Ochratoxin A
Ochratoxin A is a mycotoxin produced by Aspergillus ochraceus and Penicillium verrucosum and is found worldwide as a food contaminant. It is known to cause porcine nephropathy and may be associated with a human kidney disease endemic to the Balkan region Bondy and Pestka 2000 . Mice and rats exposed to ochratoxin A in utero had altered immune responses compared to controls. A single dose of och-ratoxin A 10 to 500 mg kg to pregnant mice decreased thymic CD4 and increased thymic CD4 CD8...
Antineoplastic Drugs
Busulfan, an early antileukemic alkylating agent, was reported to cause severe thymic hypoplasia in mice receiving a single dose during midgestation PintoMachado 1970 . This observation resulted in concern over possible similar effects with other therapeutic alkylating agents, for instance, cyclophosphamide or chlorambucil. Cyclophosphamide treatment in adult rodents is particularly toxic to B lymphocytes Poulter and Turk 1972 Misra and Bloom 1991 , and results in impaired antibody production...
Therapeutic Immunosuppressant Levels In Mammary Gland Secretions
Many of the immunosuppressive drugs used during pregnancy are also found in breast milk. Currently, the American Academy of Pediatrics AAP provides guidelines for breastfeeding based on the excretion rate and potential teratogenic effects of each drug Tendron et al. 2002 . For example, limited concentrations lt 10 of prednisone and prednisolone have been measured in breast milk, levels perceived by the AAP as nonthreatening to the breastfed infant Coulam et al. 1982 Ost et al. 1985 . Thus,...
Embryology of the Lymphatic System
The lymphatic system includes lymph vessels and trunks, spleen, thymus, lymph nodes, bone marrow, intestines, tonsils, and lymphoid follicles in the mucous membranes of the alimentary canal and respiratory organs. Only the spleen, thymus, and lymph nodes will be discussed in this section. Since there is limited published information on this topic in the monkey, extrapolation has been done from human data, as needed, to provide a framework for the macaques. In the human, development of the first...
Timing Of Immune Assays For Detecting Developmental Immunotoxicity
Development of the immune system has been more studied and better defined in the mouse than any other species see Chapter 1 . With this in mind, many immune function tests utilized in adult mouse models are not valid in perinatal mice simply because of the immaturity of their immune systems. Therefore, an adult mouse immunotoxicity risk assessment screening battery must be modified to be age-appropriate, if it is to be used for detecting postnatal immune deficits following prenatal chemical...
Contributors
Virginia Polytechnic Institute and State John M. Armstrong Senior Clinical Scientist Department of Medical Affairs Centocor, Inc. John B. Barnett Department of Microbiology, Immunology and Cell Biology Robert C. Byrd Health Sciences Center West Virginia University Morgantown, West Virginia Research Triangle Park, North Carolina Benny L. Blaylock School of Pharmacy College of Health Sciences University of Louisiana at Monroe Monroe, Louisiana Rodney R. Dietert Department of Microbiology and...
Chlordane Biodegradation And Elimination
Chlordane is a cyclodiene organochlorine insecticide. Figure 9.1 illustrates the structure of chlordane and its common major contaminants and metabolites. The pathway for metabolic degradation of chlordane in adult research animals is char- Figure 9.1 Structure of the isomers, high-abundance contaminants, and metabolites of technical-grade chlordane. Figure 9.2 Schematic of the metabolic breakdown of the chlordane isomers. Heavy bold arrows denote the major metabolic pathway, thin arrows denote...
Embryogenesis Of Hematopoietic And Lymphopoietic Organs
Establishment of hematolymphopoietic organs in the mouse initiates with the formation of pluripotential hemolymphopoietic stem cells HSC in intraembryonic splanchnopleura and is followed by a temporal migration of these HSC from intraembryonic mesenchyme in this region to the fetal liver, fetal spleen, and ultimately to final residence in bone marrow and in the thymus Metcalf and Moore 1971 Diet-erlen-Lievre 1975 Good 1995 Medvinsky and Dzierzak 1996 . HSC are a unique Figure 1.1 Overview of...
References Avr
Blaylock BL, Holladay SD, Comment CE, Heindel JJ, and Luster MI. 1992. Exposure to tetrachlorodibenzo-p-dioxin TCDD alters fetal thymocyte maturation. Toxicol Appl Pharmacol 112 207-213. Chapin RE, Harris MW, Davis BJ, Ward SM, Wilson RE, Mauney MA, Lockhart AC, Smialowicz RJ, Moser VC, Burka LT, and Collins BJ. 1997. The effects of perinatal juvenile methoxychlor exposure on adult rat nervous, immune, and reproductive system function. Fundam Appl Toxicol 40 138-157. Dietert RR, Etzel RA, Chen...
Lead 1
A variety of environmental and occupational metals have been identified that alter immune function in humans and laboratory rodents Zelikoff and Thomas 1995 . One such metal is lead, a naturally occurring element found in the earth's crust as well as throughout the biosphere. Present-day concentrations of lead in the atmosphere are due primarily to anthropogenic sources, with insignificant contribution from natural sources. Lead exposure to both humans and animals at sufficiently toxic doses...
The Pigs Intestinal Immune System During Postnatal Development
The early postnatal development of the gut immune system is important for effective immunological responses towards nutritional and microbial antigens in the intestinal lumen. Adaptation to the commensal flora, defense against pathogens, and the development of oral tolerance to food components are essential immunological processes. Depending on the food composition and on the presence of oral food components, the morphology of both the intestinal mucosa and the intestinal immune cells changes...
