Increased lead absorption with anemia and slowed nerve conduction in children near a lead smelter

Studies to evaluate the prevalence, sources, and health consequences of lead absorption were conducted among children living near a primary lead smelter. Lead levels in air, soil, and dust were highest at the smelter and decreased with distance. Ninety-nine percent of one- to nine-year-old children living within 1.6 kilometers had blood lead levels greater than or equal 40 mug/dl, indicating increased absorption, and 22% had levels greater than or equal 80 mug/dl. The prevalence of lead levels greater than or equal 40 mug/dl decreased with distance; at 72 kilometers from the smelter it was 1%. Erythrocyte protoporphyrin levels increased with blood lead levels: 17% of children with lead levels of greater than or equal 80 mug/dl were anemic. There was no overt neurologic toxicity. Significant negative correlation was found in 202 five- to nine-year-old children between blood lead levels and motor nerve conduction velocity (r = 0.38, p less than 0.02).     

Impact of air pollution by lead on the heme biosynthetic pathway in school-age children

Blood-lead level (Pb-B), erythrocyte delta-aminolevulinic acid dehydratase (ALAD) activity, free erythrocyte porphyrin (FEP) concentration, delta-aminolevulinic acid concentration in urine (ALAU), hematocrit value, and hemoglobin concentration were compared for groups of children 10-13 years old from areas differently polluted by lead (rural area and lead smelter area). The biological responses of the children were also compared with those observed in adults similarly exposed to lead (Pb-B: 10-40 mug/100 ml). Compared with the rural children, children living less than 1 km from the smelter exhibited a significant increase of Pb-B and FEP, a significant inhibition of ALAD, and a slight positive correlation of ALAU with Pb-B; however, they showed no biological signs of anemia. In children living approximately 1.5 km from the smelter, there was still a significant increase of Pb-B and a concomitant inhibition of ALAD, but no change in FEP concentration. Comparison of the dose-response curves between Pb-B and FEP in adult males, adult females, and children indicates that the sensitivity to lead is in the order of children larger than or equal to women greater than men. Based on the FEP response, it is proposed that 25 mug Pb/100 ml blood be regarded as the maximum biologically allowable concentration of lead in blood of school-age children.     

A survey of blood lead levels in dogs and cats

The blood of 206 dogs and 26 cats was analyzed for lead by non-flame atomic absorption giving mean levels of 6.4 mug/100 ml for dogs and 5.2 mug/100 ml for cats. Statistical treatment of the results using a paired Students' t-test showed significant differences by age for dogs but not for cats. Urban dogs had significantly higher blood lead levels than country dogs (P less than 0.05) thus indicating that dogs can be regarded as useful environmental monitors for lead pollution.     

Assessment of lead exposure in schoolchildren from Jakarta

Children attending schools in urban areas with high traffic density are a high risk group for lead poisoning. We assessed the magnitude of lead exposure in schoolchildren from Jakarta by analyzing blood lead concentrations and biomarkers of heme biosynthesis. A total of 131 children from four public elementary schools in Jakarta (two in the southern district and two in the central district) were enrolled in the study. To evaluate lead pollution in each area, soil samples and tap water were collected. The mean blood lead concentration was higher in the central district than in the southern district (8.3 +/- 2.8 vs. 6.9 +/- 3.5 microg/100 ml; p<0.05); 26.7% of the children had lead levels greater than 10 microg/100 ml. In 24% of the children, zinc protoporphyrin concentrations were over 70 micromol/mol hemoglobin; in 17% of the samples, hemoglobin was less than 11 g/100 ml. All other values were within the physiological range. Blood lead concentration and hematological biomarkers were not correlated. Analyses of tap water revealed lead values under 0. 01 mg/l; lead contamination of soil ranged from 77 to 223 ppm. Our data indicate that Indonesian children living in urban areas are at increased risk for blood lead levels above the actual acceptable limit. Activities to reduce pollution (e.g., reduction of lead in gasoline) and continuous monitoring of lead exposure are strongly recommended.     

