Cell-associated bovine immunodeficiency virus (BIV) and cell-free BIV were subjected to increasin... more Cell-associated bovine immunodeficiency virus (BIV) and cell-free BIV were subjected to increasing temperatures, including pasteurization conditions. To determine the effect of heat treatment on BIV viability, reverse transcriptase activity and infectivity of the heat-treated virus were assessed. BIV was inactivated by heating to 47 degrees C for 30 min and by low- and high-temperature pasteurization conditions.
Journal of toxicology and environmental health, Jan 5, 1996
Sodium methyldithiocarbamate (SMD) is a widely used agricultural agent that causes immunological ... more Sodium methyldithiocarbamate (SMD) is a widely used agricultural agent that causes immunological changes in B6C3F1 mice. The most prominent effects of SMD include a decrease in thymus weight and percentage of CD4+CD8+ thymocytes, an increase in spleen weight, an increase in the percentage of neutrophils in the blood, a decrease in the percentage of lymphocytes in the blood, and a decrease in natural killer (NK) cell activity in the spleen. The mechanism by which SMD causes these changes is unknown, and the relative importance of the parent compound and its decomposition products is not known. In addition, it is not known if these effects are unique to mice, or if other mammals are affected similarly. This prompted the present investigation of the major decomposition product of SMD, methylisothiocyanate (MITC), and two minor products, methylamine and carbon disulfide, in mice. Equimolar dosages of methylamine and carbon disulfide caused minimal immunological changes, and these change...
Exposure to glucocorticoids in vitro is known to suppress the production of reactive nitrogen int... more Exposure to glucocorticoids in vitro is known to suppress the production of reactive nitrogen intermediates (RNI) by macrophages, and it has been suggested that this contributes to the anti-inflammatory action of glucocorticoids in vivo. However, the effects of glucocorticoid administration in vivo on subsequent RNI production as measured in vitro are not known. In the present study, dexamethasone was administered in vivo and was also used to treat macrophages in vitro prior to, and during, stimulation of nitrite production by interferon-gamma (IFN-gamma) and/or bacterial lipopolysaccharide (LPS). Macrophages were isolated 24 h after daily administration of dexamethasone (0.1-30 mg/kg/day) to female B6C3F1 mice for 3, 6, or 16 days. In most cases, these cells produced an equal or greater concentration of nitrite in response to IFN-gamma, LPS, or IFN-gamma plus LPS, than cells from vehicle control mice. In contrast, continuous exposure of macrophages to dexamethasone during stimulati...
A test procedure for the determination of (2-methoxyethoxy)acetic acid (MEAA) was adapted and app... more A test procedure for the determination of (2-methoxyethoxy)acetic acid (MEAA) was adapted and applied to urine samples from jet fuel (JP-8)-exposed mice using capillary gas chromatography with a mass selective detector (MSD). MEAA is a metabolite and proposed biomarker for exposure to 2-(2-methoxyethoxy)ethanol, a glycol ether component in the formulation of JP-8. The collected urine samples were spiked with deuterated butoxyacetic acid internal standard, and extracted with ethyl acetate, and esterified with ethanol and sulfuric acid, and the esters of the glycol ethers were extracted with methylene chloride. The chromatographic conditions used easily separate the MEAA ethyl ester from interferences within mouse urine. The application of this procedure to urine samples collected from mice demonstrated that MEAA was detectable after oral (2000 mg/kg) or dermal (50 mu L) exposure for 7 days to JP-8 at levels as high as 8.5 or 6.5 mu g/mL, respectively. This pilot demonstration indicated that total urinary MEAA was a viable biomarker for the two routes of JP-8 exposure in laboratory mice.
