Content uploaded by Robert A Yokel
Author content
All content in this area was uploaded by Robert A Yokel on Jul 02, 2023
Content may be subject to copyright.
Aluminum bioavailability from basic sodium aluminum
phosphate, an approved food additive emulsifying agent,
incorporated in cheese
Robert A. Yokela,b, Clair L. Hicksc, and Rebecca L. Florencea
aDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky Academic Medical
Center, 725 Rose Street, Lexington, KY 40536-0082, USA
bGraduate Center for Toxicology, University of Kentucky Academic Medical Center, Lexington, KY
40536-0082, USA
cAnimal and Food Sciences Department, College of Agriculture, University of Kentucky, Lexington, KY
40546-0215, USA
Abstract
Oral aluminum (Al) bioavailability from drinking water has been previously estimated, but there is
little information on Al bioavailability from foods. It was suggested that oral Al bioavailability from
drinking water is much greater than from foods. The objective was to further test this hypothesis.
Oral Al bioavailability was determined in the rat from basic [26Al]-sodium aluminum phosphate
(basic SALP) in a process cheese. Consumption of ~ 1 gm cheese containing 1.5 or 3% basic SALP
resulted in oral Al bioavailability (F) of ~ 0.1 and 0.3%, respectively, and time to maximum
serum 26Al concentration (Tmax) of 8 to 9 h. These Al bioavailability results were intermediate to
previously reported results from drinking water (F ~ 0.3%) and acidic-SALP incorporated into a
biscuit (F ~ 0.1%), using the same methods. Considering the similar oral bioavailability of Al from
food vs. water, and their contribution to the typical human’s daily Al intake (~ 95 and 1.5%,
respectively), these results suggest food contributes much more Al to systemic circulation, and
potential Al body burden, than does drinking water. These results do not support the hypothesis that
drinking water provides a disproportionate contribution to total Al absorbed from the gastrointestinal
tract.
Keywords
Accelerator mass spectrometry; aluminum; atomic absorption spectrometry; basic sodium aluminum
phosphate; food additive; oral bioavailability
Introduction
Aluminum (Al) is a toxicant to the central nervous, skeletal and hematopoietic systems
(Krewski et al., 2007). The primary source of oral Al exposure in the U.S. for the typical human
is foods, representing ~ 95% of daily oral intake; drinking water contributes ~ 1 to 2% (WHO,
Corresponding author: Robert A. Yokel, Ph.D., 511C Pharmacy Building, 725 Rose Street, University of Kentucky Academic Medical
Center, Lexington, KY40536-0082, phone: 859-257-4855, fax: 859-323-6886, e-mail: ryokel@email.uky.edu.
Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers
we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting
proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could
affect the content, and all legal disclaimers that apply to the journal pertain.
NIH Public Access
Author Manuscript
Food Chem Toxicol. Author manuscript; available in PMC 2009 June 1.
Published in final edited form as:
Food Chem Toxicol. 2008 June ; 46(6): 2261–2266.
NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript
1997; ATSDR, 1999; Krewski et al., 2007). These typically provide a total of ~ 4000 to 9,000
µg Al/day. Consumption of antacids can provide up to 5,000,000, inhalation from
environmental and industrial air 4 to 20 and up to 25,000, and antiperspirant use up to ~ 70,000
µg/day. Injected Al in vaccines and allergy immunotherapy can provide 1 to 8 and 7 to 40 µg/
day, respectively, and probably complete absorption (Yokel and McNamara, 2001). Some
people may have further Al exposures, e.g., occupational (Elinder et al., 1991), Al-
contaminated dialysis fluid (Alfrey et al., 1976), alum instillation into a hemorrhaging urinary
bladder (Phelps et al., 1999) and illicit drug abuse, including intravenous self-injection of
methadone prepared in Al cookware (Friesen et al., 2006; Yong et al, 2006; Exley et al,
2007). Although tobacco contains considerable Al, ~ 500 to 2000 µg/cigarette, < 0.02 to ~
0.075 µg appeared in the smoke from one cigarette (Cogbill and Hobbs, 1957; Exley et al.,
2006). Even if 100% bioavailable, when compared to oral Al intake of 5000 µg/day from diet
that is 0.25% bioavailable delivering 12.5 µg to systemic circulation, a cigarette would deliver
only ~ 0.4% as much. It was suggested that drinking water provides a disproportionate
contribution to total Al absorbed from the gastrointestinal tract because it is largely un-
complexed in water, whereas organic ligands such as phytates and polyphenols in food were
suggested to complex Al and inhibit its oral absorption (Martyn et al., 1989). This notion has
been followed by ≥ 12 epidemiological studies since 1989 assessing the association between
Al in drinking water and cognitive impairment, dementia and Alzheimer’s disease (AD)
(Krewski et al., 2007). Many showed a significantly higher odds ratio for dementia among
study subjects living in areas where the drinking water had a higher Al concentration. However,
there is no evidence that drinking water is the major source of systemic Al for the typical person.
The study in this report was aimed at testing this notion.
If Al bioavailability from water is not considerably greater than from food, studies assessing
a putative link between Al in drinking water and AD might be misfocused, and studies
investigating a possible association between Al in food and cognitive impairment, dementia
and AD might be more relevant. There is only one published study assessing a putative link
between dietary Al intake in food and AD (Rogers and Simon, 1999). In 23 matched sets of
residents of a geriatric center with and without AD, the adjusted odds ratio for several food
groups, including baked goods and cheese, was elevated. However, due to the very small
sample size, most results did not reach statistical significance.
Adult daily dietary Al intake in the U.K. and U.S. has been estimated to be 3.9 and 7 to 9 mg
(depending on age and sex), respectively (UK-MAFF, 1993; Pennington and Schoen, 1995).
There have been at least 12 other estimates of adult dietary Al intake published in the past 10
years from other countries. Most reported equal or less daily Al intake than in the U.S. The
lower daily Al intake in some countries, such as in Europe, has been attributed to less use of
Al as a food additive (Müller et al., 1998).
Different food sources contribute variable amounts of Al to the human diet (Pennington,
1987; UK-MAFF, 1993; Lopez et al., 2002). Sodium aluminum phosphates (SALPs) are
generally recognized as safe (GRAS) FDA-approved food additives that contribute the greatest
amount of Al to the diet (Katz et al., 1984; Humphreys and Bolger, 1997; Saiyed and Yokel,
2005). Basic SALP is one of many “emulsifying salts” added to process cheese, cheese food
and cheese spread which react with and change the protein of cheese to produce a smooth,
uniform film around each fat droplet to prevent separation and bleeding of fat from the cheese.
