TY - JOUR

T1 - Initial hazard screening for genotoxicity of photo-transformation products of ciprofloxacin by applying a combination of experimental and in-silico testing

AU - Toolaram, Anju Priya

AU - Haddad, Tarek

AU - Leder, Christoph

AU - Kümmerer, Klaus

N1 - Copyright © 2015 Elsevier Ltd. All rights reserved.

PY - 2016/4/1

Y1 - 2016/4/1

N2 - Ciprofloxacin (CIP) is a broad-spectrum antibiotic found within μg/L concentration range in the aquatic environment. It is a known contributor of umuC induction in hospital wastewater samples. CIP can undergo photolysis to result in many transformation products (TPs) of mostly unknown toxicity. The aims of this study were to determine the genotoxicity of the UV mixtures and to understand the possible genotoxic role of the stable TPs. As such, CIP and its UV-irradiated mixtures were investigated in a battery of genotoxicity and cytotoxicity in vitro assays. The combination index (CI) analysis of residual CIP in the irradiated mixtures was performed for the umu assay. Further, Quantitative Structure-Activity Relationships (QSARs) predicted selected genotoxicity endpoints of the identified TPs. CIP achieved primary elimination after 128 min of irradiation but was not completely mineralized. Nine photo-TPs were identified. The irradiated mixtures were neither mutagenic in the Ames test nor genotoxic in the in vitro micronucleus (MN) test. Like CIP, the irradiated mixtures were umuC inducing. The CI analysis revealed that the irradiated mixtures and the corresponding CIP concentration in the mixtures shared similar umuC potentials. QSAR predictions suggested that the TPs may be capable of inducing chromosome aberration, MN in vivo, bacterial mutation and mammalian mutation. However, the experimental testing for a few genotoxic endpoints did not show significant genotoxic activity for the TPs present as a component of the whole mixture analysis and therefore, further genotoxic endpoints may need to be investigated to fully confirm this.

AB - Ciprofloxacin (CIP) is a broad-spectrum antibiotic found within μg/L concentration range in the aquatic environment. It is a known contributor of umuC induction in hospital wastewater samples. CIP can undergo photolysis to result in many transformation products (TPs) of mostly unknown toxicity. The aims of this study were to determine the genotoxicity of the UV mixtures and to understand the possible genotoxic role of the stable TPs. As such, CIP and its UV-irradiated mixtures were investigated in a battery of genotoxicity and cytotoxicity in vitro assays. The combination index (CI) analysis of residual CIP in the irradiated mixtures was performed for the umu assay. Further, Quantitative Structure-Activity Relationships (QSARs) predicted selected genotoxicity endpoints of the identified TPs. CIP achieved primary elimination after 128 min of irradiation but was not completely mineralized. Nine photo-TPs were identified. The irradiated mixtures were neither mutagenic in the Ames test nor genotoxic in the in vitro micronucleus (MN) test. Like CIP, the irradiated mixtures were umuC inducing. The CI analysis revealed that the irradiated mixtures and the corresponding CIP concentration in the mixtures shared similar umuC potentials. QSAR predictions suggested that the TPs may be capable of inducing chromosome aberration, MN in vivo, bacterial mutation and mammalian mutation. However, the experimental testing for a few genotoxic endpoints did not show significant genotoxic activity for the TPs present as a component of the whole mixture analysis and therefore, further genotoxic endpoints may need to be investigated to fully confirm this.

KW - Chemistry

KW - Combination index analysis

KW - Effect based analysis

KW - Fluoroquinolones

KW - UV photolysis

KW - Whole mixture genotoxicity

UR - http://www.scopus.com/inward/record.url?scp=84961689476&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/b11df2c5-076f-3be6-9a9e-68310aebaff5/

U2 - 10.1016/j.envpol.2015.12.040

DO - 10.1016/j.envpol.2015.12.040

M3 - Journal articles

C2 - 26748250

VL - 211

SP - 148

EP - 156

JO - Environmental Pollution

JF - Environmental Pollution

SN - 0269-7491

ER -