Symptoms of Neurotoxicity

Evaluation of neurotoxicity of a chemical substance is dependent on several parameters—for instance, changes in neurochemistry, anatomy, physiology, and or the behavior of the poisoned animal or human. Also, alterations in sensory processes such as paresthesia and visual, olfactory, and or auditory impairments have been often indicated as symptoms of neurotoxicity observed among workers exposed to different toxic substances in workplaces.  

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Neurotoxicity (damage to the nervous system by a toxic substance) may also be seen with the administration of the aminoglycosides. Signs and symptoms of neurotoxicity include numbness, skin tingling, circum-oral (around the mouth) paresthesia, peripheral paresthesia, tremors, muscle twitching, convulsions, muscle weakness, and neuromuscular blockade (acute muscular paralysis and apnea). 

Contact with the eye by the gas or liquid resulted in transient irritation and conjunctivitis. Minor skin exposure to the liquid produced erythema and edema." Prolonged or repeated contact resulted in deeper burns with delayed vesiculation." It is doubtful that significant cutaneous absorption occurs. Although victims of skin exposure may show symptoms of neurotoxicity, inhalation is considered the likely cause."... 

Ehrentheil 1957 Hann and Veale 1910), and hypoactivity (Humphreys and Halpert 1931) have been observed. Other symptoms of neurotoxicity that have been observed include coma or semi-coma (Caley and Kellock 1955 Ehrentheil 1957 Hann and Veale 1910 McCarron et al. 1981 McIntosh 1927 Wechsler and Wechsler 1951), toxic delirium and psychosis (Diaz-Rivera et al. 1950), hemiplegia (Humphreys and Halpert 1931 McCarron et al. 1981), abnormal reflexes (Wechsler and Wechsler 1951), hyperesthesia (Humphreys and Halpert... 

Besides causing other adverse health effects, prolonged periods of exposure to high concentrations of different chemical substances are known to induce neurotoxicity among workers. The symptoms of neurotoxicity become visible with the... 

Neurotoxicity is the result of improper (careless) use, handling, and negligence in the management of chemical substances such as metals, food additives, pesticides, industrial solvents, cosmetics, radiation treatment, and drug therapies. Depending upon route and dose of exposure, the symptoms of neurotoxicity appear immediately after exposure or are delayed. The symptoms include limb weakness or numbness loss of memory, vision, and/or intellect headache cognitive and behavioral problems and sexual dysfunction. Children and workers with certain existing health disorders are more vulnerable to the adverse effects of neurotoxic chemicals. 

Symptoms of neurotoxicity, which usually appear within the first 24—72 hours of administration, include tremor, myoclonus, confusion, lethargy, agitation, hallucinations, dysarthria, asterixis, ataxia, hemiparesthesia, and seizures. While aciclovir-induced neurotoxicity is most prevalent with intravenous administration, it has also been reported after oral use in patients with terminal renal insufficiency on hemodialysis. 

The cerebellar syndrome is the most common comph-cation of high-dose cytarabine therapy. In a study of the cerebellar syndrome caused by cytarabine (3), in which it was found in seven of 30 patients treated, symptoms of toxicity appeared between the third and seventh days of chemotherapy, manifesting first as lethargy and confusion (3). Within the next 24 hours there were signs of cerebellar dysfunction, including dysarthria, ataxia, tremor, nystagmus, and dysmetria. In most patients in whom neurotoxicity developed, liver function worsened during chemotherapy. Abnormal liver function at the start of therapy and the development of neurotoxicity appear to be linked. The symptoms of neurotoxicity resolved within 4-49 days. 

In animals, there is a clear relation between dosage, blood concentrations, duration of treatment, and morphological and functional disturbances of the nervous system. In the lower dose range, there is unequivocal histological evidence of neurotoxicity, but without symptoms of neurotoxicity (SEDA-9, 397) (SEDA-11, 486). 

Previous treatment with other neurotoxic agents may compound the problem. In one study symptoms of neurotoxicity were observed in one patient who received concomitant cisplatin with paclitaxel (33). However, signs and symptoms of neurotoxicity have been insignificant in combination treatments of cisplatin and paclitaxel in other trials (1). Pre-existing neuropathy as a result of previous therapy is not a contraindication to paclitaxel (7). 

More severe symptoms of neurotoxicity are not unusual and include disorientation, confusional states, feelings of detachment, overt psychosis (2), and possibly epileptiform convulsions (3), although the latter have been observed only in a case of Down syndrome. 

There are no reports of long-term repeated exposure to piperazine. Therapeutic uses of piperazine via the oral route for 1 week have resulted in symptoms of neurotoxicity in children and adults. 

Bergamaschi E, Smargiassi A, Mutti A, et al Peripheral markers of catecholaminergic dysfunction and symptoms of neurotoxicity among styrene-exposed workers. Int Arch Occup Environ Health 69 209-214,1997 Challenor J, Wright D Aggression in boat builders a search for altered mood states in boat builders exposed to styrene. Occup Med (Lond) 50 185-192, 2000 Cherry N, Rodgers B, Venables H, et al Acute behavioural effects of styrene exposure a further analysis. British Journal of Industrial Medicine 38 346-350, 1981 Cherry N, Hutchins H, Pace T, et al Neurohehavioural effects of repeated occupational exposure to toluene and paint solvents. British Journal of Industrial Medicine 42 291-300, 1985... 

Toxicity Excessive dosage to animals results in symptoms of neurotoxicity. Reversible vacuolar changes mainly affect ing the myelin of the brain and spinal cord bave been report -ed. Because of potential neurotoxicity in humans, the FDA has regulated use. See Lockhart, Pediatrics 50, 229 (1972). 

Toxicity high with symptoms of neurotoxicity, hver damage, and chloracne LD50 oral (guinea pigs) 0.0031 mg/kg, LD50 oral (mice) 0.3375 mg/kg... 

Clinical and/or behavioral signs and symptoms of neurotoxicity were recorded (iee dLeeklisi fur neiiroloxiciiy). n ... 

The microorganism makes spinosyns, unique macrocyclic lactones, containing a tetracyclic core to which two sugars are attached. Most of the insecticidal activity is due to a mixture of spinosyns A and D, commonly referred to as spinosad. Products such as Tracer Naturalyte Insect Control, and Precise contain spinosad as the active ingredient. Insects exposed to spinosad exhibit classical symptoms of neurotoxicity lack of coordination, prostration, tremors, and other involuntary muscle contractions leading to paralysis and death. Although the mode of action of spinosad is not fully understood, it appears to affect nicotinic and -aminobutyric acid receptor function through a novel mechanism. 

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