Nervous system neurotoxicity

The primary human exposure to methyl mercury is from consumption of contaminated fish. The most sensitive population is the developing fetus or infant due to the effects of methyl mercury on the nervous system (neurotoxic) and developmental effects. Exposure limits and fish consumption advisories are directed at pregnant women, women of childbearing age, and children. All agencies also recognize that fish consumption has many nutritional benefits and is an important part of many people s diet. Nevertheless, the widespread distribution of mercury and subsequent bioaccumulation of methyl mercury requires that many agencies have developed recommendation for levels of mercury in fish. Below is a list of some of these recommendations, but it is very important to consult the local fish consumption advisories. 

Heptane is toxic to the human nervous system (neurotoxic). Acute exposure symptoms include distorted perception and mild hallucinations. Humans exposed to 0.1% (1000 ppm) heptane exhibited dizziness in 6 min higher concentrations caused marked vertigo and incoordination. Humans accidentally exposed to high concentrations showed similar symptoms, as well as mucous membrane irritation, nausea, and lassitude. All these symptoms pass quickly upon recovery in fresh air, but the recovery period is longer than that for pentane or hexane. A gasoline aftertaste has been experienced by people who have been experimentally exposed to heptane. 

Soukup J +, Anaesthesist 45(1 I), 1024 Central Nervous System Neurotoxicity... 

Nervous system Neurotoxic effects of aluminium are regularly reported as a result of intravesical treatment of hemorrhagic cystitis, as a pediatric case illustrates [2 ]. 

Nervous system Neurotoxicity associated with paclitaxel b dose-related, cumulative, and characterized principally by a sensory peripheral neuropathy, although motor weakness has occasionally been reported [4H]. In patienb treated with paclitaxel 135... 

Nervous System Neurotoxicity in adult dialysis patients receiving aciclovir continues to be reported. It was presented in three case reports. In all three the patient s symptoms resolved following dialysis and cessation of aciclovir [35-37]A. 

Nervous system Neurotoxicity in adult dialysis patients secondary to valaciclovir continues to be reported in case reports [35, 37, 50 ] and observational studies [51 j. These include a case where a patient was felt to have status epilepticus due to aciclovir and valaciclovir neurotoxicity [37 ]. A Cochrane review of antiviral medications for preventing CMV disease in SOT recipients foxmd neurological dysfxmction to be more common with GCV and valaciclovir compared with placebo or no treatment [52 ]. 

Neurotoxicity (damage to the nervous system by a toxic substance) may also be seen with the administration of the aminoglycosides. Signs and symptoms of neurotoxicity include numbness, skin tingling, circum-oral (around the mouth) paresthesia, peripheral paresthesia, tremors, muscle twitching, convulsions, muscle weakness, and neuromuscular blockade (acute muscular paralysis and apnea). 

Neurotoxicity. Information in both humans and animals indicates that the nervous system is the major target of methyl parathion-induced toxicity following acute exposure by any route (Daly 1989 Dean et al. 1984 EPA 1978e Fazekas 1971 Gupta et al. 1985 Nemec et al. 1968 Roberts et al. 1988 Suba 1984 Yamamoto et al. 1982 Youssef et al. 1987). The most prominent signs of acute exposure to methyl... 

Neurotoxicity—The occurrence of adverse effects on the nervous system following exposure to a chemical. 

The distribution of endosulfan and endosulfan sulfate was evaluated in the brains of cats given a single intravenous injection of 3 mg/kg endosulfan (Khanna et al. 1979). Peak concentrations of endosulfan in the brain were found at the earliest time point examined (15 minutes after administration) and then decreased. When tissue levels were expressed per gram of tissue, little differential was observed in distribution among the brain areas studied. However, if endosulfan levels were expressed per gram of tissue lipid, higher initial levels were observed in the cerebral cortex and cerebellum than in the spinal cord and brainstem. Loss of endosulfan was most rapid from those areas low in Upid. Endosulfan sulfate levels peaked in the brain at 1 hour postadministration. In contrast, endosulfan sulfate levels in liver peaked within 15 minutes postadministration. The time course of neurotoxic effects observed in the animals in this study corresponded most closely with endosulfan levels in the central nervous system tissues examined. 

The central nervous system is a major target of endosulfan-induced toxicity in both humans and animals (Blanco-Coronado et al. 1992 Boyd and Dobos 1969 Boyd et al. 1970 Garg et al. 1980 Kiran and Varma 1988 Terziev et al. 1974). Therefore, individuals with seizure disorders, such as epilepsy, may be particularly susceptible because exposure to endosulfan may reduce the threshold for tremors, seizures, and other forms of neurotoxicity, as demonstrated in studies in rats (Gilbert and Mack 1995 Gilbert 1992). 

A striking feature of the toxic compounds considered so far is that many of them are neurotoxic to vertebrates or invertebrates or both. The nervous system of animals appears to be a particularly vulnerable target in chemical warfare. Not altogether surprisingly, all the major types of insecticides that have been commercially successful are also neurotoxins. Indeed, in 2003, neurotoxic insecticides accounted for over 70% of total insecticide sales globally (Nauen 2006). 

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). 

Animal behavior has been dehned by Odnm (1971) as the overt action an organism takes to adjnst to its environment so as to ensure its survival. A simpler definition is the dynamic interaction of an animal with its enviromnent (D Mello 1992). Another, more elaborate, one is, the outward expression of the net interaction between the sensory, motor arousal, and integrative components of the central and peripheral nervons systems (Norton 1977). The last dehnition spells out the important point that behavior represents the integrated function of the nervous system. Accordingly, disruption of the nervous system by neurotoxic chemicals may be expected to cause changes in behavior (see Klaasen 1996, pp. 466-467). 

A few OP compounds cause delayed neuropathy in vertebrates because they inhibit another esterase located in the nervous system, which has been termed neuropathy target esterase (NTE). This enzyme is described in Chapter 10, Section 10.2.4. OPs that cause delayed neuropathy include diisopropyl phosphofluoridate (DFP), mipafox, leptophos, methamidophos, and triorthocresol phosphate. The delay in the appearance of neurotoxic symptoms following exposure is associated with the aging process. In most cases, nerve degeneration is not seen with initial inhibition of the esterase but appears some 2-3 weeks after commencement of exposure, as the inhibited enzyme undergoes aging (see Section 16.4.1). The condition is described as OP-induced delayed neuropathy (OPIDN). 

Organometallic compounds such as alkylmercury fungicides, and tetraethyl lead, used as an antiknock in petrol, are neurotoxic, especially to the central nervous system of vertebrates (Wolfe et al. 1998, Environmental Health Criteria 101, and Chapter 8,... 

Many tests have been devised to provide quantitative measures of behavioral disturbances caused by neurotoxic chemicals. Tests have been devised that assess the effects of chemicals on four behavioral functions (D Mello 1992). These are sensory, cognitive, motor, and affective functions. However, because the entire nervous system tends to work in an integrated way, these functions are not easily separable from one another. For example, the outcome of tests focused on sensory perception by rats may be influenced by effects of the test chemical on motor function. 

Eldefrawi, M.E. and Eldefrawi, A.T. (1991). Nervous-System-Based Insecticides—Describes the mechanisms of action of a wide range of neurotoxic compounds, both human-made and naturally occurring. 

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