Showing papers on "Lead acetate published in 1983"

The effect of pre- or postnatal lead exposure on Hamilton Search Task in monkeys.

Abstract: Rhesus monkeys were exposed to low, chronic levels of lead acetate either pre- or postnatally. Considerable neural and behavioral evidence indicates that the hippocampus is preferentially affected by low-level lead exposure. Hippocampal dysfunction is known to result in disruption of spatial memory. The monkeys in these experiments were tested as juveniles on a spatial memory test, the Hamilton Search Task. The monkeys exposed prenatally to lead did not show a deficit, while those exposed postnatally showed a significant deficit on the Hamilton Search Task. The deficit was not apparent until the monkeys were required to meet the most strict criterion, suggesting that the impairment may be due to the memory rather than the learning components of the task. The fact that the deficit was seen more than 3 years after the end of lead exposure indicates that the lead-induced cognitive effect is quite long-lasting and perhaps permanent.

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

Abstract: 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.

Effects of Low Lead Exposure on Neuro-Behavioral Function in the Rat

Abstract: Small doses (45-180 micrograms/g) of lead acetate were administered to male rats by gavage every day during the first 3 wk of life. A blood concentration of approximately 59 micrograms/100 ml blood produced signs of disturbances in reflex development and some changes in emotional behavior. Larger doses resulted in subtle changes in the neuromotor coordination function. The effect of low levels of lead exposure on the cognitive function in operant conditioning could not clearly be observed. Brain lead concentration tended to be higher than in other tissues examined. At approximately 10 months following cessation of lead acetate administration, the brain lead concentration had decreased to almost the same level found in control rats, and no distinguishable differences were observed between the lead-treated rats and controls in emotional behavior and neuromotor coordination.

Mechanisms of ALA-D inhibition by lead and of its restoration by zinc and dithiothreitol.

Abstract: To induce the inhibition of ALA-D (delta-aminolaevulinic acid dehydratase) activity by lead in vitro, it is necessary to preincubate the enzyme fraction with lead ions and the Hb fraction (factors) together. The combination of two of the three (ALA-D fraction, lead acetate, and Hb fraction) in the preincubation has only a small effect on the activity. Lead preincubated with ALA-D and Hb fractions does not alter the affinity of the enzyme for the substrate, suggesting that the substrate can bind to the enzyme molecules (non-competitive inhibition). The restoration of activity by zinc with dithiothreitol is associated with the removal of lead from ALA-D fraction proteins to which it has bound in vivo and in vitro. The mode of the inhibitory action of tin on ALA-D is similar to that of lead because the inhibition is intensified by the addition of Hb fraction and is restored by heating. The inhibition concentration is, however, higher than that of lead. Of the three methods recovering decreased activity, heating is the most specific to detect inhibition by lead.

Redistribution and increased brain uptake of lead in rats after treatment with diethyldithiocarbamate.

Abstract: Diethyldithiocarbamate (DDTC), a chelating agent, is an active metabolite of disulfiram (Antabus®) and is used in the rubber industry. The effect of DDTC on the tissue distribution of 203Pb was studied in rats. Two groups of rats were given an i.v. injection of 100 μCi 203Pb (28.6 nmol/kg b.wt.) as lead acetate. After 10 min one group received 2 mmol/kg b.wt. of DDTC as an i.p. injection. Rats were killed 4 and 72 h after injection of 203Pb and tissue concentration and excretion of 203Pb was determined by gamma counting. The brain concentration of 203Pb in DDTC-treated rats was nine times higher than in controls after 4 h and 14 times higher after 72 h. Treatment with DDTC also increased the lead concentration in fat about seven times at both survival intervals. On the other hand, uptake of 203Pb in bone was reduced by treatment with DDTC and at 4 h also kidney and blood had a lower concentration of 203Pb in DDTC-treated rats compared to controls. Kidney and femur of DDTC-treated rats had an increased 203Pb concentration at 72 h compared to 4 h. Most of the lead was excreted via feces; 28% of the dose in DDTC-treated rats and 16% in controls during the first 72 h after injection. The urinary excretion of 203Pb was higher in control rats (11% of the dose) than in DDTC-treated rats (6%). The results indicate that a lipid-soluble complex of lead and DDTC is formed, which is capable of penetrating the blood-brain barrier to a much higher extent than inorganic lead. The toxic effects of the lead-DDTC complex are not known, but one may expect that inorganic lead is released causing adverse effects in the central nervous system, when the lead-DDTC complex is further metabolized.

