Immune systemic toxicity

In rats, the acute oral LD50 for lindane is 88-190 mg kg while for mice it is 59-562 mg kg It is also moderately toxic via the dermal route, with reported dermal LD50 values of 500-1000 mg kg in rats. The effects on the nervous system are similar to that of DDT. There are also reports of liver, kidney, and immune system toxicity. 

Toxicity of biomaterials is usually viewed at both cellular and systemic levels. Toxicity at the cellular level, also known as cytotoxicity, is often caused by direct chemical toxicity of biomaterials, inflammatory reactions, or immune responses to biomaterials. Excessive or severe cytotoxicity, inflammatory reactions, or immune responses may lead to the toxicity remote from the initial insult and affecting organs or organ systems, which is defined as systemic toxicity. It is important to emphasize that toxicity caused by biomaterials is usually dose dependent. For cytotoxicity or nonimmune systemic toxicity, a threshold below which the biomaterial reveals little toxicity may be carefully determined by in vitro and in vivo studies. However, for immune systemic toxicity, determination of such a threshold is extremely difficult because immune responses are individual-dependent and largely affected by properties, dosage, and implantation location of the biomaterials. Toxicity of nanomaterials will be further discussed in this chapter. 

The toxicity of 2,4-pentanedione is shown in Tables 3 and 11 to be similar to mesityl oxide, and greater than most other 1,2- or 1,4-diketones or monoketones. Inhalation of low levels of 2,4-pentanedione can cause nausea, eye contact can induce stinging, and recurrent exposure to high concentrations (300—400 ppm) can adversely affect the central nervous system and immune system (325). 

In addition to their endocrine disrupting properties, it must be appreciated that many of the chemicals in question possess more general toxic properties, which may be potentiated by metabolism by the organism. Several PAHs, PCBs and PCDDs are carcinogenic, while certain phthalate esters can enhance the excretion of zinc, potentially leading to zinc deficiency. Zinc, an essential element, plays a vital role in spermatogenesis and mature T-cell production. Deficiency may result in abnormalities of the male reproductive system, depletion of spermatogenesis and suppression of the immune system. 

Sharma RP, Reddy RV. 1987. Toxic effects of chemicals on the immune system. In Haley TJ, Bemdt WO, eds. Handbook of Toxicology. New York, NY Hemisphere Publishing Corp., 555-591. 

Immunologic Toxicity—The occurrence of adverse effects on the immune system that may result from exposure to environmental agents such as chemicals. 

Immunotoxicity. Limited information is available regarding the effects of endosulfan on the human immune system. However, specially designed studies using rats indicate that both humoral and cellular immune responses are depressed by ingested endosulfan at doses that do not induce any overt signs of toxicity (Banerjee and Hussain 1986,1987). In vitro studies support the possibility that endosulfan affects immune system function (Das et al. 1988). These results demonstrate that immunotoxicity may be a more sensitive end point of endosulfan-induced toxicity than other end points, and humans may be at risk for adverse immune effects following exposure to endosulfan. An intermediate-duration oral MRL was derived based on the observation of depressed immune responses (Banerjee and Hussain 1987). 

Apart from the wide range of neurotoxic and behavioral effects caused by OPs, many of which can be related to inhibition of AChE, other symptoms of toxicity have been reported. These include effects on the immune system of rodents (Galloway and Handy 2003), and effects on fish reproduction (Cook et al. 2005 Sebire et al. 2008). In these examples, the site of action of the chemicals is not identified. Indirect effects on the immune system or on reproduction following initial interaction with AChE of the nervous system cannot be ruled out. It is also possible that OPs act directly on the endocrine system or the reproductive system, and phosphorylate other targets in these locations (Galloway and Handy 2003). 

A limited study in animals also presents evidence for increased susceptibility to Streptococcus zooepidomicus (Aran d et al. 1986). Immune system effects observed in mice exposed orally to trichloroethylene included inhibition of cell-mediated immunity, delayed type hypersensitivity, and inhibition of antibody-mediated immunity (Sanders et al. 1982). Female mice appeared to be more sensitive than male mice. A study in which a susceptible strain of mice was treated with intraperitoneal injections of trichloroethylene suggests that trichloroethylene can accelerate the autoimmune response (Khan et al. 1995). The immune system may be a sensitive end point for toxic effects from low-level exposure to trichloroethylene however, no firm conclusions can be drawn from the available information. Additional human and animal studies are needed to better characterize this end point and determine the potential for immunological effects for people exposed to trichloroethylene at hazardous waste sites. 

The priority effects are carcinogenicity, mutagenicity, reproductive or developmental toxicity, endocrine disruption and neurotoxicity. Human toxicity is broader than priority effects, including acute toxicity, systemic toxicity (organ effects), immune system effects and skin/eye/respiratory damageaswellasthepriority effects. And toxicity as T includes both human toxicity and ecotoxicity. 

The cell surface contains antigens, which are referred to as CD, which stands for cluster of differentiation. The antibodies are produced against a specific antigen. When administered, usually by an intravenous injection, the antibody binds to the antigen, which may trigger the immune system to result in cell death through complement-mediated cellular toxicity, or the antigen-antibody cell complex may be internalized to the cancer cell, which results in cell death. Monoclonal antibodies also may carry radioactivity, sometimes referred to as hot antibodies, and may be referred to as radioimmunotherapy, so the radioactivity is delivered to the cancer cell. Antibodies that contain no radioactivity are referred to as cold antibodies. 

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