Archives of toxicology. Supplement. = Archiv fur Toxikologie. Supplement最新文献

Domestic animals are animals whose living conditions and reproduction, among other things, are controlled by man. As such, the current discussion about the welfare of domestic animals is similar for farm, companion, laboratory, and zoo animals. It concerns identification of the behavioral and physiological needs of the animals and development of living conditions that enable them to satisfy these needs. The paper describes two approaches that have been used in behavior biology to identify such needs. One approach is the measurement of stress responses that may be activated when an animal's needs are not fulfilled. The other approach is the use of operant conditioning techniques to establish demand functions by which the motivation of an animal to perform a specific behavior is measured. It is concluded that, since welfare is characterized by the absence of a number of factors, such as stress, pain, fear, disease, hunger etc., many types of measurements must be applied to ensure optimal welfare.

Two transgenic in vivo mutation assays are described which are based on LacZ (Muta Mouse) and LacI (Big Blue) shuttle vector systems. Their utility has already been explored by a number of investigators including our laboratory. The evaluation of data derived from these assays confirm that they offer a practical method for studying mutagenic activity and mechanism in a wide range of tissues including those of the respiratory and gastrointestinal tract. Therefore, these transgenic mutation assays are valuable tools to assess the organotropic effects of genotoxic carcinogens.

A complex chemical mixture is defined as a mixture that consists of tens, hundreds or thousands of chemicals, and of which the composition is qualitatively and quantitatively not fully known. In contrast, a simple mixture consists of a relatively small number of chemicals, say ten or less, and the composition of which is fully known. In the present paper a number of options for hazard identification and risk assessment of complex chemical mixtures is discussed, and a scheme aimed at selecting the most appropriate approach for each (type of) complex mixture is presented. A conspicuous element of this scheme is the dichotomy of complex mixtures into mixtures that are readily available and mixtures that are virtually unavailable for testing in their entirety. Another characteristic aspect of the scheme is the inclusion of the "top-ten" and "pseudo top-ten" approaches, which in essence are ways to select the, say ten, most risky chemicals or pseudocomponents to be dealt with as a simple chemical mixture.

Bis(tri-n-butyltin)oxide (TBTO) has been shown to be immunotoxic in rodents, resulting in decreased resistance to infections. The no-effect level assessed by estimating effects on host resistance in rats has been found to lie between 0.5 and 5.0 mg TBTO/kg food (0.025 and 0.25 mg/kg body weight). For risk assessment such animal data need to be extrapolated to the human situation. In risk assessment procedures uncertainty factors are used to account for interspecies variation (extrapolation from animal to man) and for variation within the human species. For both factors a value of 10 is often used, based on international guidelines. Hence, exposures below 0.00025 mg/kg body weight should not pose a risk for the human population. In the present study we have taken an alternative approach. We have produced dose-response curves for the effect of TBTO exposure on resistance to Trichinella spiralis. To extrapolate this curve to the human situation, we produced additional dose response data concerning in vitro effects of TBTO exposure on the mitogen responsiveness of both rat lymphoid cells and human blood cells. Using regression analyses of these dose-response data, we calculated a factor that accounts for interspecies variation (IEV) and a factor that accounts for intraspecies variation (IAV) within the human samples. Using these factors, we estimated the dose that decreases resistance in man to an infection. We choose 10% increase of the infectious load as a reference point which in our view is of biological significance. Based on these considerations, we estimated the dose that may affect resistance in adult humans at 0.04 mg/kg body weight. Pre- and postnatal exposure will probably result in effects at lower concentrations, due to the vulnerability of the developing immune system.