The effect of low lead doses in vitro and in vivo on the d-ala-d activity of erythrocytes, bone marrow cells, liver and brain of the mouse

Abstract: The d-ala-d activity in erythrocytes (RBC), femur bone marrow, liver and brain of mice was determined using a modification of the method of Berlin and Schaller (1974). In vitro incubation of lead acetate (PbAc) with these tissues resulted in a dose-dependent inhibition of the d-ala-d activity. The lead concentration which caused a 50% inhibition of the d-ala-d activity after 10 min incubation [ED-50(10 min)] was 0.78 mg PbAc/femur bone marrow, 3.72 micrograms PbAc/ml RBC, 15.85 micrograms PbAc/g brain and 43.05 micrograms PbAc/g liver. An increase in the incubation time to 60 min reduced these ED-50 values between 44% for the erythrocytic enzyme and 67% for the brain enzyme. In vivo treatment of mice with oral lead administration (absorbed dose range: 1-100 micrograms PbAc/kg b.w.) for 1 or 3 months led to a dose-dependent and organ-specific inhibition of the d-ala-d activity. After 3 months of oral lead supply the maximum enzyme inhibition (54%) was found in the bone marrow. At the same time the lowest enzyme inhibition could be seen in the brain which retained 73% of its activity. The erythrocytic and liver enzyme activity was 71% and 72% resp. of the appropriate control. Within 3 weeks after completing the oral lead administration the brain enzyme activity was completely restored. The erythrocytic and liver enzyme activities were still significantly, but not very markedly inhibited, whereas the bone marrow d-ala-d remained seriously depressed. According to these experiments, the lead dose which causes a long term inhibition of the bone marrow and erythrocytic d-ala-d activities is assumed to range between 50 and 100 micrograms PbAc/kg b.w. and day, as an absorbed dose.

Lead distribution in the nervous system of 8-month-old rats intoxicated since birth by lead.

Abstract: Lead levels in the nervous system of rats intoxicated for 8 months by lead acetate (0.2% in drinking water) varied according to the region: the lowest levels were observed in sciatic nerve and the highest in hippocampus and cerebral neocortex, while intermediate levels were observed in pons medulla, cerebellum, midbrain, hypothalamus and striatum.

Effects of lead exposure on peripheral nerve in the cynomolgus monkey.

Abstract: The relationship between blood lead concentration and nerve conduction velocity has been examined, using the cynomolgus monkey as a model for human lead poisoning, with lead dose and blood lead concentration maintained under controlled conditions, to determine whether nerve conduction velocity could be used as an objective measure of the effects of lead on the nervous system at subclinical concentrations. Five cynomolgus monkeys were maintained at a blood lead concentration of 90-100 micrograms Pb/100 ml for nine months by daily oral dosing with lead acetate (12-15 mg Pb/kg body weight). Motor nerve conduction velocity in the ulnar nerve was measured, together with blood lead concentrations. Blood lead concentrations were proportional to lead intake, reaching a stable level within one to two weeks. Lead did not accumulate in the blood, and blood lead concentrations were found to decrease to a maintained plateau from initial high concentrations during the first seven days of dosing. The animals showed no clinical or behavioural evidence of lead poisoning at any time during the study, although there was a progressive decrease in blood packed cell volume, haemoglobin concentration, and erythrocyte concentration. The maximal motor nerve conduction velocity of the ulnar nerve remained constant throughout the study, although changes were observed in the conduction velocity of slowly conducting nerve fibres. At termination, intranuclear inclusions were found in the renal tubular cells of all animals as were focal areas of myelin degeneration in the ulnar and sciatic nerves.

Regressive or lethal lead encephalopathy in the suckling rat. Correlation of lead levels and morphological findings.

Abstract: Lead encephalopathy was produced in immature Sprague-Dawley rats with an intraperitoneal (IP) injection of 60 µg/g body weight of lead acetate administered daily from the fifth day after birth. Macroscopic and light microscopic study of the nervous system, estimations of the blood-brain barrier permeability to proteins and brain water content were performed every two days thereafter. Lead levels in total blood, plasma, and several brain areas were measured at the same intervals by flameless atomic absorption spectrometry. Electron microscopic study of the cerebellum was done 2, 6, and 12 days after beginning lead administration. After two days of lead administration and before any pathological change occurred the increase in lead level was greater in the cerebellum than in other brain areas. After four to six days, hemorrhagic lead encephalopathy developed and was most prominent in regions with higher lead levels. From day 11 to 14, there were two possible courses: a) improvement of the clinical status and morphological findings in 25% of the animals, or b) progression of abnormal clinical signs and death. Cerebral edema, both intra- and extracellular, may have contributed to the fatal evolution. The mechanism of this edema appeared complex and may have involved resorption failure. Good correlations were observed among progression of the clinical signs, high water content in the brain, morphological evidence of cerebral edema, and a high cerebellar lead level. In contrast, high blood lead levels could be associated with clinical improvement, normal brain water content, and regression of the pathological findings. These data suggest that differences in evolution are more likely related to differences in the development of resistance of the cerebral capillary to lead, or in the efflux of lead, rather than to the blood lead concentrations

