Neurotoxicants methylmercury

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. 

Nervous System. The nervous system is also a common target of toxic metals particularly, organic metal compounds (see Chapter 16). For example, methylmercury, because it is lipid soluble, readily crosses the blood-brain barrier and enters the nervous system. By contrast, inorganic mercury compounds, which are more water soluble, are less likely to enter the nervous system and are primarily nephrotoxicants. Likewise organic lead compounds are mainly neurotoxicants, whereas the first site of inorganic lead is enzyme inhibition (e.g., enzymes involved in heme synthesis). 

Of critical concern is the possibility that developmental exposure may result in an acceleration of age-related decline in function. Animal studies have demonstrated that developmental exposure to neurotoxicants such as methylmercury, methylazoxymethanol, and ethanol may cause few or no neurotoxic effects in young animals, but marked effects in ageing animals. Investigations of effects in ageing animals are not included in regulatory guidelines. 

The definition of neurotoxicity also indicates a potential difference between the developing and the mature nervous system, to underscore the fact that developmental neurotoxicity is an important aspect of neurotoxicology. Most known human neurotoxicants are indeed developmental neurotoxicants.4 In most, but not all cases, the developing nervous system is more sensitive to adverse effects than the adult nervous system, as indicated, for example, by the most deleterious effects of ethanol, methylmercury, or lead when exposure occurs in utero or during childhood. Furthermore, the blood-brain barrier (BBB), which protects the mature nervous system from the entry of a number of substances, appears to be poorly developed at birth and during the first few years of life.6... 

The use of nonneuronal cell types may provide initial information on whether a chemical may have differential effects, or display different potencies, in neuronal versus nonneuronal cells. For example, a battery of seventeen different cell types, including cell lines and primary cells (both neuronal and glial), human and rat cells, and nervous system and nonnervous system cells, was utilized to assess the toxicity of known developmental neurotoxicants, such as methyl-mercury and polychlorinated biphenyls (PCBs).24 Endpoints were cell viability and cell proliferation, and a summary of results for methylmercury and PCB-153 is shown in Table 8.5. This simple approach would flag methylmercury as a potential neurotoxicant, as toxicity was greater in neuronal cells than in other cell types. PCB-153 would also be flagged as a potential neurotoxicant, though... 

The concerns aroused by methylmercury in fish, arising from the susceptibility of the developing brain to this neurotoxicant, led to the design and execution of two large prospective studies. One was located in the Seychelle islands, which lie in the Indian Ocean. The other was located in the Faroe Islands, which lie in the North Sea. Both communities consume large quantities of seafood. In the Seychelles, it is almost exclusively in the form of fish. In the Faroes, virtually all the methylmercury comes from the consumption of pilot whales, which are also contaminated with polychlorinated biphenyls (PCBs). Both studies assayed maternal exposures to methylmercury. In the Seychelles, maternal hair was used as the index it reflects the history of blood levels. The Faroes study relied primarily on cord blood. 

PCBs and methylmercury represent a combination of agents of public health concern that are potential neurotoxicants found in the complex mixture of biopersistent toxicants in contaminated fish from the... 

Carcinogens Organ toxicants Neurotoxicants Ethylene oxide, Cr(IV), vinyl chloride, formaldehyde, arsenic, benzidine Hg, ethanol, beryUium, benzene, carbon tetrachloride, chloroform, arsenic Methylmercury, carbon disulfide, hexane, acrylamide, lead, nicotine, arsenic... 

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