Comparison to Hepatotoxicity and Nephrotoxicity

. The immunotoxicity, hepatotoxicity, and nephrotoxicity of subacute exposure to carbon tetrachloride (CCI4) were evaluated in young adult (8-9 weeks old) male Fischer 344 rats dosed by gavage with CCI4 for 10 consecutive days at 0, 5, 10, 20 or 40 mg/kg/day. Two days following the last treatment rats were evaluated for alterations in immune function by monitoring the following; body and lymphoid organ weights; mitogen and mixed leukocyte reaction lymphoproliferative responses; natural killer cell activity; and cytotoxic T lymphocyte responses. A separate group of similarly dosed rats was immunized with sheep red blood cells (SRBQ on Day 9 of dosing, and the primary antibody response was assessed 4 days later. Hepatic and renal toxicity were assessed 2 days after the last treatment by monitoring organ weights, serum indicators of hepatic and renal damage, and hepatic cytochrome P450 levels, as well as by histological evaluation. Significant increases in relative liver weights were observed in rats dosed at 40 mg/kg/day. Histologically, these livers displayed mild to moderate vacuolar degeneration and minimal to mild hepatocellular necrosis. In addition, serum levels of aspartate aminotransferase and alanine aminotransferase were elevated at this dosage, as well as at 20 mg/kg/day. There were no renal effects observed at these dosages of CCU. In addition, no consistent alterations were observed in the immune parameters examined in these same animals nor in the rats immunized with SRBC. Furthermore, there was no difference in the antibody response to SRBC in another set of rats dosed at 40, 80, or 160 mg/kg/day CCI4. These results indicate that CCU is not immunotoxic in the rat at dosages that produce overt hepatotoxicity. C 1991 Socitty of Toxicology

Workshop to identify critical windows of exposure for children's health: immune and respiratory systems work group summary.

Fetuses, infants, and juveniles (preadults) should not be considered simply "small adults" when it comes to toxicological risk. We present specific examples of developmental toxicants that are more toxic to children than to adults, focusing on effects on the immune and respiratory systems. We describe differences in both the pharmacokinetics of the developing immune and respiratory systems as well as changes in target organ sensitivities to toxicants. Differential windows of vulnerability during development are identified in the context of available animal models. We provide specific approaches to directly investigate differential windows of vulnerability. These approaches are based on fundamental developmental biology and the existence of discrete developmental processes within the immune and respiratory systems. The processes are likely to influence differential developmental susceptibility to toxicants, resulting in lifelong toxicological changes. We also provide a template for comparative research. Finally, we discuss the application of these data to risk assessment

Role of the sympathetic nervous system in carbon tetrachloride-induced hepatotoxicity and systemic inflammation

Carbon tetrachloride (CCl4) is widely used as an animal model of hepatotoxicity and the mechanisms have been arduously studied, however, the contribution of the sympathetic nervous system (SNS) in CCl4-induced acute hepatotoxicity remains controversial. It is also known that either CCl4 or SNS can affect systemic inflammatory responses. The aim of this study was to establish the effect of chemical sympathectomy with 6-hydroxydopamine (6-OHDA) in a mouse model of CCl4-induced acute hepatotoxicity and systemic inflammatory response. Mice exposed to CCl4 or vehicle were pretreated with 6-OHDA or saline. The serum levels of aminotransferases and alkaline phosphatase in the CCl4-poisoning mice with sympathetic denervation were significantly lower than those without sympathetic denervation. With sympathetic denervation, hepatocellular necrosis and fat infiltration induced by CCl4 were greatly decreased. Sympathetic denervation significantly attenuated CCl4-induced lipid peroxidation in liver and serum. Acute CCl4 intoxication showed increased expression of inflammatory cytokines/chemokines [eotaxin-2/CCL24, Fas ligand, interleukin (IL)-1α, IL-6, IL-12p40p70, monocyte chemoattractant protein-1 (MCP-1/CCL2), and tumor necrosis factor-α (TNF-α)], as well as decreased expression of granulocyte colony-stimulating factor and keratinocyte-derived chemokine. The overexpressed levels of IL-1α, IL-6, IL-12p40p70, MCP-1/CCL2, and TNF-α were attenuated by sympathetic denervation. Pretreatment with dexamethasone significantly reduced CCl4-induced hepatic injury. Collectively, this study demonstrates that the SNS plays an important role in CCl4-induced acute hepatotoxicity and systemic inflammation and the effect may be connected with chemical- or drug-induced hepatotoxicity and circulating immune response

Experimental determination of whole body average specific absorption rate (SAR) of mice exposed to 200–400 MHz CW

A maximum of six live mice, mouse cadavers, prolate spheroids molded from muscle‐equivalent tissue, or saline‐filled culture flasks, were exposed to continuous wave radiation in a TEM cell at frequencies between 200 and 400 MHz. Whole‐body average specific absorption rate (SAR) was determined from power meter measurements of incident, reflected, and transmitted powers. The SARs for both live mice and cadavers were approximately twice that for the prolate spheroid models, and when housed in Plexiglas restraining cages, about 2 1/2 times greater. An error multiplying factor is identified, that quantitatively expresses how SAR data obtained by the three ‐power‐meter method becomes progressively more noisy as the irradiation frequency is lowered or as the TEM cell cross section is increased. Copyright © 1983 Wiley‐Liss, Inc., A Wiley Compan