This produces a soft texture, easy melting characteristics and desirable slicing properties
(Ellinger, 1972). Basic SALP is permitted by the FDA up to 3% in pasteurized process cheese
(21CFR133.169), pasteurized process cheese food (21CFR133.173), and pasteurized process
cheese spread (21CFR133.179). The FDA regulates basic SALP as an emulsifier that is GRAS
(FASEB, 1975). Basic SALP is also permitted up to 3.5% in cheese in Canada (Food and Drugs
Act – Food and Drug Regulations, Part B, Division 16;
Yokel et al. Page 2
Food Chem Toxicol. Author manuscript; available in PMC 2009 June 1.
NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript
http://www.hc-sc.gc.ca/fn-an/alt_formats/hpfb-dgpsa/pdf/legislation/e_c-tables.pdf), as
potassium aluminum silicate up to 10 g/kg in Australia and New Zealand
(
http://www.foodstandards.gov.au/_srcfiles/FSC_Amend_Standard_1_2_4_Labelling_of_Ingred_v91.pdf#search=%22potassium%20aluminium%20silicate%2010g%2Fkg%22
), but evidently not by the E.U. or U.K., although other Al-containing compounds are permitted
in cheese, up to 10 g/kg (E 554, E 555, E 556 and E 559)
(http://ec.europa.eu/food/fs/sfp/addit_flavor/flav11_en.pdf
http://ec.europa.eu/food/fs/sc/scf/reports/scf_reports_40.pdf). Studies of the Al content of
unprocessed cheese generally reported < 10 mg Al/kg (Delves et al., 1989; Schenk et al.,
1989; Müller et al., 1998; Dolan and Capar, 2002). In contrast, some process cheeses (often
marketed as sliced, American) were reported to contain 695 (Gormican, 1970), 411
(Pennington, 1989), 320 (Pennington and Schoen, 1995), 1440 (Greger, 1985), and 470 mg
Al/kg (Saiyed and Yokel, 2005). The cheese of frozen pizzas that contained basic SALP was
reported to contain up to ~ 750 mg Al/kg, whereas ready-to-eat restaurant pizza cheese had <
10 mg Al/kg (Saiyed and Yokel, 2005). Basic SALP (Na8Al2(OH2)((PO)4)4) has a 4:1:2 ratio
of Na:Al:P. It is ~ 10% Al.
Concern about the safety of the addition of Al in foods was expressed long ago (Gies, 1911)
and again recently. Department of the Planet Earth (a non-profit NGO) petitioned the FDA in
2005 to rescind the GRAS status for Al-based food additives
(http://www.deptplanetearth.com/aboutus.html). A Joint FAO (Food and Agriculture
Organization of the UN)/WHO Expert Committee on Food Additives established a revised
provisional tolerable weekly intake (PTWI) for all Al compounds in foods, including additives,
of 1 mg/kg/bw. The Expert Committee noted the potential for Al to effect the reproductive and
developing nervous system at lower doses than those used to establish the previous PTWI of
7 mg/kg/bw (FAO/WHO, 2006). The Committee commented on the “probable lower
bioavailability of the less soluble Al compounds present in food” and that the PTWI was likely
to be exceeded by some population groups, particularly children, who regularly consume foods
containing Al additives.
To better understand the relative contribution of food and water to human Al intake, it has been
noted that research needs to be conducted to more accurately determine the oral bioavailability
of Al from the typical diet (Personal communication from Amal M. Mahfouz, US EPA). Oral
bioavailability (fractional absorption) is the amount absorbed compared to the amount
administered. For Al, systemic bioavailability, the fraction that reaches systemic circulation
from which it has access to the target organs of its toxicity, is most relevant.
Several studies have estimated oral Al bioavailability under conditions that model Al
consumption in drinking water. Oral Al bioavailability from alum-treated water obtained from
a municipal water treatment facility was estimated to be 0.36% in a study of 21 humans (Stauber
et al., 1999). Two studies in humans that utilized 26Al but only two subjects each, therefore
providing limited confidence in the results, estimated oral Al bioavailability to be 0.1 and
0.22%, respectively (Hohl et al., 1994; Priest et al., 1998). The above studies estimated oral
Al absorption based on urinary Al excretion. However, not all absorbed Al appears in the urine,
which accounts for ~ 98% of excreted Al, or the bile, which accounts for most of the other 2%.
Some absorbed Al is retained. Secondly, if Al in the urine is used as an endpoint for absorption,
the experimenter would have to continue to determine this endpoint until sure that all had been
eliminated. There are a few reports where the amount of Al in the urine was corrected for these
2 factors (not all absorbed Al appears in the urine and the study was not conducted long enough
to collect all excreted Al). Stauber et al. (1999) multiplied the amount of Al that appeared in
the urine in the 24 hours after oral Al consumption by 2.2, to correct for partial Al elimination
(only 72% of intravenously injected Al was found in the urine after 7 days (Talbot et al.,
1995) and only 62 to 63% of the Al in the urine recovered in 7 days was found in the first day
Yokel et al. Page 3
Food Chem Toxicol. Author manuscript; available in PMC 2009 June 1.
NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript
(Priest, 1993)). Stauber et al only collected urine for 24 hours. They did not correct for absorbed
Al that was retained. The large correction factor reduces confidence in the accuracy of the
reported oral bioavailability. Hohl et al. (1994) took into consideration that only about 80% of
injected Al was found in the urine after 10 days and commented that the amount of Al excreted
in the urine after their 4 days of collection was probably not great. They provided an estimate
of the percentage of Al absorbed as 0.1%, not presenting this as a precise value. In two studies
that used the methods employed in the present report oral Al bioavailability in the rat averaged
0.28% and 0.29% (Yokel et al., 2001; Zhou and Yokel, 2006).
