TY - CHAP

T1 - Photodegradation of thalidomide: Identification of transformation products by LC-UV-FL-MS/MS, assessment of biodegradability, cytotoxicity and mutagenicity.

AU - Mahmoud, Waleed M. M.

AU - Toolaram, Anju Priya

AU - Schneider, Mandy

AU - Kümmerer, Klaus

N1 - Conference code: 4

PY - 2012

Y1 - 2012

N2 - The presence of pharmaceuticals in the environment has become an important emerging environmental issue. The ecological impacts, possible human health effects, and potential risks associated with releases of pharmaceuticals into the environment have become an increasingly important issue for scientists, the public, and environmental regulators. In 1998, Thalidomide (TD), notorious for its teratogenicity, was approved by the FDA for the treatment of erythema nodusum leprosum associated with leprosy. Recently, TD is a promising drug in the treatment of a number of cancers and inflammatory diseases [1]. Consequently, a potential increased influx of TD into the environment makes it imperative to assess the fate of TD and its possible degradation products. In this study the behavior of TD was monitored during photoirradiation using medium-pressure Hg-lamp in different reactors. Biodegradation of TD and its phototreaction products was assessed in Closed Bottle Test (CBT). Cytotoxicity and Mutagenicity of TD and photodegradation products (after 2, 4, 8, 16 and 32 min of irradiation) were done with Salmonella typhimurium strains TA 98, and TA 100 in the Ames MPF with and without metabolic activation.The primary elimination of TD was monitored and structures of photodegradation products (PPs) were assessed by LC-UV-FL-MS/MS. New PPs were formed of which two were isomers of TD with the same molecular mass. Further, TD and its PPs were neither readily biodegradable in CBT nor exhibited cytotoxic nor mutagenic activities at the highest tested concentration of 50 mg/L. Additional toxicity studies with other endpoints (bacterial toxicity, genotoxicity) and structure-activity relationship will be applied for the further characterization of the environmental and human risks connected with the presence TD and its PPs in the environment. References[1]M. E. Bosch, A. R. Sánchez, F. S. Rojas, C. B. Ojeda. Journal of Pharmaceutical and Biomedical Analysis 2008, 46 (1), 9.

AB - The presence of pharmaceuticals in the environment has become an important emerging environmental issue. The ecological impacts, possible human health effects, and potential risks associated with releases of pharmaceuticals into the environment have become an increasingly important issue for scientists, the public, and environmental regulators. In 1998, Thalidomide (TD), notorious for its teratogenicity, was approved by the FDA for the treatment of erythema nodusum leprosum associated with leprosy. Recently, TD is a promising drug in the treatment of a number of cancers and inflammatory diseases [1]. Consequently, a potential increased influx of TD into the environment makes it imperative to assess the fate of TD and its possible degradation products. In this study the behavior of TD was monitored during photoirradiation using medium-pressure Hg-lamp in different reactors. Biodegradation of TD and its phototreaction products was assessed in Closed Bottle Test (CBT). Cytotoxicity and Mutagenicity of TD and photodegradation products (after 2, 4, 8, 16 and 32 min of irradiation) were done with Salmonella typhimurium strains TA 98, and TA 100 in the Ames MPF with and without metabolic activation.The primary elimination of TD was monitored and structures of photodegradation products (PPs) were assessed by LC-UV-FL-MS/MS. New PPs were formed of which two were isomers of TD with the same molecular mass. Further, TD and its PPs were neither readily biodegradable in CBT nor exhibited cytotoxic nor mutagenic activities at the highest tested concentration of 50 mg/L. Additional toxicity studies with other endpoints (bacterial toxicity, genotoxicity) and structure-activity relationship will be applied for the further characterization of the environmental and human risks connected with the presence TD and its PPs in the environment. References[1]M. E. Bosch, A. R. Sánchez, F. S. Rojas, C. B. Ojeda. Journal of Pharmaceutical and Biomedical Analysis 2008, 46 (1), 9.

KW - Chemistry

KW - Pharmaceuticals

KW - Environment

KW - Transformation products

KW - UV treatment

KW - Toxicity

UR - http://www.chemicke-listy.cz/common/content-issue_s4-volume_106-year_2012.html

M3 - Published abstract in conference proceedings

VL - 106

T3 - Chemické listy

SP - 650

BT - 4th EuCheMS Chemistry Congress

PB - Association of Czech Chemical Societies

T2 - 4th Congress of the European Association for Chemical and Molecular Sciences- EuCheMS 2012

Y2 - 26 August 2012 through 30 August 2012

ER -