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K S Subramanian

Publications and source records attributed to K S Subramanian.

At least 19 recordsLinked to original sources

A multi-element profile of housedust in relation to exterior dust and soils in the city of Ottawa, Canada.

This paper presents multi-element profiles of indoor dust versus exterior soils and dusts from 50 residences located in 10 neighborhoods across Ottawa, the capital city of Canada. Mercury concentrations were determined using nitric-sulphuric acid digestion and cold vapor AAS. Concentrations of 31 other elements were determined using nitric-hydrofluoric acid digestion and ICP-MS. Comparisons of household dust, garden soil and street dust at the individual residence scale and at the community scale were based on a consistent 100-250-microm particle size fraction. Results showed housedust samples to contain significantly higher concentrations of many key elements, including lead, cadmium, antimony and mercury, than either street dust or garden soil samples. Also, housedust profiles revealed a distinct multi-element signature in relation to exterior dust and soil samples. Interestingly, garden soil contained higher concentrations of aluminum, barium and thallium than either house or street dust. Geometric mean concentrations (mg/kg) of these elements in household dust/garden soil were: lead 233/42; cadmium 4.42/0.27; antimony 5.54/0.25; mercury 1.728/0.055; aluminum 24281/55677; barium 454/763; and thallium 0.14/0.29. Street dust contained lower geometric mean concentrations than garden soil for 23 out of a total of 32 elements. In general, indoor/outdoor concentration ratios varied widely from one element to another, and from one residence to another within the community. In the case of Ottawa, which is a city with a low concentration of heavy industries, it would be difficult-to-impossible to accurately predict indoor dust concentrations based on exterior soil data. It is concluded that dust generated from sources within the house itself can contribute significantly to exposures to certain elements, such as lead, cadmium, antimony and mercury.

Canada↗

DNA-protein crosslinks induced by nickel compounds in isolated rat lymphocytes: role of reactive oxygen species and specific amino acids.

Isolated rat lymphocytes in salts-glucose medium (pH 7.2) were incubated with nickel chloride, nickel acetate, nickel sulfate, and a soluble form of nickel subsulfide (0-2 mM) at 37 degrees C for 2 h. The soluble form of nickel subsulfide induced a significant increase in DNA-protein crosslinks (DPXLs) (111%) beginning at 0.5 mM and a maximum increase of 700% from that of the control value was reached at a 2 mM concentration, whereas nickel sulfate produced only a 65% increase of such crosslinks at the 2 mM concentration only. No significant reduction in viability of rat lymphocytes (as measured by trypan blue exclusion) due to these nickel compounds was observed at any concentration used. Time-course studies of DPXLs and cellular viability due to 2 mM nickel subsulfide indicate that DPXL formation may not be due in part to cellular necrosis. Coincubation of nickel subsulfide (2 mM) with l-histidine (16 mM), l-cysteine (4 or 8 mM), or l-aspartic acid (24 mM) significantly reduced the DPXLs induced by 2 mM nickel subsulfide. But Mg(2+) even at 24 mM failed to antagonize nickel subsulfide-induced increase in DPXLs. High concentrations of these amino acids significantly decreased the accumulation of Ni(2+) from nickel subsulfide in lymphocytes, suggesting that such reduction of cellular uptake of Ni(2+) by these amino acids is partly responsible for the potent protective effects of these amino acids against such genotoxicity of nickel subsulfide. In vitro exposure of lymphocytes to nickel subsulfide (0-2 mM) increased the formation of reactive oxygen species (ROS) in a concentration-dependent manner. Furthermore, coincubation of 2 mM nickel subsulfide with catalase, dimethylthiourea, mannitol, or vitamin C at 37 degrees C for 2 h resulted in a significant decrease of nickel subsulfide-induced formation of DPXLs, suggesting that nickel subsulfide-induced DPXLs formation in isolated rat lymphocytes is caused by the formation of ROS. The amino acid treatment also abrogated Ni(3)S(2)-induced generation of ROS. Deferoxamine (a highly specific iron chelator) treatment prevented nickel subsulfide-induced DNA-protein crosslink formation, suggesting that Ni(2+)-induced DPXL formation in rat lymphocytes is caused by the induction of Fenton/Haber-Weiss reaction, generating hydroxyl radicals. The potent protective effects of these specific amino acids against nickel subsulfide-induced DPXL formation in isolated rat lymphocytes may be due in part to impaired cellular uptake of Ni(2+), inhibition of the binding of Ni(2+) to deproteinized DNA, and a reduction in reactive oxygen species.

