Lead in Calcium Supplements.
Intercalibrated measurements of lead in calcium supplements indicate the importance of rigorous analytical techniques to accurately quantify contaminant contaminant /con·tam·i·nant/ (kon-tam´in-int) something that causes contamination.
something that causes contamination. exposures in complex matrices. Without such techniques, measurements of lead concentrations in calcium supplements may be either erroneously low, by as much as 50%, or below the detection limit needed for new public health criteria. In this study, we determined the lead content of 136 brands of supplements that were purchased in 1996. The calcium in the products was derived from natural sources (bonemeal bone´meal`
n. 1. ground bones, used as a fertilizer or as a component in animal feed; - it is high in phosphate content.
Noun 1. , dolomite dolomite (dō`ləmīt', dŏl`ə–).
1 Mineral, calcium magnesium carbonate, CaMg (CO3)2. , or oyster shell) or was synthesized and/or refined (chelated che·late
Having chelae or resembling a chela.
A chemical compound in the form of a heterocyclic ring, containing a metal ion attached by coordinate bonds to at least two nonmetal ions. and nonchelated calcium). The dried products were acid digested and analyzed for lead by high resolution-inductively coupled plasma-mass spectrometry. The method's limit of quantitation averaged 0.06 [micro]g/g, with a coefficient of variation Coefficient of Variation
A measure of investment risk that defines risk as the standard deviation per unit of expected return. of 1.7% and a 90-100% lead recovery of a bonemeal standard reference material. Two-thirds of those calcium supplements failed to meet the 1999 California criteria for acceptable lead levels (1.5 [micro]g/daily dose of calcium) in consumer products. The nonchelated synthesized and/or refined calcium products, specifically antacids Antacids Definition
Antacids are medicines that neutralize stomach acid.
Antacids are used to relieve acid indigestion, upset stomach, sour stomach, and heartburn. and infant formulas, had the lowest lead concentrations, ranging from nondetectable to 2.9 [micro]g Pb/g calcium, and had the largest proportion of brands meeting the new criteria (85% of the antacids and 100% of the infant formulas). Key words: antacids, bonemeal, calcium supplements, dolomite, inductively coupled plasma-mass spectrometry (ICP-MS ICP-MS Inductively Coupled Plasma Mass Spectroscopy ), infant formulas, lead, nutritional supplements Nutritional Supplements Definition
Nutritional supplements include vitamins, minerals, herbs, meal supplements, sports nutrition products, natural food supplements, and other related products used to boost the nutritional content of the diet. , oyster shell, vitamins. Environ Health Perspect 108:309-313 (2000). [Online 21 February 2000]
Most Americans ([is greater than] 50% of all children under 5 and [approximately equals] 85% of teenage girls) do not ingest in·gest
tr.v. in·gest·ed, in·gest·ing, in·gests
1. To take into the body by the mouth for digestion or absorption. See Synonyms at eat.
2. enough calcium (1,2) and many still ingest too much lead (3-5). Lead, in contrast to calcium, is not an essential nutrient An essential nutrient is a nutrient required for normal body functioning that cannot be synthesized by the body and must be obtained from a dietary source. Some categories of essential nutrient include vitamins, dietary minerals, essential fatty acids, and essential amino acids. , and it has no established toxicity threshold concentration (6). As a biochemical analog of calcium, lead interferes with calcium metabolism calcium metabolism The constellation of ionic checks & balances that maintain Ca2+ homeostasis in the blood and tissues. See Calcium. and many of its biologic functions (7-9). Recent studies indicate that low levels of lead exposure are correlated with irreversible fetal brain damage, hypertension, cardiovascular disease Cardiovascular disease
Disease that affects the heart and blood vessels.
Mentioned in: Lipoproteins Test
cardiovascular disease , kidney dysfunction, impaired bone synthesis, impaired sperm production, and osteoporosis (6). Because these diseases are in part attributed to perturbations of the calcium cycle by lead, the adverse effects of insufficient calcium and elevated lead intakes are additive (6).
Several studies indicate that lead absorption, bone lead remobilization, and lead toxicity are all reduced with a balanced diet balanced diet
A diet that furnishes in proper proportions all of the nutrients necessary for adequate nutrition.
balanced diet and adequate calcium intake (6). These studies have often involved dietary calcium supplements because most foods have relatively low concentrations of calcium (1). However, some calcium supplements may also contain relatively high amounts of lead.
The primary "natural" sources of calcium for nutritional supplements (bonemeal, dolomite, and fossil oyster shells) all contain lead. Like calcium, lead is a naturally occurring element, and it is cycled through the biosphere biosphere, irregularly shaped envelope of the earth's air, water, and land encompassing the heights and depths at which living things exist. The biosphere is a closed and self-regulating system (see ecology), sustained by grand-scale cycles of energy and of as a calcium analogue (10). Although natural lead concentrations in calcium matrices are usually relatively low (e.g., [is less than] 0.5 [micro]g/g dry weight), the concentrations may be markedly elevated by environmental and industrial lead contamination. Therefore, this paper describes a methodology for quantifying that contamination.