Tissue distribution of lead in the neonatal rat exposed to multiple doses of lead acetate

Abstract: The tissue distribution of lead (Pb) was examined in the neonatal rat intragastrically administered lead acetate (50 mg/kg, containing 210Pb) beginning on d 6 postpartum and thereafter at 3-d intervals to d 18. A time-dependent pattern of uptake was observed in bone, kidney, liver, and brain, while stomach, lung, heart, and spleen had no accumulation of Pb. The highest concentration of Pb at d 21 was detected in bone, and the least amount was found in blood and brain. Body weight was not significantly affected by the level of Pb exposure employed.

Effect of Lead on Reproductive Capacity and Development of Mammals

Abstract: The hazards of lead to reproduction are reviewed on the basis of the concentrations found in the environment. It appears evident that lead has no direct action on male reproductive capacity. Most likely, indeed, alterations in sperm morphology reported by several authors reflect the general cytotoxicity of the metal and not any mutagenic action since recent reviews concluded that lead is neither mutagenic nor clastogenic. This is also confirmed by the outcome of the dominant lethality and fertility tests which gave negative results. Lead crosses the placental barrier, a fact demonstrated in man as well as in experimental animals, but the human placenta presents a partial barrier to the transfer of lead. Given to pregnant mice, lead delays embryonic development and also has an indirect effect by modifying hormonal production needed for the implantation process. The toxic action on the fetus at late stages of pregnancy is caused mainly by an interference with heme synthesis but also by a lowered blood flow through the placenta.

Cardiac effects of lead.

Abstract: Symptoms consistent with cardiac disease have been noted as part of the syndrome of lead (Pb) intoxication. All types of cardiotoxicity noted in patients have been reproduced in experimental animals exposed acutely to high concentrations of Pb, or chronically exposed to lower levels. Types of cardiac effects observed include negative inotropism and electrocardiogram abnormalities, particularly conduction defects. Neonatal rats exposed to Pb via the milk of dams provided a drinking solution of lead acetate exhibit approximately four times the sensitivity to the arrhythmogenic effect of norepinephrine as adults compared with controls. Cardiotoxicity occurs after exposure as short as the first 10 postnatal days, but is not expressed until the rats are adult. Increased sensitivity to the arrhythmogenic effect of norepinephrine was seen in Pb-exposed animals in vivo and in isolated hearts from Pb-exposed animals in vitro. Norepinephrine arrhythmogenesis in vivo was attenuated by atropine or vagotomy, which indicates vagal nerve involvement. Possible mechanisms including interference with central gamma-aminobutyric acid systems, alteration of adrenergic nerve development, and Pb-Ca interaction are discussed.

Impact of lead on nucleic acids and incorporation of labelled amino acid into protein.

Abstract: The effects of high administration of lead acetate (3.4 mg/100 g of body weight) for a period of 4 days were studied in albino rats. The weights of lead treated rats were not affected while the liver showed enlargement following treatment. Administration of lead reduced the protein content of liver and concentration of DNA decreased to a slight extent. Protein/DNA ratio in liver remained unaltered and this unaltered protein/DNA ratio following lead treatment suggested nonimpairment of cellular protein concentration. The RNA content of liver was increased following treatment and protein/RNA ratio was reduced. RNA per unit amount of DNA was found to be increased and this increased cellular concentration of RNA might result from the degradation of RNA. Lead administration caused a reduction in the incorporation in vivo 14C-leucine into protein of liver. It has been suggested that the diminished incorporation of amino acid into protein following lead treatment might be affected at the translational level of protein biosynthesis.