N,N-diethyl-meta-toluamide (DEET) is a particularly effective broad-spectrum insect repellent use... more N,N-diethyl-meta-toluamide (DEET) is a particularly effective broad-spectrum insect repellent used commonly in recreational, occupational and military environments. Due to its widespread use and suggested link to Gulf War Illness, this study examined the immunotoxicity of DEET. Adult female B6C3F1 mice were injected sc for 14 days with DEET at 0, 7.7, 15.5, 31, or 62 mg/kg/day. Due to differences in the dermal absorption of DEET between mice and humans, this study eliminated this confounding factor by utilizing sc injection and measured circulating blood levels of DEET to assess bioavailability from sc administration. Effects on lymphocyte proliferation, natural killer cell activity, thymus and spleen weight and cellularity, the antibody plaque-forming cell (PFC) response, and thymic and splenic CD4/CD8 lymphocyte subpopulations were assessed 24 h after the last dose. No effect was observed in lymphocyte proliferation, natural killer cell activity, thymic weight, splenic weight, thymic cellularity, or splenic cellularity. Significant decreases were observed in the percentage of splenic CD4-/CD8- and CD4+/CD8- lymphocytes but only at the 62 mg DEET/kg/day treatment level and not in absolute numbers of these cells types. Additionally, significant decreases in the antibody PFC response were observed following treatment with 15.5, 31, or 62 mg DEET/kg/day. Pharmacokinetic (PK) data from the current study indicate 95% bioavailability of the administered dose. Therefore, it is likely that DEET exposure ranges applied in this study are comparable to currently reported occupational usage. Together, the evidence for immunosuppression and available PK data suggest a potential human health risk associated with DEET in the occupational or military environments assuming similar sensitivity between human and rodent responses.
Journal of Toxicology and Environmental Health, Part A, 2004
JP-8 is the primary jet fuel used by the U.S. Air Force and NATO allies. Exposure is likely to be... more JP-8 is the primary jet fuel used by the U.S. Air Force and NATO allies. Exposure is likely to be widespread and to include both military and aviation industry personnel as well as residents living near fuel contaminated sites. This study examines the effects of JP-8 on humoral and cell-mediated and hematological parameters. A suite of immunotoxicological endpoints was evaluated in adult female B6C3F1 mice gavaged with JP-8 (in an olive oil carrier) ranging from 250-2500 mg/kg/d for 14 d. One day following the last exposure, significant increases in liver mass were detected beginning at exposure levels of 1000 mg/kg/d, while thymic mass was decreased at exposure levels of 1500 mg/kg/d and above. Decreases in thymic cellularity, however, were only observed at exposure levels of 2000 mg/kg/d and above. Mean corpuscular volume was increased (1500-2500 mg/kg/d), while the hematocrit, hemoglobin concentration, and red blood cell count were decreased only at the 2500 mg/kg/d exposure level. Natural killer cell (NK) activity and T- and B-cell proliferation were not altered. Decreases in the plaque-forming cell (PFC) response were dose responsive at levels of 500 mg/kg/d and greater, while unexpectedly, serum levels of anti-SRBC immunoglobulin M (IgM) were not altered. Alterations were detected in thymic and splenic CD4/8 subpopulations, and proliferative responses of bone marrow progenitor cells were enhanced in mice exposed to 2000 mg/kg/d of JP-8. This study establishes that humoral immune function is impaired with lower exposure levels of JP-8 than are required to affect primary and secondary immune organ weights and cellularities, CD4/8 subpopulations, and hematological endpoints.
Journal of Environmental Science and Health, Part A, 2008
A genetically-prone murine lupus model was used to assess the developmental effects of trichloroe... more A genetically-prone murine lupus model was used to assess the developmental effects of trichloroethylene (TCE) exposure on disease symptom onset (e.g., autoantibody production and proteinuria), lymphocyte proliferation, splenic B-cell populations, and thymic and splenic T-cell populations. MRL +/+ mice were exposed to TCE (0, 1,400 or 14,000 ppb) via drinking water beginning on gestation day (GD) 0 and continuing until 12 months of age. With the exception of splenic CD4-/CD8-cells in female mice only, no alterations were observed in splenic T-cell populations, numbers of splenic B220+ cells, or in lymphocyte proliferation at 12 months of age. Furthermore, populations of all thymic T-cell subpopulations were decreased in male but not female mice following exposure to 14,000 ppb TCE. Autoantibody levels (anti-dsDNA and anti-GA) were assessed periodically from 4 to 12 months of age. Over this period, no increase in autoantibody levels as compared to control was detected, suggesting that TCE did not contribute to or accelerate the development of autoimmune disease markers following lifetime exposure. Not only does this study offer encouraging results, but it is the first study to approach the development of autoimmunity in a novel lifetime exposure paradigm, using an autoimmune prone model, at environmentally relevant exposure levels.
Serotype A extracellular polysaccharide produced by Pasteurella multocida is composed largely of ... more Serotype A extracellular polysaccharide produced by Pasteurella multocida is composed largely of hyaluronic acid and is an important virulence factor in avian pasteurellosis. Hyaluronidase, mechanical shearing, and serial subculturing were employed to ...
