Toxicologic studies

An understanding of the role of toxicokinetics and toxicodynamics in the manifestation of hazard is fundamental to designing safer chemicals and can guide early design choices. Toxicokinetics and toxicodynamics use the same principles to study toxicological phenomena as those that are used to study the therapeutic use of chemicals as medicines. Toxicokinetics is concerned with the time course of action of chemicals that involves the disposition of a chemical affected by absorption, distribution, metabohsm and excretion commonly referred to by the acronym ADME. 

Cory-Slechta DA, Weiss B, Cox C. 1989. Tissue distribution of Pb in adult vs. old rats A pilot study. Toxicology 59 139-150. 

Ladies, G.S. et al., Possible incorporation of an immunotoxicological functional assay for assessing humoral immunity for hazard identification purposes in rats on standard toxicology study, Toxicology, 96, 225, 1995. 

Anonymous, Report of validation study of assessment of direct immunotoxicity in the rat. The ICICIS Group Investigators. International Collaborative Immunotoxicity Study, Toxicology, 125, 183, 1998. 

Van Loveren, H. et al., Immunotoxicological consequences of perinatal chemical exposures a plea for inclusion of immune parameters in reproduction studies, Toxicology, 185, 185, 2003. 

Singh A, Villeneuve DC, Bhatnagar MK, et al. 1982. Ultrastructure of the thyroid glands of rats fed photomirex An 18-month recovery study. Toxicology 23 309-319. 

Based on the view that the transition to external feeding is a critical step to independence, and that the stages before this step constitute an extension of embryonic development after hatching (the eleutheroembryo) [37], zebraflsh assays during the initial endotrophic nutritional period (0-120 hpf) are considered nonanimal based assays by Directive 86/609/EEC and 2010/63/EU. In the principle of 3Rs (reduce, refine, replace), it is important to have an animal model that meets these requirements to a maximum level and the zebraflsh eleutheroembryo is for all the aforementioned reasons an ideal candidate to study toxicology. 

Woutersen RA, Appleman LM, et al Inhalation toxicity of acetaldehyde in rats. III. Carcinogenicity study. Toxicology 41(2) 213-231, 1986... 

Germolec, D.R., Nyska, A., Kashon, M., Kuper, C.F., Portier, C., Kommineni, C., Johnson, K.A. and Luster, M.l. (2004) Extended histopathology in immunotoxicity testing interlaboratory validation studies. Toxicological Sciences, 78, 107-115. 

Van Loveren, H., Vohr, H.-W, Hartung, T. and Gribaldo, L. (2007) In vitro tests to evaluate immunotoxicily a preliminary study. Toxicology, 229, 11—22. 

Kaminski NE, Stevens WD. 1992. The role of metabolism in carbon tetrachloride-mediated immunosuppression, /r v/fro studies. Toxicology 75 175-188. 

Professional literature should be reviewed. Manuals of analytical methods ( 1,2) describe various sampling scenarios and considerations. Overview references (3) discussing processes similar to the one proposed for study may also be available. Professional publications e.g., The Journal of the American Industrial Hygiene Association, Journal of Occupational Medicine, may outline specific aspects of the process to be studied. Toxicological texts (4,.5,.6 7) provide information about potentially hazardous agents. These sources can provide information about the character of exposure, and their relative expected concentration or intensity, and methods previously used for detection, sampling and analysis. 

Timbrell JA. Study Toxicology Through Questions. London Taylor Francis, 1997. 

Kathryn E. Kelly received her doctorate in public health from Columbia University, with a concentration in environmental toxicology and the health effects of hazardous waste incineration. She also studied toxicology at the New York University Institute of Environmental Medicine. Dr. Kelly is the founder and president of three companies Delta Toxicology, Inc., Crystal Bay, Nevada Environmental Toxicology International, Seattle, Washington and Alden Analytical Laboratories, Seattle, Washington. She has broad experience in toxicology, waste combustion, environmental policy, and risk communication. 

Subakir SB, Setiadi E, Affandi B, Pringgoutomo S, Freisleben HJ. Benefits of vitamin E supplementation to Norplant users—in vitro and in vivo studies. Toxicology 2000 148(2-3) 173-8. 

Bernard, A.M. 1995. Biokinetics and stability aspects of biomarkers Recommendations for application in population studies. Toxicology 101(l-2) 65-71. 

Farber, T.M. (1987). Pesticide assessment guidelines, subdivision F, position document Selection of a maximum tolerated dose (MTD) in oncogenicity studies. Toxicology Branch, Hazard Evaluation Division, Office of Pesticides Programs, USEPA. NTIS PB88-116736. 

LaKind, J. S., Berlin, C. M. Jr., et al (2008) Lifestyle and polybrominated diphenyl ethers in human milk in the United States a pilot study. Toxicological and Environmental Chemistry, 90(6) 1047-1054. 

Although the present review focuses on the MULTICASE SAR methodology (3-5), the concepts discussed herein apply to all generally available SAR techniques used to study toxicological phenomena. Basically SAR approaches that have been used fall into two categories those that are based on statistical automated algorithms not dependent on prior expert judgment and those that are a priori... 

At that time, a full review of companies and institutions conducting non-clinical safety studies (toxicology) was undertaken by the FDA and although, in general, the industry was found to be credible, one company (Industrial Biotest) was found to be generating extremely poor-quality data, in many instances, in a fraudulent manner. This, therefore, caused the FDA to put together and implement the GLPs.[" ""l... 

Sondergaard D, Meyer O, Wurtzen G. Magnesium stearate given perorally to rats a short term study. Toxicology 1980 17 51-55. 

Lavenhar, S.R. and Maczka, C.A. (1985). Structure-Activity Considerations in Risk Assessment a Simulation Study. Toxicology Industrial Health, 1,249-259. 

Sinensky MC, Leiser AL Babich H (1995) Oxidative stress aspects of the cytotoxicity of carbamide peroxide in vitro studies. Toxicology Letters 15 101-109. 

Berry JP, Meignan M, Escaig F, and Galle P (1988) Inhaled soluble aerosols insolubilised by lysosomes of alveolar cells. Application to some toxic compounds electron microprobe and ion microprobe studies. Toxicology 14 127-139. 

Carfi M, Gennari A, Malerba I, Corsini E, Pallardy M, Pieters R et al (2007) In vitro tests to evaluate immunotoxicity a preliminary study. Toxicology 229 11-22... 

McGrath JP. 1993. Assessment of hemolytic and hemorrhagic anemias in preclinical safety assessment studies. Toxicologic Pathology 21(2) 158-163. 

Finlay, Mary F Benedict College, Columbia, SC Pilot study—Toxicological effects of PCB during spermatogenesis NCRR... 

Gilroy C, Connell BJ, Singh A, et al. 1998. PCB congener 77-induced ultrastructural alterations in the rat liver a quantitative study. Toxicology 127 179-185. 

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