The presence of lead in calcium supplements is of concern because some lead concentrations have been measured at toxic levels. These levels were initially detected in calcium supplements (bonemeal) in the 1960s (11) and precipitated a study and U.S. Food and Drug Administration warnings of potential lead contamination in calcium supplements (12,13). These initial concerns were substantiated in the 1980s by observations of the association of neurologic disorders in some patients who were taking either dolomite or bonemeal supplements and had relatively elevated lead concentrations in their hair (14). Those observations were further substantiated by a study in the early 1990s that also found relatively high, potentially toxic, levels of lead in some calcium supplements (15,16). More recently, lead contamination in a multivitamin mul·ti·vi·ta·min
Containing many vitamins.
A preparation containing many vitamins.
multivitamin was sufficient to confound a major evaluation of chelation therapy Chelation Therapy Definition
Chelation therapy is an intravenous treatment designed to bind heavy metals in the body in order to treat heavy metal toxicity. in children with blood lead concentrations [is greater than] 20 [micro]g/dL (17). Further investigation determined that the contaminated contaminated,
v 1. made radioactive by the addition of small quantities of radioactive material.
2. made contaminated by adding infective or radiographic materials.
3. an infective surface or object. ingredient was ferrous fumarate fumarate /fu·ma·rate/ (fu´mah-rat) a salt of fumaric acid.
a salt of fumaric acid. (18).
Health concerns for the relatively high concentrations of lead in some calcium supplements, and any other ingested in·gest
tr.v. in·gest·ed, in·gest·ing, in·gests
1. To take into the body by the mouth for digestion or absorption. See Synonyms at eat.
2. material, have increased with the results of recent lead toxicity studies. These studies failed to establish a discernible threshold for some measures of sublethal sublethal /sub·le·thal/ (-le´thal) insufficient to cause death.
Not sufficient to cause death. lead toxicity in humans (19). Consequently, the level of concern for childhood lead poisoning lead poisoning or plumbism (plŭm`bĭz'əm), intoxication of the system by organic compounds containing lead. has recently been further lowered to blood lead concentrations of 10 [micro]g/dL (20), and the adequacy of even that new standard has been questioned (10).
All of these concerns have led to the enactment of numerous state and federal measures both to reduce permissible levels of environmental and industrial lead exposure (6) and to advise the public of potential health risks associated with elevated lead exposures. In California, health advisory warnings must be put on the labels of consumer products with lead concentrations that amount to [is greater than] 1.5 [micro]g/daily dose (21). These values are based on a recommended adult daily dosage of 1 g calcium. [The recommended daily dosage of calcium for children 1-3 and 4-8 years of age is 500 and 800 mg, respectively; recommendations for older adults range from 1,000 to 1,300 mg calcium (2).] Consequently, relatively sophisticated analytical techniques are now required to accurately determine whether such advisories are appropriate and needed for different consumer products, including calcium supplements.
Samples. One hundred thirty-six brands of nutritional supplements containing calcium were purchased in 1996 from commercial outlets in California. The nutritional supplements included calcium supplements (83 brands), vitamin-mineral supplements (27 brands), antacids (20 brands), and infant formulas (6 brands). To determine whether the lead concentrations of those diverse samples were representative of the different products and types of calcium supplements, we measured interlot variations for 28 brands. We analyzed two to nine (average n = 6) lot samples of those products.
The calcium used in the supplements was either from a natural source or was synthesized and/or refined (as specified on the product label). The advertised natural calcium sources were bonemeal [hydroxyapatite hydroxyapatite /hy·droxy·ap·a·tite/ (-ap´ah-tit) an inorganic calcium-containing constituent of bone matrix and teeth, imparting rigidity to these structures. or calcium phosphate calcium phosphate
1. A colorless deliquescent powder, Ca(H2PO4)2, used in baking powders, as a plant food, as a plastic stabilizer, and in glass.
2. (Ca[PO.sub.4])], dolomite [CaMg[([CO.sub.3]).sub.2]], and fossil oyster shell (Ca[CO.sub.3]). There were two major types of synthesized and/or refined sources of calcium: calcium salts and calcium bound with various organic chelates. Calcium carbonate calcium carbonate, CaCO3, white chemical compound that is the most common nonsiliceous mineral. It occurs in two crystal forms: calcite, which is hexagonal, and aragonite, which is rhombohedral. (Ca[CO.sub.3]) was the most commonly reported calcium salt. Other synthesized products included calcium phosphate, calcium sulfate Noun 1. calcium sulfate - a white salt (CaSO4)
gypsum - a common white or colorless mineral (hydrated calcium sulphate) used to make cements and plasters (especially plaster of Paris) , and calcium chloride calcium chloride, CaCl2, chemical compound that is crystalline, lumpy, or flaky, is usually white, and is very soluble in water. The anhydrous compound is hygroscopic; it rapidly absorbs water and is used to dry gases by passing them through it. . Many of the chelated-calcium products contained one or more of the following chelates: citrate citrate /cit·rate/ (sit´rat) a salt of citric acid.
citrate phosphate dextrose (CPD) anticoagulant citrate phosphate dextrose solution. , gluconate, aspartate aspartate /as·par·tate/ (ah-spahr´tat) a salt of aspartic acid, or aspartic acid in dissociated form.