Acetates↗

Toxicity and bioaccumulation of nickel sulfate in Sprague-Dawley rats following 13 weeks of subchronic exposure.

Adult male Sprague-Dawley rats were given 0, 0.02, 0.05, and 0.1% nickel sulfate (NiSO4-6H2O) or 0, 44.7, 111.75, and 223.5 mg Ni/L, respectively, in their drinking water for 13 wk. Twenty-four hours following the end of such treatment, all animals survived and no apparent clinical signs of toxicity were noted. The final mean body weights of various nickel sulfate-treated rats were not significantly decreased except for the 0.1% nickel sulfate treated group when compared to those in the control. The absolute and relative organ weights were either increased or decreased or remained unchanged, depending on the organ and the dose of nickel sulfate. Total plasma proteins, plasma albumin and globulins, and plasma glutamic pyruvic transaminase activity were all significantly decreased in 0.1% nickel sulfate-treated rats. Lymphocyte subpopulations (T and B cells) were induced at lower dose levels, but suppressed at the highest (0.1%) dose group. A significant decrease in urine volume and an increase in BUN were observed at the highest dose group. Biochemical analysis of bronchoalveolar lavage fluid and lung tissue showed some lung damage, whereas no damage to the testis or DNA in liver and kidneys were found. No gross or microscopic changes were seen in any of the various tissues examined. The relative order of bioaccumulation of nickel in different organs of rats when treated at 0.1% nickel sulfate (223.5 mg Ni/L) was kidneys > testes > lung = brain > spleen > heart = liver. But with regard to order of toxicity, both immune and pulmonary systems were found to be very sensitive targets, followed by kidney.

Analysis of Variance↗

DNA-Protein crosslinks induced by nickel compounds in isolated rat renal cortical cells and its antagonism by specific amino acids and magnesium ion.

Suspensions of isolated renal cortical cells in modified Krebs-Henseleit buffer (pH 7.4) were incubated with nickel chloride, nickel acetate, nickel sulfate, and nickel subsulfide (0-2 mM) at 37 degreesC for 2 h. A significant increase (63%) in DNA-protein crosslinks was observed at 2 mM nickel sulfate, whereas nickel subsulfide induced a significant increase in such crosslinks beginning at 0.5 mM concentration and a maximum increase of 200% of the control value reached at 2 mM concentration. No significant reduction in viability of renal cortical cells (as measured by trypan blue exclusion) was observed due to these nickel compounds at any concentration used. In the second series of experiments, coincubation of nickel subsulfide (2 mM) with l-histidine (8 or 16 mM), l-cysteine (4 or 8 mM), or l-aspartic acid (8 or 24 mM) significantly reduced the DNA-protein crosslinks induced by 2 mM nickel subsulfide. Similarly Mg2+ (24 mM), but not Ca2+ (24 mM), was able to antagonize nickel subsulfide-induced increase in DNA-protein crosslinks. High extracellular levels of Mg2+ and these amino acids significantly decreased the accumulation of Ni2+ from nickel subsulfide in renal cortical cells. Furthermore, these amino acids at high concentrations significantly inhibited the binding of Ni2+ from nickel subsulfide to deproteinized DNA from renal cortical cells, whereas such inhibition due to Mg2+ was close to significant (0.1 > p > 0.05). In vitro exposures of renal cortical cells to nickel subsulfide (0-2 mM) increased the formation of reactive oxygen species in concentration-dependent manner. Furthermore, coincubation of 2 mM nickel subsulfide with either catalase, dimethylthiourea, mannitol, or vitamin C at 37 degreesC for 2 h resulted in a significant decrease of nickel subsulfide-induced formation of DNA-protein crosslinks, suggesting that nickel subsulfide-induced DNA-protein crosslink formation in isolated rat renal cortical cells is caused by the formation of reactive oxygen species. The potent protective effects of these specific amino acids and Mg2+ against nickel subsulfide-induced DNA-protein crosslink formation in isolated renal cortical cells are due to reduction of cellular uptake of Ni2+ and inhibition of the binding of Ni2+ to deproteinized DNA.

Amino Acids↗

Antimony in drinking water, red blood cells, and serum: development of analytical methodology using transversely heated graphite furnace atomization-atomic absorption spectrometry.

