Immunotoxicity defined

Immune system receptors and soluble signal proteins represent targets of a large group of biopharmaceuticals. This means that immunotoxicity, defined as the unintended suppression or enhancement of immune function, is an impor-... 

Immunotoxicology studies the effects of xenobiotics on the immune system an immunotoxic compound is defined as a compound that can alter one or more immune functions, resulting in an adverse effect for the host. In particular, two main immunotoxic effects can be identified ... 

A review of the literature on chemical-induced immunosuppression in rats and mice, exposed during the pre- and/or postnatal period, was compared to exposure of adults. Five known immunosuppressants (i.e., TCDD, TBTO, DES, Pb, and diazepam) were reviewed. The data revealed that the developing immune system was more sensitive to chemical exposure than the mature immune system. Based on these evaluations, the authors concluded that it was reasonable to assume that testing only in adults would not provide a sufficient level of sensitivity to define immunotoxicity in the neonate 132. In summary, this chapter provides compelling evidence that the developing, compared to the mature, immune system is more vulnerable to perturbation. 

Immunotoxicity. No information on immunotoxicity after exposure to 1,3,5-TNB by any of the three routes is available in humans or animals. Therefore, animal studies following acute, intermediate, and chronic exposure to 1,3,5-TNB via all three routes would help in estimating the potential immunotoxic effects in humans. Spleen enlargement was reported in acute-(Blackburn et al. 1988) and intermediate-duration (Cody et al. 1981 Linder et al. 1986) studies in animals. These effects, however, were secondary to adverse hematological effects. Studies in laboratory animals following acute exposure to 1,3-DNB by the oral route would help define possible effects on antibody production and cellular immunity. This information could be used to determine populations sensitive to possible exposure to 1,3-DNB at locations close to ammunition plants or in specific workplaces. 

Although human exposure studies to date found no conclusive evidence of immunotoxicity, the animal data show that the immune system is a target for CDD toxicity in many species. However, a defined... 

If one examines immune development, there are specific functionally distinct windows during which the immune system might be expected to have different susceptibilities based on critical biological events. By defining functionally distinct immune developmental windows, it is possible to make direct comparisons of differential immunotoxic susceptibilities using exposure assessment. 

The most important aspect is the continuum of immunotoxicity [32] It is based on the recognition that immune responses in the normal human population varies considerably. This means that immunomodulation not necessarily brings an individual out of a healthy response pattern. Figure 1 shows the population distribution of immune response strength (if something like this can be defined...) and how an individual within this population is shifted by an immune response modifier (toxicant) toward... 

Methods such as the TDAR assay have been shown to predict immunotoxicity in humans (Vos and Van Loveren, 1998). The factors to consider for conducting a TDAR assay are defined in the ICH S8 guidance (2006). This assay should be used along with standard immunotoxicity end points, results of other specialized immunotoxicity tests, and clinical data, when available, in a weight-of-evidence approach (see Chapter 2). 

Immunotoxicity. No information on immunotoxicity after exposure to MBOCA by any of the three routes is available in humans or animals. Studies in laboratory animals following acute inhalation, oral, and dermal exposure to MBOCA would help define possible effects on antibody production and cellular immunity. This information would be useful for determining sensitive populations. 

Other immunotoxicants. The list of potentially immunotoxic substances is large (see reviews cited above), and includes diverse compounds—heavy metals such as lead (Blakley and Archer, 1981) and fungal alkaloids such as trichothecene alkaloids (Nasuda et al., 1982). The obvious questions raised are defining the range of compounds in our diet which are immunotoxic and the quantitation of the health risk associated with toxicant consumption. The lack of correlation between some in vivo and in vitro studies (e.g., Blakley and Archer, 1982) indicate that risk will be difficult to assess. 

A critique of this issue is beyond the scope of this book but not irrelevant to its goals. It is valid and useful to ask whether class-stratified lead exposures in ancient cultures and societies defined macroscale dose—population responses for toxic endpoints and to define such endpoints at the higher end of the entire dose—response spectrum. Lead-associated impairments of function at executive and other levels would be consistent with, if not the sole basis of, the political and anthropological histories of the Imperial era. One can also argue that even a contributory role for lead reproductive and other systemic toxicity as a risk factor in the survival of lead-exposed populations merits consideration. At minimum, lead would be a serious risk factor for multiple reproductive, developmental neurotoxic, immunotoxic, and endocrinological effects. 

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