triethyllead and Body-Weight

This study was undertaken to ascertain the neuropathologic effects of low level exposure of triethyl lead (3EL) to young male rats. Groups of 20 male Sprague-Dawley weanling rats were given 3EL at 0, 0.05, 0.10, 0.20, 0.50, and 1.00 mg/kg body wt for 91 days, 5 days/week by oral gavage. Lead acetate (PbHOAC) was given at 200 mg/kg body wt/day as a positive control. Animals (five or six) were perfused with glutaraldehyde following barbiturate anesthesia at the termination of the experiment. These animals and the remaining members of the group received a thorough gross and microscopic postmortem examination. Sections of the central, peripheral, and autonomic nervous systems were examined and lesions scored. No lesions were noted in the brain, but randomly distributed light microscopic changes of spinal cord Wallerian degeneration were noted to increase in a dose responsive manner (rho = 0.48; p < 0.01), with 3EL administration. Ultrastructural examination of selected sections of the lumbosacral nerves, revealed lesions characterized by reduced neurofilaments and neurotubules, and irregular lamellated axoplasmic dense bodies in all animals receiving lead. Organolead was only detected in animals receiving 3EL, but lead cations were detected in all lead-treated animals. The brain lead levels of 1.00 mg/kg/day and 200 mg Pb acetate positive control animals were equivalent. As distinctive ultrastructural lesions were seen in all rats treated with 3EL, we suggest that the no observed adverse effect level (NOAEL) for 3EL be lowered to less than 0.05 mg/kg/day.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Autonomic Nervous System; Body Weight; Brain; Male; Microscopy, Electron; Nervous System Diseases; Organometallic Compounds; Peripheral Nerves; Rats; Rats, Sprague-Dawley; Spinal Cord; Wallerian Degeneration; X-Ray Diffraction

This study was designed to ascertain the effects of low level exposure of triethyl lead (3EL) to the male weanling rat. Groups of 20 animals were administered by gavage 3EL at 0.05, 0.10, 0.20, 0.50, and 1.00 mg/kg body wt for 91 days, 5 days/week. Lead acetate (PbHOAC) at 200 mg/kg body wt/day was given as a positive control. Weight gain was reduced in those animals receiving 1.0 3EL. Spleen and kidney weights were elevated in the PbHOAC group. Residues of 3EL and its metabolites diethyl lead (2EL) and lead (Pb) accumulated in a dose-dependent manner in blood, liver, kidney, and brain; 3EL accumulated preferentially in the liver while inorganic lead accumulated in the kidney. Dose-dependent changes occurred in serum calcium which was decreased and in phosphorus which was elevated for all dose groups. Serum cholesterol was elevated in the three highest 3EL groups as was alkaline phosphatase. LDH was lowered in the PbHOAC-treated group but microsomal aniline hydroxylase was elevated. Hematological changes consisted of elevated platelet counts in the 1.0 3EL group and decreased mean corpuscular hemoglobin content and mean corpuscular volume in the PbHOAC-treated group. Treatment related histopathological changes were seen in thyroid, liver, kidney, and bone marrow. Based on these data a no observed adverse effect level for 3EL was set at 0.10 mg/kg/body wt.

Topics: Administration, Oral; Animals; Body Weight; Kidney; Liver; Male; Organ Size; Organometallic Compounds; Porphobilinogen Synthase; Rats; Rats, Inbred Strains; Tissue Distribution

Female mice were injected intraperitoneally daily from day 18 of gestation and throughout lactation with triethyl lead chloride (TEL; 0.0, 0.5 and 1.0 mg/kg body wt). Off-spring of treated mothers displayed a slight perinatal growth retardation. Male off-spring appeared to be more sensitive to TEL, as indicated by their lower body weights. During the latter half of the lactation period the treated sucklings grew faster than controls, thereby compensating for their initially retarded growth, by the time of weaning. The hepatic cytochrome P-450 content of 9 to 10-day old sucklings of treated mothers was lower than in corresponding controls. We suggest that perinatal growth retardation is initiated by a disturbance in the uterus, e.g. reduced nutrient transport across the placenta.

