by the Cornell International Institute for Food and Agricultural Development (CIIFAD) at Cornell University and the Uganda National Agricultural Research Organization. UMR147 and T. pyriformis B2082 II were provided by Dr. Peter Graham (Rhizobium Research Laboratory at the University of Minnesota) and Dr. P.J. Bruns (Cornell University), respectively.
Patrick K. Jjemba holds a Master's degree in Soil Science and a Ph.D. in Soil Microbiology. He is currently a Director of Laboratory at Environmental Associates Ltd. in Ithaca, NY.
References (28)
- et al.
Kinetics of subcellular distribution of multiply ionizable compounds: a mathematical description and its use in QSAR
Journal of Theoretical Biology
(1996) - et al.
Toxicity of mono-, di- and tri-chlorophenols to lux marked terrestrial bacteria, Burkholderia species Rasc c2 and Pseudomonas fluorescens
Chemosphere
(2001) - et al.
Structure–toxicity relationships for phenols to Tetrahymena pyriformis
Chemosphere
(1996) - et al.
Notes on protozoa in agricultural soil with emphasis on heterotrophic flagellates and naked amoebae and their ecology
FEMS Microbiology Review
(1994) - et al.
Occurrence, fate and effects of pharmaceutical substances in the environment – a review
Chemosphere
(1998) - et al.
Possible determinants of rhizosphere competence of bacteria
Soil Biology and Biochemistry
(1999) - et al.
Biodegradability of some antibiotics, elimination of the genotoxicity and affection of wastewater bacteria in a simple test
Chemosphere
(2000) - et al.
Sorption and mobility of metronidazole, oloquindox, oxytertacycline and tylosin in soil
Chemosphere
(2000) Photosensitizing properties of quinine and synthetic antimalarials
Journal of Photochemistry and Photobiology B: Biology
(1998)Chlorotetracycline and oxytetracycline effects on plant growth and development in liquid culture
Journal of Environmental Quality
(1981)
Chlorotetracycline and oxytetracycline effects on plant growth and development in soil systems
Journal of Environmental Quality
The contribution of metronidazole and two metabolites to the mutagenic activity detected in urine of treated humans and mice
Cancer Research
The persistence of feacal-borne antibiotics in soil
Journal of AOAC International
Antiprotozoal drugs
Cited by (55)
Tracing COVID-19 drugs in the environment: Are we focusing on the right environmental compartment?
2023, Environmental PollutionEnvironmental impacts of COVID-19 treatment: Toxicological evaluation of azithromycin and hydroxychloroquine in adult zebrafish
2021, Science of the Total EnvironmentA critical review on environmental presence of pharmaceutical drugs tested for the covid-19 treatment
2021, Process Safety and Environmental ProtectionCitation Excerpt :One of the major concerns expressed by the authors is that the presence of this drug in drinking water causes the drug to lose its therapeutic efficiency and leads bacteria to develop natural resistance to it. Jjemba (2002) reports a study on the effects of three antimicrobial agents on the soil, where soybean planting was later carried out. Their results show that a low amount of CQ (2−4 mg g−1 of soil) caused most of the seeds to germinate normally, however, when the dosage was increased (8−16 mg g−1 of soil), the dosage had become lethal, causing some plants to have stunted development, or to not develop after 13 days of planting.
Reclaimed wastewater as a viable water source for agricultural irrigation: A review of food crop growth inhibition and promotion in the context of environmental change
2020, Science of the Total EnvironmentCitation Excerpt :Aqueous LOAECs ranged from 10−7 g/L water (ethinyl estradiol exposure reduced lettuce germination rate by 8% (D'Abrosca et al. 2008)) to 1 g/L (acetaminophen reduced grain weight of maize ~36% (Hammad et al. 2018)). Soil LOAECs ranged from 10−3 g/kg soil [carrot and lettuce exposed to oxytetracycline had a slight decrease in plant weight (Boxall et al. 2006) and zucchini exposed to carbamazepine had a ~45% decrease in root dry weight (Carter et al. 2015)] to 10 g/kg [soybean exposed to quinacrine, decrease also not quantified (Jjemba 2002a)]. Several xenobiotics did not affect specific crops even at very high exposure concentrations.
Patrick K. Jjemba holds a Master's degree in Soil Science and a Ph.D. in Soil Microbiology. He is currently a Director of Laboratory at Environmental Associates Ltd. in Ithaca, NY.