Comparative observations on inorganic and organic lead neurotoxicity.

Abstract

Environmental and occupational exposure to lead still generates concern, and recent studies have focused such concern on the role of body burden of lead during the fetal/neonatal period, especially in the genesis of disturbed central nervous system development. This discussion provides some comparative observations on the neurotoxicity of inorganic and organic lead species. The characteristic acute, predominantly cerebellar encephalopathy associated with neonatal high lead exposure contrasts to the subtle, axo-dendritic disorganization shown to be associated with low-level neonatal inorganic Pb2+ exposure. There is a preferential involvement of the hippocampus in both low-level inorganic Pb2+ and organolead exposure, and the clinical syndromes of irritability, hyperactivity, aggression, and seizures are common features of disturbed hippocampal function.Neurotransmitter system abnormalities have been described with inorganic Pb2+, but recent attention has focused on the abnormalities in glutamate, dopamnine, and/or 'y-aminoboutyric acid (GABA) uptake, efflux, and metabolism. Abnonnalities of GABA and glutamate metabolism are also found with the organolead species.While the pathogenesis is still unclear, the interactive role of Pb2+ on mitochondrial energy metabolism, Ca2+ uptake, intracellular CaF+ homeostasis, and neurotransmitter influx/efflux is considered. Consideration is given to low-dose inorganic Pb2+ and organolead effects on mitochondrial and/or plasmalemmel membranes inducing either Cl-/OH-antiport-linked depolarization, inhibition of intracellular ATP biosynthesis and transduction, and/or abnormalities induced due to the preferential affinity of Pb2+ for intracellular Ca2+-cytoplasmic proteins, e.g., calmodulin. Testable hypotheses are presented that may provide an understanding of the pathogenesis underlying dystrophic neuronal development under the influence of inorganic or organolead intoxication.

Seasonality and Children’s Blood Lead Levels: Developing a Predictive Model Using Climatic Variables and Blood Lead Data from Indianapolis, Indiana, Syracuse, New York, and New Orleans, Louisiana (USA)

“…EPA 1994). To develop an exposure regime for the IEUBK model input, we note that indoor residential dusts generally show Pb concentrations about two times higher, on average, than the corresponding outdoor soils, although these results may have been influenced by fine particulate automotive Pb emissions (Clark et al 1988; Rabinowitz et al 1985; Thornton et al 1990). More recent data are available as summaries from 299 residential locations in eight different Idaho communities for the Human Health Risk Assessment for the Coeur d’Alene Basin showed an average enrichment factor of 1.6 for Pb concentration in carpet dusts compared with outdoor soils (TerraGraphics and URS Greiner 2001; von Lindern et al 2003).…”

Severe Neurotoxicity Following Ingestion of Tetraethyl Lead

“…Organolead exposure also inhibits dopamine, GABA, and glutamate uptake [5] and results in exaggerated motor responses to dopaminergic agents which may explain the neuromuscular effects seen with toxicity [11]. The successful attenuation of hallucinations induced by huffing leaded gasoline through treatment with haloperidol also supports the theory that organolead's hallucinogenic effects are mediated by dopaminergic pathways [8,11].…”

“…Unlike inorganic lead, organolead compounds have a distinct toxic syndrome which reflects their unique neurotoxic pathophysiology. Signs of acute intoxication include: lethargy, tremor, increased muscle tone, exaggerated tendon reflexes, psychosis, and encephalopathy which can progress to convulsions, paralysis, and death [3,[5][6][7]. Chronic organolead exposure from huffing leaded gasoline can result in persistent neuropsychiatric symptoms including: encephalopathy, dementia, cerebellar signs, and organic psychosis [7,8].…”

“…Histologic changes of the brain occur primarily in the limbic system and frontal cortex and include: loss of neurons, spongiose transformation of white matter, and myelinolysis [3,5]. Neuronal necrosis has also been documented in the brainstem, midbrain, pontine, basal, and anterior cervical spinal cord nuclei [6,12].…”

Mitigative Effects of Koenidine in Reducing the Toxicity Induced by Heavy Metal Lead in Human Neuroblastoma Cells

“…This can lead to the changes in the learning and psychological function of children behavior [1][2][3]. The primary target for the lead induced poisoning is the developing nervous system [4,5].…”