1. A salt of aspartic acid.
2. , ascorbate a·scor·bate
A salt of ascorbic acid.
a compound or derivative of ascorbic acid. See also sodium ascorbate. , stearate stearate /ste·a·rate/ (ste´ah-rat) any salt (soap), ester, or anionic form of stearic acid.
A salt or ester of stearic acid.
any compound of stearic acid. , malate malate /ma·late/ (ma´lat) any salt of malic acid.
A salt or ester of malic acid.
a salt of malic acid. , fumarate, and lysinate. Calcium citrate calcium citrate
Cal-Citrate-225, Cal-Citrate-250, Citracal, Citracal Liquitabs, Citrus Calcium
Pharmacologic class: Mineral
Therapeutic class: Dietary supplement, electrolyte replacement agent
was the most common of those chelates.
The vitamin-mineral and calcium supplements included both natural source calcium (bonemeal, dolomite, and fossil oyster shell) and synthesized and/or refined calcium (chelated and nonchelated). We analyzed 26 oyster shell brands, 9 bonemeal brands, and 5 dolomite brands (natural source supplements). We analyzed 33 chelated and 37 nonchelated brands (synthesized and/or refined calcium supplements).
Sample processing. The samples were digested in Teflon labware that had been cleaned in a high-efficiency particulate air-(HEPA HEPA
1. high-efficiency particulate air
2. high-efficiency particulate arresting ) filtered, trace-metal-clean laboratory to minimize contamination (19). This protocol involved sequentially cleaning the labware in a series of baths in solutions (1 week each) and rinses (five per solution) in a three-step order: a) we used a detergent solution (Micro; American Scientific Products, McGraw Park, IL) and deionized water Deionized water (DI water or de-ionized water; also spelled deionised water, see spelling differences) is water that lacks ions, such as cations from sodium, calcium, iron, copper and anions such as chloride and bromide. rinses; b) we used a 6-N HCl (reagent grade) solution and ultrapure (Milli-Q; Millepore mil·le·pore
Any of various reef-building hydrocorals of the order Milleporina of tropical marine waters, forming white or yellowish calcareous structures and resembling the true corals of the class Anthozoa. Corp., Bedfor, MA; 18 M[Omega]/cm) water rinses; and c) we used a 7.5-N [HNO HNO Hals Nasen Ohrenheilkunde
HNO Hals-Nasen-Ohren Heilkunde (German: throat, nose and ear medicine)
HNO Host Network Operator
HNO Harvard News Office
HNO Helvetica Narrow Oblique (font) .sub.3] (trace metal grade) solution and ultrapure water rinses. The labware was then air dried in a polypropylene laminar laminar /lam·i·nar/ (lam´i-nar)
1. pertaining to a lamina or laminae.
3. of, pertaining to, or being a streamlined, smooth fluid flow. airflow-exhausting hood.
After we determined the mean product weight of 5-10 sample units (e.g., tablets or capsules) or a 15-mL solution within each lot, we placed aliquots of sample homogenates (0.25-0.5 g powder or 10-15 mL liquid) in the containers. The weighed product units were ground into a fine powder using an acid-cleaned mortar and pestle A mortar and pestle is a tool used to crush, grind, and mix substances. The pestle is a heavy stick whose end is used for pounding and grinding, and the mortar is a bowl. The substance is ground between the pestle and the mortar. . Sample aliquots were placed in acid-cleaned Teflon screw-cap vials, dried overnight in an oven at 75 [degrees] C, cooled to the ambient temperature Outside temperature at any given altitude, preferably expressed in degrees centigrade. , and then weighed.
The dried samples were dissolved in 10 mL concentrated [HNO.sub.3] (trace metal grade). When necessary, some sample vials were placed in an ice bath and the acid was slowly and incrementally added to control rapid oxidation (e.g., foaming) of the samples. The dissolved solutions were refluxed in the capped vials on a ceramic hot plate (modified for trace metal analyses) for 4 hr at a low ([is less than or equal to] 50 [degrees] C) temperature to prevent excessive foaming. The dissolved solutions were then refluxed at a higher temperature ([is greater than] 85 [degrees] C) until the solution was transparent, as specified by the National Food Library (NFL NFL
National Football League
NFL (US) n abbr (= National Football League) → Fußball-Nationalliga ) (22). Finally, the samples were evaporated to dryness and reconstituted in 10-mL 1N [HNO.sub.3] (trace metal grade) for elemental analyses.
However, that digestion was insufficient for lead concentration measurements by graphite furnace atomic absorption Graphite furnace atomic absorption spectrometry (GFAAS) (also known as Electrothermal Atomic Absorption Spectrometry (ETAAS)) is a type of spectrometry that uses a graphite-coated furnace to vaporize the sample. spectroscopy (GFAAS GFAAS Graphite Furnace Atomic Absorption Spectrometry ). We then determined that to accurately analyze by GFAAS, the digested sample solutions must be both transparent and colorless, indicating the total breakdown of the organometal complexes. This additional requirement substantially increased the time for the digestion step from 1-2 days to 7-10 days, based on a series of analyses in our laboratory and corroborated cor·rob·o·rate
tr.v. cor·rob·o·rat·ed, cor·rob·o·rat·ing, cor·rob·o·rates
To strengthen or support with other evidence; make more certain. See Synonyms at confirm. by the NFL (22).