The bioavailability of hydrophilic substances that are not well absorbed can be determined by
comparing the areas under the concentration × time curve (AUC) for the test substance given
po and iv. This approach was used in the only study reported to date that estimated oral Al
bioavailability from a specific food product. In that study, oral Al bioavailability in rats that
ate ~ 1 gm of biscuit containing [26Al]-labeled acidic SALP averaged ~ 0.12% (Yokel and
Florence, 2006). This approach was used in the present study in which the po dose was given
as 26Al and the iv dose as 27Al to the same subject at the same time. Compared to an
experimental design where a rat receives the two doses at different times, this method reduces
variability by concurrently determining the AUCs from the po and iv doses in the rat. To
determine the oral bioavailability of Al from basic SALP in a process cheese, [26Al]-containing
basic SALP was prepared and incorporated into a process cheese that was presented to rats for
their consumption. Blood was repeatedly obtained from the rats in which 26Al and total Al
(essentially 27Al) were analyzed by accelerator mass spectrometry (AMS) and electrothermal
atomic absorption spectrometry (ETAAS), respectively. The absence of significant 26Al in the
environment or in normal biological organisms avoids the interference of endogenous Al in
studies of Al pharmacokinetics. When 4 mg of 27Al is added to 26Al-containing samples to
establish the 27Al concentration, as in the present study, AMS can measure the 26Al:27Al ratio
with a detection limit of ~ 10−14 (~ 4 × 10−17 g of 26Al) or ~ 1,000,000 atoms. This enables
the conduct of pharmacokinetic studies of Al at physiological concentrations, as conducted
herein. In addition to oral bioavailability, two other standard pharmacokinetic parameters, the
time to maximum serum 26Al concentration of (Tmax) and the maximum serum 26Al
concentration of (Cmax), were determined (Bauer, 2006). These methods enabled us to address
the objectives of the present study: to determine the oral bioavailability of Al from processed
cheese that contains basic SALP, at a concentration relevant to its use in cheese, and to
determine standard pharmacokinetic parameters of the absorbed Al.
Methods
Materials
Details of the preparation and characterization of the basic SALP containing 26Al (basic 26Al-
SALP) were described (Yokel et al., 2005). 26Al was provided by the Purdue Rare Isotope
Measurement Laboratory (PRIME Lab), supplied in 0.06 N HCl containing 13.78 nCi (725
ng) 26Al/ml and with a 34:1 27Al:26Al ratio. Briefly, Al-containing sodium aluminate was
prepared then characterized by elemental analysis of Na and Al and Raman spectroscopy. It
was incorporated into the synthesis of basic SALP (CAS [7785-88-8], INS No. 541) by the
method of (Bell, 1973). The basic SALP was characterized by near infrared spectroscopy, x-
ray powder diffraction spectroscopy, and elemental analysis of Na, Al and P. 26Al-containing
basic SALP was concurrently and identically prepared. Non-26Al-containing basic SALP was
used to dilute 26Al-containing samples to ~ 1 nCi 26Al/15 or 30 mg basic SALP. The 26Al-
basic SALP was incorporated into a process cheese. These two concentrations (1.5 and 3%
basic SALP) were studied to ascertain if there was concentration-dependent absorption and to
stay within the maximum permitted use level of 3 to 3.5% for basic SALP as an emulsifying
agent in process cheese. Cheese containing 26Al-basic SALP was prepared from 8.8 gm aged
Yokel et al. Page 4
Food Chem Toxicol. Author manuscript; available in PMC 2009 June 1.
NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript
(1 year) Kroger brand sharp cheddar cheese, ~ 1 gm water and 150 or 300 mg basic SALP (to
make 1.5 and 3% SALP in cheese). To produce a moderately firm cheese product the
ingredients were heated in a microwave oven for 13 sec, stirred for 15 sec, heated for another
5 sec, stirred 10 sec and some samples further heated and stirred. Identical process cheeses
were prepared containing 1.5, 2.25 and 3% SALP without 26Al. They were used to condition
the rats to eat the process cheese and to dose the control (non-26Al-treated) rats, as described
below.
The 26Al concentration in the process cheese was determined as follows. Three samples, ~ 30
to 35 mg, of the 1.5 and 3% 26Al-basic SALP were transferred to 7 ml screw cap Teflon®
Tuftainers® and 4 mg Al (Sigma ICP/DCP standard) added, and the sample dried. Samples
were then digested in 1.5 ml 1M KOH and sonicated to create a solution, as described (Saiyed
and Yokel, 2005), serially diluted 10-fold 4 times, and an aliquot transferred to a porcelain
crucible and 4 mg of Al standard added. This was slowly heated to 1000 °C in a muffle furnace
to convert the Al to Al oxide that was analyzed by AMS, as described below. The process
cheeses containing 1.5 and 3% basic 26Al-SALP had 1.80 nCi (95.0 ng) and 1.57 nCi (82.6
ng) 26Al/gm, respectively.
Animals
This study used 15 male Fisher 344 rats, weighing 272 ± 11g (mean ± SD) that were housed
individually prior to the study in the University of Kentucky Division of Laboratory Animal
Resources facility. Animal work was approved by the University of Kentucky Institutional
Animal Care and Use Committee. The research was conducted in accordance with the Guiding
Principles in the Use of Animals in Toxicology.
Experimental procedures
The rats were acclimated to a 10% protein diet designed to minimize food retention in the
stomach (Harlan Teklad 95215). They had food access from 08:00 to 18:00 h daily for at least
5 days prior to the determination of oral Al bioavailability. This diet was shown to result in
the absence of food in the stomach 14 h after its withdrawal when fecal recycling (coprophagia)
was prevented by a fecal collection cup, as described and used in this study (Yokel et al.,
2001). Drinking water was freely available throughout the study except for the period from 14
h before to 4 h after presentation of cheese containing basic SALP.
The rats were conditioned to eat 1 g of process cheese containing 1.5% and 3% basic SALP
(containing no 26Al) on alternate days which was presented, with access to 2 ml of MilliQ
polished water, 14 h after diet removal daily for at least 4 days. Rats that readily ate the cheese
within 15 min were surgically prepared 1 day prior to oral dosing with two venous cannulae
introduced into the femoral veins. They terminated in the vena cava. One cannula was used for
iv administration, the other for blood withdrawal. The former terminated down-stream of the
latter. The amount of cheese containing 26Al-basic SALP that was consumed was determined
by pre-weighing the presented cheese then rigorously recovering from the rat’s cage 30 min
later the uneaten cheese, which was weighed. Calculations were based on the weight of
consumed cheese.
