Toxicity markers

This system has already been used to identify markers of prostate cancer and changes in renal cell carcinoma. It also has been applied to the discovery of new toxicity markers (Grizzle et al. 2004 Jr et al. 1999 Paweletz et al. 2001 Vlahou et al. 2001). Taking advantage of the recent development in SELDI and the... 

Ongoing progress in identifying new blood, urine, or other biofluid markers of toxicity - potentially assessable in current animal models - also provides optimism that such refinements will expand the translational usefulness of these preclinical studies.6-7 Recent examples of emerging or novel biomarkers that may become mainstream toxicity markers (as in research hospital clinical pathology assessments) are troponin markers for cardiac and skeletal muscle toxicity,32 and kidney biomarkers to delineate specific regional toxic effects in the renal tubule/parenchyma.33 Further development of these and similar assessable markers of toxicity will be pursued and usefully applied both pre-clinically and clinically. 

Lithium has also been used in the measurement of cardiac output, where it can act as a suitable non-toxic marker that is easily detected by an ion-selective electrode and that, in the time scale of the measurement (30 seconds), is not taken up into cells. ... 

Thome-Kromer B, Bonk I, Klatt M, et al. (2003). Toward the identification of liver toxicity markers A proteome study in human cell culture and rats. Proteomics. 3 1835-1862. 

Theravath TP, Czerny C, Ramshesh VK, Zhong Z, Chavin KD, Lemasters JJ (2008) C-Jun N-terminal kinase 2 promotes graft injury via the mitochondrial ptameability transitirai after mouse liver transplantation. Am J Transplant 8(9) 1819-1828 Thome-Kromer B, Bonk 1, Klatt M, Nebrich G, Taufinann M, Bryant S, Wacker U, Kopke A (2003) Toward the identification of liver toxicity markers a proteome study in human cell culture and rats. Proteomics 3(10) 1835-1862... 

While air Pb levels declined considerably in recent years, so did the threshold values for exposures and toxicity markers identified in sensitive subsets of human populations such as infants and toddlers. In fact, the scientific and health policy consensus growing in multiple deliberative settings is... 

FLUOROTRIAZINES Riag-fluoriaated triaziaes are used ia fiber-reactive dyes. Perfluoroalkyl triaziaes are offered commercially as mass spectral markers and have been iatensively evaluated for elastomer and hydraulic fluid appHcations. Physical properties of representative fluorotriaziaes are listed ia Table 13. Toxicity data are available. For cyanuric fluoride, LD g =3.1 ppm for 4 h (iahalatioa, rat) and 160 mg/kg (skin, rabbit) (127). 

Systemic treatment of 13-cis retinoic acid frequently leads to cheilitis and eye irritations (e.g., unspecific cornea inflammation). Also other symptoms such as headache, pruritus, alopecia, pains of joints and bone, and exostosis formation have been reported. Notably, an increase of very low density lipoproteins and triglycerides accompanied by a decrease of the high density lipoproteins has been reported in 10-20% of treated patients. Transiently, liver function markers can increase during oral retinoid therapy. Etretinate causes the side effects of 13-cis retinoid acid at lower doses. In addition to this, generalized edema and centrilobulary toxic liver cell necrosis have been observed. 

The first issue lies in the whole realm of the human disease process itself. Many adverse drug events mimic diseases and vice versa. Is an adverse event really an adverse event, or is it merely a natural occurrence of a disease process that is entirely independent of drug exposure The science of drug safety is often complicated by the lack of objective markers of drug toxicity that can systematically separate a disease process from an adverse drug event process [2]. Clinical trials, often viewed as the gold standard to assess efficacy, are simply too limited in scope to answer safety questions in a systematic way. 

Although this study (Hart 1980) did not identify an effect level, the NOAEL is below the LOEL found in all studies examining the toxicity of diisopropyl methylphosphonate. The LOEL for diisopropyl methylphosphonate is 262 mg/kg/day for male mink and 330 mg/kg/day for female mink (Bucci et al. 1997), doses at which statistically significant decreases in plasma cholinesterase (butyrylcholinesterase) but not RBC cholinesterase (acetylcholinesterase) activity were observed (Bucci et al. 1997). In general, a decrease in plasma cholinesterase activity is considered to be a marker of exposure rather than a marker of adverse effect, while a decrease in RBC acetylcholinesterase activity is a neurological effect thought to parallel the inhibition of brain acetylcholinesterase activity and is thus considered an adverse effect. Diisopropyl methylphosphonate was not found to inhibit red blood cell cholinesterase at doses at which plasma cholinesterase was significantly inhibited. No effects were observed in males at 45 mg/kg/day (Bucci et al. 1997) or at 63 mg/kg/day (Bucci et al. 1994), and no effects were observed in females at 82 mg/kg/day (Bucci et al. 1994), or at 57 mg/kg/day (Bucci et al. 1997). 

ATSDR. 1995. Multisite lead and cadmium exposure study with biological markers incorporated. Atlanta, GA U.S. Department of Health and Human Services, Public Health Service, Agency for Toxic Substances and Disease Registry. 

Hu H, Rabinowitz M, Smith D. 1998. Bone lead as a biological marker in epidemiologic studies of chronic toxicity conceptual paradigms. Environmental Health Perspectives 106(1) 1-8. 

Rininger JA et al. Differential gene expression technologies for identifying surrogate markers of dmg efficacy and toxicity. DDT 2000 5 560-568. 

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