The transferability from XXXX subacute 4-week @entity137 study to translational research exemplified by two pharmaceutical immunosuppressants and two environmental pollutants with immunomodulating properties.

@entity15213 @entity1 @entity32 @entity137 @entity500 @entity3014 @entity205 @entity35 @entity99
UNASSIGNED: Exposure to chemicals may have an influence on the immune system. Often, this is an unwanted effect but in some pharmaceuticals, it is the intended mechanism of action. Immune function tests and in depth histopathological investigations of immune organs were integrated in rodent @entity137 studies performed according to an extended OECD test guideline 407 protocol. Exemplified by two immunosuppressive drugs, @entity500 and @entity205 , and two environmental chemicals, @entity15213 and @entity3014 , results of subacute @entity35 studies were compared to knowledge in other species particular in @entity1 . Although immune function has a high concordance in @entity1 species, regarding the transferability from rodents to @entity1 various factors have to be taken into account. In @entity35 , sensitivity seems to depend on factors such as strain, sex, stress levels as well as metabolism. The two immunosuppressive drugs showed a high similarity of effects in animals and @entity1 as the immune system was the most sensitive target in both. @entity15213 gave an inconsistent pattern of effects when considering the immune system of different species. In some species pronounced @entity32 was observed, whereas in primates @entity99 seemed more obvious. Generally, the immune system was not the most sensitive target in @entity15213 -treatment. Immune function tests in @entity35 gave evidence of a reaction to systemic @entity32 rather than a direct impact on immune cells. Data from @entity1 are likewise equivocal. In the case of @entity3014 , the immune system was the most sensitive target in @entity35 . In the in vitro plaque forming cell assay (Mishell-Dutton culture) a direct comparison of cells from different species including @entity35 and @entity1 was possible and showed similar reactions. The doses in the @entity35 study had, however, no realistic relation to @entity1 exposure, which occurs exclusively in mixtures and in a much lower range. In summary, a case by case approach is necessary when testing immunotoxicity. Improvements for the translation from animals to @entity1 related to immune cells can be expected from in vitro tests which offer direct comparison with reactions of @entity1 immune cells. This may lead to a better understanding of results and variations seen in animal studies.