The rats were randomly assigned to be given 1 g process cheese containing 1.5 or 3%
basic 26Al-SALP (n = 6/group), in the absence of food in the stomach. Three control rats were
included to document 26Al contamination. They received process cheese containing 2.25%
basic SALP (n=2) or intragastric administration of 1 ml of water (n=1) without 26Al. They
served as monitors for 26Al contamination. The rats were studied in pairs that received the
same 27Al infusion but different oral treatments.
Yokel et al. Page 5
Food Chem Toxicol. Author manuscript; available in PMC 2009 June 1.
NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript
Oral Al bioavailability was determined in the un-anesthetized rat. Oral bioavailability was
determined using a modification of the standard method of comparing the areas under the
concentration × time curve (AUC). To enable concurrent administration of the oral and iv Al
dose, the tracer 26Al was used as the oral dose and 27Al for the iv dose. To give a large enough
bolus iv dose of 27Al that would be significantly above the normal endogenous Al concentration
in serum for a long enough period of time to determine its AUC would require a dose that
would exceed the transferrin binding capacity for Al (~ 1350 µg Al/L). Therefore the chemical
species of the 27Al in serum would be different (not all Al-transferrin, but for the Al beyond
the transferrin binding capacity probably Al citrate) and might be handled differently than
the 26Al that is absorbed and could bind to transferrin after enough of the 27Al had been cleared
to free up binding sites on transferrin. Therefore, we replaced the iv bolus dose with an iv
infusion to generate a 27Al serum concentration significantly above the endogenous Al
concentration (so the Al in the serum could be attributed to the 27Al infusion [iv dose]) but
below the transferrin binding capacity. In summary, doseiv was replaced by 27Al infusion rate
× 27Al infusion duration, as reported in Data analysis.
The rat was iv infused at 100 µg 27Al/kg/h to produce an estimated 500 µg Al/l in blood plasma
for the 27Al dose, as described (Yokel et al., 2001). To accomplish this in the present study,
AlK(SO4)2 was infused from 14 h prior to 60 h after oral dosing. Blood was withdrawn 1 h
prior to and 0, 1, 2, 4, 8, 24, 36, 48 and 60 h after oral dosing. The withdrawn blood (0.3 ml
for the −1 to 4 h samples, 0.5 ml for the 8 h sample, 2.1 ml at 24 h and 4.1 ml at 36 and 48 h),
was replaced by an equal volume of injected saline. Additionally, the rats had access to free
water and food (10% protein diet) beginning 4 h after dosing. The 60-h blood sample was
obtained by anesthetizing the rat and exsanguination from a femoral cannula and then the heart.
Serum was obtained for 26Al and 27Al analysis. Blood urea nitrogen (BUN) and creatinine
were determined in the 60 h sample.
Analysis of total Al by electrothermal atomic absorption spectrometry (ETAAS)
This was conducted as described (Yokel and Florence, 2006).
Analysis of 26Al by accelerator mass spectrometry (AMS)
The procedures were as described (Yokel et al., 2001). A serum QC sample was included with
each of the four batches of processed samples. All results were within 10% of the mean of the
5 initial replicates determined when these QC samples were prepared.
Data analysis
A criterion for acceptance of post-treatment serum 26Al concentrations considered to be
reliably above pre-treatment serum values was established as > 2 SD above the mean pre-
treatment serum 26Al concentration. This criterion was 0.34 fg 26Al/ml. Values below this
criterion are not presented graphically and were not used in the data analysis. This criterion
was met by all of the samples from the 26Al-treated rats. The initial and 2nd half-lives of 26Al
elimination, determined using RSTRIP (Fox and Lamson, 1989), were not different between
the two treatment groups, therefore they were combined. The mean initial and 2nd half-lives
were 4.4 and 7.2 h, respectively. Therefore, blood was obtained for > 3 half-lives, sufficient
time to determine the AUC of the 26Al. Each subject’s pre-treatment serum 26Al concentration
was subtracted from its post-treatment values. Oral 26Al bioavailability (F) was calculated as
follows and expressed as a percent:
Yokel et al. Page 6
Food Chem Toxicol. Author manuscript; available in PMC 2009 June 1.
NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript
Time to maximum serum 26Al concentration (Tmax) and the maximum concentration (Cmax)
were calculated using RSTRIP (Fox and Lamson, 1989).
Unpaired two-tailed t-tests (Mann Whitney tests when the variance was dissimilar) were used
to test for differences in Al oral bioavailability, Tmax and Cmax from the 1.5% compared to 3%
basic SALP. When not statistically significantly different, the combined basic SALP results
were compared to acidic SALP in biscuit and water, which were previously conducted (Yokel
and Florence, 2006). A difference of P < 0.05 was accepted as statistically significant.
Results
The rats given cheese containing 26Al-SALP consumed 0.44 to 1.05 (mean = 0.87) gm cheese.
Each rat’s serum 26Al results were normalized to its 26Al dose. The BUN and serum creatinine
values ranged from 7.5 to 17.9 and from < 0.2 to 0.5 mg/dl, well within normal limits (< 30
and 1 mg/dl, respectively). Serum 26Al concentration in all but one rat prior to 26Al (or 26Al
vehicle) dosing ranged from 0 to 0.4 (mean = 0.12) fg/ml. Initial samples from one control rat
were contaminated. Its pre-treatment and first 4 post-treatment samples ranged from 0.6 to
12.1 fg 26Al/ml, whereas the 6th to 9th samples from this control rat had 0.1 to 0.2 fg 26Al/ml.
Results from this animal have been deleted from the data analysis. The concentration of 26Al
in the 8 samples from each of the other two non-26Al-treated rats after vehicle dosing ranged
from 0 to 0.5 fg/ml (mean = 0.18). The 60 hour sample 26Al concentration in the 26Al-treated
rats ranged from 0.4 to 3.8 fg/ml. Therefore, contamination appears to have been limited to the
5 samples from the one rat.
Peak serum 26Al concentration ranged from 55.9 to 159.5 fg/ml after oral 26Al dosing in 1.5%
basic SALP and 28.9 to 146.1 fg/ml after 3% basic SALP. The oral 26Al dose increased peak
serum 26Al at least 200-fold above mean pre-treatment values. The time courses of
serum 26Al following oral 26Al dosing for the two treatment groups are shown in Figure 1.