Conversely, the initial digestion to a merely transparent solution proved sufficient for lead concentration measurements by high resolution inductively coupled plasma-mass spectrometry (ICP-MS). This method involves atomizing the solution in a plasma with a temperature of approximately 7,000 K. The high temperature is sufficient to destroy any organometal complexes before elemental analyses, as indicated by the quantitative recovery (96.3 [+ or -] 4.8%) of lead in a bonemeal standard reference material [SRM (1) (Storage Resource Management) The management of the storage resources in an organization in order to avoid duplication of files and to determine space utilization across all servers. 1486; National Institute of Standards and Technology National Institute of Standards and Technology, governmental agency within the U.S. Dept. of Commerce with the mission of "working with industry to develop and apply technology, measurements, and standards" in the national interest. (NIST (National Institute of Standards & Technology, Washington, DC, www.nist.gov) The standards-defining agency of the U.S. government, formerly the National Bureau of Standards. It is one of three agencies that fall under the Technology Administration (www.technology. ), Gaithersburg, MD) by ICP-MS as compared to the relatively low (51.0 [+ or -] 5.6%) recovery by GFAAS.
Instrumental analyses. As previously indicated, the initial attempts to measure lead concentrations in the sample solutions were made by GFAAS, using a SIMAA 6000 (Perkin-Elmer, Norwalk, CT) with Zeeman background correction. The instrument was initially calibrated cal·i·brate
tr.v. cal·i·brat·ed, cal·i·brat·ing, cal·i·brates
1. To check, adjust, or determine by comparison with a standard (the graduations of a quantitative measuring instrument): with replicate analyses (n = 7) of a Perkin-Elmer certified mixed element standard, with lead recovery of 98.9 [+ or -] 1.7%. To control for matrix effects, samples were measured using a matrix modifier (programming) modifier - An operation that alters the state of an object. Modifiers often have names that begin with "set" and corresponding selector functions whose names begin with "get". [[NH.sub.4][H.sub.2][PO.sub.4] + Mg[([NO.sub.3]).sub.2]]. Although concentrations were calculated using the method of standard additions, this still did not appear to correct for all matrix effects.
Based on problems incurred with the initial GFAAS analyses, subsequent measurements were made by ICP-MS. These measurements proved more accurate and efficient for measuring lead in calcium supplements. The analyses were made with a Finnegan MAT Element high-resolution magnetic sector inductively coupled plasma-mass spectrometer (Finnegan, Bremen, Germany). To maintain high quality instrument performance, solutions for ICP-MS analysis did not exceed 0.1% total dissolved solids Total dissolved solids (often abbreviated TDS) is an expression for the combined content of all inorganic and organic substances contained in a liquid which are present in a molecular, ionized or micro-granular (colloidal sol) suspended form. . These digest solutions were made with 25- to 50-fold dilutions with a 1-[micro]g/L (ppb) bismuth bismuth (bĭz`məth) [Ger. Weisse Masse=white mass], metallic chemical element; symbol Bi; at. no. 83; at. wt. 208.9804; m.p. 271.3°C;; b.p. about 1,560°C;; sp. gr. 9.75 at 20°C;; valence +3 or +5. internal standard solution in 1 N [HNO.sub.3] (i.e., 100-250 [micro]L digest was added to 5 mL 1 [micro]g/L bismuth solution in tracemetal-clean polypropylene vials). The calibration standards (0, 0.5, 1.0, 2.5, and 5.0 [micro]g/L) were also spiked with 1 [micro]g/L bismuth.
We derived the lead concentration analyses from instrumental scans of three lead isotopes ([sup.206]Pb, [sup.207]Pb, and [sup.208]Pb) and bismuth ([sup.209]Bi). The sum of intensities for the stable lead isotopes was normalized to the bismuth internal standard to correct instrumental variations in sensitivity. Spiking the samples with [sup.209]Bi precluded the analysis of supplements containing large amounts of bismuth, but an alternative internal standard such as thallium thallium (thăl`ēəm), metallic chemical element; symbol Tl; at. no. 81; at. wt. 204.383; m.p. 303.5°C;; b.p. about 1,457°C;; sp. gr. 11.85 at 20°C;; valence +1 or +3. could be used for analyses of that type of supplement.
Quality assurance. We used quality assurance samples from each sample batch to assess the precision and accuracy of analyses within our laboratory. Ten percent of the samples for each batch were digested and analyzed in duplicate to determine the precision of the digestion, and we used replicate instrument measurements to determine instrument precision. We assessed replicate dilutions of the digest solutions for ICP-MS analyses to determine the precision of pipetting the sample digests. We analyzed three solutions of a standard reference material (NIST SRM 1486 bonemeal) concurrently with each sample batch to quantify the accuracy of the measurements. Three procedural blanks were analyzed concurrently with each sample batch to quantify the sample contamination associated with processing and the detection limit.
