Immune system animal tests

Dioxins are of concern because they accumulate in the biosphere, where they have highly deleterious effects. Tests have shown that when the concentration of dioxins in the blood of laboratory animals reaches a critical level, reproductive and immune system defects result. Moreover, recent data indicate that the concentration of dioxins in the blood of the average U.S. resident has nearly reached that level. A major reason is that dioxins are not veiy water-soluble, so they accumulate in the body rather than being readily processed and excreted. Consequently, several groups, including the American Public Health Association, have issued calls for phasing out the use of industrial chlorine. 

The majority of early publications that can be reasonably identified as comprising immunotoxicology reported altered resistance to infection in animals exposed to various environmental or industrial chemicals. Authors logically concluded that xenobiotic exposure suppressed immune function since the immune system is ultimately responsible for this resistance to infection. Subsequent studies demonstrated that suppression of various cellular and functional endpoints accompanied or preceded increased sensitivity to infection, and that administration of known immunosuppressants likewise decreased host resistance. The human health implications of these studies, that chemical exposure reduced resistance to infection, drove the initial focus of many immunotoxicologists on functional suppression, and provided the theoretical and practical underpinnings of immunotoxicity testing. 

With the exception of whole-animal host resistance assays, the actual testing approach can be described as ex vivo-in vitro in that exposure of the immune system to potential immunotoxicants takes place in vivo, with subsequent immunological evaluation taking place in vitro. Although this approach obviates many uncertainties (effect of xenobiotics on primary or secondary lymphoid tissue, potential requirements for metabolism/bio-transformation, etc.), the use of whole animals presents many secondary issues, such... 

Relatively few reports have examined the benefits or perils of herb combinations. Because the activity of a particular herb in a mixture might differ from its activity as a single component, it would be prudent to test the effects of prescribed formulas. The potential for herbal formulae to affect the immune system are increasingly being found in the use of Kampo (Japanese herbal) medicinals as described in an excellent review by Borchers and colleagues. [94], For example, Shosaiko-to is a seven-herb mixture that has been shown to protect patients from viral hepatitis via modulation of several cytokines such as IFN-a/p, G-CSF, and TNF-a. Animal studies have been conducted to evaluate the immunomodulatory effects of the various herbs in Shosaiko-to. Interestingly, four of its individual constituents induced several-fold higher levels of TNF-a when... 

Host-resistance assays can be used to assess the overall immunocompetence of the humoral or cell-mediated immune systems of the test animal (host) to fend off infection with pathogenic microbes, or to resist tumorigenesis and metastasis. These assays are performed entirely in vivo and are dependent on all of the various components of the immune system to be functioning properly. Thus, these assays may be considered to be more biologically relevant than in vitro tests that only assess the function of cells from one source and of one type. Since these assays require that the animal be inoculated with a pathogen or exogenous tumor cell, they cannot be performed as part of a general preclinical toxicity assessment, and are thus classified as Type 2 tests in the revised Redbook. These assays are also included as Tier II tests by the NTP. 

Is the effect reversible Reversibility of a response is dependent on the drug itself, exposure levels/duration, and factors related to the test animal (metabolic capability, genetic susceptibility, etc.). Most effects produced by immunosuppressive drugs have been shown to be reversible after cessation of therapy, such as those produced during cancer chemotherapy. However, if a tumor develops before the immune system is restored, the effect is not reversible, as is the case of secondary tumors related to chemotherapy. 

Immunotoxicity. No information was located on the immunological effects of bromomethane in humans or animals exposed by any route. A battery of immune function tests in several animal species exposed to bromomethane by the inhalation and the oral routes would be valuable in determining if the immune system is adversely affected, and if so, in determining species and route specificity, as well as the threshold for those effects. 

Once the hapten has been designed and prepared, it is conjugated with a carrier protein to induce the best immunogenicity as possible to elicit an immune response in the animal (most commonly a mouse) in which it is inoculated. The antibodies produced by the defense mechanism of the adaptive immune system that specifically recognizes the hapten are then isolated, overproduced, and purified for testing their catalytic activity toward the targeted chemical reaction. 

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. 

Immunotoxicity. There are currently no data on the effects of 2-hexanone on the human immune system via any route of exposure. Animal data included an inhalation study in which there was a 40% decrease in peripheral white blood cells in rats exposed to 2-hexanone (Katz et al. 1980). In addition, 2,5-hexanedione, a metabolite of 2-hexanone, was shown to adversely affect lymphoid organs of the immune system in rats and to cause impairment of immunity in mice (Upreti and Shanker 1987). Immunological assessments, including analysis of peripheral blood components and effects on lymphoid tissue, conducted as part of intermediate-or chronic-duration studies and skin sensitization tests would be useful in developing a dose-response relationship and assessing the potential risk to chronically exposed persons in the vicinity of hazardous waste sites or to exposed workers. 

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