Oral bioavailability (F) was calculated as described in Data analysis as the (sum of 26Al AUC/
sum 27Al AUC) × the sampling duration × 27Al hour infusion rate × body weight × 100%. For
one of the rats that consumed cheese containing 1.5% SALP F was 0.12%, calculated from
((the sum of the trapezoidal AUCs for 26Al [each area calculated as the mean of the 26Al
concentration in the two samples, in fg/ml × the trapezoidal time interval, in hr]/sum of
trapezoidal AUCs for 27Al [each area calculated as the mean of the 27Al concentration in the
two samples, in fg/ml] × the trapezoidal time interval, in hr) × ((the total duration of the serum
sampling period, in hr × the 27Al infusion rate, in fg/kg/hr × the rat’s body wt, in kg)/(52630000
× nCi 26Al/gm cheese × gm cheese consumed by the rat))) × 100, where the sum of the 26Al
AUCs was 2013 fg/ml/hr, the sum of the 27Al AUCs was 25728 ng/ml/hr, the 27Al infusion
rate was 100000000000 fg/kg/hr, the rat’s body weight was 0.254 kg, 52630000 converts
nCi 26Al to fg 26Al, the cheese had 1.804 nCi 26Al/gm, the rat consumed 0.97 gm cheese, and
100 converts to percent.
The percentage of the AUC included in the AUCtime to last sample/AUCinfinity was > 95% in all
cases, indicating that samples were collected for sufficient time to adequately determine oral
Al absorption. Oral Al bioavailability and the results of RSTRIP analyses (Tmax and Cmax) are
shown in Table 1. Oral bioavailability was marginally significantly different (P = 0.045)
between the two groups. Therefore, the results from both treatment groups were compared to
results obtained in oral bioavailability studies of Al in water and as acidic SALP in biscuit
(Table 1). The differences in sum AUC 26Al, sum AUC 27Al, Al Tmax, Cmax, and Cmax % dose/
ml serum results from rats consuming 1.5% compared to 3% basic SALP were not statistically
significant. Therefore, the differences in these measures from the combined 1.5% and 3% basic
SALP data were compared to results from studies of Al absorption from water and as acidic
SALP in biscuit (Table 1).
Yokel et al. Page 7
Food Chem Toxicol. Author manuscript; available in PMC 2009 June 1.
NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript
Discussion
The present study found a marginally significant effect of the Al concentration on Al
bioavailability, for the two concentrations of basic SALP tested, which are in the range of those
permitted by the FDA. The difference between the oral bioavailability of the two groups that
received 1.5% and 3% basic SALP in cheese was due to the differences in their serum total Al
concentration × time profiles (as shown in Table 1, Sum AUC for iv 27Al) rather than their
serum 26Al concentration × time profiles (as shown in Table 1, Sum AUC for po 26Al and
Figure 1). As rats were studied in pairs, errors in the 27Al infusion should be reflected in both
rats of the pair. This was not seen. We assume that the 3 rats in the group that ate 1.5% basic
SALP in cheese that had higher than average serum 27Al, and therefore AUCs for iv 27Al,
renally cleared the 27Al infusion more slowly than most rats. It would be anticipated that the
clearance of 26Al would be similar, concomitantly increasing the AUC for 26Al. Therefore,
these results seem valid. Had the serum 27Al concentrations in these rats been lower and 26Al
concentrations not different, oral Al bioavailability would have been higher. Therefore, the
oral bioavailability of Al from basic SALP incorporated into cheese in the rat appears to be at
least 0.1%.
The few studies conducted to date to address the possibility that Al bioavailability is dose-
dependent have also not resulted in robust findings. Oral Al bioavailability from Al lactate in
the rabbit dosed with 108 or 540 mg Al/kg, as Al lactate, was 0.7 and 1.9%, although not
significantly different (Yokel and McNamara, 1985). Urinary 26Al excretion was higher in two
rats after administration of 20 ng of 26Al with 10 mg 27Al than with 0.2 mg 27Al as the chloride
(0.032 vs. 0.018% of the 26Al dose). Serum 26Al was also higher 1, 5 and 24 hours after the
larger total Al dose (Ittel et al., 1993). These results suggest a positive correlation between
aluminium dose and bioavailability. On the other hand, Al absorption into rat blood and tissues
after perfusion of the gut with 48 or 64 mM Al chloride at pH 3 was not concentration dependent
(Arnich et al., 2004).
The later Tmax of Al from basic SALP in process cheese observed in the present study,
compared to water, is consistent with the apparent site of Al absorption, the upper intestine
and delayed gastric emptying of food compared to water (Froment et al., 1989; Nagy and Jobst,
1994; Whitehead et al., 1997; Arnich et al., 2004). Cmax values were lower after oral
consumption of 26Al in process cheese than water, as expected when oral bioavailability is
lower and Tmax is later.
The FDA acceptance of basic SALP as a food additive is based on a review conducted in 1975
(FASEB, 1975). The reviewers cited unpublished studies that demonstrated a consistent
increase in renal microconcretions in female, but not male, rats consuming a diet containing
0.03 to 3% basic SALP (~ 4 to 40 mg Al/kg/day) for 90 days and an in-consistent increase of
this endpoint in male and female beagle dogs that consumed basic SALP delivering 7 to 70
mg Al/kg/day. The review panel noted that care should be taken by patients with kidney disease
when consuming food containing high levels of Al salts. However, they did not mention
dialysis encephalopathy, which has been attributed to Al, or the controversial role of Al in AD.
Description of these clinical problems began about 1975. Since that review the contribution of
Al from Al cooking utensils to serum Al and urinary Al excretion in patients with chronic renal
insufficiency was demonstrated (Lin et al., 1997) and numerous studies have described toxic
endpoints of Al exposure (Krewski et al., 2007).
Some studies have been conducted to assess potential toxicity from basic SALP. A study was
conducted by Stauffer Chemical Company in male rats fed their basic SALP-containing
products. The treatment groups ate feed for 28 days containing: 3% KASAL (1866 mg Al/kg
diet; ~ daily dose 141 mg/kg bw), 0.7% KASAL II (908 mg Al/kg diet; ~ daily dose 67 mg Al/
Yokel et al. Page 8
Food Chem Toxicol. Author manuscript; available in PMC 2009 June 1.
NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript
kg bw), 30,000 ppm KASAL II (3761 mg Al/kg diet; ~ daily dose 288 mg Al/kg bw), 14,470
ppm Al hydroxide as a positive control (4034 mg Al/kg diet; ~ daily dose 302 mg Al/kg bw),
or the basic (control) diet (66 mg Al/kg diet; ~ daily dose 5 mg Al/kg bw) (Hicks et al.,
1987). Other than a significant increase of serum sodium, no significant effects were seen in
bone Al, gross autopsy, histopathology, food consumption, hematology, clinical chemistry or
organ weight. A study was conducted in dogs fed diets containing KASAL that produced daily
mean Al intakes of ~ 10, 25, or 78 mg Al/kg for 26 weeks, compared to a control diet delivering
~ 4 mg Al/kg/day (Pettersen et al., 1990). The highest dose of Kasal resulted in a sharp, 1.5
week decrease in food consumption and body weight in males, a decrease in testis weight,
seminiferous tubule germinal cell degeneration and atrophy, hepatocyte vacuolation, and
tubular-glomerularnephritis. There were no significant effects on serum chemistry,
hematology, urinalysis or bone or brain Al, except for a significant increase of brain Al in
female dogs consuming the highest Al containing diet. Neither of these studies addressed
bioavailability.
There have been studies to estimate oral Al bioavailability from foods. A project was
commissioned to determine the relative uptake of Al in many foods (UK-MAFF, 1993).
However, the methods did not enable determination of bioavailability and the trial foods did
not contain cheese (UK-MAFF, 1993). Al bioavailability from diets containing ~ 5 mg Al daily
was estimated, based on urinary Al excretion compared to dietary Al intake, to be 0.78% in
young human males (Greger and Baier, 1983). However, cheese was not included in this study
nor in a study by (Stauber et al., 1999) who estimated Al bioavailability from drinking water
and food in humans to be comparable from these two sources, ~ 0.3%. Oral Al bioavailability
from food has been estimated to be ~ 0.1% based on average daily urinary Al excretion
compared to average daily Al intake from food (Powell and Thompson, 1993; Priest, 1993;
Nieboer et al., 1995). The only reported study that determined the bioavailability of Al from a
specific food used similar methods to the study reported herein and found it to be ~ 0.1% from
acidic SALP incorporated into biscuit (Yokel and Florence, 2006).
In summary, the present estimate of oral Al bioavailability from a dietary component suggests
modestly lower or comparable oral Al bioavailability from food than previously reported in
studies of water, conducted in the human and rat (Introduction). The results of this study of
oral Al bioavailability from basic SALP in a process cheese suggest ~ 0.1 to 0.3% of the Al
was orally absorbed. A prior study and a recent replication of that study, using the same methods
(Yokel et al., 2001; Zhou and Yokel, 2006), suggested ~ 0.3% of Al was orally absorbed from
water. Other substances in drinking water might alter Al. For example, citrate doubled Al
absorption from water (Zhou et al., 2008). A comparison of the arithmetic products of the
absorbed percentage of Al times their contribution to the diet suggests food typically provides
at least 90% of dietary Al that reaches systemic circulation. This is based on consumption of
5 to 10 mg of Al in the diet × 0.1 to 0.3% absorption, delivering 5 to 30 µg of Al to systemic
circulation daily vs. consumption of 0.1 mg Al daily in drinking water × up to 0.6% absorption,
delivering up to 0.6 µg of Al to systemic circulation daily. These results suggesting food is a
more important source of absorbed Al than is drinking water, as noted in the Introduction. This
suggests that further study of a potential link between orally consumed Al in food and cognitive
deficits may be more appropriate than studies of Al in drinking water.
Acknowledgement
This work was supported by NIH Grant R01 ES11305.
References
Alfrey AC, LeGendre GR, Kaehny WD. The dialysis encephalopathy syndrome. Possible aluminum
intoxication. NEJM 1976;294:184–188. [PubMed: 1244532]
Yokel et al. Page 9
Food Chem Toxicol. Author manuscript; available in PMC 2009 June 1.
NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript
Arnich N, Cunat L, Lanhers MC, Burnel D. Comparative in situ study of the intestinal absorption of
aluminum, manganese, nickel, and lead in rats. Biol. Trace Elem. Res 2004;99:157–171. [PubMed:
15235150]
ATSDR. Toxicological profile for aluminum. Atlanta, GA: Agency for toxic substances and disease
registry; 1999. 257 p.
Bauer, LA. Clinical pharmacokinetics handbook. New York: McGraw-Hill, Medical Pub. Division; 2006.
p. 16
Bell, RN. US Patent. NY: Assigned to Stauffer Chemical Company; 1973. Sodium aluminum phosphate
cheese emulsifying agent.
Cogbill EC, Hobbs ME. Transfer of metallic constituents of cigarettes to the main-stream smoke. Tobacco
Science 1957;1:68–73.
Delves, HT.; Suchak, B.; Fellows, CS. The determination of aluminium in foods and biological materials.
In: Massey, R.; Taylor, D., editors. Aluminium in food and the environment. The proceedings of a
symposium organized by the Environment and Food Chemistry Groups of the Industrial Division of
the Royal Society of Chemistry, Special Publication No.73. London: The Royal Society of Chemistry,
Thomas Graham House; 1989. p. 52-67.
Dolan SP, Capar SG. Multi-element analysis of food by microwave digestion and inductively coupled
plasma-atomic emission spectrometry. J. Food Comp. Analysis 2002;15:593–615.
Elinder C-G, Ahrengart L, Lidums V, Pettersson E, Sjögren B. Evidence of aluminium accumulation in
aluminium welders. Br. J. Ind. Med 1991;48:735–738. [PubMed: 1954151]
Ellinger, RH. Phosphates as food ingredients. Cleveland, OH: CRC Press; 1972. p. 73
Exley C, Begum A, Woolley MP, Bloor RN. Aluminum in tobacco and cannabis and smoking-related
disease. Am. J. Med 2006;119:276 e9–276 e11. [PubMed: 16490479]
Exley C, Ahmed U, Polwart A, Bloor RN. Elevated urinary aluminium in current and past users of illicit
heroin. Addiction Biol 2007;12:197–199.
FAO/WHO. Summary and conclusions of the sixty-seventh meeting of the Joint FAO/WHO Expert
Committee on Food Additives (JECFA), Sixty-seventh meeting in Rome; 20–29 June 2006; 2006.
issued 7 July, 2006 http://www.who.int/ipcs/food/jecfa/jecfa67_call%20final.pdf
FASEB, (Federation of American Societies for Experimental Biology); Life Sciences Research Office.
