Ppm Lead Acetate Research Articles

Effects of lead on neurophysiological and performance measures: animal and human data.

This paper reports lead-induced changes in neuropsychological measures and behavioral performance measures in monkeys and children. Monkeys were pre- and postnatally exposed to lead via the diet. Blood lead levels at the time of testing were 9.3, 40.3, and 55.7 micrograms/dL in controls, and animals exposed to 350 ppm or 600 ppm lead acetate, respectively. Flash-evoked and brainstem auditory-evoked potentials were recorded in adult animals. Results indicate latency increases in both measures as well as amplitude decreases in the flash-evoked response. Delayed reaction time and serial choice reaction were determined as measures of behavioral performance in lead-exposed school-age children from two lead smelter areas. In addition, pattern-reversal-evoked potentials and nerve conduction velocity were investigated. Neither nerve conduction velocity nor latency of the pattern-reversal-evoked potential were consistently influenced by lead. Of the behavioral measures, serial choice reaction performance revealed a consistent lead-related deficit, which became more pronounced with increasing task difficulty.

The effects of thiamin on the tissue distribution of lead

The effects of thiamin on the tissue distribution of lead were evaluated in Sprague-Dawley rats exposed to 1000 ppm lead acetate in drinking water and treated daily with thiamin (25 or 50 mg kg-1 body weight, i.p.), calcium ethylenediamine tetraacetic acid (50 mg kg-1 body weight, i.p.) or their combination for 8 weeks. The subtoxic dose of lead did not alter weight gains, feed and water consumption during the treatment period. Thiamin decreased the blood (P less than 0.0001), liver (P less than 0.0001) and kidney (P less than 0.0001) concentrations of lead. Thiamin (50 mg kg-1 body weight) reduced the lead concentrations in tissues more effectively than thiamin (25 mg kg-1 body weight). The combined treatment was more effective than the respective individual treatments.

Alterations in tissue Pb distribution and hematopoietic indices during advanced age

The inevitable degenerative processes accompanying advanced age suggest that senescent organisms might exhibit differences in toxicokinetics or an altered manifestation of toxic effects. This hypothesis was tested in the present experiment which compared tissue distribution and hematopoietic indices in groups of adult (8 months) and old male Fischer-344 rats (16 months) exposed to concentrations of 0, 250 or 500 ppm lead (Pb) acetate in drinking water for 7 months. A group of young (weanling) rats was included as a partial comparison. Blood lead (PbB), zinc protoporphyrin (ZPP) and urinary delta-aminolevulinic acid levels were determined after both 3 and 7 months of exposure. Organ weights, tissue Pb concentrations and urinary excretion of Pb, calcium, copper, and zinc were examined after 7 months of exposure. Tissue Pb distribution was markedly altered in old rats: bone and kidney Pb were reduced; liver Pb was substantially increased, even though PbB levels in adult and old rats were comparable at both measurement intervals, as was urinary Pb excretion at 7 months. Pb-induced elevation of ZPPs exhibited differential changes between 3 and 7 months: values in adults declined while levels in old rats increased or remained unchanged. These findings show that the responses of adult rats to Pb do not predict those of older rats and indicate the need for further characterization and elaboration of mechanisms of toxic effects with advanced age.

Alteration of the visual evoked potential and the electroretinogram in lead-treated monkeys

Rhesus monkeys were pre- and postnatally exposed to either 0, 350, or 600 ppm lead acetate in lab chow. At the age of 7− 7 1 4 years visual evoked potentials (VEP) and electroretinograms (ERG) were recorded. Flashes were used as stimuli. The VEP was taken under two background illuminance conditions. Lead-related decreases in amplitudes and increases in latencies were observed. Effects on amplitudes were more pronounced under the dark condition while latencies were more affected at the bright background level. The ERG was studied during the course of dark adaptation. The increase in amplitudes of the b-wave during the adaptation period was more prominent in lead-exposed subjects than in controls. Oscillatory potentials were not altered by lead. The findings are discussed in terms of the physiological mechanisms underlying these different potentials.

Evaluation of the relationship between chemical and biological monitoring of low‐level lead poisoning

Blood lead levels, together with delta-aminolevulinic acid dehydratase activity determinations have been measured on rats dosed with up to 1000 ppm lead acetate in their drinking water for periods up to 5 weeks. Despite evidence of a compensation mechanism developing in the enzyme determinations, enzyme activity ratios, if properly chosen, still correlate reasonably well (r = 0.87) with blood lead levels. Activity ratios using data on the shoulders of pH-activity profiles (e.g. activity ratios of 6.4 and 7.2), however, give much less satisfactory correlations. These data provide a more stringent test of the chemical monitor-biological monitor correlation than has previously been possible.