Toxicological sciences : an official journal of the Society of Toxicology, 1999
In immunotoxicology, the critical functions of the immune system (host resistance to infection an... more In immunotoxicology, the critical functions of the immune system (host resistance to infection and neoplasia) cannot be measured directly in humans. It is theoretically possible to predict changes in host resistance based on changes in immunological functions known to mediate host resistance. However, quantitative predictive models of this type have not yet been achieved in humans or in animal models. Multivariate statistical methods were developed for analysis and modeling of the effects of several explanatory variables on a dependent variable, and they seem well suited for attempts to predict host resistance changes caused by changes in immunological parameters. However, these methods were developed with the assumption that all variables can be measured for each experimental subject. For a number of reasons, this generally cannot be done in comprehensive immunotoxicology evaluations. In the present study, the suitability of multivariate methods for analysis of variables measured i...
Approximately 5,000 to 80,000 of the US service personnel involved in the Persian Gulf War have c... more Approximately 5,000 to 80,000 of the US service personnel involved in the Persian Gulf War have complained of a variety of nonspecific symptoms since their return in 1991. These symptoms have been collectively labeled Gulf War Illness and include muscle fatigue, general malaise, myalgia, impaired cognition, ataxia, headaches, fever, joint pain, skin rash, gastrointestinal disturbances, sleep disturbances, and respiratory difficulties. Exposures of military and service personnel were diverse and included the prescribed anti-nerve gas agent pyridostigmine bromide (PYR), N.N-diethyl-m-toluamide (DEET) insect repellent, and environmental exposures to jet fuel. Thus, studies in our laboratory were undertaken to determine if concurrent exposure to these agents, singly or in combination, would contribute to significant alterations in immunological function and disease susceptibility. To assess immune status, eight-week old B6C3F1 female mice were exposed for 14 days to single compounds or tertiary mixtures of 15.5 mg/kg DEET, 2 mg/kg PYR, and 500 mg/kg JP-8 (termed low dose), or 31 mg/kg DEET, 5 mg/kg PYR, and 1,000 mg/kg JP-8 (termed high dose). Immunosuppression was assessed 24 h after the last exposure. No remarkable alterations were evident in hematological parameters, spleen and thymus organ weight and total cellularity, natural killer (NK) cell activity, cytotoxic T-cell activity, or mitogen-induced lymphocyte proliferation after exposure to either single or tertiary mixtures at low or high doses. A few changes in CD4/CD8 flow cytometric lymphocyte subpopulations were detected after exposure to the tertiary mixture at the high dose. Delayed type hypersensitivity (DTH) was decreased by 88% after exposure to the high-dose mixture, and suppression of antibody-specific IgM immune responses (plaque-forming cell, PFC) occurred after exposure to all single and tertiary mixtures at both dose levels. In the PFC response, antagonism was apparent in the mixture, while coexposure to these agents resulted in a synergistic effect in the DTH response. Susceptibility to B16F10 tumor or Listeria monocytogenes challenge was not affected after single or tertiary exposures. These data suggest that combined exposure to DEET, PYR, and JP-8 does not profoundly alter many immunological endpoints, but does selectively target functional endpoints such as the PFC and DTH response. This should be considered when assessing human health risks in the military environment.
Developmental immunotoxicity (DIT) occurs when exposure to environmental risk factors prior to ad... more Developmental immunotoxicity (DIT) occurs when exposure to environmental risk factors prior to adulthood, including chemical, biological, physical, or physiological factors, alters immune system development. DIT may elicit suppression, hyperactivation, or misregulation of immune responses and may present clinically as decreased resistance to pathogens, allergic and autoimmune diseases, and inflammatory diseases. Immunotoxicity testing guidelines established by the Environmental Protection Agency for adult animals (OPPTS 8703.7800) require functional tests and immunophenotyping that are suitable for detecting immunomodulation, especially immunosuppression. However, evaluating immune function in offspring that are not fully immunocompetent yields results that are challenging to interpret. Therefore, this unit will describe an optimum exposure scenario, reference two assays (immunophenotyping and histopathology) appropriate for detecting immunomodulation in weaning-age offspring, and reference four assays (immunophenotyping, histopathology, T cell-dependent antibody responses, and delayed-type hypersensitivity) appropriate for detecting immunomodulation in immunocompetent offspring. The protocol also will reference other assays (natural killer cell and cytotoxic T lymphocyte) with potential utility for assessing DIT.