Urinary coproporphyrin in lead intoxication: a study in the rabbit

Abstract: 1. Lead acetate was administered to adult New Zealand White rabbits in their drinking water. Their mean blood lead level rose to 4.5 μmol/l within a week and then remained relatively constant. 2. The rabbits developed a marked coproporphyrinuria. Plasma levels of coproporphyrin increased but not in proportion to the urine excretion. Thus the renal clearance of coproporphyrin rose from a mean of 1.8 ml/min to 32.2 ml/min whilst creatinine clearance remained constant. 3. The concentration of coproporphyrin in renal venous blood from control rabbits was found to be slightly lower than that in arterial blood. In the lead intoxicated rabbits the concentration of coproporphyrin in renal venous blood was approximately three times higher than the arterial concentration. 4. Significantly higher levels of lead, porphobilinogen, uroporphyrin, coproporphyrin and protoporphyrin were found in renal tissue than in brain, heart or liver. 5. Renal tissue homogenates from control rabbits were able to synthesize porphobilinogen, uroporphyrin, coproporphyrin and protoporphyrin when incubated with 5-aminolaevulinic acid. Renal tissue from lead intoxicated rabbits was also able to synthesize these haem precursors although at a reduced rate. 6. Three enzymes from the haem biosynthetic pathway were assayed in renal mitochondria. Compared with those from controls, mitochondria from lead intoxicated rabbits showed no significant difference in ferrochelatase activities, but the activities of coproporphyrinogen oxidase were decreased, and those of 5-aminolaevulinate synthase were increased. 7. It was concluded that a large portion of the excess coproporphyrin excreted by the lead intoxicated rabbits was of renal origin.

Neonatal lead exposure in rats: II. Effects on the hippocampal afterdischarge.

Abstract: Male Sprague-Dawley rats were exposed to lead from parturition to weaning via the dams' milk. Dams were provided with drinking water containing 1.0 (LL), 2.5 (ML), or 5.0 (HL) mg/ml lead acetate or 1.25 (C) mg/ml sodium acetate. Beginning at 15 weeks of age, characteristics of the electrically elicited hippocampal afterdischarge (AD) and its alteration by phenytoin (PHT) were assessed in these rats. A separate group of rats was sacrificed at 20 weeks for hippocampal metal analysis. Increases in primary AD duration were observed in LL and ML, significant in ML. Significantly fewer wet dog shakes occurred in all lead groups. HL animals displayed shorter rebound ADs. All groups responded to PHT with increases in primary AD duration, but the increases in the ML and HL groups were significantly greater than in the C group. Hippocampal lead, zinc, and copper were not different from control. It is concluded that a brief lead exposure can have persistent effects on hippocampal function and that these effects are not due to altered hippocampal metal concentrations. The findings are discussed in relation to the known effects of postnatal lead exposure on hippocampal neuronal development.

Neonatal lead exposure in rats: I. Effects on activity and brain metals.

Abstract: Upon parturition, Sprague-Dawley dams were administered 1.0 (LL), 2.5 (ML), 5.0 (HL) mg/ml of lead acetate or 1.25 mg/ml sodium acetate (C) in their drinking water. Pups were weaned to tap water at 22 days of age. The developmental pattern of neonatal activity was characterized by monitoring spontaneous activity of single pups for 30 minutes on days 12, 14, 16, 18, 20, and 22, and for one hour in adults. Brains were removed at weaning for subsequent analyses of lead, zinc, and copper. The effects of lead on neonatal activity were considered to be minor because only the ML group differed significantly from C and exhibited hyperactivity on day 16. Adult activity levels, however, were decreased in a dose-dependent fashion. At 22 days of age, whole brain metal analyses revealed a dose-dependent increase in lead levels and a decrease in zinc. These results do not strongly support a hypothesis of lead-induced neonatal hyperactivity.

Influence of dietary lead and calcium on tissue lead accumulation and depletion, lead metabolism and tissue mineral composition in sheep.

Abstract: Two experiments were conducted to study the metabolism and tissue accumulation and depletion of dietary Pb in sheep. In Exp. 1, a feeding trial, 33 wethers, 56 kg initially, were assigned randomly to two dietary treatments: .25% Ca plus 1,000 ppm Pb or .50% Ca plus 1,000 ppm Pb. Supplemental Ca and Pb were supplied as reagent grade calcium carbonate or reagent grade lead acetate. The experiment was divided into two phases of 75 and 180 d; during the first phase, diets contained 1,000 ppm supplemental Pb and during the second phase, diets contained 3 ppm Pb. Calcium level remained constant within treatments throughout both phases. Sheep were slaughtered at various intervals during both phases and tissue samples taken. Lead increased in all tissues during the accumulation period and decreased during the depletion period; however, kidney was the only tissue in which Pb concentration declined to control values by 180 d. Dietary Ca reduced (P less than .05) the concentration of Pb deposited in liver, but not in other tissues. Interactions of dietary Ca and Pb on tissue concentration of various minerals occurred. In Exp. 2, a balance trial, 27 wethers, 53 kg initially, were allotted randomly to four treatments in a 2 X 2 factorial arrangement. Diets contained either 0 or 1,000 ppm supplemental Pb as reagent grade lead acetate and .25 or .50% total Ca with supplemental Ca from calcium carbonate. Increasing dietary Pb increased (P less than .05) percentage of Pb retained and increased (P less than .01) whole blood Pb concentration (1.0 vs 1.42 micrograms/ml).

