Neurotoxicity causes

Starvation or disease can lead to rapid release of the stored xenobiotic and to delayed toxic effects. In one well-documented case in the Netherlands (see Chapter 5), wild female eider ducks (Somateria mollissima) experienced delayed neurotoxicity caused by dieldrin. The ducks had laid down large reserves of depot fat before breeding, and these reserves were run down during the course of egg laying. Dieldrin concentrations quickly rose to lethal levels in the brain. Male eider ducks did not lay down and mobilize body fat in this way and did not show delayed neurotoxicity due to dieldrin. 

Thus there are mechanisms to ensure that NTs neither persist uncontrollably at the synapse nor produce dramatic effects distal from it. Studies of glutamate release always show a measurable basal level (1-3 pM), although this may not all be of NT origin, and yet it is very difficult to increase that level even by quite intense stimulation. Whether this is a safeguard against the neurotoxicity caused by the persistent intense activation... 

It is not entirely clear whether the acetone co-exposure in the Sanagi et al. (1980) study contributed to the observed effects. Indirect evidence from an occupational study (Cardona et al. 1996) showed that workplace acetone concentrations had a statistical correlation with the ratio of urinary -hexane metabolites to /i-hcxanc air concentration, although it did not correlate with measured urinary metabolites. No animal studies are available describing the effects of inhalation co-exposure to acetone and -hexane, although there are several studies which report interactions between acetone and the neurotoxic metabolite of -hexane 2,5-hexanedione (See Section 2.4, Mechanisms of Action). Oral administration of acetone has been reported to potentiate the neurotoxicity caused by oral exposure to the neurotoxic u-hexane metabolite 2,5-hexanedione in rats (Ladefoged et al. 1989, 1994). Oral exposure to acetone alone in rats at 650 mg/kg/day resulted in a statistically significant decrease in motor nerve conduction velocity after 6 weeks co-exposure to acetone and 2,5-hexanedione resulted in greater effects... 

Price WA, Giannini AJ. Neurotoxicity caused by lithium-verapamil synergism. J Clin Pharmacol 1986 26(8) 717-9. 

Linssen-Schuurmans CD, van Kan EJ, Feith GW, Uges DR. Neurotoxicity caused by valacyclovir in a patient on hemodialysis. Ther Drug Monit 1998 20(4) 385-6. 

Neurotoxicity caused by chemical substances requires careful interpretation based on well confirmed data on experimental animals and surveys of workers and the general population. Neurotoxicity is one of several noncancer end-points that share common default assumptions and principles. The interpretation of data as indicative of a potential neurotoxic effect involves the evaluation of the validity of the database. Attention should be given to the existing gaps—for instance, (1) identification of the specific toxic substance, (2) knowing the observed effects and significance in terms of neurotoxicity, and (3) whether the conclusions made agree... 

Johnson, M.K., Lotti, M. (1980). Delayed neurotoxicity caused by chronic feeding of organophosphates requires a high point of inhihition of neurotoxic esterase. Toxicol. Lett. 5 99-102. 

Disulfiram-induced neurotoxicity caused parkinsonism in a man who had been an alcoholic for 10 years (10). 

Two adults with acute lymphoblastic leukemia developed unusually severe neurotoxicity caused by vincristine, which was probably the result of an interaction with itraconazole suspension (127). 

Stavudine (d4T) is a nucleoside reverse transcriptase inhibitor. While it has only minor hema-totoxic potential, the dmg is markedly neurotoxic, causing dose-limiting peripheral neuropathy. Resistance occurs via mutations in the pol gene, which encodes for several proteins including reverse transcriptase. The answer is (B). 

Caroldi. S., and Lotti, M. (198J). Delayed neurotoxicity caused by a single massive do.se of dichlorvos to adult hens. Toxicol. Lett. 9, 157-159. 

TPP is neurotoxic, causing paralysis at high dosages. Like tri-o-cresyl phosphate (TOCP), it is a cholinesterase inhibitor. The acute oral toxicity is low. The acute toxicity via subcutaneous administration is low to moderate. The toxic symptoms from high dosages in test animals were tremor, diarrhea, muscle weakness, and paralysis. 

Somkuti et al. (1987) reported testicular toxicity of TOCP in adult leghorn roosters. Birds dosed with 100 mg/kg/day exhibited limb paralysis in 7-10 days. Such symptoms are characteristics of delayed neurotoxicity caused by organophosphorus compounds. Analysis at the termination of 18 days indicated a significant inhibition of neurotoxic esterase activity in both brain and testes, and a decrease in sperm motility and brain acetylcholinesterase activity. 

MSUD is an autosomal recessive disorder caused by deficiency of branched-chain a-ketoacid dehydrogenase (Pig. 47.1). The a-ketoadds derived from isoleucine, valine and leucine (branched-chain amino adds) accumulate and are excreted in the urine, giving it the peculiar odour of maple syrup. The branched-chain amino acids and the branched-chain a-ketoacids that accumulate in the blood are neurotoxic, causing severe neurological symptoms, cerebral oedema and mental retardation. A diet low in branched-chain amino acids is an effective treafinenL... 

Hexane Neurotoxic causing peripheral neuropathy manifested by mobihty loss, reduced sensations in extremeties 2,5-Di- methyl- hexane Lacks toxicity characteristics of n-hexane, significantly higher boiling point may be a disadvantage... 

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