Absence of peripheral neuropathy in long-term lead-exposed subjects

The safety of a blood lead concentration of 70 microgram/100 ml as a hygienic border value with regard to development of lead neuropathy was tested in 95 employees, who had been exposed occupationally to lead for more than 9 years. The blood lead concentration was slightly above the border value in nine subjects, while the erythrocyte-Zn-protoporphyrin concentration was significantly elevated in 81 subjects, indicating an abnormal accumulation of metabolically active lead. None of the group showed clinical evidence of peripheral neuropathy, and the vibratory perception thresholds as well as motor conduction data from the median, radial, and common peroneal nerves were normal, as compared with an age-matched control group of 21 non-exposed normal subjects. The amplitude ratio between proximally and distally evoked muscle action potentials was normal in all lead-exposed subjects. These findings suggest that lead-exposed subjects are well protected against peripheral lead neuropathy, when blood lead levels are kept below the hygienic border value.     

Effect of 1-deamino-5-D-arginine vasopressin (DDAVP) on plasma cortisol (hydrocortisone)

The influence of 1-deamino-8-D-arginine vasopressin (DDAVP), the new antidiutetic polypeptide without any side effects on plasma cortisol, was investigated in 30 healthy persons. A dose of 4 mug DDAVP administered intravenously induced a rise in plasma cortisol (hydrocortisone) levels greater than 3.5 mug/100 ml in 12 out of 20 persons studied. In this group (group I), the average increase at 15 minutes was 6.92+/-1.74 mug/100 ml (P less than 0.005), while in the remaining eight persons (group II) plasma cortisol levels decreased according to the usual normal daily rhythm. DDAVP, 80 mug, administered intranasally had no demonstrable influence on physiologic plasma cortisol regulation. On the basis of the present findings with relatively low doses, pituitary responsiveness (ACTH release) might be expected to occur in a higher percentage of persons after giving high intravenous doses of DDAVP. Further efforts are necessary to develop a safe vasopressin test for clinical examination of adenohypophyseal function.     

Effect of the thyroid in the development of intestinal hydroxylases

The authors studied the saccharidase levels in the intestines of rats during the perinatal period. Sucrase and maltase values increase with advancing time, while lactase values decrease also age-dependently. The thyroid gland has a decisive role in the intestinal maturation of fats. In an assessment of circulating blood thyroxin levels, the authors found that the amount of thyroxin at birth is practically undetectable (less than 0,05 mug/100 ml expressed in iodine), rapidly increasing up to adult levels (3,8 mug/100 ml) 22 days after birth.     

Lead in tissues of deceased lead smelter workers

Smelter workers are exposed to a number of metals and other substances in dust, fumes and gases. The concentrations of lead in liver, lung, kidney, brain, hair and nails were determined in 32 deceased, long-term exposed male lead smelter workers, and compared with those of 10 male controls. The lead levels in liver, lung, kidney and brain were analyzed by atomic absorption spectrophotometry. X-ray fluorescence was used for the determinations in hair and nails. Lead in blood had been determined repeatedly in the lead workers since 1950, which made it possible to calculate a time-integrated blood lead index for each worker. The highest lead levels in soft tissues were found in liver, followed in order of concentration by kidney, lung and brain, among both exposed workers and controls. These organ lead concentrations were all significantly higher among the workers as compared with the control group (p < or = 0.02). The largest difference between workers and controls was found in brain tissue (ratio between median values = 5.6). The lead levels in hair and nails were of the same magnitude in the two groups. The workers showed positive correlations between lead concentrations in liver and kidney (Spearman's rho = rs = 0.59; p < 0.001), liver and hair (rs = 0.51; p = 0.003), liver and nails (rs = 0.52; p = 0.002) and hair and nails (rs = 0.52; p = 0.002). Lead concentrations in kidney correlated well with lead levels in hair (rs = 0.57; p = 0.001) and nails (rs = 0.51; p = 0.003), respectively. The positive correlation between the lead concentrations in liver and kidney indicates that these organs belong to the same soft tissue lead pool in the body. In retired lead workers, positive correlations were observed between the lead concentrations in liver and the cumulative blood lead index (CBLI) (rs = 0.50; p = 0.016), as well as between lead levels in kidney and CBLI (rs = 0.51; p = 0.014).     