Behavioral effects following rehabilitation from postnatal exposure to lead acetate.

At 21 days of age three groups of male hooded rats of the Sprague-Dawley strain were exposed to either untreated water or lead acetate at concentrations of 25 or 50 ppm provided ad lib. in the drinking water for 40 days. When tested for spontaneous alternation, the subjects receiving both 50 ppm and 25 ppm lead acetate exhibited significantly reduced rates of alternation below those of untreated control subjects. Immediately subsequent to testing, lead was removed from the diet of the experimental groups and water substituted which was provided ad lib. for the duration of the experiment. This regimen of rehabilitation was continued for 70 days at which time all subjects were tested on the problems of the Hebb-Williams closed-field maze-learning task. No significant differences were found in the time taken to traverse the maze enclosure, the number of squares traversed, or in the total number of error zones entered over the 12 test problems, although significantly increased latencies to leave the start box were noted for subjects previously exposed to lead acetate. These data indicate that some deficits produced by postweaning lead acetate exposure may be reversible and not persist beyond a period of rehabilitation.

Performance and exposure indices of rats exposed to low concentrations of lead

To further characterize the lower end of the function relating lead exposure and biological exposure indices to behavior, male weanling rats were exposed chronically to drinking solutions containing 25 ppm sodium acetate (controls) or 25 ppm lead acetate. Behavioral training began when the animals reached 50 days of age, and performance on a fixed-interval 1-min schedule of food reinforcement was then assessed over 90 experimental sessions (136 days). This exposure produced overall response rate increases over the first 40 sessions that were similar to those observed previously with higher concentrations of lead. Response rates of the two groups tended to merge subsequently. The increased overall response rates in the treated group derived primarily from an increased frequency of shorter interresponse times (IRTs) and increased running rates (calculated without the postreinforcement interval). Blood lead (PbB) and zinc protoporphyrin (ZPP) values were determined following sessions 30, 60, and 90. PbB values of the lead-exposed group averaged 15 to 20 μg/dl throughout the study; ZPP did not differ. The mean brain lead value of the treated group was 0.07 μg Pb/g. Blood-brain ratios (1.38 to 4.06) were substantially greater than those previously observed at higher exposures. These data extend to even lower exposures, and lower blood lead concentrations, the effective concentration for behavioral effects, and further emphasize the importance of the sensitivity of the endpoint in assessing behavioral toxicity.

Delayed behavioral toxicity of lead with increasing exposure concentration

Twenty-one-day-old male Long-Evans hooded rats were exposed chronically to drinking solutions containing 500 ppm sodium acetate (controls) or 50, 100, or 500 ppm lead acetate. Performance on a fixed interval 1-min schedule of food reinforcement was assessed over 155 sessions. Blood lead values were monitored serially and brain lead determinations made at the end of testing (335 days of lead exposure). The lowest concentration of lead in the drinking water was associated with increases in the rate of fixed-interval responding over the first 30 sessions. At the two higher concentrations, response rate values similar to controls over the first 40 sessions were followed by rate increases. The latency to maximum rate depended on concentration; the highest concentration was associated with the longest latency. Response rates of rats exposed to 50 ppm lead gradually returned to control levels after 120 sessions, while increased rates were sustained in rats at 100 and 500 ppm lead, even 100 days after lead exposure was terminated. Marked individual differences in susceptibility to lead-induced rate increases were observed in all treatment groups. Serial blood lead values were related both to exposure concentration and duration. Brain lead values also reflected exposure concentrations. Blood-brain ratios averaged 0.743 to 0.913, which agree with other data for the rat and human. These results confirm the vulnerability to lead of rats beyond the neonatal period, and extend the range of conditions under which such effects occur.

Effect of low-level lead exposure on antibody-dependent and natural killer cell-mediated cytotoxicity

Splenic antibody-dependent, cell-mediated cytotoxicity against chicken red blood cell targets {ADCC (CRBC)} and natural killer cell-mediated cytotoxicity (NKMC) were determined in C57BL/6 mice given 1300 ppm lead acetate (827 ppm lead) in their drinking water for 8 weeks. ADCC in lead exposed mice was significantly lower than controls at effector to target cell ratios of 100:1, 50:1, and 25:1. In contrast, no significant difference in unstimulated NKMC was seen in lead exposed mice and control mice at effector to target cell ratios of 200:1, 100:1, and 50:1, Moreover, in vivo poly I:C-enhanced NKMC in lead-treated mice was similar to controls at an effector to target cell ratio of 200:1. Blood lead levels averaged 40.5 ± 1.2 μg% in lead-exposed mice and 1.9 ± 0.3 μg% in controls. These findings suggest that chronic low-level lead exposure in mice results in significant suppression of ADCC (CRBC) but does not alter natural killer activity.