Cell-associated bovine immunodeficiency virus (BIV) and cell-free BIV were subjected to increasin... more Cell-associated bovine immunodeficiency virus (BIV) and cell-free BIV were subjected to increasing temperatures, including pasteurization conditions. To determine the effect of heat treatment on BIV viability, reverse transcriptase activity and infectivity of the heat-treated virus were assessed. BIV was inactivated by heating to 47 degrees C for 30 min and by low- and high-temperature pasteurization conditions.
Journal of toxicology and environmental health, Jan 5, 1996
Sodium methyldithiocarbamate (SMD) is a widely used agricultural agent that causes immunological ... more Sodium methyldithiocarbamate (SMD) is a widely used agricultural agent that causes immunological changes in B6C3F1 mice. The most prominent effects of SMD include a decrease in thymus weight and percentage of CD4+CD8+ thymocytes, an increase in spleen weight, an increase in the percentage of neutrophils in the blood, a decrease in the percentage of lymphocytes in the blood, and a decrease in natural killer (NK) cell activity in the spleen. The mechanism by which SMD causes these changes is unknown, and the relative importance of the parent compound and its decomposition products is not known. In addition, it is not known if these effects are unique to mice, or if other mammals are affected similarly. This prompted the present investigation of the major decomposition product of SMD, methylisothiocyanate (MITC), and two minor products, methylamine and carbon disulfide, in mice. Equimolar dosages of methylamine and carbon disulfide caused minimal immunological changes, and these change...
Exposure to glucocorticoids in vitro is known to suppress the production of reactive nitrogen int... more Exposure to glucocorticoids in vitro is known to suppress the production of reactive nitrogen intermediates (RNI) by macrophages, and it has been suggested that this contributes to the anti-inflammatory action of glucocorticoids in vivo. However, the effects of glucocorticoid administration in vivo on subsequent RNI production as measured in vitro are not known. In the present study, dexamethasone was administered in vivo and was also used to treat macrophages in vitro prior to, and during, stimulation of nitrite production by interferon-gamma (IFN-gamma) and/or bacterial lipopolysaccharide (LPS). Macrophages were isolated 24 h after daily administration of dexamethasone (0.1-30 mg/kg/day) to female B6C3F1 mice for 3, 6, or 16 days. In most cases, these cells produced an equal or greater concentration of nitrite in response to IFN-gamma, LPS, or IFN-gamma plus LPS, than cells from vehicle control mice. In contrast, continuous exposure of macrophages to dexamethasone during stimulati...
A test procedure for the determination of (2-methoxyethoxy)acetic acid (MEAA) was adapted and app... more A test procedure for the determination of (2-methoxyethoxy)acetic acid (MEAA) was adapted and applied to urine samples from jet fuel (JP-8)-exposed mice using capillary gas chromatography with a mass selective detector (MSD). MEAA is a metabolite and proposed biomarker for exposure to 2-(2-methoxyethoxy)ethanol, a glycol ether component in the formulation of JP-8. The collected urine samples were spiked with deuterated butoxyacetic acid internal standard, and extracted with ethyl acetate, and esterified with ethanol and sulfuric acid, and the esters of the glycol ethers were extracted with methylene chloride. The chromatographic conditions used easily separate the MEAA ethyl ester from interferences within mouse urine. The application of this procedure to urine samples collected from mice demonstrated that MEAA was detectable after oral (2000 mg/kg) or dermal (50 mu L) exposure for 7 days to JP-8 at levels as high as 8.5 or 6.5 mu g/mL, respectively. This pilot demonstration indicated that total urinary MEAA was a viable biomarker for the two routes of JP-8 exposure in laboratory mice.
