IDENTIFICATION OF FLUOROQUINOLONE ANTIBIOTICS AS THE MAIN SOURCE OF umuC GENOTOXICITY IN NATIVE HOSPITAL WASTEWATER

Abstract

Abstract-Previous work revealed genotoxic effects in the wastewater of a large university hospital using a bacterial short-term genotoxicity assay, based on a umuC::lacZ fusion gene (umuC assay). These studies ruled out disinfectants and detergents as main causative agents of the genotoxic effects. This paper focuses on specific hospital-related drugs as the cause. The ratio of theoretical mean wastewater concentrations (derived from consumption data) and lowest observable effect concentrations of selected pharmaceuticals were used to calculate umuC induction probabilities. The fluoroquinolone antibiotics Ciproxin and Noroxin showed the highest induction probabilities and exceeded all other investigated drugs by at least one order of magnitude in significance. Antineoplastic drugs, originally thought to be the main effectors, were found to be of marginal significance using the umuC assay. These findings were further supported by investigation of urine samples of hospital patients with the umuC assay. The determination of ciprofloxacin in native hospital wastewater by reversed-phase high-performance liquid chromatography and fluorescence detection revealed concentrations from 3 to 87 g/L. umuC induction factor and ciprofloxacin concentrations in 16 hospital wastewater samples showed a log-linear correlation (r 2 ϭ 0.84, p Ͻ 0.0001). These results suggest that the previously measured umuC genotoxicity in the wastewater of the hospital under investigation is caused mainly by fluoroquinolone antibiotics, especially by ciprofloxacin. On the basis of these findings, the role of the umuC assay as a screening tool for wastewater genotoxicity assessment is discussed.

Assessing of genotoxicity of 16 centralized source-waters in China by means of the SOS/umu assay and the micronucleus test: Initial identification of the potential genotoxicants by use of a GC/MS method and the QSAR Toolbox 3.0

“…Several DNAdamaging agents, such as fluoroquinolone (FQ) antibiotics and nitroarenes, were identified as major mutagens in waters by combination of the SOS/umu test as a genotoxicity bioassay and HPLC as a fractionation method. Hartmann et al [19] used HPLC coupled with fluorescence detection to quantify fluoroquinolone antibiotics, and found one major DNA-damaging agent (ciprofloxacin) in the wastewater of a hospital in Switzerland. Ma et al [12] used S. typhimurium strain TA1535/pSK100 and the O-acetyltransferaseoverexpressing strain NM 2009 in different fractions of river waters in the Jialu River basin, China, and found that flumequine and a MN ratio significantly increased compared with concurrent solvent control (one-way ANOVA, p < 0.05).…”

“…A causal relationship has been established between genotoxic effects and potential genotoxicants in native hospital wastewater [19] and ground waters [12]. However, due to the existence of various chemical contaminants at low concentrations in source waters and the lack of data on genotoxicity of many pollutants, identifying the chemical responsible for genotoxicity is not an easy task with respect to source waters.…”

Genotoxicity of quinolones: Substituents contribution and transformation products QSAR evaluation using 2D and 3D models

“…It was reported that the cyanobacterium (Microcystis aeruginosa) and duckweed (Lemna minor) were quite sensitive to fluoroquinolones, the median effective concentrations (EC 50 ) of levofloxacin for 5-d growth reproduction of M. aeruginosa and 7-d reproduction of L. minor were 7.9 and 51 lg/L, respectively (Robinson et al, 2005;Ebert et al, 2011). Most of quinolones exhibited mutagenicity to bacteria (Mamber et al, 1993), and a large proportion of hospital sewages containing quinolone-like antibiotics induced bacterial genotoxicity (Hartmann et al, 1998). In addition, it was reported that more than 70% of bacteria had become insensitive against at least one antibiotic and exhibited multiple resistance patterns (Hirsch et al, 1999), and the antibiotic resistance of bacteria has become a serious issue.…”

Acute toxicity evaluation for quinolone antibiotics and their chlorination disinfection processes

“…For example, eight quinolones were the prominent contaminants in sediments and aquatic plants of the Baiyangdian Lake, China, with the concentrations of 65.5-1166 and 8.37-6532 μg/kg, respectively . Ciprofloxacin, one of the most commercial quinolones, was found in Switzerland hospital effluents as high as 89 μg/L (Hartmann et al, 1998). It was reported that ciprofloxacin and enrofloxacin were not readily biodegradable by sewage sludge organism (Ebert et al, 2011).…”

“…Hu et al (2007) investigated genotoxicity potential of 20 quinolones by umuC bioassay; the result indicated that all the tested compounds showed high toxicity with 10% of the maximum response concentration (EC 10 ) ranged from 0.61 to 2917 nmol/L. In addition, it was reported that genotoxicity in the wastewater of the hospital was mainly caused by quinolone antibiotics (Hartmann et al, 1998). The removal of those compounds in sewage treatment plants is a complex issue, and their toxicity patterns are flexible under various treatment processes, such as ozonation, UV photolysis and chlorination disinfection.…”