We also used quality assurance samples to compare the precision and accuracy of analyses between laboratories (Table 1). A highly refined Ca[CO.sub.3] product (Specialty Minerals, Inc., Adams, MA) was analyzed by four laboratories. The laboratories included the manufacturer's laboratory, two independent laboratories contracted by the manufacturer, and our laboratory at the University of California The University of California has a combined student body of more than 191,000 students, over 1,340,000 living alumni, and a combined systemwide and campus endowment of just over $7.3 billion (8th largest in the United States). Santa Cruz Santa Cruz, city, United States
Santa Cruz (săn`tə krz), city (1990 pop. 49,040), seat of Santa Cruz co., W Calif., on the north shore of Monterey Bay; inc. 1866. (UCSC UCSC University of California, Santa Cruz (since 1965; Santa Cruz, California)
UCSC University of South Carolina
UCSC University of Colombo School of Computing (Colombo, Sri Lanka) ). All of the laboratories measured lead concentrations in the Ca[CO.sub.3] product using three instruments: GFAAS, quadrapole ICP-MS, and high resolution magnetic sector ICP-MS, respectively.
Table 1. Lead concentration ([micro]g/g) measurements for a highly refined calcium carbonate powder for four laboratories using three instruments.
Lead concentration ([micro]g/g dry weight) Laboratory Instrument Mean [+ or -] SD No. Manufacturer GFAAS 0.187 [+ or -] 0.006 13 Independent A GFAAS 0.184 [+ or -] 0.005 3 Independent B Quadropole ICP-MS 0.177 [+ or -] NA 1 UCSC High resolution ICP-MS 0.167 [+ or -] 0.004 3
UCSC, University of California Santa Cruz. Interlaboratory calibration: lead analysis of refined Ca[CO.sub.3] powder (lot no. A-3-070-26; Specialty Minerals, Inc., Adams, MA).
Because the sample matrices for most calcium supplements are much more complex than those of refined calcium supplements, we also conducted a second interlaboratory calibration with the NFL in Dublin, California (Table 2). This intercalibration included analyses of seven brands of calcium supplements, with one or two samples from each of the five types of calcium supplements. Twenty tablets of each product were ground, homogenized ho·mog·e·nize
v. ho·mog·e·nized, ho·mog·e·niz·ing, ho·mog·e·niz·es
1. To make homogeneous.
a. To reduce to particles and disperse throughout a fluid.
b. , and dried using trace-metal-clean techniques. At the NFL, the sample aliquots were acid digested and analyzed by GFAAS, with Zeeman effect background correction and using the standard additions method with a matrix modifier [Pd + Mg[([NO.sub.3]).sub.2]]. At UCSC, the sample aliquots were processed and measured by high resolution ICP-MS, as detailed in this paper.
Table 2. Interlaboratory calibration: lead analysis of calcium supplements.
Sample type Sample code NFL (GFAAS) UCSC (ICP-MS) RPD Refined, lozenge 216-ref-z 0.06 0.06 2.4 Oyster, tablet 161-oys-t 1.07 1.21 12 Oyster, tablet 94-oys-t 1.74 1.53 13 Refined, capsule 206-ref-c 0.99 0.83 17 Chelated, tablet 209-che-t 1.42 1.18 19 Bonemeal, capsule 220-bon-c 0.48 0.38 24 Dolomite, tablet 139-dol-t 2.60 1.72 41
RPD RPD Rapid
RPD Radiation Protection Dosimetry
RPD Rapid Product Development
RPD Rochester Police Department
RPD Recurrent Pattern Detection (Commtouch anti-spam engine)
RPD Relative Percent Difference
RPD Removable Partial Denture , relative percent difference. Measured lead concentration ([micro]g/g dry weight).
Quality assurance comparisons with recent measurements of lead in calcium supplements. Current levels of sensitivity [method detection limits (MDLs) and limit of quantitation] and precision [coefficient of variation (CV)] in measurements of lead in calcium supplements are listed in Table 3, which summarizes reported analytical parameters for the measurements using different instrumentation (23-25). These instruments include anodic an·ode
1. A positively charged electrode, as of an electrolytic cell, storage battery, or electron tube.
2. The negatively charged terminal of a primary cell or of a storage battery that is supplying current. stripping voltametry (ASV ASV
American Standard Version
ASV n abbr (= American Standard Version) → traduction de la Bible
ASV n abbr (Bible) (= ), flame and graphite atomic absorption spectrometry Absorption spectrometry
A scientific procedure to determine chemical makeup of samples.
Mentioned in: Herbalism, Traditional Chinese (FAAS FAAS Federation of American Aquarium Societies
FAAS Flame Atomic Absorption Spectroscopy
FAAS Foreign Affairs Administrative Support
FAAS Front Arabo-Africain de Salut (Arabic-African Salvation Front) and GFAAS, respectively), and quadrapole ICP-MS. We also used high-resolution magnetic sector ICP-MS; those measurements are detailed in this paper.
