triethyllead and Lead-Poisoning

The long-term consequences of neonatal exposure to triethyl lead, the putative neurotoxic metabolite of the anti-knock gasoline additive tetraethyl lead, were examined with respect to central nervous system (CNS) development. We presently report a series of studies in which exposure of neonatal rats to organic lead produces profound CNS damage in adulthood as indicated by dose-dependent, persistent behavioral hyperreactivity as well as dose-dependent, preferential, and permanent damage to the hippocampus. General morphological parameters of brain development were not altered. Pharmacological probes of neurotransmitter system integrity suggested a functional and dose-dependent relationship between this behavioral hyperreactivity and hippocampal damage via cholinergic, but not dopaminergic, pathways. Furthermore, these alterations were not accompanied by long-term alterations in motor activity and were not attributable to the presence of lead in adult neural tissue. Finally, these behavioral, anatomical, and pharmacological indices of developmental exposure to organic lead were dissociable from any effects of early undernutrition. These data collectively indicate that organolead compounds may pose a potent neurotoxic threat to the developing CNS.

Topics: Animals; Animals, Newborn; Cholinergic Fibers; Dose-Response Relationship, Drug; Female; Hippocampus; Hyperkinesis; Lead Poisoning; Male; Motor Activity; Nutritional Status; Organometallic Compounds; Rats; Rats, Inbred F344

One group of rabbits were injected intraperitoneally with diethyllead dichloride (7.7 mg Pb/kg) and another group of rabbits were likewise injected with an equivalent lead dose of lead acetate. These rabbits were followed up for changes in the lead amounts excreted daily in the urine and feces from 24 h through 7 d after the injection, respectively. In the group of rabbits injected with diethyllead dichloride (one of 3 rabbits died during the observation), an amount of lead equivalent to about 25% of the injected dose was excreted in the urine during the first 24 h after the injection. Also, an amount of lead equivalent to about 28% of the injected lead was excreted in the feces during the first 3 d, and the total lead excretion during the 7 d after the injection corresponded to about 60% of the injected dose of diethyllead. One day after dosing, the total lead in the urine was made up of about 92% diethyllead, about 7% inorganic lead and about 1% triethyllead. One day after dosing, the total lead in the feces consisted of about 63% inorganic lead, about 28% diethyllead and about 9% triethyllead. Three days after dosing, the total lead in feces comprised about 98% inorganic lead, about 1% diethyllead and about 1% triethyllead. In the group of 3 rabbits injected with lead acetate, the total lead amount excreted in both the urine and feces during the 7 d after the injection corresponded to only about 9% of the injected dose of lead acetate.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Bone and Bones; Bone Marrow; Feces; Female; Injections, Intraperitoneal; Lead; Lead Poisoning; Organometallic Compounds; Rabbits

Alkyl leads (R x Pb) are environmentally prevalent compounds which have been shown to produce a variety of neurological and behavioral deficits in both laboratory animals and man. Due to the increasing commercial use of these compounds, the episodes of human poisoning, and the limited understanding of their sites and mechanisms of toxicity, the organoleads, as a class, remain potentially important environmental health hazards. Recent data indicate that the constellation of behavioral effects produced by these compounds resembles the behavioral sequelae of limbic system damage. For example, alterations in sensory responsiveness and/or behavioral reactivity and task-dependent changes in avoidance learning are observed following organolead exposure and experimental disruption of the limbic system. Furthermore, neurochemical changes induced by organoleads are regionally-specific and restricted to the limbic forebrain and frontal cortex. The present review will summarize the toxic properties of organoleads, discuss their neurobehavioral effects, and suggest that these effects might be attributable to a disruption of the limbic forebrain.

Topics: Animals; Behavior, Animal; Brain Diseases; Chemical Phenomena; Chemistry; Disease Models, Animal; Humans; Kinetics; Lead; Lead Poisoning; Limbic System; Organometallic Compounds; Rats; Tetraethyl Lead

Recent reports have demonstrated that organolead and -tin compounds can alter behavioral reactivity to noxious stimuli. To further define the dose response and temporal characteristics of these neurobehavioral effects, male Fischer 344 rats were injected sc with either one-fourth, one-half, or three-fourths the acute LD50 of triethyl lead (TEL), triethyl tin (TET), trimethyl lead (TML), trimethyl tin (TMT), or distilled water and tested on a 57.5 degrees C hot plate 1, 7, 14, 21, and 28 days after dosing. All four organometals altered hot plate latencies, but the magnitude and time course of these effects differed among the compounds. TEL produced a dose-related increase in latencies which was maximal 1 and 7 days postdosing and had dissipated by 28 days. In contrast, the group administered TML (3/4 LD50) exhibited a late developing antinocioception which became evident 14 days after dosing and persisted throughout the period of testing. The intermediate dose of TMT (1/2 LD50) also produced a delayed increase in response times which was observed 21 and 28 days post-treatment. The 3/4 LD50 dose of TMT produced increased hot plate latencies on all post-treatment test days except Day 14. TET (1/2 LD50) produced increased hot plate latencies 1, 7, 14, and 21 days postdosing and also induced a reversible ataxia and akinesia. Higher doses of TET proved lethal to 80% of the animals and lower doses failed to alter response times in the hot plate. These data demonstrate that trialkyl lead and tin compounds can produce time- and dose-related increases in hot plate latencies.

Topics: Animals; Central Nervous System Diseases; Dose-Response Relationship, Drug; Lead; Lead Poisoning; Lethal Dose 50; Male; Organometallic Compounds; Organotin Compounds; Pain; Rats; Rats, Inbred F344; Reaction Time; Tetraethyl Lead; Time Factors; Triethyltin Compounds; Trimethyltin Compounds

Topics: Acute Disease; Humans; Lead; Lead Poisoning; Organometallic Compounds; Tetraethyl Lead

Topics: Animals; Brain; Lead; Lead Poisoning; Myelin Proteins; Myelin Sheath; Organometallic Compounds; Rats

Topics: Animals; Animals, Newborn; Body Weight; Brain; Brain Chemistry; Cerebrosides; Cholesterol; Glycolipids; Lead; Lead Poisoning; Lipids; Myelin Sheath; Organ Size; Organometallic Compounds; Phospholipids; Rats; Sulfoglycosphingolipids

Topics: Administration, Oral; Animals; Chlorides; Lead; Lead Poisoning; Organometallic Compounds; Rats; Tetraethyl Lead

Topics: Lead Poisoning; Organometallic Compounds; Sulfhydryl Compounds

Topics: Humans; Lead Poisoning; Liver; Organometallic Compounds; Tetraethyl Lead