TY - CHAP

T1 - Using (Quantitative) Structure-Activity Relationships in Pharmaceutical Risk Assessment

AU - Kümmerer, Klaus

PY - 2004/1/1

Y1 - 2004/1/1

N2 - Sound risk assessment depends on the availability of sufficient good quality data. To remove the shortcomings of experimental testing, for some time, attempts have been made to reduce the amount of money and time it requires. One option is to correlate the structure of a chemical or parts of its structure with a certain activity or with physicochemical properties (structure-activity relationship = SAR). Computer based expert systems are used for this purpose (“in silico testing”). Such an approach has a comparatively long tradition in the development of new drugs and is an important tool in the drug development process (Kellogg and Semus 2003; Cronin 2003). These systems are used for screening drugs and other chemicals for unwanted side effects (Polloth and Mangelsdorff 1997) and for predicting the physicochemical properties of new compounds such as water solubility and K ow. In the meantime, SAR has become an increasingly important tool in the regulatory process and has now reached the stage where some regulatory agencies such as the US Environmental Protection Agency routinely use QSAR-predicted toxicities as well as environmentally important properties for regulatory purposes (e.g. with the software suite EPISUITE (EPA 2001) which can be downloaded free of charge from the US EPA homepage). It is anticipated that such use will increase in future. The EU will probably accord QSARs greater prominence in the new technical guidance documents which form the basis for risk assessment. There is a good deal of literature describing the application and evaluation of QSAR software in ecotoxicology (for a overview: ECETOC 1998; ECVAM 1997; Boethling and Mackay 2000; Dearden 2002).

AB - Sound risk assessment depends on the availability of sufficient good quality data. To remove the shortcomings of experimental testing, for some time, attempts have been made to reduce the amount of money and time it requires. One option is to correlate the structure of a chemical or parts of its structure with a certain activity or with physicochemical properties (structure-activity relationship = SAR). Computer based expert systems are used for this purpose (“in silico testing”). Such an approach has a comparatively long tradition in the development of new drugs and is an important tool in the drug development process (Kellogg and Semus 2003; Cronin 2003). These systems are used for screening drugs and other chemicals for unwanted side effects (Polloth and Mangelsdorff 1997) and for predicting the physicochemical properties of new compounds such as water solubility and K ow. In the meantime, SAR has become an increasingly important tool in the regulatory process and has now reached the stage where some regulatory agencies such as the US Environmental Protection Agency routinely use QSAR-predicted toxicities as well as environmentally important properties for regulatory purposes (e.g. with the software suite EPISUITE (EPA 2001) which can be downloaded free of charge from the US EPA homepage). It is anticipated that such use will increase in future. The EU will probably accord QSARs greater prominence in the new technical guidance documents which form the basis for risk assessment. There is a good deal of literature describing the application and evaluation of QSAR software in ecotoxicology (for a overview: ECETOC 1998; ECVAM 1997; Boethling and Mackay 2000; Dearden 2002).

KW - Chemistry

KW - Quantitative Structure Activity Relationship Model

KW - Quantitative Structure Property Relationship

KW - Drug Development Process

KW - Anaerobic Biodegradation

KW - Aerobic Biodegradation

UR - https://www.mendeley.com/catalogue/50796acb-d4bc-37b6-9895-0b6223b0c7af/

U2 - 10.1007/978-3-662-09259-0_28

DO - 10.1007/978-3-662-09259-0_28

M3 - Contributions to collected editions/anthologies

SN - 3-540-21342-2

SN - 978-3-662-09261-3

SP - 387

EP - 390

BT - Pharmaceuticals in the Environment

A2 - Kümmerer, Klaus

PB - Springer

CY - Berlin

ER -