Peripheral nervous system, neurotoxic effects

Neurotoxicity can be defined as any adverse effect on the structure or function of the nervous system related to exposure to a chemical substance (US-EPA 1998, OECD 2004c). According to the TGD (EC 2003), neurotoxicity can be defined as the induction by a chemical of adverse effects in the central or peripheral nervous system, or in sense organs and a substance is neurotoxic if it induces a reproducible lesion in the nervous system or a reproducible pattern of neural dysfunction. ... 

Although w-heptane exposure produces narcotic effects, it has not been shown to cause the type of peripheral neuropathy associated with -hexane at the same exposure levels. A metabolic study of heptane in rats and humans showed that only a very small amount of 2,5-heptanedione, the purportedly neurotoxic metabolite responsible for peripheral neuropathy, is produced. Clinical damage to the peripheral nervous system after w-heptane exposure, therefore, seems unlikely. ... 

Chronic effects of arsenic poisoning include neurotoxic effects to the central and peripheral nervous systems. Symptoms include sensory changes, muscle sensitivity, prickling and tingling sensations (paresthesia), and muscle weakness. Liver injury is a common symptom of chronic arsenic poisoning. Studies of victims of chronic arsenic poisoning from contaminated drinking... 

All the BTEXs cause neurological effects. Neurological effects are the basis for MRLs for both acute and chronic exposures to toluene and mixed xylenes, and for intermediate exposures to benzene neurological effects are not as sensitive for ethylbenzene. The neurological effects consist primarily of central nervous system depression. Toluene s neurotoxicity also includes ototoxicity. Evidence of hearing loss has been seen in both occupationally exposed humans and in animals. There is limited evidence that chronic inhalation exposure to benzene may affect the peripheral nervous system this evidence is from a single study of occupationally exposed humans who also had aplastic anemia. 

Later studies in animals and in humans confirmed the neurotoxicity of diiodoethyltin. It was characterised by intramyelinic vacuolation and astrocyte swelling, with no evidence of neuronal degeneration. Effects were confined to the central nervous system, rather than involving the peripheral nervous system. The Stalinon episode illustrated the tragic consequences of inadequate preclinical and quality testing, and it was to prove the forerunner of a major disaster that was to follow from inadequate medicines testing. 

The solvent hexane causes a different type of neurotoxicity, involving swelling and degeneration of motor neurones. This leads to paraesthesia and sensory loss in the hands and feet, and weakness in toes and fingers. Hexane has been widely used in industry as a solvent, and there have been many cases of neuropathy reported from different parts of the world. The toxicity is due to the metabolite 2,5-hexanedione which arises by co-1 oxidation at the 2- and 5-positions to 2,5-hexanediol, and then further oxidation to the diketone (figure 4.9). The 2,5-hexanedione then reacts with protein to form pyrrole adducts. The v-diketone structure is important, as 2,3- and 2,4-hexanedione are not neurotoxic. Methyl -butyl ketone also causes similar neurotoxic effects and is also metabolized to 2,5-hexanedione. The lipophilicity of the molecule allows distribution to many tissues including the nervous system. Thus, chemical structure and metabolism are important prerequisites for this toxicity. Exposure to the solvent carbon disulphide in industry causes neuronal damage in the central and peripheral nervous system. 

Neurotoxicity Toxic effects on the central or peripheral nervous system causing behavioral or neurological abnormalities. 

The delayed neurotoxic effect, also called OrganoPhosphate Induced Delayed Neurotoxicity (Neuropathy) (OPIDN), is characterized by sensoric and motoric disturbances of the peripheral nervous system (degeneration of... 

Neurotoxic chemicals can induce an adverse effect on the structure or function of the central and/or peripheral nervous system, which can be permanent or reversible. In some cases the detection of neurotoxic effects may require specialized laboratory techniques, but often they can be inferred from behavior such as slurred speech and staggered gait. Many neurotoxins... 

The neurotoxicity of acrylamide in humans is well known from occupational and accidental exposures [51], For instance, Calleman et al. [52] reported peripheral neuropathy symptoms to highly exposed workers in China. It is characterized by skeletal muscle weakness, numbness of hands and feet, and ataxia. Acrylamide has been shown to be toxic to both the central and the peripheral nervous system [53], although the nerve terminal is now considered to be the primary site of acrylamide action [54,55]. Acrylamide induces nerve terminal degeneration and has effects on the cerebral cortex, thalamus, and hippocampus [56]. In double-blind studies of factory workers, no neurotoxicity was found in workers exposed to less than 3.0 mg/kg/ day as determined by biomonitoring [55]. A very recent study demonstrates structural and ultra structural evidence of neurotoxic effects of fried potato chips on rat postnatal development. 

In a study where both peripheral and central nervous system effects were measured in rats co-exposed to u-hexane and toluene (Pryor and Rebert 1992), toluene exposure at 1,400 ppm for 14 hours a day for 9 weeks prevented the peripheral neurotoxicity (decreased grip strength and nerve conduction velocities) caused by exposure to 4,000 ppm 77-hcxanc alone. There was no reciprocal action of 77-hexane on the motor syndrome (shortened and widened gait and widened landing foot splay) and hearing loss caused by toluene. Brainstem auditory response amplitudes were decreased by 77-hcxanc, co-exposure to toluene did not block this effect. 

There is no simple or correct way to examine the causes of neurotoxicity. I have divided them into three overlapping areas neurotransmitter/receptor effects, which are often transient damage to the peripheral nerves, which is often permanent and damage to the developing nervous system, which is almost always permanent. 

The main dose-limiting toxicity is neurotoxicity, usually expressed as a peripheral sensory neuropathy, although autonomic nervous system dysfunction with orthostatic hypotension, urinary retention, paralytic ileus, or constipation, cranial nerve palsies, ataxia, seizures, and coma have been observed. While myelosuppression occurs, it is generally milder and much less significant than with vinblastine. The other potential adverse effect that can develop is the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). 

Environmental agents have been associated with neurotoxic effects in infants and children (IPCS, 1986a, 2001b). Given the ability of agents to impact various target sites or pathways (e.g. autonomic, peripheral, or central nervous system), a diverse range of outcomes should be considered. To this end, clinical assessment... 

Exposure to neurotoxicants or neurotoxic chemical substances causes severe adverse health effects to the nervous system, which is very sensitive to organometallic compounds and sulfide compounds. These compounds disrupt the normal functioning of the central nervous system, peripheral nerves or sensory organs, and the conduction of nerve impulses. Thus, chemical substances are considered neurotoxicants when they induce a consistent pattern of neural dysfunction. The chemical substances include but are not limited to carbon disulfide, manganese, methyl mercury, organic phosphorous insecticides, tetraethyl lead, thallium, and trialkyl tin compounds. 

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