Ruptures of the tricuspid chordae

Mouse ova with or without follicular cells (denuded) were treated with wheat germ agglutinin (WGA) in concentrations ranging from 5-500 mug/ml and fertilized in vitro. Ova subjected to concentrations greater than 10 mug/ml WGA were incapable of fertilization in vitro, although sperm were observed adhering to the zona pellucida after treatment in concentrations as high as 500 mug/ml WGA. At concentrations of 50 mug/ml or higher, WGA adversely affected the shape of the vitellus. Of various saccharides employed to block the effects of WGA D-glucose was the most effective. Injections of 0.03 ml of 100 mug/ml WGA into the ovarian bursa two to three hours before the expected time of ovulation had little or no effect on fertilization in vivo.     

Using analog baselines to assess the effects of naltrexone on self-injurious behavior

Healthy male and female human volunteers were exposed to 50 ppm or 100 ppm trichloroethylene (Tri) by inhalation for 4 h. Blood and urine samples were taken at various times before, during, and after the exposure period for analysis of glutathione (GSH), related thiols and disulfides, and GSH-derived metabolites of Tri. The GSH conjugate of Tri, S-(1,2-dichlorovinyl)glutathione (DCVG), was found in the blood of all subjects from 30 min after the start of the 4-h exposure to Tri to 1 to 8 h after the end of the exposure period, depending on the dose of Tri and the sex of the subject. Male subjects exposed to 100 ppm Tri exhibited a maximal content of DCVG in the blood at 2 h after the start of the exposure of 46.1 +/- 14.2 nmol/ml (n = 8), whereas female subjects exposed to 100 ppm Tri exhibited a maximal content of DCVG in the blood at 4 h after the start of the exposure of only 13.4 /- 6.6 nmol/ml (n = 8). Pharmacokinetic analysis of blood DCVG concentrations showed that the area under the curve value was 3.4-fold greater in males than in females, while the t1/2 values for systemic clearance of DCVG were similar in the two sexes. Analysis of the distribution of individual values indicated a possible sorting, irrespective of gender, into a high- and a low-activity population, which suggests the possibility of a polymorphism. The mercapturates N-acetyl-1,2-DCVC and N-acetyl-2,2-DCVC were only observed in the urine of 1 male subject exposed to 100 ppm Tri. Higher contents of glutamate were generally found in the blood of females, but no marked differences between sexes were observed in contents of cyst(e)ine or GSH or in GSH redox status in the blood. Urinary GSH output exhibited a diurnal variation with no apparent sex- or Tri exposure-dependent differences. These results provide direct, in vivo evidence of GSH conjugation of Tri in humans exposed to Tri and demonstrate markedly higher amounts of DCVG formation in males, suggesting that their potential risk to Tri-induced renal toxicity may be greater than that of females.     

Chronic carvedilol reduces mortality and renal damage in hypertensive stroke-prone rats

The effects of carvedilol, a novel vasodilating beta-blocker and antioxidant, and propranolol on survival, neurobehavioral deficits, cardiovascular parameters, plasma renin, plasma aldosterone levels and renal pathology were determined in stroke-prone spontaneously hypertensive rats. Stroke-prone spontaneously hypertensive rats were allowed access to 1% NaCl as the drinking solution and a high fat diet supplemented with carvedilol (1200 or 2400 ppm) or propranolol (2400 ppm). The control group consisted of stroke-prone spontaneously hypertensive rats placed on the same diet with no drug supplement. Animals fed propranolol had a blood level of 864 +/- 68 ng/ml, whereas carvedilol-fed animals had blood levels of 24 +/- 4 ng/ml at 1200 ppm and 471 +/- 145 ng/ml at 2400 ppm. Carvedilol and propranolol treatment resulted in significant beta adrenoceptor blockade. Both compounds reduced heart rate, but had no significant effects on systolic arterial blood pressure. Carvedilol- and propranolol-treated animals also exhibited significant, prolonged protection from neurobehavioral deficits and mortality (P < .01). Elevated plasma renin activity and aldosterone levels seen in untreated controls were significantly decreased by propranolol (P < .05), and to a considerably greater extent by the same dose of carvedilol (P < .01). Carvedilol decreased renal histopathological damage and cardiac hypertrophy to a greater extent (P < .01) than propranolol (at equal doses). Both carvedilol (P < .01)- and propranolol (P < .01)-treated animals had considerably reduced renal damage at 18 weeks of treatment. Carvedilol reduced renal damage more than propranolol (P < .05). In addition, the lower (1200 ppm) dose of carvedilol, which decreased neurobehavioral deficits and mortality, had no significant effects on organ mass or renal function, but significantly (P < .01) reduced renal damage. These data indicate that both beta adrenoceptor blockers, especially carvedilol to a considerably greater degree, convey significant protection in a genetic model of severe hypertension that results in renal and cardiovascular organ pathology, neurobehavioral deficits and premature death.     

