Specificity immunotoxicity

If we consider both the specific immunotoxicity assays surveyed earlier in this chapter and the arrays of endpoints evaluated in traditional toxicology studies, which may be indicative of an immune system effect, these guidelines leave many potential questions unanswered. As additional data on individual endpoints indicative of... 

Immunotoxicity. Information regarding immunological effects of NDMA in humans is not available. Immunosuppression by NDMA has been demonstrated in a number of intraperitoneal injection studies, but not in an oral study, with mice. Specific immunotoxicity tests or a battery of immunotoxicity tests in which NDMA is administered by the oral route would provide a better assessment of possible immunotoxic effects. Sensitization tests in animals could provide information on whether an allergic response to NDMA is likely in humans. Additional studies also could determine if NDMA is a transplacental carcinogen. 

TABLE 5.1-3 Algorithm for Immunotoxicity Evaluation Using Host Resistance Assays Targeted Host Resistance Assays to Evaluate Specific Immunotoxicity Questions... 

The algorithm in Table 5.1-3 lists targeted host resistance assays that are useful to evaluate specific immunotoxicity questions. 

Figure 9.1 CDER flowchart for determining when to conduct specific immunotoxicity testing [19].

Immunotoxicity. Only a single case report of skin allergy to methyl parathion has been reported in humans (Lisi et al. 1987). No studies are available in humans exposed to methyl parathion via the inhalation or oral route. Based on limited animal studies, immunotoxicity may be a sensitive end point of methyl parathion-induced toxicity (Shtenberg and Dzhunusova 1968 Street and Sharma 1975). Thus, humans may be at risk for adverse immunological effects following exposure to methyl parathion. The limited information available on the effects of combined exposure to methyl parathion suggest the its toxicity is not route-dependent. Therefore, there is no reason to suspect that the immunotoxic effects observed following oral exposure of animals are route-specific. 

Some animal studies indicate that dietary exposure to methyl parathion causes decreased humoral and cellular responses (Shtenberg and Dzhunusova 1968 Street and Sharma 1975). A more recent, well-designed animal study that included a battery of immuno/lymphoreticular end points showed few effects at the nonneurotoxic doses tested (Crittenden et al. 1998). No adequate studies are available in humans to assess the immunotoxic potential of methyl parathion. Therefore, studies measuring specific immunologic parameters in occupationally exposed populations are needed to provide useful information. Further studies are also needed to investigate the mechanism for methyl parathion-induced immunotoxicity since this information would help to identify special populations at risk for such effects. 

Immunotoxicity. No information was found on the immunological effects of acrylonitrile in humans or animals by any route of exposure. Because no Immunopathological effects have been reported in subchronic and chronic studies involving multiple species, additional studies employing a more specific testing battery are not warranted at this time. 

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... 

Pb exposure at relevant levels does not produce overt cytotoxicity of immuno-cytes. Instead, immune-associated health effects result from dysregulation and shifts in functional capacity rather than profound lymphoid deficiencies. As a result, the most sensitive biomarkers and indicators of Pb-induced immunotoxicity are those associated with specific functional capacities as opposed to more classical measures of cell enumeration and/or lymphoid organ pathology. 

This chapter presents specific information with regard to the effects of environmental and occupational exposure to arsenic on inflammatory processes, the immune system, and host defense. While the focus is on the in vivo and in vitro effects of arsenic on host immune responses (e.g., immunotoxicity and hypersensitivity) and their relationship to clinically observed manifestations of arsenic toxicity (e.g., inflammation and skin cancer), information on the potential mechanisms through which arsenic may exert its biological effects is also provided. 

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