Table 3. Comparison of quality assurance parameters(a) with previously reported analytical lead measurements(b) in calcium supplements.
Instrument MDL ([micro]g/g) LOQ ([micro]g/g) Anodic stripping 0.42(c) 1.4 voltametry (ASV) FAAS 0.50(c) 1.7 GFAAS 0.12(c) 0.40 0.042(d) 0.14 0.05(e) 0.15 ICP-MS (quadrapole) 0.01(c) 0.03 0.02(e) 0.06 ICP-MS (magnetic sector) 0.02(f) 0.06 Instrument CV (%) Recovery (%) Anodic stripping 18 92 voltametry (ASV) FAAS 29 147 GFAAS 7 100 8 100 11.6 80-120 ICP-MS (quadrapole) 9 89 4.9 80-120 ICP-MS (magnetic sector) 1.7 90-100
Data are from the analysis of standard reference materials with a matrix comparable to calcium supplements (e.g., NIST SRM 1486 bonemeal).
(a) Parameters include MDL MDL - (Originally "Muddle"). C. Reeve, Carl Hewitt and Gerald Sussman, Dynamic Modeling Group, MIT ca. 1971. Intended as a successor to Lisp, and a possible base for Planner-70. Basically LISP 1.5 with data types and arrays. LOQ LOQ Limit of Quantitation
LOQ Limit Of Quantification
LOQ Loquitur (Latin: speaks)
LOQ Level of Quantification
LOQ List Of Questions
LOQ Laugh Out Quiet
LOQ Leadership Opinion Questionaire , and CV.
(b) Instrumentation includes ASV, FAAS and GFAAS, and ICP-MS
(c) Bourgoin et al. (15).
(d) Siitonen and Thompson (25).
(e) Vest Coast Analytical Service (24).
(f) This paper.
Results and Discussion
Two-thirds of the 136 products purchased in 1996 failed to meet the 1999 California criteria for acceptable lead levels in consumer products. Although there is no statistically significant difference (p [is less than] 0.05, analysis of variance) between the supplement types measured in this study, antacids had the lowest average lead concentration with the least variation (Table 4). We did not include the infant formulas (all [is less than] MDLs) in the statistical test.
Table 4 Reported lead concentrations ([micro]g/g dry weight) in various calcium supplements by several investigators over a 20-year period
Reference Bonemeal Dolomite Crosby 1977 (11) 190 -- n = 1 -- Capar and Gould 4.16 [+ or -] 1.78 -- 1979 (12) (1.5-8.3) -- n = 20 -- Roberts 1983 (14) 9.88 [+ or -] 7.32 5.84 [+ or -] 7.99 (2-20) (0.5-19.6) n = 8 n = 8 Dabeka and -- -- McKenzie 1987 (27) -- -- -- -- -- -- -- -- Boulos and von -- -- Smolenski 1988 (26) -- -- Bourgoin et al 2.67 [+ or -] 2.74 1.11 [+ or -] 0.71 1993 (23) (0.64-8.83) (0.52-2.52) n=6 n = 9 Siitonen and 4.27 [+ or -] 2.71 0.94 [+ or -] 0.51 Thompson 1994 (25) (1.21-6.39) (0.55-1.51) n=3 n = 3 This paper (brands 0.60 [+ or -] 0.39 0.97 [+ or -] 0.49 purchased in 1996) (0.21-1.38) (0.39-1.56) n = 9 n = 5 Reference Oyster shell Refined Crosby 1977 (11) -- -- -- -- Capar and Gould -- -- 1979 (12) -- -- -- -- Roberts 1983 (14) -- 0.30 [+ or -] 0.35 -- (0.08-0.7) -- n = 3 Dabeka and -- -- McKenzie 1987 (27) -- -- -- -- -- -- -- -- Boulos and von -- -- Smolenski 1988 (26) -- -- Bourgoin et al 2.11 [+ or -] 1.33 0.34 [+ or -] 0.24 1993 (23) (0.36-4.88) (0.04-0.92) n = 25 n = 17 Siitonen and 0.67 [+ or -] 0.54 -- Thompson 1994 (25) (0.17-1.26) -- n = 4 -- This paper (brands 0.88 [+ or -] 0.51 0.73 [+ or -] 1.60 purchased in 1996) (0.12-2.10) (0-10.05) n = 26 n = 37 Refined Reference antacids Chelated Crosby 1977 (11) -- -- -- -- Capar and Gould -- -- 1979 (12) -- -- -- -- Roberts 1983 (14) -- -- -- -- -- -- Dabeka and -- -- McKenzie 1987 (27) -- -- -- -- -- -- -- -- Boulos and von 1.03 -- Smolenski 1988 (26) n = 1 -- Bourgoin et al -- 0.26 [+ or -] 0.36 1993 (23) -- (0.03-1.21) -- n = 13 Siitonen and -- 0.60 [+ or -] 0.84 Thompson 1994 (25) -- (ND-1.19) -- n = 2 This paper (brands 0.12 [+ or -] 0.16 0.57 [+ or -] 0.54 purchased in 1996) (0.01-0.71) (0.04-2.8) n = 20 n = 33 Infant formulas Infant formulas Reference (powder) (canned liquid) Crosby 1977 (11) -- -- -- -- Capar and Gould -- -- 1979 (12) -- -- -- -- Roberts 1983 (14) -- -- -- -- -- -- Dabeka and 88.7 (9-532) 27.4 (5.8-67) McKenzie 1987 (27) n = 25(a) n = 22(b) 11.5(4-19) 3.5 (1.2-9.8) n = 6(c) n = 8(d) -- -- Boulos and von -- -- Smolenski 1988 (26) -- -- Bourgoin et al -- -- 1993 (23) -- -- -- -- Siitonen and -- -- Thompson 1994 (25) -- -- -- -- This paper (brands <0.02 <0.02 purchased in 1996) n = 3(e) n = 3(d) -- --
n, number of brands analyzed. Values are mean [+ or -] SD (range)
(a) Collected in 1980.
