Though the results suggest some benefits of smoking reduction, more evidence is needed. (C) 2013 The Author. Published by Elsevier Inc. All rights reserved.”
“Antibody drug conjugates (ADCs) include monoclonal antibodies that are linked to cytotoxic small molecules. A number of these agents are currently being developed
as anti-cancer agents designed to improve the therapeutic index of the cytotoxin (i.e., cytotoxic small molecule or cytotoxic agent) by specifically delivering it to tumor cells. This paper presents primary considerations for the nonclinical safety evaluation of ADCs and includes strategies for the evaluation of the entire ADC or the various individual components (i.e., antibody, linker or the cytotoxin). Considerations are presented on how to design a nonclinical safety assessment program to identify the on- and off-target toxicities GSK621 supplier to enable first-in-human (FIH) studies. Specific discussions are also included that provide Blasticidin S molecular weight details as to the need and how to conduct the studies for evaluating ADCs in genetic toxicology, tissue cross-reactivity, safety pharmacology, carcinogenicity, developmental and reproductive toxicology, biotransformation, toxicokinetic monitoring, bio-analytical assays, immunogenicity
testing, test article stability and the selection of the FIH dose. Given the complexity of these molecules and our evolving understanding of their properties, there is no single all-encompassing nonclinical strategy. Instead, each ADC should be evaluated on a case-by-case scientifically-based approach that is consistent with ICH and animal research guidelines. (C) 2013 Elsevier Inc. All rights reserved.”
“Neutral Methacrylate
Copolymer is a fully polymerised copolymer used in the pharmaceutical industry to permit EPZ015666 chemical structure pH-independent delayed release of active ingredients from oral dosage forms. This function has potential use with food supplements and this article describes available information on the safety of the substance.
Oral administration of radiolabelled copolymer to rats resulted in the detection of chemically unchanged copolymer in the faeces, with negligible absorption. Safety studies revealed no adverse toxicity following repeated administration at doses of up to 2000 mg/kg bw/d in a sub-chronic study in rats or 250 mg/kg bw/d in a sub-chronic study in dogs. No reproductive toxicity occurred at up to 2000 mg/kg bw/d in rats or rabbits. The substance shows no evidence of genotoxicity, has low acute toxicity and no irritation or sensitisation potential.
An ADI value of 20 mg/kg bw was concluded from two alternative approaches. Daily exposure from use in dietary supplements is estimated as up to 10.0 mg/kg bw in adults and 13.3 mg/kg bw in children. There would therefore appear to be no safety concerns under the intended conditions of use. The information provided is intended to support an evaluation that the substance may be “”generally recognized as safe”" (GRAS). (C) 2013 Elsevier Inc. All rights reserved.