Evaluation of the health aspects of aluminum compounds as food ingredients. Prepared for Bureau
of Foods, Food and Drug Administration, Contract No. FDA 223-75-2004, U.S. FDA Report FDA/
BF-77/24, NTIS-PB 262 655, 26 pages. 1975.
Fox, JL.; Lamson, ML. RSTRIP: pharmacokinetic data stripping/least squares parameter optimization.
Salt Lake City, UT: MicroMath, Inc.; 1989.
Friesen MS, Purssell RA, Gair RD. Aluminum toxicity following IV use of oral methadone solution.
Clin. Toxicol. (Phila) 2006;44:307–314. [PubMed: 16749550]
Froment DP, Molitoris BA, Buddington B, Miller N, Alfrey AC. Site and mechanism of enhanced
gastrointestinal absorption of aluminum by citrate. Kidney Int 1989;36:978–984. [PubMed: 2601265]
Gies WJ. Some objections to the use of alum baking-powder. JAMA 1911;57:816–821.
Gormican A. Inorganic elements in foods used in hospital menus. J. Am. Diet. Assoc 1970;56:397–403.
[PubMed: 5439980]
Greger JL. Aluminum content of the American diet. Food Technol 1985;39:73–80.
Greger JL, Baier MJ. Excretion and retention of low or moderate levels of aluminium by human subjects.
Food Chem. Toxicol 1983;21:473–477. [PubMed: 6684629]
Hicks JS, Hackett DS, Sprague GL. Toxicity and aluminium concentration in bone following dietary
administration of two sodium aluminium phosphate formulations in rats. Food Chem. Toxicol
1987;25:533–538. [PubMed: 3623343]
Hohl C, Gerisch P, Korschinek G, Nolte E, Ittel TH. Medical application of 26Al. Nucl. Instr. Meth. Phys.
Res. Ser. B 1994;92:478–482.
Humphreys, S.; Bolger, PM. A public health analysis of dietary aluminium. In: Zatta, PF.; Alfrey, AC.,
editors. Aluminium toxicity in infants' health and disease. Singapore: World Scientific, Singapore;
1997. p. 226-237.
Yokel et al. Page 10
Food Chem Toxicol. Author manuscript; available in PMC 2009 June 1.
NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript
Ittel TH, Gerisch P, Nolte E, Sieberth HG. Fractional absorption of aluminium is dose-dependent: A
26Al tracer study. Nephrol. Dial Transplant 1993;8:993.(An abstract)
Katz AC, Frank DW, Sauerhoff MW, Zwicker GM, Freudenthal RI. A 6-month dietary toxicity study of
acidic sodium aluminium phosphate in beagle dogs. Food Chem. Toxicol 1984;22:7–9. [PubMed:
6537941]
Krewski D, Yokel RA, Nieboer E, Borchelt D, Cohen J, Harry J, Kacew S, Lindsay J, Mahfouz AM,
Rondeau V. Human health risk assessment for aluminium, aluminium oxide, and aluminium
hydroxide. J. Toxicol. Environ. Health, Part B: Critical Reviews 2007;10:1–269.
Lin JL, Yang YJ, Yang SS, Leu ML. Aluminum utensils contribute to aluminum accumulation in patients
with renal disease. Am. J. Kid. Disease 1997;30:653–658. [PubMed: 9370180]
Lopez FE, Cabrera C, Lorenzo ML, Lopez MC. Aluminum levels in convenience and fast foods: in vitro
study of the absorbable fraction. Sci. Total Environ 2002;300:69–79. [PubMed: 12685472]
Martyn CN, Barker DJ, Osmond C, Harris EC, Edwardson JA, Lacey RF. Geographical relation between
Alzheimer's disease and aluminum in drinking water. Lancet 1989;i:59–62. [PubMed: 2562879]
Müller M, Anke M, Illing-Günther H. Aluminium in foodstuffs. Food Chem 1998;61:419–428.
Nagy E, Jobst K. The kinetics of aluminium-containing antacid absorption in man. Eur. J. Clin. Chem.
Clin. Biochem 1994;32:119–121. [PubMed: 8031961]
Nieboer E, Gibson BL, Oxman AD, Kramer JR. Health effects of aluminum: a critical review with
emphasis on aluminum in drinking water. Environ. Rev 1995;3:29–81.
Pennington, JA. Dietary intake of aluminum. In: Gitelman, HJ., editor. Aluminum and health: A critical
review. New York: Marcel Dekker, Inc.; 1989. p. 67-100.
Pennington JA, Schoen SA. Estimates of dietary exposure to aluminium. Food Addit. Contam
1995;12:119–128. [PubMed: 7758626]
Pennington JAT. Aluminium content of foods and diets. Food Addit. Contam 1987;5:161–232. [PubMed:
3360205]
Pettersen JC, Hackett DS, Zwicker GM, Sprague GL. Twenty-six week toxicity study with KASAL®
(basic sodium aluminum phosphate) in beagle dogs. Environ. Geochem. Health 1990;12:121–123.
Phelps KR, Naylor K, Brien TP, Wilbur H, Haqqie SS. Encephalopathy after bladder irrigation with alum:
case report and literature review. American journal of medicine 1999;318:181–185.
Powell JJ, Thompson RP. The chemistry of aluminium in the gastrointestinal lumen and its uptake and
absorption. Proc. Nutr. Soc 1993;52:241–253. [PubMed: 8493270]
Priest ND. The bioavailability and metabolism of aluminium compounds in man. Proc. Nutr. Soc
1993;52:231–240. [PubMed: 8493269]
Priest ND, Talbot RJ, Newton D, Day JP, King SJ, Fifield LK. Uptake by man of aluminium in a public
water supply. Hum. Exp. Toxicol 1998;17:296–301. [PubMed: 9688351]
Rogers MAM, Simon DG. A preliminary study of dietary aluminium intake and risk of Alzheimer's
disease. Age and Ageing 1999;28:205–209. [PubMed: 10350420]
Saiyed SM, Yokel RA. Aluminium content of some foods and food products in the USA, with aluminium
food additives. Food Addit. Contam 2005;22:234–244. [PubMed: 16019791]
Schenk, RU.; Bjorksten, J.; Yeager, L. Composition and consequences of aluminum in water, beverages
and other ingestibles. In: Lewis, TE., editor. Environmental chemistry and toxicology of aluminum.