(b) Lead-soldered cans.
(c) Collected in 1985.
(d) Lead-free cans.
(e) Collected in 1996.
Lead concentrations in synthesized and/or refined calcium supplements. Figure 1 illustrates the distribution of lead in supplements made with synthesized calcium. Three nonchelated brands and six chelated brands exceeded the federal limit of 7.5 [micro]g lead/g calcium (or 6 [micro]g lead/800 mg calcium) (Figure 1). Although approximately three-fourths of the nonchelated brands (n = 28) and almost two-thirds of the chelated brands (n = 21) met the July 1997 California limit of 4 [micro]g lead/g calcium (or 3.2 [micro]g lead/800 mg calcium), only a small proportion of these (10 nonchelated and 3 chelated) would meet the new April 1999 California limit (21) of 1.5 [micro]g lead/g calcium (or 1.2 [micro]g lead/800 mg calcium).
[Figure 1 ILLUSTRATION OMITTED]
Generally, the lowest lead levels in all of the materials that we analyzed were found in the infant formulas and the antacids, which all contained either synthesized and/or refined calcium. Lead concentrations were nondetectable ([is less than] 0.02 [micro]g/g) in all infant formulas tested, and all brands of infant formulas and antacids were in compliance with both the federal and the California limits for lead that were in effect at the time of analysis. However, three brands of antacids, based on these analyses, would now be in noncompliance noncompliance
failure of the owner to follow instructions, particularly in administering medication as prescribed; a cause of a less than expected response to treatment.
noncompliance with the new (April 1999) standards in California (Figure 1) (21).
Lead concentrations in natural calcium supplements. Figure 2 shows the distribution of lead concentrations in the natural source calcium products. Two dolomite brands and one oyster shell brand exceeded the federal limit (Figure 2). Two of five dolomite brands met the California July 1997 limit, and none of these would meet the lower April 1999 limit. Nineteen of 26 oyster shell brands met the California July 1997 limit, only 5 of which would meet the lower April 1999 limit. All nine bonemeal brands met the federal limit; however, although eight brands met the California July 1997 limit, only half of these would meet the California April 1999 limit.
[Figure 2 ILLUSTRATION OMITTED]
Comparisons with previously reported measurements of lead in nutritional supplements. Analyses of lead in calcium supplements were initiated by Capar and Gould (12) 20 years ago. They digested the supplements with perchloric acid perchloric acid /per·chlor·ic ac·id/ (per-klor´ik) a colorless volatile liquid, HClO4, which can cause powerful explosions in the presence of organic matter or anything reducible.
n. , then measured their lead concentrations using differential pulsed anodic stripping voltametry. Bourgoin et al. (23) subsequently conducted an interlaboratory comparison of techniques to measure lead concentrations in calcium supplements using nitric acid nitric acid, chemical compound, HNO3, colorless, highly corrosive, poisonous liquid that gives off choking red or yellow fumes in moist air. It is miscible with water in all proportions. or hydrochloric acid hydrochloric acid: see hydrogen chloride.
or muriatic acid
Solution in water of hydrogen chloride (HCl), a gaseous inorganic compound. digestions and four different instruments (ASV, FAAS, GFAAS, and ICP-MS). Bourgoin et al. (23) showed that the quadrapole ICP-MS was the most sensitive instrument; GFAAS and ICP-MS were the most precise and accurate; ASV was relatively accurate but not very sensitive or precise; and FAAS was the least sensitive, precise, and accurate of the four types of instruments. Although later studies (24,25) corroborated the relatively high sensitivity of quadrapole ICP-MS measurements, they also documented a substantial improvement in the sensitivity of GFAAS measurements (Table 3).
Some of the historical reports of measurements of lead in nutritional supplements are listed in Tables 3 and 4. Table 3 shows the marked improvement in the precision (CV) in lead analyses over the past 20 years. This is notable because previous levels of precision are insufficient for measurements to meet the new advisory requirements for lead exposure (i.e., 1.5 [micro]g lead/dose).