Methoxychlor
The 1993 National Research Council NRC report, Pesticides in the Diets of Infants and Children identified the immune, reproductive, and nervous systems as potential targets of pesticide exposure. Alterations in the development of these systems, which continues through puberty, make them potential targets of toxicity due to pesticide exposure through food consumption, possibly resulting in long-term functional deficits. A collaborative research project between the National Institute of...
Tcdd
TCDD 2,3,7,8-tetrachloridebenzo-p-dioxin , the most studied chemical for suppression of the immune system, is also a persistent environmental contaminant Holladay 1999 . Although TCDD does not readily cross the placenta 1 of the maternal dose , a single dose or subacute exposure 1.5 or 3.0 mg kg causes a very significant involution of the fetal thymus, along with an inhibition of thymocyte differentiation at both prenatal and postnatal time points Holladay and Smialowicz 2000 . Prenatal...
Diazepam Valium
Diazepam DZP is a benzodiazepine BDZ with central nervous system CNS -depressant properties. It has anxiolytic, sedative hypnotic, muscle relaxant, and anticonvulsant effects. DZP is used in humans for the short-term relief of symptoms related to anxiety disorders the treatment of agitation, tremors, delirium, seizures, and hallucinations as a result of alcohol withdrawal the relief of muscle spasms in certain neurological diseases and the control of active seizures Costa and Guidotti 1979 ....
Organotins
Organotins have a wide variety of industrial and commercial applications including use as wood preservatives, agricultural pesticides, chemical catalysts, plastic heat stabilizers, marine antifoulants, and curing agents Piver 1973 . Certain dialkyl-and trialkyl-substituted organotins e.g., di-n-octyltin dichloride DOTC and di-n-butyltin dichloride DBTC , and tributyltin oxide TBTO , alter the structure and function of the thymus and consequently affect primarily T cell-dependent immune function...
Postnatal Immune System
Continued maturation of the macaque immune system has been provided by evaluation of various serum parameters during the postnatal period. Longitudinal measurements of CD4 CD8 T cell ratios have been reported in colony-bred rhesus Dykhuizen et al. 2000 and cynomolgus Bleavins et al. 1993 Baroncelli et al. 1997 macaques using flow cytometry. In both macaques, the CD4 CD8 ratios slowly decline with age, predominantly due to decreasing CD4 T cell counts Table 7.7 . The CD4 CD8 values between 6...
Preface
This textbook of developmental immunotoxicology was created to provide a nonexhaustive but reasonably extensive overview of available information concerning adverse postnatal consequences of perinatal immunotoxicant exposure. A general familiarity with development of the immune system greatly assists understanding of how early-life toxicant challenges may transiently or permanently change later immune responsiveness. For this reason we begin with two chapters that review immune system...
Differential Expression of Lymphocyte Markers
The surface marker expression on the individual T cell CD3e, CD4, and CD8 and B-cell CD20, IgM subsets in the fetal rhesus monkey is summarized in Table 7.6. Approximating the proportions of CD4 and CD8 expressing lymphocytes with the use of CD3e coincident staining shows significant differences in the various Table 7.5 Frequency of IL6-Secreting Cells 106 MNC in Normal Rhesus Macaque Fetal Tissues at Different Gestational Ages Table 7.5 Frequency of IL6-Secreting Cells 106 MNC in Normal Rhesus...
Proposed Content Of A Developmental Immunotoxicity Study
Although the need for developmental immunotoxicity testing has long been recognized by the scientific and regulatory communities NRC 1993b USEPA 1999, 2002b , there is currently no formal EPA testing guideline protocol for this study. Studies have, however, been conducted in numerous laboratories to assess the developmental immunotoxic potential for a myriad of pharmaceuticals, pesticides, and environmental pollutants. Additionally, the National Toxicology Program NTP has devised an...
Dimethoate and Methylparathion
Dimethoate DM and methylparathion MPT are organophosphate insecticides and acaricides used to control many biting or sucking insect pests of agricultural crops. They kill insects systemically and on contact by stomach and respiratory action. They are used against a wide range of insects, including house flies as well as aphids, thrips, planthoppers, and whiteflies on ornamental plants, cotton, grains, vegetables, nuts, fruits, and tobacco. The mode of action of these organophosphate...
Fetal Liver As A Hematopoietic Organ
Table 1.1 Hematopoietic Colony Formation In Vitro Colony Stimulating Factor In Vitro Colony Cell Types in Colony neutrophils monocytes neutrophils monocytes eosinophils erythrocytes erythrocytes lymphocytes specific cytokine stimulation, they differentiate, lose the capacity to proliferate, and eventually undergo apoptosis Bradley and Metcalf 1966 . Colonies enumerated in most of these in vitro assays, then, are primarily composed of nonproliferating end cells and contain few cells with...
Development of the Rodent Immune System
Kenneth S. Landreth and Sarah V. M. Dodson CONTENTS Embryogenesis of Hematopoietic and Lymphopoietic Fetal Liver as a Hematopoietic Splenic Embryonic Emergence of the Embryonic Emergence of Secondary Lymphoid Hematopoietic Development of the Bone Hematopoietic Postnatal Development of the Immune Establishment of Immune Memory and Immune Critical Developmental Windows for the Immune System in Rodents 12 In Vivo Reconstitution of Immunocompetent