TY - JOUR

T1 - Transformation products in the water cycle and the unsolved problem of their proactive assessment

T2 - A combined in vitro/in silico approach

AU - Menz, Jakob

AU - Toolaram, Anju Priya

AU - Rastogi, Tushar

AU - Leder, Christoph

AU - Olsson, Oliver

AU - Kümmerer, Klaus

AU - Schneider, Mandy

N1 - Copyright © 2016 Elsevier Ltd. All rights reserved.

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Transformation products (TPs) emerging from incomplete degradation of micropollutants in aquatic systems can retain the biological activity of the parent compound, or may even possess new unexpected toxic properties. The chemical identities of these substances remain largely unknown, and consequently, the risks caused by their presence in the water cycle cannot be assessed thoroughly. In this study, a combined approach for the proactive identification of hazardous elements in the chemical structures of TPs, comprising analytical, bioanalytical and computational methods, was assessed by the example of the pharmaceutically active micropollutant propranolol (PPL). PPL was photo-transformed using ultraviolet (UV) irradiation and 115 newly formed TPs were monitored in the reaction mixtures by LC-MS analysis. The reaction mixtures were screened for emerging effects using a battery of in vitro bioassays and the occurrence of cytotoxic and mutagenic activities in bacteria was found to be significantly correlated with the occurrence of specific TPs during the treatment process. The follow-up analysis of structure-activity-relationships further illustrated that only small chemical transformations, such as the hydroxylation or the oxidative opening of an aromatic ring system, could substantially alter the biological effects of micropollutants in aquatic systems. In conclusion, more efforts should be made to prevent the occurrence and transformation of micropollutants in the water cycle and to identify the principal degradation pathways leading to their toxicological activation. With regard to the latter, the judicious combination of bioanalytical and computational tools represents an appealing approach that should be developed further.

AB - Transformation products (TPs) emerging from incomplete degradation of micropollutants in aquatic systems can retain the biological activity of the parent compound, or may even possess new unexpected toxic properties. The chemical identities of these substances remain largely unknown, and consequently, the risks caused by their presence in the water cycle cannot be assessed thoroughly. In this study, a combined approach for the proactive identification of hazardous elements in the chemical structures of TPs, comprising analytical, bioanalytical and computational methods, was assessed by the example of the pharmaceutically active micropollutant propranolol (PPL). PPL was photo-transformed using ultraviolet (UV) irradiation and 115 newly formed TPs were monitored in the reaction mixtures by LC-MS analysis. The reaction mixtures were screened for emerging effects using a battery of in vitro bioassays and the occurrence of cytotoxic and mutagenic activities in bacteria was found to be significantly correlated with the occurrence of specific TPs during the treatment process. The follow-up analysis of structure-activity-relationships further illustrated that only small chemical transformations, such as the hydroxylation or the oxidative opening of an aromatic ring system, could substantially alter the biological effects of micropollutants in aquatic systems. In conclusion, more efforts should be made to prevent the occurrence and transformation of micropollutants in the water cycle and to identify the principal degradation pathways leading to their toxicological activation. With regard to the latter, the judicious combination of bioanalytical and computational tools represents an appealing approach that should be developed further.

KW - Chemistry

KW - Bioactivity

KW - Biohazards

KW - Chemical analysis

KW - Computational methods

KW - Degradation

KW - Hazards

KW - Mixtures (Q)SAR

KW - Emerging contaminant

KW - Hazard Assessment

KW - Micropollutants

KW - Propranolol

KW - Micropollutant

KW - Hazard assessment

KW - Risk assessment

KW - (Q)SAR

UR - http://www.scopus.com/inward/record.url?scp=84998774671&partnerID=8YFLogxK

U2 - 10.1016/j.envint.2016.11.003

DO - 10.1016/j.envint.2016.11.003

M3 - Journal articles

C2 - 27855972

VL - 98

SP - 171

EP - 180

JO - Environmental international

JF - Environmental international

SN - 0160-4120

ER -