The Science of the Total Environment 216 Ž1998.

55]61

Urine arsenic concentrations in healthy adults as indicators

of environmental contamination: Relation with
some pathologies

´ a,U , H. Lopez G a-de la Serranaa ,

M.L. Ruiz-Navarro a , M. Navarro-Alarcon
b a
´
V. Perez-Valero ´
, M.C. Lopez-Martinez
a
Department of Nutrition and Bromatology, Faculty of Pharmacy, Uni¨ersity of Granada, E-18071 Granada, Spain
b
Laboratory of Clinical Analyses, Hospital of Motril, Motril, Granada, Spain

Received 9 December 1997; accepted 28 January 1998

Abstract

Arsenic concentrations were determined in 126 urine samples by hydride generation atomic absorption spectrome-
try. Samples were mineralized with nitric acid in a thermostated mineralization block. This technique was compared
with a method that involves mineralization in a microwave digestion bomb. A mean recovery percentage of
100.80" 5.57% was obtained. The relative standard deviation ranged from 1.7 to 10.52%. It was found that subject
sex and age did not affect urine As levels Ž P) 0.05.. The mean urine As levels in patients with hepatic injury
Ž4.24" 1.98 m grl., diabetes Ž3.44" 2.36 m grl. and myocardial infarction Ž3.64" 1.85 m grl. were not statistically
different Ž P) 0.05. to that found in the control group Žhealthy subjects. Ž3.68" 2.27 m grl.. This result could be
related to the fact that the regulation of As in the human organism is independent of these diseases. Measured As
concentrations in the eight basic health zones of the study area were not statistically different Ž P ) 0.01.. This fact
demonstrates the existence of a similarly low environmental As distribution in coastal and mountainous zones.
Q 1998 Elsevier Science B.V.

Keywords: Urine; Total arsenic; Sex; Location; Pathology influence

1. Introduction 1975; Reilly, 1980; Oster and Prellwitz, 1985;

Arsenic is a trace element which has generated
increased interest in recent years due to its toxic-
ity and its possible essential character ŽWoolson,
U
Corresponding author: Tel.: q34 58 243863; fax: q34 58
243869; e-mail: nalarcon@platon.ugr.es
0048-9697r98r$19.00 Q 1998 Elsevier Science B.V. All rights reserved.
PII S0048-9697Ž98.00136-3
Nielsen, 1988.. Its toxic effects appear principally
in people living near contaminated zones ŽAndren
et al., 1988; Linn, 1989.. It has been indicated
that chronic exposure to inorganic As has several
health effects such as cancer ŽChen et al., 1988a;
Bates et al., 1992; Carlson-Lynch et al., 1994; Das
et al., 1995., peripheral vascular diseases ŽChen et
al., 1988b. and blackfoot diseases ŽWang, 1996..
56 M.L. Ruiz-Na¨arro et al. r The Science of the Total En¨ironment 216 (1998) 55]61
Generally, As can enter the human organism
via the workplace environment or from the con-
sumption of dietary foodstuffs, previously affected
by As contaminated soil, air and water ŽLeo and
Russell, 1978; Saady et al., 1987; Navarro et al.,
1993; Chatterjee et al., 1995; Das et al., 1995;
Vahter et al., 1995.. Marine foods are the main
As source in the diet and could supply 52% of the
total daily dietary intake of As ŽVan Dokkum et
al., 1989. or even more depending on the food
habits of populations } among them, special
crustacea and fish feeding in marine sediment
have a higher capacity to accumulate As ŽNorin
and Ryhage, 1985.. Taking into consideration the
high consumption of marine foods by Spaniards
Žapprox. 33 kg of marine food per person per
year., this pathway constitutes the most important
As source. As absorption and bioavailability de-
pend on the physical and chemical form of the
arsenic compound, its As oxidation state and
solubility ŽReilly, 1980.. Analysis of arsenic in
urine is a good way to evaluate exposure to this
element ŽChatterjee et al., 1995; Das et al., 1995.
as between 10 and 25% of As is excreted in urine
as inorganic As, approx. 15% as monomethyl-
arsenic acid ŽMMAA., and between 60 and 70%
as dimethylarsenic acid, DMAA ŽFarmer and
Johnson, 1990; Kalman et al., 1990; Chatterjee et
al., 1995; Das et al., 1995.. This is due to the
existence of a methylation mechanism involving
the conversion of AsŽV. to AsŽIII. } thus the
less toxic methylated and more easily excretable
forms of this element are obtained. The specific
mechanism of methylation in human beings is still
unknown ŽHopenhayn-Rich et al., 1993..
Excreted As levels in urine vary depending on
the type of exposure which the persons under
investigation have been subjected, e.g. how urine
As concentrations in persons decrease with dis-
tance from a copper smelter ŽPolissar et al., 1990..
As levels in most foodstuffs are normally low
ŽNavarro et al., 1992a.. However, marine food
Že.g. crustacea . has the highest As content and,
therefore, provides a higher As intake in the daily
diet ŽNavarro et al., 1992b. of those inhabitants
living in the study area. Nevertheless, As appears
principally in these foodstuffs as arsenobetaine, a
non-accumulative organic form of this element in
man ŽBoudene, 1990..
There are a variety of methods in the literature
for the decomposition of urine for total As analy-
sis ŽChana and Smith, 1987; Quiao and Zhang,
1994.. In this study we developed a simple diges-
tion method to determine As concentrations in
urine by hydride generation atomic absorption
spectrometry. This technique was compared to
that involving microwave oven digestion bomb
previously optimized for different biological sam-
´ ´ et
ples ŽNavarro et al., 1992a,b; Lopez-Gonzalez
al., 1995.. Urine As concentrations were mea-
sured in a total of 49 healthy individuals and 77
patients with hepatopathies, diabetes or acute
myocardial infarction ŽAMI. in southern Granada
Žsouth-eastern Spain.. We also tried to determine
whether these diseases influenced corporal As
regulation in patients with different pathologies.
Thus, a statistical comparison between As con-
centrations in the urine of healthy subjects Žcon-
trol group. with respect to patients, was es-
tablished. Moreover, the influence of sex and age
of healthy individuals on urine As levels was
estimated. Finally, we also attempted to compare
urine As concentrations from healthy individuals
divided according to their geographical location
Žeight basic health zones. in order to differences
between typically rural and mountainous regions
ŽAlpujarra. and more developed coastal towns.
The present study is a continuation of those
previously carried out in the same area on As
levels in foodstuffs ŽNavarro et al., 1992a,b., wa-
ter and soil ŽNavarro et al., 1993.. Taking into
account the As concentrations present in seafood
of the area ŽNavarro et al., 1992b. and the high
consumption of fish by Spaniards, the present
study was carried out on biological samples Žurine.
because of the correlation existing between the
As intake in the daily diet and As levels present
in urine.
2. Materials and methods
2.1. Subjects
Urine samples } 49 from healthy individuals
and 77 from patients Ž10 with hepatopathies, 38
 M.L. Ruiz-Na¨arro et al. r The Science of the Total En¨ironment 216 (1998) 55]61 57

