The basic research program for the immunotoxicology studies conducted by NTP includes testing for the potential to modulate immune function in mice and/or rats and hypersensitivity testing in mice.
Immune Function Testing
Immunotoxicology testing typically starts with a screening study on immune function using a standard protocol. Additional testing or endpoints may be gathered for a more in-depth study.
The screening program is designed to evaluate the basic functional aspects of diverse immune system components:
- Innate immune function
Adaptive immune function
- Humoral mediated immunity
- Cell-mediated immunity
Typical Screening Study
Typically, studies designed to screen for effects on immune function use female B6C3F1/N mice, have a vehicle and five treatment groups, and collect these endpoints:
- Immunopathology including histopathology, clinical pathology, complete blood count and hematology
Evaluation of innate immunity
- Macrophage function (phagocytosis)
- Natural killer cell assay
Evaluation of cell–mediated immunity
- Cytotoxic T lymphocyte activity
- Proliferative responses that signal through the T cell receptor
Evaluation of humoral-mediated immunity
- IgM and IgG antibody production following challenge with T-dependent antigens
Quantification of leukocyte subpopulations
- T cells, T cell sub populations, B cells, macrophages, natural killer cells in the blood or from the spleen
In-depth studies may have additional endpoints such as:
- Bone marrow cytology and colony formation
- Disease resistance assays involving challenge with rodent pathogens or tumor cells
Most NTP studies to evaluate contact hypersensitivity use female BALB/c mice. The standard research program begins with a combined Irritancy/Local Lymph Node assay (IRR/LLNA). By combining the two tests in one assay, NTP minimizes the use of animals needed for in vivo screening.
Depending on the results of the IRR/LLNA, a mouse ear swelling test may also be conducted. This assay provides additional information on the sensitization and challenge phases of the response to contact sensitizers.
Mechanistic information on the specific cell population affected by chemical sensitizers may be obtained by assessment of leukocyte subsets in the lymph nodes that are associated with the site of exposure. However, these studies are not conducted as part of the routine screening program.
Evaluation of Alternative Toxicological Methods
The NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM) is working to assess the use of in vitro methods to screen chemicals for their potential to induce allergic contact dermatitis.