N,N-diethyl-meta-toluamide (DEET) is a particularly effective broad-spectrum insect repellent use... more N,N-diethyl-meta-toluamide (DEET) is a particularly effective broad-spectrum insect repellent used commonly in recreational, occupational and military environments. Due to its widespread use and suggested link to Gulf War Illness, this study examined the immunotoxicity of DEET. Adult female B6C3F1 mice were injected sc for 14 days with DEET at 0, 7.7, 15.5, 31, or 62 mg/kg/day. Due to differences in the dermal absorption of DEET between mice and humans, this study eliminated this confounding factor by utilizing sc injection and measured circulating blood levels of DEET to assess bioavailability from sc administration. Effects on lymphocyte proliferation, natural killer cell activity, thymus and spleen weight and cellularity, the antibody plaque-forming cell (PFC) response, and thymic and splenic CD4/CD8 lymphocyte subpopulations were assessed 24 h after the last dose. No effect was observed in lymphocyte proliferation, natural killer cell activity, thymic weight, splenic weight, thymic cellularity, or splenic cellularity. Significant decreases were observed in the percentage of splenic CD4-/CD8- and CD4+/CD8- lymphocytes but only at the 62 mg DEET/kg/day treatment level and not in absolute numbers of these cells types. Additionally, significant decreases in the antibody PFC response were observed following treatment with 15.5, 31, or 62 mg DEET/kg/day. Pharmacokinetic (PK) data from the current study indicate 95% bioavailability of the administered dose. Therefore, it is likely that DEET exposure ranges applied in this study are comparable to currently reported occupational usage. Together, the evidence for immunosuppression and available PK data suggest a potential human health risk associated with DEET in the occupational or military environments assuming similar sensitivity between human and rodent responses.
Journal of Toxicology and Environmental Health, Part A, 2004
JP-8 is the primary jet fuel used by the U.S. Air Force and NATO allies. Exposure is likely to be... more JP-8 is the primary jet fuel used by the U.S. Air Force and NATO allies. Exposure is likely to be widespread and to include both military and aviation industry personnel as well as residents living near fuel contaminated sites. This study examines the effects of JP-8 on humoral and cell-mediated and hematological parameters. A suite of immunotoxicological endpoints was evaluated in adult female B6C3F1 mice gavaged with JP-8 (in an olive oil carrier) ranging from 250-2500 mg/kg/d for 14 d. One day following the last exposure, significant increases in liver mass were detected beginning at exposure levels of 1000 mg/kg/d, while thymic mass was decreased at exposure levels of 1500 mg/kg/d and above. Decreases in thymic cellularity, however, were only observed at exposure levels of 2000 mg/kg/d and above. Mean corpuscular volume was increased (1500-2500 mg/kg/d), while the hematocrit, hemoglobin concentration, and red blood cell count were decreased only at the 2500 mg/kg/d exposure level. Natural killer cell (NK) activity and T- and B-cell proliferation were not altered. Decreases in the plaque-forming cell (PFC) response were dose responsive at levels of 500 mg/kg/d and greater, while unexpectedly, serum levels of anti-SRBC immunoglobulin M (IgM) were not altered. Alterations were detected in thymic and splenic CD4/8 subpopulations, and proliferative responses of bone marrow progenitor cells were enhanced in mice exposed to 2000 mg/kg/d of JP-8. This study establishes that humoral immune function is impaired with lower exposure levels of JP-8 than are required to affect primary and secondary immune organ weights and cellularities, CD4/8 subpopulations, and hematological endpoints.
Journal of Environmental Science and Health, Part A, 2008
A genetically-prone murine lupus model was used to assess the developmental effects of trichloroe... more A genetically-prone murine lupus model was used to assess the developmental effects of trichloroethylene (TCE) exposure on disease symptom onset (e.g., autoantibody production and proteinuria), lymphocyte proliferation, splenic B-cell populations, and thymic and splenic T-cell populations. MRL +/+ mice were exposed to TCE (0, 1,400 or 14,000 ppb) via drinking water beginning on gestation day (GD) 0 and continuing until 12 months of age. With the exception of splenic CD4-/CD8-cells in female mice only, no alterations were observed in splenic T-cell populations, numbers of splenic B220+ cells, or in lymphocyte proliferation at 12 months of age. Furthermore, populations of all thymic T-cell subpopulations were decreased in male but not female mice following exposure to 14,000 ppb TCE. Autoantibody levels (anti-dsDNA and anti-GA) were assessed periodically from 4 to 12 months of age. Over this period, no increase in autoantibody levels as compared to control was detected, suggesting that TCE did not contribute to or accelerate the development of autoimmune disease markers following lifetime exposure. Not only does this study offer encouraging results, but it is the first study to approach the development of autoimmunity in a novel lifetime exposure paradigm, using an autoimmune prone model, at environmentally relevant exposure levels.
Serotype A extracellular polysaccharide produced by Pasteurella multocida is composed largely of ... more Serotype A extracellular polysaccharide produced by Pasteurella multocida is composed largely of hyaluronic acid and is an important virulence factor in avian pasteurellosis. Hyaluronidase, mechanical shearing, and serial subculturing were employed to ...
