Toxicology cellular studies

Hecdth effects data come from three types of studies clinical, epidemiological, and toxicological. Clinical and epidemiological studies focus on human subjects, whereas toxicological studies are conducted on animals or simpler cellular systems. Ethical considerations limit human exposure to low levels of air poUutants which do not have irreversible effects. Table 7-1 lists the advantages and disadvantages of each type of experimental informahon. 

We postulate that the double13C -labeling technique presented in this chapter could be used to study adducts on large pieces of DNA and even follow the chemical details cellular metabolic processes in real time. The double 13C-labeling technique is currently being developed to solve problems in metabolism and toxicology. 

In the last 30 years, the use of in vitro tools for toxicological studies and evaluation has become relevant and the number of scientific works and techniques has increased day by day. One of the most important advantages of in vitro systems is their ability to serve as model for the central events in the in vivo toxicological process, and a depth evaluation of the intrinsic cellular toxicity can provide useful information for toxicological safety evaluation. 

Immunotoxicity. No information was found regarding immunotoxicity in humans from inhalation, oral, or dermal exposures to fuel oils. Only two animal studies were identified that tested immunological effects, both using mice. These studies identified cellular effects in the bone marrow, lymph nodes, and/or thymus and decreases in the relative weights of the lymph nodes and thymus from acute dermal exposures to kerosene (Upreti et al. 1989) and chronic dermal exposures to JP-5 and marine diesel fuel (NTP/NIH 1986). However, the toxicological significance of these effects on the immune system cannot be determined from these data. Additional data are needed to identify the toxic potential of fuel oils on the immune system by all routes of exposure and in different animal systems. 

Prior to undertaking efficacy studies, baseline pharmacokinetic (PK) and toxicity data are needed, including an initial analysis of cellular/organ toxicity. It should be noted that the toxicity and therapeutic profile can differ significantly between push and continuous infusion. Thus, PK studies can help focus the initial dose finding and toxicological studies. 

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