Basic Lead Acetate: Promoting Effect on the Development of Renal Tubular Cell Tumors in Rats Treated With <italic>N</italic>-Ethyl-<italic>N</italic>-hydroxyethylnitrosamine

The development of renal tubular cell tumors by the end of experimental week 32 was studied in inbred Wistar male rats fed a diet containing 1,000 or 500 ppm N-ethyl-N-hydroxyethylnitrosamine (EHEN) for 2 weeks and then given 1,00 ppm basic lead acetate (LA) for 20 weeks. A low dose of LA enhanced the development of renal tubular cell tumors in rats treated with EHEN and increased the number and size of the tumors. The incidence of renal tubular cell tumors at the end of week 32 was 50% in rats treated with 1,000 ppm EHEN for 2 weeks and 100% in rats treated with 1,000 ppm EHEN for 2 weeks and then given 1,000 ppm LA for 20 weeks. The incidences of renal tumors of more than 3 mm in diameter were 70% in rats treated with 1,000 ppm EHEN plus LA and 0% in rats treated with EHEN or LA alone. The low dose of LA showed the enhancing effect of the development of renal tubular cell tumors in rats treated with a subthreshold dose of 500 ppm EHEN.

Lead acetate: toxicity without effcts on the locomotor activity of the bluegill sunfish, Lepomis macrochirus Rafinesque

The concentration of lead acetate which caused 50% mortality of bluegill in 96 h (96 h LC50) is approximately 400 ppm. Sublethal concentrations of 0.1, 1, 10, 100, 200 and 300 ppm lead acetate did not produce any effects on the locpmotor activity of the bluegill. The observation that lead can reach concentrations which are lethal without sublethal effects on locomotor activity at lower concentrations is unusual and in sharp contrast to studies with other metals (Ellgaard et al.. 1978).

Chronic lead exposure of rats: open-field performance.

Three groups of male hooded rats were chronically exposed to lead in the acetate form prenatally, as well as postnatally via the dam's milk and in the drinking water, at concentrations of 0 ppm, 19 ppm, and 38 ppm for 35 days. No significant differences were found in weight gain, although significant increases in food consumption were noted in animals receiving 19 ppm lead acetate and increased ingestion of lead acetate in animals receiving 19 ppm and 38 ppm. When subjects were tested in an open-field task, no significant differences were found in emotionality, the number of squares traversed, frequency and duration of rearing, or in frequency of grooming. However, subjects receiving 38 ppm lead displayed a significant reduction in duration of grooming when compared to animals receiving either 19 ppm or 0 ppm. The results suggest that prenatal lead exposure, followed by postnatal exposure, may affect some elements of activity, while having little effect on others.

Effect of chronic lead ingestion by rats on glucose metabolism and acetylcholine synthesis in cerebral cortex slices.

The effect of chronic low-level lead (Pb2+) ingestion on the metabolic pathways leading to the acetyl moiety of acetylcholine (ACh) was examined. Cerebral cortex slices, prepared from untreated or Pb2+-exposed rats (600 ppm lead acetate in the drinking water for 20 days), were incubated in Krebs-Ringer bicarbonate buffer with 10 mM glucose and tracer amounts of [6-3H]glucose and either [6-14C]glucose or [3-14C] beta-hydroxybutyrate. Altering the concentration of Pb2+ in the drinking water produced a dose-related increase in blood and brain lead levels. When tissue from Pb2+-exposed rats was incubated with mixed-label glucose, incorporation into lacate, citrate, and ACh was considerably decreased, although no changes occurred in the 3H/14C rations. Similar effects of Pb2+ were found when 14C-labeled beta-hydroxybutyrate was substituted for the [14C]glucose. It appears from these data that Pb2+ exerts a generalized effect on energy metabolism and not on a specific step in glucose metabolism. The impairment of glucose metabolism may explain partially the Pb2+-induced changes observed in cholinergic function.