Interactions of lead, calcium, vitamin D, and nutrition in lead-burdened children

This study was undertaken to evaluate relationships between blood or serum levels of lead (Pb), calcium, and 25-hydroxyvitamin D (25-OHD), within the framework of a nutritional survey of lead-burdened children. The results demonstrate that: regardless of blood Pb concentration and season of the year, serum 25-OHD concentration reflects vitamin D intake; high blood Pb (greater than or equal to 60 microgram/dl) was associated with decreased levels of 25-OHD (18+/--1 ng/ml vs. 32+/- in controls, P less than .001); concentrations Pb and calcium were inversely correlated in control and lead-burdened children; and children in the high blood Pb group (greater than or equal to 60 microgram/dl) had lower mean daily intakes of both calcium (610 +/- 20 mg vs. 770 +/- 20 in controls, P less than .001) and vitamin D (210 +/- 17 IU vs. 325 +/- 20 in controls, P less than .001). These data indicate that, in Pb-burdened children, multiple factors modify the absorption and toxicity of Pb, and relative vitamin D deficiency, not excess, is associated with high blood Pb levels. Assessment of nutrition, calcium metabolism, and vitamin D status is recommended in evaluating children known to have undue absorption of Pb.     

The structure and innervation of the sinu-atrial node of the mole heart

Low concentrations (less than or equal 20 mug/ml) of 8-azaguanine are 1000 fold more toxic to V79 Chinese hamster cells in medium containing 10% dialyzed fetal calf serum than in medium containing 10% undialyzed serum. Serum enzyme activity that converts AG to nontoxic 8-azaxanthine degrades AG at the same rate, whether or not the serum is dialyzed. However, cytotoxicity results similar to those obtained with US were produced in medium containing DS and 2.5 mug of hypoxanthine (HX)/ml (DSH). Therefore, serum HX is considered to be responsible for the relatively low cytotoxicity of AG in medium containing US. Colonies that arose in medium containing AG were isolated and characterized. Those that remained resistant to AG (40 mug/ml) and sensitive to aminopterin in the presence of HX and thymidine (HAT) were considered mutants; non-mutants were sensitive to AG and resistant to HAT. Colonies isolated from medium containing DSH or US and low concentrations of AG were not mutants, but those from medium containing high concentrations (greater than or equal 30 mug/ml) of AG were mutants. Spontaneous and N-methyl-N-nitro-N-nitrosoguanidine induced mutants were detectable in medium containing DSH without replating the cells prior to adding AG (greater than or equal 30 mug/ml), but in order to detect MNNG induced mutations in medium containing DS replating was essential. In DS, the mutation frequency increased as an exponential function of the toxicity of MNNG, but remained two orders of magnitude lower than the induced mutation frequencies that occurred in DSH. HX, in DSH or US, produced profound effects, other than interference with AG toxicity, that distort the results of mutagenesis assays. To study mutation using AG resistance as the endpoint, it is essential to use dialyzed serum.     

