Neuro toxic effect

With hepatic encephalopathy, there is often an increase in short-chain fatty acids such as propionate, butyrate, valerate and octa-noate in the serum and CSF. They are formed as a result of incomplete p-oxidation of long-chain fatty acids in the intestine. They are not - or only inadequately — metabolized in the damaged liver. The neuro toxic effect is based upon inhibition of various enzymes (including enzymes of the urea cycle) and competitive... 

Different lines of Not stated treatment (up to four), neuro toxic effects... 

In keeping with the purpose of this book, the discussion of the neurotoxic effects of single chemicals will serve only as an introduction to the discussion of the neuro-toxic effects of chemical mixtures. 

There are of course many mathematically complex ways to perform a risk assessment, but first key questions about the biological data must be resolved. The most sensitive endpoint must be defined along with relevant toxicity and dose-response data. A standard risk assessment approach that is often used is the so-called divide by 10 rule . Dividing the dose by 10 applies a safety factor to ensure that even the most sensitive individuals are protected. Animal studies are typically used to establish a dose-response curve and the most sensitive endpoint. From the dose-response curve a NOAEL dose or no observed adverse effect level is derived. This is the dose at which there appears to be no adverse effects in the animal studies at a particular endpoint, which could be cancer, liver damage, or a neuro-behavioral effect. This dose is then divided by 10 if the animal data are in any way thought to be inadequate. For example, there may be a great deal of variability, or there were adverse effects at the lowest dose, or there were only tests of short-term exposure to the chemical. An additional factor of 10 is used when extrapolating from animals to humans. Last, a factor of 10 is used to account for variability in the human population or to account for sensitive individuals such as children or the elderly. The final number is the reference dose (RfD) or acceptable daily intake (ADI). This process is summarized below. 

Intermediate-Duration Exposure. No reliable information is available on the effects of repeated-dose exposure in humans. Limited information is available on the effects of repeated inhalation and oral exposures to 1,1-dichloroethane in animals. The studies reviewed indicate that 1,1-dichloroethane is possibly nephrotoxic, but this effect has only been demonstrated at high doses in one of several species tested. No other toxic effects have been attributed to 1,1-dichloroethane following repeated-dose exposures in animals. An intermediate MRL could not be derived for any routes of exposure. More information on the systemic effects of repeated-dose exposures in animals, particularly by the inhalation route since this is the most likely route of human exposure, would be useful to determine whether nephrotoxic effects observed in one study are an actual result of exposure to 1,1-dichloroethane, to determine if 1,1-dichloroethane reacts like other chlorinated aliphatics (e.g., causes neuro-and liver toxicity), and to more fully assess potential human health hazards from repeated exposure to 1,1-dichloroethane. This latter justification is particularly important since repeated exposure to low levels of 1,1-dichloroethane may be of more concern than short-term exposure to very high levels based on the current use and/or disposal of this chemical. 

Int Arch Occup Environ Health 41 1-6,1978 Ross WD, Sholiton MC Specificity of psychiatric manifestations in relation to neuro-toxic chemicals. Acta Psychiatr Scand Suppl 303 100-104,1983 Ross WD, Emmett EA, Steiner J, et al Neurotoxic effects of occupational exposure to organotins. Am J Psychiatry 138 1092-1095,1981... 

In order to avoid serious side effects of cisplatin (kidney- and neuro-toxicity) alternative Pt compounds have been developed. The most important of these is carboplatin in which the ci.s-chlorides are replaced by the 0-chelate, cyclobutanedicarboxylate but all of them have ligands with NH groups which facilitate the hydrogen bonding thought to stabilize the distortions of the DNA structure. 

Za omik J, Schein W, Heimbei K, Shaheeti FAM, Stockenhuber F. Potentiation of neuro-toxic side effects by coadministration of imipenem to cyclo rine therapy in a kidney transplant recipient—S3mergism of side effects cr drug interaction Clin Nephrol ( 9Z6)26y 265-6. 

Within the exposure categories, (3) and (4) are subcategories characterized by the types of low-level neurodevelopmental toxic effects, e.g., neuro-cognitive impairments, mobility, measures of academic achievement, impaired social conduct, physioanatomical measures of development and activity. 

Less well-known are the effects of falcarinol (1), which produces pronounced neuro-toxic symptoms upon injection into mice with an LD50 of 100 mg/kg whereas the related falcarindiol (2) does not seem to have any acute effect (Crosby and Aharonson 1967). The type of neuro toxic symptoms produced by falcarinol is similar to those of oenanthotoxin and cicutoxin, although it is much less toxic. 

A Physiological Ion.— In plants, Ca + tends to antagonise the toxic effects of K+, Na+, and Mg++. In animals, an increase in the concentration of Ca++ (or Mjg++, or H+) within critical limits tends to depress neuro-motor excitabilii and nerve conductivity. 

Almost all systemic effects of methyl parathion are related to the action of this compound on the nervous system or are secondary to this primary action. It is therefore necessary to preface a description of the mechanisms of toxicity of methyl parathion with a brief discussion of the nervous system and neuro-humoral transmitters (excerpted from Lefkowitz et al. 1996). 

Cholinesterase inhibitors are a very important class of compounds related to cholinomimetics. Besides their therapeutic importance, a few of them are used as pesticides in agriculture, and the most toxic are used as chemical poisoning agents. Use of these substances is based on changes that take place after inactivation of cholinesterase or pseudocholinesterase (a less specific enzyme), i.e. effects observed as a result of acetylcholine buildup in neuro-effector compounds. Cholinesterase inhibitors are classified both by their chemical structure as well as by the type of their chemical reaction with the enzyme, which determines their temporary action. 

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