An atomic absorption spectrometric (AAS) method has been developed for determining microg/L levels of Sb in samples of water and blood. The AAS method is based on the concept of stabilized temperature platform furnace atomization (STPF) realized through the use of a transversely heated graphite atomizer (THGA) furnace, longitudinal Zeeman-effect background correction, and matrix modification with palladium nitrate-magnesium nitrate-nitric acid. The method of standard additions is not mandatory. The detection limit (3 standard deviations of the blank) is 2.6 microg Sb/L for the water, red blood cells (RBCs), and serum samples. Data are presented on the degree of accuracy and precision. The THGA-AAS method is simple, fast, and contamination-free because the entire operation from sampling to AAS measurement is carried out in the same tube. The method has been applied to the determination of Sb in some leachate tap water samples derived from a static copper plumbing system containing Sn/Sb solders, and in small samples (0.5 ml) of RBCs and serum derived from rats given Sb-supplemented drinking water.

Animals↗

Canadian Human Specimen Bank: an emerging Great Lakes health effects program.

Plans for establishing a Canadian human specimen bank as part of the Great Lakes Health Effects program initiated by the Environmental Health Directorate, Health and Welfare Canada, have been under consideration since 1990. This presentation delineates the program rationale, our objectives in establishing the bank and the progress we have made to-date in achieving our goal. This paper is intended to be a planning document.

Canada↗

Bone-lead analysis: development of analytical methodology for milligram samples.

A graphite platform-in-furnace atomic absorption spectrometric (GFAAS) method for determining micrograms/g levels of Pb in 10-20 mg cortical and trabecular primate bone samples is described. The GFAAS method is based on an ambient temperature nitric acid digestion of the sample, matrix modification with palladium nitrate, stabilized temperature platform furnace atomization, and a systematic evaluation of the temperature program of the atomizer. The method of standard additions is mandatory. The detection limit (3 standard deviations of the blank) is 0.19 micrograms Pb/g dry weight for a 10-mg sample taken up in a 1-mL volume. Data are presented on the degree of accuracy and precision. The accuracy of the proposed GFAAS method has been assessed using the IAEA bone reference material, H-5, and by comparing the values obtained in a bone sample with an isotope dilution mass spectrometric (IDMS) procedure. The GFAAS method can be applied to the determination of Pb in 10-20 mg bone samples and for concentrations which are > or = 10 x detection limit. The method is simple, fast, and contamination-free since the entire operation from weighing to GFAAS measurement is carried out in the same centrifuge tube. The method has been applied to the determination of total-Pb in some adult and fetal primate cortical and trabecular bone specimens.

Animals↗

Sampling of cortical and trabecular bone for lead analysis: method development in a study of lead mobilization during pregnancy.

The paper describes a methodological approach to the investigation of maternal-fetal transfer of lead in a non-human primate species, with particular focus on skeletal tissue, which is known to be a site of lead deposition. Eight female cynomolgus monkeys were dosed with lead acetate during gestation, and in four of the animals, the isotopic composition of the lead was modified by enriching the amount of the stable isotope 204Pb included in the dose. Biopsy and dissection procedures for the preparation of bone samples for lead analysis and stable lead isotope analysis are described. Emphasis is placed on the containment of potential contamination of the samples by lead during preparation. Containment procedures included: use of a Class 100 clean room, special cleaning regimes and use of Teflon containers and stainless steel instruments. Preliminary data of lead concentrations in adult bone (trabecular and cortical) and fetal bone subsequent to the dosing regimen of lead during pregnancy, suggest notable differences between the two bone "compartments" examined. The bone samples of fetuses from the dams which had received enriched 204Pb showed drastically reduced 206Pb/204Pb isotope ratios.

Animals↗

Biological monitoring for occupational cadmium exposure: the urinary metallothionein.

The relationship between urinary metallothionein and kidney and liver cadmium levels was examined in 68 active and retired smelter workers. Metallothionein was analyzed by a radioimmunoassay and liver and kidney cadmium levels were determined by in vivo neutron activation. Four workers suffered from severe renal dysfunction and excreted high amounts of total protein and beta 2-microglobulin and greater than 1 mg metallothionein/g creatinine. In the remaining 64 workers the urinary metallothionein levels correlated significantly with the cadmium levels in both liver and kidney. Similarly, in these individuals urinary metallothionein was significantly related to cadmium in blood and urine. These results demonstrate that urinary metallothionein is a sensitive biological indicator of cadmium exposure and body burden, before the onset of severe renal dysfunction.

