Neurotoxic substances

K. Presad and A. Vemadakis, eds.. Mechanisms ofHction of Neurotoxic Substances, Raven Press, New York, 1982. 

Paralytic shellfish poison, like botulinum toxin, is a neurotoxic substance and can also affect certain muscles, including the heart, which are under nervous system control. Some poisoned humans who have recovered from the effects of PSP have described the early stages of intoxication as not at all unpleasant a tingling sensation in the lips and face and a feeling of calm. Those who die from PSP ingestion do so because of respiratory failure. 

The basis of the recommended approach to a hazard assessment of the potential neurotoxicity of a substance is that a number of neurotoxic substances can be identified via the standard tests for systemic toxicity. Special studies to characterize effects of concern for neurotoxicity are used only when necessary for adequate hazard assessment. The nature of special studies, and when they should be conducted, need to be decided on a case-by-case basis. 

Lactitol 40 is a disaccharide that has been used in the management of hepatic encephalopathy, a major neuropsychiatric complication of both acute and chronic liver failure. It has mild laxative properties and is used to reduce the production and absorption of gut-derived neurotoxic substances symptomatic of hepatic encephalopathy. Although long considered a first-line pharmacological treatment, there is a lack of sufficient evidence to support lactitol s efficacy and continued use when weighed against other suitable therapeutic alternatives such as oral antibiotics <2006MI94>. 

Lithium is a highly neurotoxic substance with a generally suppressive effect on neuronal function and mental function in the commonly prescribed therapeutic range. It is poisonous to brain cells. The much-promoted concept that lithium and other mood stabilizers are somehow protective of brain cells is fantastical. 

It has been reported that about 12% of the 63 million children under the age of 18 in the United States suffer from one or more mental disorders, and exposure to toxic substances before or after birth has been identified as one of the several risk factors that appear to make certain children vulnerable to these disorders. Reports have also indicated that fetuses and children are more vulnerable to the effects of certain neurotoxic substances than are adults. Children exposed to a mix of pesticides, including organophosphates, showed diminished short-term memory and disturbed hand-eye coordination and drawing ability, whereas unexposed children of the same tribe showed normal development. Preschool children from agricultural communities in the United States showed poorer performance on motor speed and latency than did those of urban communities. ... 

Iregren A, Gamberale F. 1990. Human behavioral toxicology Central nervous effects of low-dose exposure to neurotoxic substances in the work environment. In Behavioral and Psychophysiological Effects of the Physical Work Environment International Workshop, Stockholm, Sweden, April, 1988. Scand J Work Environ Health 16(Suppl 1) 17-25. 

Other neurotoxic substances (isoniazid, metronidazole, dapsone, vincristine, pyridoxine, stavidine, zalcitabine, and others)... 

Neurotoxicity. Neurological effects including headache, nausea, vertigo, and confusion have been reported in case studies of humans exposed to nitrobenzene by inhalation. In orally exposed persons, apnea and coma have additionally been reported. No data are available in humans exposed via the dermal route. In animal studies, brain lesions have been observed in mice and rats exposed by inhalation and in rats that received a single oral dose. No data are available in animals exposed via the dermal route. Toxicokinetic studies in mice and rats provide evidence that nitrobenzene is distributed to brain tissue. Both the human and animal data provide clear evidence that nitrobenzene is a neurotoxic substance. Further studies in this area do not appear to be needed. In addition, results of the CUT two-year bioassay may provide further information on this end point. 

The seven types of botulinum toxin " and the tetanus toxin " are the most neurotoxic substances known. Only 10 molecules are sufficient to kill a mouse. Both toxins are zinc proteases, which block presynaptic transmitter release by cleaving specific synaptic vesicles proteins (see p. 1780 and Fig. 

The neurotoxic substance MPTP produces a clinical syndrome strikingly similar to idiopathic PD in humans (Langston et al., 1983), and induces nigrostriatal cell loss with concomitant decrease in DA and its metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid (3-methoxy-4-hydroxyphenylacetic acid), in monkeys (Burns et... 

It is unlikely, however, that ammonia s direct and indirect effects on brain functions are the sole cause of neurologic dysfunction in liver failure. Other neurotoxic substances such as manganese and proinflammatory cytokines could gain entry to brain in liver failure and act synergistically with ammonia-related mechanisms. 

Solomon LM, Fahrner L, West DP (1977) Gamma benzene hexachloride toxicity a review. Arch Dermatol 113 353-357 Spencer PS, Bischoff MC (1987) Skin as an entry for neurotoxic substances. In Marzulli FN, Maibach HI (eds) Dermatotox-icology. Hemisphere, New York, pp 625-640 Stanley BE, Frank JE (1971) Mercury poisoning from application to omphalocele. JAMA 216 2144-2145 Steele CE, Trasler DG, New DA (1983) An in vivo/in vitro evaluation of the teratogenic action of excess vitamin A. Teratology 28 209-214... 

The cyanobacteria produce a plethora of natural products with a wide variety of bioactivities. Many of these compounds are potent toxins and pose a significant hazard to human health and the environment. In freshwater systems, blooms of hepatotoxic cyanobacteria are of greatest concern, while in marine environments neurotoxic species are more problematic. More than 65 neurotoxins have been isolated from cyanobacteria to date. Most notably, these include the highly potent alkaloids anatoxins and saxitoxins (also known as paralytic shellfish toxins, PSTs) however, a variety of other neurotoxic substances have also been isolated from cyanobacteria including the lipopeptides, jamaicamide, antillatoxin, and kalkitoxin, as well as the nonproteinogenic amino acid, p-W-methylamino-L-alanine (BMAA). 

Venom is a mixture of various substances produced in a specific gland in the body of the venomous animal and introduced through a piercing injecting mechanism into the body of another animal in order to paralyze it or to kill it. In nature, venoms are employed by slow predatory animals in order to capture through an immediate paralysis their relatively fast prey organisms [1]. In the laboratory, however, venoms are employed as sources for the search of various pharmacological and mainly neurotoxic substances. 

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