Chronic postweaning lead exposure and response duration performance

Twenty-one-day-old male weanling rats were started on a chronic exposure regimen of 0, 100, or 300 ppm lead acetate in distilled water. They were trained to press a lever for food reward at 55 days of age. Subsequently, a schedule of differential reinforcement of minimum response duration was imposed, in which only lever press durations greater than or equal to a required duration were followed by food presentation. Under these conditions, response durations of control animals approximated schedule requirements; lead treatment shortened response durations. Treated rats also paused for longer periods before initiating responses. Differences between the treated groups were not apparent. Individual differences were observed in susceptibility to lead-induced behavioral changes. Some treated animals tended to show greater session-to-session variability than did controls. Even when a tone was added to signal that the required duration had elapsed, certain treated rats failed to show modal response duration values consistent with the schedule requirement. Failure to improve performance of lead-treated rats by external stimulus control has not previously been reported.

Effects of postnatal lead acetate exposure on activity and emotionality in developing laboratory rats

At 21 days of age three groups of female hooded rats were exposed to lead at concentrations of 0 ppm, 25 ppm, or 50 ppm provided ad lib in the acetate form for 35 days in the drinking water. No significant differences were found in food consumption, lead acetate or water con sumption, and weight gain. When subjects were tested in an open-field task, no significant differences were found in either the duration or frequency of grooming or rearing behavior, or the number of squares traversed. However, significant differences in emotionality were observed. Subjects receiving 50 ppm lead acetate exhibited markedly greater emotionality when compared with subjects receiving either 25 ppm lead acetate or 0 ppm lead acetate. The results appear to indicate that postnatal lead exposure may affect some elements of emotional behavior, while having little effect on activity.

Lead-induced crop dysfunction in the pigeon

Pigeons treated with lead acetate (12, 36, or 72 mg Pb/kg/day by gavage or 1000 or 3000 ppm lead acetate in drinking water) displayed crop dilatation and stasis and motor incoordination, regurgitated crop fluid, and suffered severe wasting of breast muscle. Ball bearings inserted in the crop failed to pass to the stomach. Such retardation of motility reliably preceded signs of overt toxicity. The etiology of the crop stasis could not be determined by histopathologic examination, suggesting a subcellular mechanism. The results suggest that behavioral changes induced by lead in pigeons cannot be attributed to CNS dysfunction alone, but may arise from starvation, or from combined CNS damage and starvation and that GI impaction in aves resulting from lead exposure appears to be a systemic, rather than a local effect.

Behavioral effects of postnatal lead acetate exposure in developing laboratory rats

At 23 days of age, three groups of male albino Sprague-Dawley rats were exposed to lead at concentrations of 0, 25, or 50 ppm, provided ad lib, in the acetate form, for 35 days in the drinking water. When tested on the problems of the Hebb-Williams closed-field maze learning task, the subjects receiving both 50 ppm lead acetate and 25 ppm lead acetate displayed significantly impaired learning ability when compared to water-fed controls in the total number of error zones entered over the 12 test problems. The time taken to traverse the maze enclosure, however, was significantly reduced only in the group receiving 50 ppm lead acetate. None of the overt manifestations characteristic of lead poisoning were observed. Learning deficits can be produced in the weanling rat at levels of exposure similar to those which cause encephalopathy in the developing neonate.

Behavioral toxicity of chronic postweaning lead exposure in the rat

Effects in the rat of chronic postweaning exposure to 50, 300, or 1000 ppm lead acetate in drinking water were assessed on responding maintained by a fixed-interval 30-s food reinforcement schedule. On this schedule, food reinforcement followed the first lever press response occurring at least 30 s after the preceding food delivery. Exposure to 50 and 300 ppm lead acetate increased response rates and intersubject variability, while latency, or time to initiation of responding in the interval, decreased. Exposure to 1000 ppm initially decreased rates and increased latency values. Following termination of exposure to 50 ppm, response rates and latency values gradually returned to control levels. Behavioral effects produced by exposure to 50 and 300 ppm lead were similar in magnitude but varied in time to onset and decline, suggesting time-dependent, rather than concentration-dependent effects of lead.

Interaction of lead and zinc on the prothrombin activity in rats

In 1955 Saita and coworkers reported a defect in blood coagulation in workers exposed to lead. Very little attention has been given to this observation. In our study in rats receiving 100 ppm lead (acetate) on an adequate semi-purified diet we observed a decreased prothrombin activity. This condition was more severe when dietary zinc was low (5 ppm) than when superoptimal (50 ppm). The correlation between prothrombin time and blood lead was highly significant (r = 0.842, P < 0.001). Although it has been generally accepted that altered prothrombin activity may arise from liver dysfunction, nevertheless serum glutamate-oxaloacetate transaminase (SGOT), a measure of liver function, was normal in all animals. Changes were observed, however, in serum protein pattern due to lead, the A/G ratio was lowered in lead-exposed rats receiving low zinc thus indicating a possible hepatic alteration.