Adult↗

Transtentorial brain herniation in the monkey: analysis of brain stem auditory and somatosensory evoked potentials.

A monkey model of transtentorial brain herniation (TBH) was created to simulate the clinically encountered situation of a gradually expanding intracranial lesion. TBH was produced by extradural balloon inflation over a 4-hour period and documented by the appearance of the pupils as dilated or fixed at midposition. Intracranial pressure (ICP), brain stem auditory evoked potentials (BAEP), and short-latency somatosensory evoked potentials (SSEP) were recorded before, during, and after TBH. Statistical significance from baseline values to TBH was found for diminution of the BAEP amplitude, rise of the ICP, and diminution of the SSEP amplitude. An ICP rise to twice the baseline value and a 25% decrease in Wave V amplitude was found 1 hour before TBH. Changes in BAEP and SSEP took several minutes after deflation to return to baseline values. Analysis of Wave V of the BAEP was as sensitive as ICP in warning of TBH. Discussion centers upon previous animal studies of brain herniation and ICP elevation, and findings reported in humans deteriorating as a result of intracranial mass lesions. BAEP and SSEP monitoring may be used as noninvasive tests for brain stem compression in the setting of primate TBH, and in the future may be used to guide the effectiveness of therapy.

Animals↗

Determination of lead in blood by graphite furnace atomic absorption spectrometry--a critique.

Graphite furnace atomic absorption spectrometry (GFAAS) is increasingly becoming the method of choice for the determination of Pb in blood. The major GFAAS methods that have been published to date include: (i) direct introduction of the sample into the furnace; (ii) dilution with water, Triton X-100 or acid; (iii) deproteinization with nitric acid; (iv) matrix modification; and (v) solvent extraction. This review focuses on the difficulties associated with each of these methods, and highlights recent attempts to overcome matrix interferences and improve the accuracy and precision of Pb determination in blood using modern furnace technology, especially the stabilized temperature platform furnace.

Humans↗

Lead concentrations in human bones from the Canadian population.

Stable lead was determined in post-mortem samples of human bones from three Canadian cities. All age groups and both sexes were represented. The cities selected for investigation were Winnipeg, Montreal and Charlottetown. No significant difference was found between the locations, although levels tended to be higher for Montreal. Mean lead concentrations (micrograms Pb/g ash) were 8.98 +/- 1.17, 11.11 +/- 1.74 and 8.47 +/- 1.06 for Winnipeg, Montreal and Charlottetown, respectively. Corresponding geometric means were 6.21, 7.88 and 6.71, respectively. Individual values ranged from 0.45 to 240.07 micrograms Pb/g ash. Concentrations were highest in the greater than 20-year age group, indicating increased body burden with age. An increase in lead concentration was observed for the ages 1-11 years with a decrease for the 12-19-year age group. Differences in concentrations between the sexes were not significant. Higher than average concentrations were observed in samples obtained from Winnipeg for the period 1976-1980, particularly in the 1-4-year age group. A similar pattern was observed in the air lead concentrations, suggesting a possible correlation between the concentrations of lead in the air and in bones at Winnipeg.

Age Factors↗

Determination of lead in blood--an interlaboratory study.

An international co-operative blood-Pb interlaboratory study and a Canadian co-operative blood-Pb interlaboratory study were conducted using freeze-dried bovine blood samples with different endogenous Pb levels. The samples were prepared from whole blood of a nonexposed cow and another fed with a single dose of lead acetate. The mean values computed for the two samples analyzed by 25 international participants from 13 countries were 55 and 250 micrograms Pb l-1, respectively. These results showed a positive bias of 10% for the low level and 9% for the high Pb level with respect to the reference values obtained by isotope dilution mass spectrometry. In the case of the Canadian interlaboratory survey the mean values computed for the two samples analyzed by the 12 participants were 40 and 229 micrograms Pb l-1, respectively. These results showed a negative bias of 20 and 0.4% in relation to the target values of 50 and 230 micrograms Pb l-1, respectively. Despite such a bias, the data, on the whole, were of acceptable precision and accuracy when compared with previous interlaboratory blood-Pb surveys.

Animals↗