Toxicity evaluation parameters

The duration of repeat-dose studies should be at least as long as the proposed clinical study. These studies are designed to establish a dose-response relationship, define target organ(s) of toxicity, and determine whether observed toxicities are reversible. Evaluation parameters should include not only those routinely performed in the acute studies, but those performed in the additional studies as well. Special tests, such as ophthalmoscopic, electrocardiograph, body temperature, and blood... 

Comparative Media Evaluation. Table 4 is a summary of trace element occurrences for water, sediment, fish and rocks in Oregon as compared with concentrations measured elsewhere in the world. Details of the comparison parameters are provided in the footnotes to Table 4. The table indicates that no excessively high concentrations of potentially toxic trace elements exist in Willamette River water relative to "uncontaminated sites. 

The most difficult problem of risk evaluation linked to chemicals will be discussed in this Part. This is primarily a medical problem, which therefore comes within the competence of the company medical officer and epidemiologists, but neverthel need not only be dealt with by them. The person in charge of safety control in a place where chemicals are handled also has to tackle this problem. This person will have to take into account the level of toxicity risk of a substance. This will determine the constraint level of the measures to be taken, its favoured means of penetration, which depends on the activity, and its penetration properties specific to the organism. The physical properties of the substance (which will determine the nature of the precautions to be taken) and also the values of toxicity parameters have to be taken into account. He has to check the container labelling and know how to interpret and explain the toxicity instructions on this labelling. 

The multimedia model present in the 2 FUN tool was developed based on an extensive comparison and evaluation of some of the previously discussed multimedia models, such as CalTOX, Simplebox, XtraFOOD, etc. The multimedia model comprises several environmental modules, i.e. air, fresh water, soil/ground water, several crops and animal (cow and milk). It is used to simulate chemical distribution in the environmental modules, taking into account the manifold links between them. The PBPK models were developed to simulate the body burden of toxic chemicals throughout the entire human lifespan, integrating the evolution of the physiology and anatomy from childhood to advanced age. That model is based on a detailed description of the body anatomy and includes a substantial number of tissue compartments to enable detailed analysis of toxicokinetics for diverse chemicals that induce multiple effects in different target tissues. The key input parameters used in both models were given in the form of probability density function (PDF) to allow for the exhaustive probabilistic analysis and sensitivity analysis in terms of simulation outcomes [71]. 

Elbetieha A, Da as SI, Khamas W et al (2001) Evaluation of the toxic potentials of cypermethrin pesticide on some reproductive and fertility parameters in the male rats. Arch Environ Contam Toxicol 41 522-528... 

Furthermore, it is necessary to evaluate the isolated and complex physiological effects of some toxic and essential metals on such endpoints (biomarkers) as the neurobehavioral and psycho-physiological parameters and also cardiovascular and immune parameters. The effect depends on metals content in the human body. Moreover, it depends on physiological effects, not only the daily intake. 

Sperling, F. (1976). Nonlethal parameters as indices of acute toxicity Inadequacies of the acute LD5o. In Advances in Modem Toxicology, Vol. 1, Part 1 New Concepts in Safety Evaluation (Mehlman, M., Shapiro, R. and Blumenthal, H., Eds.). Hemisphere Publishing, Washington, D.C., pp. 177-191. 

---