Topics: Animals; Animals, Newborn; Body Weight; Cytochrome P-450 Enzyme System; Female; Fetal Growth Retardation; Fetus; Maternal-Fetal Exchange; Mice; Organometallic Compounds; Pregnancy

Triethyllead chloride and 2,5-hexanedione are known neurotoxicants that apparently work through separate mechanisms. The effect of combined treatment of triethyllead chloride and 2,5-hexanedione for 6 weeks on Fischer 344 rats was investigated. Ten rats were given 0.7 mg/kg triethyllead chloride in a volume of 2 ml/kg by gavage while another group was given 0.5% 2,5-hexanedione in drinking water and vehicle by gavage (2 ml/kg). A third group was given a combination of the two treatments. A fourth group served as controls and was given vehicle by gavage. 2,5-Hexanedione produced a reversible loss of body weight, decreased grip strength, and decreased horizontal motor activity. Triethyllead chloride alone increased hot-plate latencies. Triethyllead chloride and 2,5-hexanedione treated animals recovered 4 weeks after cessation of treatment. Neither treatment alone produced fatalities. In combination (2,5-hexanedione + triethyllead chloride) decreases in body weight appeared additive and there was a 40% mortality by 6 weeks of dosing. Rats given the combined treatment had significant loss of both grip strength and increased hot-plate latencies. Neurobehavioral deficits and neuropathological changes were greater in the combined treatment with 2,5-HD and TEL than when either chemical was used alone; there was little indication of a synergistic interaction between these two types of neurotoxicants.

Topics: Administration, Oral; Animals; Body Weight; Drug Synergism; Hexanones; Ketones; Liver; Male; Motor Activity; NADH Dehydrogenase; Organometallic Compounds; Rats; Rats, Inbred F344; Reaction Time; Sciatic Nerve

The dose-related behavioral effects produced by triethyl (TEL) (2.6 to 7.9 mg/kg) and trimethyl lead (TML) (8.8 to 26.2 mg/kg) were assessed 2, 7, 14, 21 and 28 days following injection. TEL, but not TML, produced dose- and time-related decreases in body weight. Both agents decreased vertical and horizontal components of motor activity 2 days postdosing; increased activity was seen consistently in TEL-exposed rats 7 to 21 days after dosing. TML increased fore- and hindlimb strength for up to 28 days postdosing. TEL had no consistent effect on this measure. Both TEL and TML decreased responsiveness to an acoustic stimulus during the first two weeks postdosing. Latency to respond to a thermal stimulus was increased 2 to 14 days after TEL with the peak change occurring from 2 to 7 days. The peak of effect following TML was two weeks postdosing. In general, there was a significant correlation between both TEL and TML-induced changes in blood and brain lead levels and decreased sensitivity to a thermal stimulus. The apparent delayed onset of TML-induced neurobehavioral effects may be related to a longer time to obtain peak blood or brain levels. Histopathological assessment of rats 7 or 28 days after TEL and TML indicated that TEL caused structural abnormalities in the hippocampus and dorsal root ganglion, while TML produced changes primarily in the spinal cord and brain stem.

Topics: Animals; Behavior, Animal; Body Weight; Brain; Dose-Response Relationship, Drug; Male; Motor Activity; Organometallic Compounds; Rats; Rats, Inbred F344; Reaction Time; Reflex, Startle; Sensory Thresholds; Spinal Cord; Tetraethyl Lead

In order to study the effect of organolead on the placental transfer of amino acids, triethyl lead chloride was administered by i.p. injections to pregnant guinea-pigs. The following day, the fetal part of the placenta was perfused in situ during i.v. infusion of alpha-aminoisobutyric acid (AIB) to the dam. It was found that triethyl lead treatment (2.5 mg/kg body wt) decreased the AIB-concentration in perfusion media compared with that of the control group. Treatment with 1 mg/kg body wt has no effect. It was also shown that the placental uptake of AIB in animals receiving 2.5 mg/kg body wt is significantly reduced compared with that of the control group. No such effect was obtained in animals receiving 1 mg/kg body wt. It is suggested that triethyl lead may inhibit placental Na+-K+-adenosinetriphosphatase, an enzyme involved with placental amino acid transport. Another possible explanation is a reduction in maternal placental blood flow.

Topics: Aminoisobutyric Acids; Animals; Body Weight; Female; Guinea Pigs; Lead; Male; Organometallic Compounds; Placenta; Pregnancy

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: Animals; Behavior, Animal; Body Weight; Brain; Depression, Chemical; Ethane; Ethyl Chloride; Female; Lead; Lipid Metabolism; Male; Myelin Sheath; Organometallic Compounds; Rats; Time Factors