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.
Recently, we showed for the wastewater of a large Swiss university hospital that primary DNA damage, assessed by a bacterial SOS repair assay (umuC test), could be largely assigned to a specific class of antibiotics, the fluoroquinolones (FQs) (Hartmann et al. [1998] Environ Toxicol Chem 17:377-382). In an attempt to confirm the significance of FQs for the bacterial DNA damaging effects in native hospital wastewaters, 25 samples from five German clinics were screened in this study by the umuC test. The results were compared to HPLC-derived concentrations of ciprofloxacin, an important member of the FQs. Ten samples (40%) were umuC-positive and ciprofloxacin concentrations ranged from 0.7 to 124.5 microg/L (n = 24). Primary DNA damage, as indicated by the umuC test, correlated strongly with ciprofloxacin concentrations in a logistic, dose-dependent manner (r2 = 0.896), almost irrespective of the use of S9 metabolic activation. The lowest observed effect concentration (LOEC) for ciprofloxacin was 5.2 microg/L (+S9) and 5.9 microg/L (-S9). Similar to our previous findings, these results indicate that positive umuC results in hospital wastewater are strongly dependent on the presence of fluoroquinolone antibiotics. In a second part of the study, previously generated Ames and V79 chromosomal aberration data of the same samples (Gartiser and Brinker [1995] in Umweltbundesamt Texte 74/95) were compared with the newly generated results. Neither the mutagenic effects detected by the Ames assay (8%, n = 25) nor the positive V79 results (46% n = 13) seemed to be caused by ciprofloxacin. Therefore, the Ames and V79 results suggest the presence of additional mutagens that are yet to be identified.
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