Toxicological sciences : an official journal of the Society of Toxicology, 1999
In immunotoxicology, the critical functions of the immune system (host resistance to infection an... more In immunotoxicology, the critical functions of the immune system (host resistance to infection and neoplasia) cannot be measured directly in humans. It is theoretically possible to predict changes in host resistance based on changes in immunological functions known to mediate host resistance. However, quantitative predictive models of this type have not yet been achieved in humans or in animal models. Multivariate statistical methods were developed for analysis and modeling of the effects of several explanatory variables on a dependent variable, and they seem well suited for attempts to predict host resistance changes caused by changes in immunological parameters. However, these methods were developed with the assumption that all variables can be measured for each experimental subject. For a number of reasons, this generally cannot be done in comprehensive immunotoxicology evaluations. In the present study, the suitability of multivariate methods for analysis of variables measured i...
Approximately 5,000 to 80,000 of the US service personnel involved in the Persian Gulf War have c... more Approximately 5,000 to 80,000 of the US service personnel involved in the Persian Gulf War have complained of a variety of nonspecific symptoms since their return in 1991. These symptoms have been collectively labeled Gulf War Illness and include muscle fatigue, general malaise, myalgia, impaired cognition, ataxia, headaches, fever, joint pain, skin rash, gastrointestinal disturbances, sleep disturbances, and respiratory difficulties. Exposures of military and service personnel were diverse and included the prescribed anti-nerve gas agent pyridostigmine bromide (PYR), N.N-diethyl-m-toluamide (DEET) insect repellent, and environmental exposures to jet fuel. Thus, studies in our laboratory were undertaken to determine if concurrent exposure to these agents, singly or in combination, would contribute to significant alterations in immunological function and disease susceptibility. To assess immune status, eight-week old B6C3F1 female mice were exposed for 14 days to single compounds or tertiary mixtures of 15.5 mg/kg DEET, 2 mg/kg PYR, and 500 mg/kg JP-8 (termed low dose), or 31 mg/kg DEET, 5 mg/kg PYR, and 1,000 mg/kg JP-8 (termed high dose). Immunosuppression was assessed 24 h after the last exposure. No remarkable alterations were evident in hematological parameters, spleen and thymus organ weight and total cellularity, natural killer (NK) cell activity, cytotoxic T-cell activity, or mitogen-induced lymphocyte proliferation after exposure to either single or tertiary mixtures at low or high doses. A few changes in CD4/CD8 flow cytometric lymphocyte subpopulations were detected after exposure to the tertiary mixture at the high dose. Delayed type hypersensitivity (DTH) was decreased by 88% after exposure to the high-dose mixture, and suppression of antibody-specific IgM immune responses (plaque-forming cell, PFC) occurred after exposure to all single and tertiary mixtures at both dose levels. In the PFC response, antagonism was apparent in the mixture, while coexposure to these agents resulted in a synergistic effect in the DTH response. Susceptibility to B16F10 tumor or Listeria monocytogenes challenge was not affected after single or tertiary exposures. These data suggest that combined exposure to DEET, PYR, and JP-8 does not profoundly alter many immunological endpoints, but does selectively target functional endpoints such as the PFC and DTH response. This should be considered when assessing human health risks in the military environment.
Developmental immunotoxicity (DIT) occurs when exposure to environmental risk factors prior to ad... more Developmental immunotoxicity (DIT) occurs when exposure to environmental risk factors prior to adulthood, including chemical, biological, physical, or physiological factors, alters immune system development. DIT may elicit suppression, hyperactivation, or misregulation of immune responses and may present clinically as decreased resistance to pathogens, allergic and autoimmune diseases, and inflammatory diseases. Immunotoxicity testing guidelines established by the Environmental Protection Agency for adult animals (OPPTS 8703.7800) require functional tests and immunophenotyping that are suitable for detecting immunomodulation, especially immunosuppression. However, evaluating immune function in offspring that are not fully immunocompetent yields results that are challenging to interpret. Therefore, this unit will describe an optimum exposure scenario, reference two assays (immunophenotyping and histopathology) appropriate for detecting immunomodulation in weaning-age offspring, and reference four assays (immunophenotyping, histopathology, T cell-dependent antibody responses, and delayed-type hypersensitivity) appropriate for detecting immunomodulation in immunocompetent offspring. The protocol also will reference other assays (natural killer cell and cytotoxic T lymphocyte) with potential utility for assessing DIT.
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Papers by Deborah Keil