Chelsea, MI: Lewis Publishers; 1989. p. 247-269.
Stauber JL, Florence TM, Davies CM, Adams MS, Buchanan SJ. Bioavailability of Al in alum-treated
drinking water. Journal AWWA (American Water Works Association) 1999;91:84–93.
Talbot R, Newton D, Priest N, Austin J, Day J. Inter-subject variability in the metabolism of aluminium
following intravenous injection as citrate. Hum Exp Toxicol 1995;14:595–599. [PubMed: 7576820]
UK-MAFF (United Kingdom Ministry of Agriculture Fisheries and Food). Aluminium in food. The thirty
ninth report of the Steering Group on Chemical Aspects of Food Surveillance. Food Surveillance
Paper No. 39. In 48 + 3 appendices. London: HMSO (Her Magesty's Stationery Office); 1993.
Whitehead MW, Farrar G, Christie GL, Blair JA, Thompson RP, Powell JJ. Mechanisms of aluminum
absorption in rats. Am. J. Clin. Nutr 1997;65:1446–1452. [PubMed: 9129475]
WHO. Environmental Health Criteria 194. Geneva: World Health Organization; 1997. International
Programme on chemical safety, Aluminium.
Yokel et al. Page 11
Food Chem Toxicol. Author manuscript; available in PMC 2009 June 1.
NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript
Yokel RA, Florence RL. Aluminum bioavailability from the approved food additive leavening agent
acidic sodium aluminum phosphate, incorporated into a baked good, is lower than from water.
Toxicology 2006;227:86–93. [PubMed: 16949191]
Yokel RA, McNamara PJ. Aluminum bioavailability and disposition in adult and immature rabbits.
Toxicol. Appl. Pharmacol 1985;77:344–352. [PubMed: 3975904]
Yokel RA, McNamara PJ. Aluminum toxicokinetics: An updated mini-review. Pharmacol. Toxicol
2001;88:159–167. [PubMed: 11322172]
Yokel RA, Rhineheimer SS, Brauer RD, Sharma P, Elmore D, McNamara PJ. Aluminum bioavailability
from drinking water is very low and is not appreciably influenced by stomach contents or water
hardness. Toxicology 2001;161:93–101. [PubMed: 11295258]
Yokel RA, Urbas AA, Lodder RA, Selegue JP, Florence RL. 26Al-containing acidic and basic sodium
aluminum phosphate preparation and use in studies of oral aluminum bioavailability from foods
utilizing 26Al as an aluminum tracer. Nucl. Instr. Meth. Physics Res. Sec. B 2005;229:471–478.
Yong RL, Holmes DT, Sreenivasan GM. Aluminum toxicity due to intravenous injection of boiled
methadone. NEJM 2006;354:1210–1211. [PubMed: 16540630]
Zhou, Y.; Yokel, RA. The effect of citrate, maltolate and fluoride on oral 26Al absorption. J. Inorganic
Biochem. 2006. http://dx.doi.org/10.1016/j.jinorgbio.2007.11.019
Abbreviations
AD, Alzheimer’s disease
Al, aluminum
AMS, accelerator mass spectrometry
AUC, area under the (concentration x time) curve
Cmax, maximum serum concentration
ETAAS, electrothermal atomic absorption spectrometry
F, oral bioavailability
GRAS, generally recognized as safe
PTWI, provisional tolerable weekly intake
SALP, sodium aluminum phosphate
Tmax, time to maximum serum concentration
Yokel et al. Page 12
Food Chem Toxicol. Author manuscript; available in PMC 2009 June 1.
NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript
Figure 1.
Concentration of 26Al in serum versus time after consumption of basic 26Al-SALP in a process
cheese containing 1.5% (square) or 3% (triangle) basic SALP. The values are mean ± SD from
6 rats in each group.
Yokel et al. Page 13
Food Chem Toxicol. Author manuscript; available in PMC 2009 June 1.
NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript
NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript
Yokel et al. Page 14
Table 1
The results of major determinates of oral Al bioavailability, the oral bioavailability of Al, and other pharmacokinetic
parameters in rats dosed with 1.5 or 3% basic SALP, containing 26Al, in cheese (this study) and prior studies with
acidic SALP in biscuit or in water. Values are mean ± SD.
1.5% basic SALP in
cheese 3% basic SALP in
cheeses acidic SALPa in
biscuit Waterb
Sum AUC for po 26Al (pg/l/
h) 2219 ± 1127 c2022 ± 1372 729 ± 481 5054 ± 1756
Sum AUC for iv 27Al (µg/l/
h) 68745 ± 63166 d20922 ± 8933 25829 ± 23790 21320 ± 17772
Oral Al bioavailability (%) 0.10 ± 0.07 e0.29 ± 0.18 f0.12 ± 0.11 0.28 ± 0.16
Tmax (h) 8.0 ± 2.6 c8.6 ± 1.6 4.8 ± 1.6 1.5 ± 1.0
Cmax (pg/l serum) 104 ± 38 c79 ± 37 50 ± 33 607 ± 295
Cmax (% of dose/ml serum) 0.00011 ± 0.00003 d0.00013 ± 0.00008 0.00014 ± 0.00007 0.00088 ± 0.00045
aResults from Yokel and Florence (2006). This study used 10 male Fisher 344 rats weighing 322 ± 32 gm that consumed ~ 1 gm biscuit containing ~ 1
nCi 26Al in 1 or 2% acidic SALP.
bResults from Yokel et al. (2001) and Zhou and Yokel (2006). These studies used male Fisher 344 rats; 19 weighing 280 ± 42 gm (Yokel et al., 2001)
and 5 weighing 268 ± 18 gm (Zhou and Yokel, 2006), that were given an intra-gastric dose of 1 ml ~ pH 5 water solution containing ~ 1 nCi 26Al.
cThe combined results from 1.5 and 3% basic SALP in cheese were significantly different from acidic SALP in biscuit and Al in water.
dThe combined results from 1.5 and 3% basic SALP in cheese were significantly different from Al in water.
eSignificantly different from 3% SALP in cheese and Al in water.
fSignificantly different from Al in biscuit.
Food Chem Toxicol. Author manuscript; available in PMC 2009 June 1.