Neurotoxicants

Many pesticides are neurotoxicants poisoning the nervous system. A number of pesticides are acetyl cholinesterase inhibitors (Serat and Mengle 1973). Generally, pesticides determination has been performed by GC since the 1960 s (Morrison and Durham 1971 Fournier et al. 1978). There are no reference materials for pesticides in urine or serum, although as with PAHs there are a number biological matrices certified for the content of various pesticides available for environmental food and agriculture analysis and which may have some application in clinical chemistry. 

Results from inhalation studies in animals suggest that hydrogen sulfide may be a developmental neurotoxicant. Neurochemical changes (in particular levels of the neurotransmitters gamma-aminobutyric acid, norepinephrine, and serotonin) and levels of the amino acids aspartate, glutamate, and taurine have been observed in various regions of the brain (Hannah et al. 1989, 1990 Skrajny et al. 

Epidemiologic study of neurobehavioral National Institute for effects due to neurotoxicant exposure Occupational Safety and... 

Simmons-Willis, T. A., et al. Transport of a neurotoxicant by molecular mimicry the methylmercury-l-cysteine complex is a substrate for human L-type large neutral amino acid transporter (LAT) 1 and LAT2. Biochem. J. 2002, 367, 239-246. 

Zinc is important to the normal functioning of the central nervous system (CNS). At low concentrations, zinc protects mammalian brain neurons by blocking N-methyl-D-aspartate receptor-mediated toxicity. At high concentrations, zinc is a potent, rapidly acting neurotoxicant in the mammalian brain, as judged by zinc-induced neuronal injury of in vitro mature cortical cell cultures (Choi et al. 1988). Increased brain levels of zinc are associated with Pick s disease in certain strains of rodents with inherited epileptic seizures. Intravenous injection of zinc in rats with genetically inherited epilepsy produces seizures a similar response occurs with intracranial injection of zinc in rabbits with inherited audiogenic seizures (Choi et al. 1988). 

Pyrethroid insecticides are generally recognized as potent neurotoxicants that interfere with nerve membrane function by interaction with the sodium channel (Elliott and Janes 1978 Vijverberg et al. 1982 Gilbert et al. 1989 Haya 1989). Synthetic pyrethroids are more toxic against insect pests, up to 10 times more potent in some cases, than other insecticides now in general use (Bradbury... 

The sodium channel in the nerve membrane is the major target site for all synthetic pyrethroid insecticides (and many other neurotoxicants)... 

At present, professional toxicologists should determine more clearly a range of neurotoxicants, which can be used with maximal... 

The metabolism of 77-hexane takes place in the liver. The initial reaction is oxidation by cytochrome P-450 isozymes to hexanols, predominantly 2-hexanol. Further reactions convert 2-hexanol to 2-hexanone, 2,5-hexanediol, 5-hydroxy-2-hexanone, 4,5-dihydroxy-2-hexanone and the neurotoxicant 2,5-hexanedione. Hydroxylation at the 1- and 3- positions can be considered detoxification pathways hydroxylation at the 2- position is a bioactivation pathway. A diagram of the proposed pathway for mammalian metabolism of -hexane is presented in Figure 2-3. 

No studies have been conducted to evaluate the neurotoxicity of endrin aldehyde or endrin ketone in humans or animals by an inhalation, oral, or dermal route of exposure. Additional studies using all three of these potential exposure routes are needed to determine if endrin aldehyde and endrin ketone are potential neurotoxicants and to determine threshold levels for effects that may exist. 

Costa LG. 1992. Effect of neurotoxicants on brain neurochemistry. In Tilson HA, Mitchell CL, eds. Target organ toxicology series Neurotoxicology. New York, NY Raven Press, 101-124. 

Neurotoxicants, immunotoxicants, and teratogens were also further explored, and it was concluded that, except for the organophosphorous neurotoxicants, such compounds would be covered by the stmcmre-based, tiered TTC approach. For organophosphates, a human exposure threshold of... 

Lead Metal - widely distributed in environment when used as a gasoline additive and in paint. Now banned from use in gasoline and paint. Potent child neurotoxicant... 

Ancient Worldwide Mercury Mine workers poisoned 1930s hat industry (the Mad Hatters) 1950s Japan, mercury in fish 1970s mercury in seed grain acceptance of mercury as a developmental neurotoxicant released from coal-fired electrical plants ongoing contamination of fish... 

Although the CNS is protected from a number of xeno-biotics by the blood-brain barrier, the barrier is not effective against lipophilic compounds, such as solvents or insecticides (Fig. 7.1). Similarly, the peripheral nervous system is protected by a blood-neural barrier. The barriers are less well developed in the immature nervous system, rendering the fetus and neonate even more susceptible to neurotoxicants. Neural tissue susceptibility is due in large part to its high metabolic rate, high lipid content, and for the CNS, high rate of blood flow. 

A study of the behavioral and neurochemical effects of the putative serotonergic neurotoxicant methylenedioxymethamphetamine (MDMA) or dexfenfluramine in rhesus macaques failed to reveal any effects on shortterm memory, motivation learning, and color and position discrimination (Frederick et al. 1995, 1998). 

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