Temporal variations of lead in calcium supplements. The data in Table 4 provide some perspective on historic and current variations in lead concentrations in calcium supplements over the past 20 or more years (11,12,14,16,25-27). As previously indicated, concerns with lead contamination in nutritional supplements were catalyzed by reports of remarkably elevated lead levels (20-532 [micro]g/g) in dolomite, bonemeal, and infant formulas (11,14,27) and relatively high levels (4.88 [micro]g/g) in oyster shell supplements (16). The mean lead concentrations for each corresponding supplement type purchased in 1996 were lower than the first published values. There is a statistically significant decrease (p [is less than] 0.05, t-test) in lead concentrations in some types of supplements (e.g., bonemeal, oyster shells, and infant formulas), but not in others (e.g., dolomite). There also appear to have been relatively high variations in lead concentrations in refined and chelated calcium supplements throughout that period.
The apparent temporal decrease in lead concentrations in bonemeal, oyster shells, and infant formulas is tentatively attributed to corresponding reductions in lead contamination and improvements in processing those materials. Environmental exposures to industrial lead have decreased by orders of magnitude after the systematic elimination of leaded gasoline emissions in much of North America and Europe over the past 20 years (28). Food and nutritional products, such as infant formulas, are mostly stored in lead-free cans instead of lead-soldered ones. Many manufacturers that used bonemeal for calcium supplements now use the bones of younger bovines or equines, which have less accumulation of industrial lead. And, most recently, many manufacturers have shifted to using only red bone marrow red bone marrow
Bone marrow characterized by meshes of the reticular network that contain the developmental stages of red blood cells, white blood cells, and megakaryocytes.
red bone marrow
see bone marrow. because it contains less lead and is less subject to lead contamination than outer bone. Similarly, many manufacturers that use fossil oyster shells for calcium supplements have been using older deposits that contain less lead. Those temporal reductions contrast with the relative consistency in lead concentrations in dolomite supplements over the past 20 years, which may be due to the relative homogeneity of lead concentrations in those deposits (15).
These data are consistent with previous measurements of lead in calcium supplements. They indicate that some contain relatively low concentrations of lead ([is less than] 0.5 [micro]g/g dry weight), whereas others contain relatively high concentrations. Some of the latter concentrations exceed the most recent criteria established to limit lead exposure in California ([is greater than] 1.5 [micro]g/g).
The temporal decrease of lead concentrations in some calcium supplements, indicated by previous analyses, is substantiated by this study. This includes decreases in lead concentrations in products derived from bonemeal and oyster shells, but not those derived from dolomite, over the past 20 years. In addition, the data corroborate To support or enhance the believability of a fact or assertion by the presentation of additional information that confirms the truthfulness of the item.
The testimony of a witness is corroborated if subsequent evidence, such as a coroner's report or the testimony of other previous reports of the relatively high variations in lead concentrations in refined and chelated calcium supplements during that period.
These new data demonstrate that relatively low concentrations ([is less than] 0.5 [micro]g/g dry weight) may now be accurately measured in complex calcium matrices. These matrices require the adaptation of trace-metal-clean techniques to minimize contamination during sampling, processing, and analyses. The matrices also require the adaptation of rigorous quality assurance protocols to preclude erroneous measurements, which will tend to underestimate lead concentrations in calcium supplements.
As previously noted, these reported concentrations are for a limited number of analyses of the brands that we collected in 1996. The analyses were conducted before the settlement of litigation An action brought in court to enforce a particular right. The act or process of bringing a lawsuit in and of itself; a judicial contest; any dispute.
When a person begins a civil lawsuit, the person enters into a process called litigation. on the disclosure of lead concentrations in calcium supplements in California. The disclosure of lead concentrations in calcium supplements catalyzed efforts to further reduce lead concentrations in those supplements. Consequently, lead concentrations in some of those products may now be lower than the values in this paper.
In addition, the exposure risk from lead in calcium supplements may be relatively small, even though the contribution of lead from a daily dose of those supplements (median = 2.38 [micro]g) to the average total daily dietary intake (5-11 [micro]g/day) may be relatively large (29). This disparity is due to the much higher supplemental concentrations of calcium, which decrease gastrointestinal lead absorption (30). Several studies of factors that influence the dietary assimilation of lead show this decrease in lead absorption (31).
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Address correspondence to G. Scelfo, Environmental Toxicology, Applied Sciences 269, University of California, Santa Cruz The University of California, Santa Cruz, also known as UC Santa Cruz or UCSC, is a public, collegiate university, one of the ten campuses of the University of California. , CA 95064 USA. Telephone: (831) 459-3563. Fax: (831) 459-2088. E-mail: email@example.com
We thank S. Hibdon and R. Franks for analytical support.
This research was partially supported by funds from the California Attorney General's Office, the Natural Resources Defense Council The Natural Resources Defense Council (NRDC) is a New York City-based, non-profit non-partisan international environmental advocacy group, with offices in Washington, D.C., San Francisco, Los Angeles, Chicago, and Beijing. Founded in 1970, NRDC today has 1. , and the University of California Toxic Substances Research and Teaching Program.
Received 1 July 1999; accepted 26 October 1999.
Genine M. Scelfo and A. Russell Flegal Environmental Toxicology, University of California, Santa Cruz, California, USA