The human placenta's lead level as a parameter of the ecological lead exposure. Its validity in comparison to the lead level in blood, the activity of the delta-aminolevulinic acid dehydratase and the concentration of the free erythrocyte porphyrins of newborns and their mothers (author's transl)

In order to estimate the ecological exposure of lead, placenta- and blood-investigations were made at four collectives from variously industrialized regions (Ruhrregion, Middle Frankonia Centre, Bavarian Forest). 148 normal births and 19 premature births (in each case mothers and newborns) were listed as well as twelve abortions. We investigated the lead-level in blood, the activity of delta-aminolaevulinic acid dehydratase (ALA-D) the concentration of free erythrocyte porphyrine (FEP) and the placentas' lead concentration. Though in the Ruhrregion (Dortmund) significantly higher lead levels in blood were found compared to the Bavarian Forest, the results together, were in the normal range, less than 35 mug%. In an average the mothers' lead level in blood was around 1.4 times (ca. 5 mug%) above that of their newborns; analysing this statistically, highly significant correlations were found. However for the ALA-D activity and the FEP-results no direct dependence of the lead levels in blood could be found. In the placentas mean lead concentrations between 1.94 mug and 2.23 mug per gram dry-weight (30.6 mug-38.9 mug/100 g wet-weight) were gained. In the contrary to the measured results of lead in blood the average placentas' lead level of the most and least industrialized regions were almost identical. A correlation between the mothers' respectively their children's lead levels in blood and the placental lead concentrations could not be proved. No relation could be found between the results and the gestation ages. As final results: 1. The placenta is no ideal investigation object concerning the environment's lead exposure. 2. It has no special barriere - or depot - function in lead metabolism. 3. In order to estimate the environment's lead exposure the determination of the lead level in blood will also be in future the optimal method. This investigation is of special value because of its validity of the results and the practicability of winning the samples compared to other parameters and biological materials.     

Effects of nitrogen oxides,sulfur dioxide,and ferric ions on the corrosion of mild steel in concentrated sulfuric acid

Effects of nitrate ions, nitrous acid, sulfur dioxide, and ferric ions on the corrosion of mild steel in unstirred, concentrated sulfuric acid were determined in laboratory tests. Nitrate and nitrous acid at levels up to 1000 ppm accelerate corrosion. At concentrations greater than 1000 ppm nitrate passivates the steel. Sulfur dioxide and ferric ions have no detectable influence on the corrosion. Reaction mechanisms are presented to explain the observed effects. The impact of nitrogen oxides on the storage and handling of sulfide smelter by-product acid is discussed.     

Biotin deficiency in chicks fed a wheat-based diet

A wheat-based diet produced severe biotin deficiency symptoms appearing at the age of ten to fourteen days and becoming very severe in the third and fourth week (group 1). Biotin supplementation with 50 mug/kg (group 2) reduced the symptoms almost completely, but did not restore completely growth compared to chicks receiving the diet supplemented with 300 mug biotin/kg compared to chicks receiving the diet supplemented with 300 mug biotin/kg (group 3). The plasma level of biotin was about, or lower than, 100 ng/100 ml plasma in groups 1 and 2, indicating biotin deficiency. In group 3, plasma biotin was above 200 ng/100 ml. Liver biotin, after two weeks, was low in group 1 (less than 600 ng/g), medium in group 2 (1000 to 1500 ng/g) and in group 3 above 2000 ng/g. Plasma and liver biotin levels are found to be suitable parameters for diagnosis of subclinical biotin deficiency in chicks.     

Effects of 16-week dietary administration of 2-amino-3,8-dimethylimidazo[4, 5-f]quinoxaline in rats

2-Amino-3,8-dimethylimidazo[4, 5-f]quinoxaline (MeIQx), a heterocyclic amine found in cooked meats, is carcinogenic in mice and rats at high doses. In order to examine the toxicity including preneoplastic changes at the lower doses, a total of 170 male Fischer 344 rats were administered MeIQx for 16 weeks at a dose of 100, 10, 1, 0.1, 0.01, 0.001 ppm or 0 ppm in the diet. The numbers of GST-P positive foci and BrdU-labeling indices in the liver were significantly increased by the dietary administration of 10 ppm and 1 ppm or more of MeIQx respectively, when compared with the basal diet-fed control rats. Aberrant cry p tfoci (ACF) were also significantly increased in the 100 ppm MeIQx group as compared to the control value. No histopathological changes indicating obvious toxicity of MeIQx were observed in the major organs other than the liver and large intestine. In conclusion, our results clearly indicate that MeIQx selectively targets the liver and large intestine of rats as organs for the toxicity, but dose not affect the other major organs at low doses.     