[Peripheral blood and bone marrow cell status of white rats with long-term lead exposure].

Abstract: Blood test and bone marrow examination in experiments with albino rats weighing 100-110 g subjected to long-term lead influence (1% lead acetate per os) showed availability of reticulocytosis with thrombocytopenia (on the 62d day) and thrombocytosis on the 92d day of the experiment) in peripheral blood. Reduction of the bone marrow neutrophil index and leuko-erythroblastic ration due to an increase of an erythroblastic radicle was recorded in the bone marrow.

Concentrations of Lead, Magnesium, Calcium, Zinc and Cadmium in Twenty Rabbit Tissues after Exposure to Low Lead Doses and Atherogenic Diet

Abstract: Four groups of 6 rabbits were subjected to the following diets for 25 weeks: I (controls), II (water with 9.66 µmol/l of lead), III (atherogenic) and IV (atherogenic + 9.66 µmol/l of lead). Lead, magn

[Are suppressor T-cells the primary target cells of lead immunotoxicity?].

Abstract: Studies were performed to investigate the effect of chronic low level lead exposure on the regulatory functions of T cells in the humoral immune response to sheep red blood cells (SRBC) in mice. Female mice were exposed to lead (as lead acetate) in the diet at 545 (group 1) and 2180 ppm (group 2) for 10 weeks. Lead exposure resulting in blood lead levels (PbB) of about 50 micrograms/100 g (group 1) produced a substantial increase of the number of IgG antibodies secreting spleen cells on days 3 and 4 after challenge. At the higher exposure level (group 2; PbB 60-80 micrograms/100 g) a suppression of the number of IgG plaque forming cells was observed. The IgM response was much smaller than the IgG response. Although differences between the group means were small, the results indicate that there also is an enhancement of the IgM response in the lower dosage group on days 3 and 4. In a second experiment the effect of in vivo lead exposure on antigenic competition was examined. Lead substantially reduced the effect of antigenic competition. Results of both experiments suggest that suppressor T cells rather than helper T cells may represent the primary target for lead. Throughout this study serum complement C3 levels were determined. Complement C3 levels tended to be reduced in the lead exposed groups before as well as after inocculation with SRBC.

[Lead deposits in bone--the roentgen picture as a demonstration method?].

Abstract: Current concepts concerning the deposition, distribution and radiological demonstration of lead in the skeleton were investigated in five series of rats; some of these were young and others more than a year old. 10 mg of lead acetate/kg body weight were administered over a period of five to 41 days, giving a minimum of 8.4 mg and maximum of 40.4 mg of lead. A comparable control group was given similar amounts of sodium acetate. The distribution and concentration of lead in the femur was determined by the use of 210Pb. Contact autoradiographs showed band-shaped lead accumulation in the endosteal and periosteal growth regions. The degree of darkening depended on the amount of lead administered and permitted a rather coarse quantitative relationship to be drawn. Measurements of radioactivity produced similar distribution patterns. The relationship of lead concentration of epi- and metaphysis to the diaphysis averaged 2:1. The factor mainly responsible for lead deposition depended on the metabolic potential of the tissue, which itself depends largely on the growth regions. Radiologically, there was definite evidence of demineralization in the areas of lead deposition; this could be confirmed histologically by lack of trabeculae, thinning of the cortex and destruction of bone matrix. Despite its much greater absorption co-efficient, the tiny quantities of lead, compared with the bone mass (even in the highest concentrations in our experiments) cannot be detected radiologically. Biophysical calculations have been made which indicate that similar conditions occur in man. Radiological examination of the skeleton, which is used as a screening method for chronic lead poisoning, is not suitable for this purpose.

Cerebellar Purkinje neuron hypoexcitability induced by chronic perinatal lead exposure.

Abstract: The effects of perinatal lead administration on developing rat brain were studied by using cerebellar grafts in oculo. With 1% lead acetate in the drinking water, little change was seen in the histological organization of the graft. In marked contrast, virtually all Purkinje cell spontaneous discharge was absent in these grafts. This was seen even though 4-5 months had elapsed between the recording and the cessation of lead treatment. There was no alteration in electrophysiological properties of transplant Purkinje cells from sodium acetate-treated animals. Moreover, host in situ cerebellar Purkinje cells in both groups of animals discharged normally. These data indicate that lead administration, to elicit blood levels of 450-550 micrograms/liter, produces a long-lasting selective electrophysiological deficit in developing brain in oculo.