Assessment bone cells

As an example, the appropriate sequence of studies for the development of a new biodegradable bone regeneration material might be (1) biomaterial synthesis and structural characterization (2) scaffold fabrication and measurements of mechanical and degradation properties in vitro (3) biocompatibihty and bone formation assessed by cell culture in vitro (4) biocompatibihty and degradation of the material in vivo, typically by subcutaneous implantation in a lower-level animal model such as a rat, (5) if no significant toxic effect is observed, the material is then evaluated for its intended appKcation such as an appropriate bone defect model in a higher-level animal such as a rabbit (6) if the material functions well... 

Hematology. The functional status of blood and of the blood-forming tissues can be assessed by tests which include red and white blood cell counts, platelet counts, clotting time, coagulation tests, and examination of bone marrow. Such tests, in addition to detecting abnormahties, may also allow differentiation between primary and secondary effects on blood and blood-forming tissues (75). 

Gao and Yamaguchi, 1999b Mouse bone marrow cells cultured for 7 d with bone resorbing factors (PTH, PGE2, EPS) +/- genistein osteoclast formation assessed by TRAP enzyme Genistein (10 Yi0 M) inhibited osteoclast formation. Mechanism may involve cAMP signalling. 

The absorption efficiency term allows estimation of the effective dose or the amount of pollutant which crosses the membrane of the exposed tissue (e.g., the lung) and reaches a target organ (e.g., the liver). For many pollutants this type of metabolic data is not available and consequently 100% absorption is a common preliminary assumption in exposure assessments. For well-studied substances such as radionuclides, a methodology for calculation of target organ doses has been developed for bone marrow, lungs, endosteal cells, stomach wall, lower intestine wall, thyroid, liver, kidney, testes and ovaries as well as for the total body. 

The O Flaherty Model simulates the age-dependence of lead kinetics on such factors as absorption efficiency, excretion efficiency, uptake into bone and loss from bone, and partitioning between plasma and red blood cells. The model does not incorporate age, dose rate, or time dependence of lead accumulation in every organ (e g., kidney) because the complex patterns of lead accumulation in certain tissues are not known (O Flaherty 1991a) (see Section 2.4.1). However, the basic model structure allows for additional modules to be incorporated, depending on its intended use in risk assessment. For example, additional modules that are currently being developed are a pregnancy model and a model of net bone loss in older women and men. 

Flow cytometry is now commonly used in immunotoxicity studies to assess changes in relative frequency and number of lymphoid and myeloid cells in the spleen, lymph nodes, bone marrow and/or peripheral blood of rodents, and in the peripheral blood of humans. A list of selected cell surface markers useful in immunotoxicity studies is shown in Table 7.3. Notably, the majority of available reagents are specific for murine antigens with human reagent availability a close second. Reagents for rat, primate, and... 

A reduction in total white blood cell counts to 60% of control values (p<0.05), but no changes in differential white cell counts or evidence of bone marrow damage, was found in rats intermittently exposed to 700 ppm 2-hexanone after 8 weeks during an 11-week study (Katz et al. 1980). These findings, although inconclusive, suggest that immunological effects may warrant some consideration in future assessments of the potential toxicity of inhalation exposure to 2-hexanone. 

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