Toxicity of methylmercury chloride in rats. III. Long-term toxicity study

In the range-finding test, 6 groups of 4 male and 4 female weanling rats were given dietary levels of 0, 0.1,0.5, 2.5, 12.5 and 250 ppm methylmercury chloride (MeHgCl) for 2 weeks. Signs of central nervous system toxicity, weight loss and high mortality appeared at 250 ppm but not at lower levels. No haematological changes were observed at 0.1-12.5 ppm. The relative weights of the liver in females on 2.5 and 12.5 ppm and of the kidneys in females on 12.5 ppm were significantly increased; the effects in males were less marked. Total mercury concentration in the kidneys increased proportionally with increasing dietary levels of MeHgCl. In the short-term test, 5 groups of 15 male and 10 female weanling rats were given dietary levels of 0, 0.1, 0.5, 2.5 and 25 ppm MeHgCl for 12 weeks. Toxic signs, weight loss and restricted food intake were observed at 25 ppm starting from week 9 onwards. Haematological, serum enzyme and urinalysis changes were seen at 25 ppm. Liver microsomal enzyme activity was increased non-significantly and liver glycogen was depressed at 25 ppm. Organ weight changes were evident at 25 ppm and histological changes seen in the spleen, kidneys, brain, spinal cord and peripheral nerves were confined to the 25 ppm level. Histochemical changes in kidney enzymes occured at 2.5 and 25 ppm. Hg concentrations in blood, hair, kidneys, liver and brain were higher at 12 weeks than 6 weeks and generally increased with increasing MeHgCl level in the diet.     

Diamagnetic levitation in the fractionally superconducting bile cholates

Plasma zinc levels were measured in both healthy and diabetic individuals having an age range of 10-93 years. No significant differences in plasma zinc concentrations were found between males and females in either healthy or diabetic individuals. Up to the age of 50 years, the mean plasma zinc of normal individuals remained relatively constant at 70 +/- 32 mug/100 ml (+/- 2 SE) after which the levels decreased. This decreasing pattern was absent in diabetics, whose plasma zinc of 65 +/- 32 mug/100 ml remained constant over the entire age range. For women on oral contraceptive agents, the mean plasma zinc was 59 +/- 18 mug/100 ml, which was significantly lower than that of controls.     

Prevalence of hypercalcaemia in a health screening in Stockholm

A free health check, offered to 21417 20-63-year-old employees of the Stockholm City and County Council in 1971-73, was accepted by 15903 persons. The examination included a multichannel chemical analysis of a single blood sample. Serum calcium levels greater than or equal to 11.0 mg/100 ml (2.75 mmol/l) and greater than or equal to 11.1 mg/100 ml (2.78 mmol/l) were encountered in 3.9% and 1.1% of the population, respectively. Among subjects below 50 years of age, the calcium concentration was significantly higher in males than in females. This difference disappeared in older subjects, essentially because the calcium level decreased with advancing age in the men. To a further investigation were invited 178 subjects with a single serum calcium registration greater than or equal to 11.1 mg/100 ml (2.78 mmol/l). Of this group, 95 persons (53.4%) exhibited hypercalcaemia (HC) on repeated testing. Twelve had been operated on prior to the actural follow-up and found to have parathyroid adenomata. Twenty subjects were on continuous treatment with diuretics of the thiazide type and seven had diseases that might induce HC (two had hyperthyroidism, two hypothyroidism, one sarcoidosis, one hypernephroma and one mammary carcinoma). In 56 patients the laboratory and physical examinations did not reveal any obvious cause for the HC except possible hyperparathyoidism (HPT). Eighty (84.2%) of the 95 HC subjects were women, mostly over 50 years. The 95 persons constituted 6% of the total number of health-screened persons. The highest prevalence, 13%, was recorded for women aged 60-63. The prevalence of HPT in the total material was 3.6%, which is higher than that found in several other studies. This is based on surgical findings to date.