with diabetes and 29 with myocardial infarction .
} were collected in the Hospital of Motril
Žsouth-eastern Spain.. The samples of 49 healthy
individuals included in the control group were
classified according to sex, age group and geo-
graphical location Žeight basic health zones.. The
release of the human urine samples was approved
by the Ethics Committee of the Hospital of Motril.
The sensitivity found equivalent to 0.0044 units
of absorbance was 0.094 m grl. For instrumental
conditions used in sample analyses, our calculated
analytical detection limit ŽLong and Winefordner,
1983. was 0.19 m grl. As levels in all samples
exceeded the analytical detection limit.
2.4. Accuracy and precision

2.2. Urine collection Spiked samples were analyzed for As in order

Fasting urine samples were sent to the labora- to establish the accuracy of the method. Mean As
tory of clinical analyses of the Motril Hospital in recoveries varied from 98.04 to 105.04 with a
polyethylene containers where they were cen- mean value of 100.80 ŽTable 1.. The precision
trifuged at 3000 = g for 10 min and the resultant expressed as repeatability was calculated by mak-
supernatant taken out and frozen at y 258C for ing seven determinations in different samples fol-
transportation and storage in the Department of lowing a statistical treatment previously described
Nutrition and Bromatology ŽUniversity of by Stiel Ž1982.. The R.S.D. was not higher than
Granada. until analyzed. 11% ŽTable 2.. Moreover, the method was vali-
dated by comparison with the digestion method
2.3. Analytical method using HNO3 with V2 O5 in a previously optimized
microwave acid digestion bomb ŽNavarro et al.,
All homogenized urine samples Ž1.5-ml 1992a,b.. Mean As concentrations determined in
aliquots. were treated with 1.5 ml of HNO3 in a the 10 urine samples considered for the present
multiplace mineralization block. Digestion was method Ž3.73" 1.97 m grl. agreed and were not
completed in 1 h at 808C. When cool, the digest statistically different Ž P) 0.05. to those obtained
was diluted to a 10-ml volume with a 1.5% HCl for the microwave acid digestion method, 3.72"
solution. Finally, the analytical dissolution ob- 2.00 m grl ŽParr model 4782, Parr Instruments,
tained was transferred to a reaction vessel in the Mouline, IL. ŽChen et al., 1988b; Farmer and
MHS-10 system and analyzed by hydride genera- Johnson, 1990; Kalman et al., 1990..
tion atomic absorption spectrometry, HG-AAS
Žatomic absorption spectrophotometer Perkin- Table 1
Elmer Model 1100B equipped with a hydride Arsenic recoveries obtained in the analysis of three urine
generator Perkin-Elmer Model MHS-10, Nor- samples
walk, CT.. After hydride generation using the
Sample As As As As
NaBH 4 solution, As determination was carried
present added found recoveries
out in a quartz cuvette heated over an Žng. Žng. Žng. Ž%.
air]acetylene flame at 193.7 nm wavelength. All
samples were analyzed in triplicate. No. 25 2.41 0.00 2.41 100.0
2.41 0.50 2.79 95.9
The calibration graph was prepared in the range
2.41 1.00 3.30 96.8
0.5]4.0 m grl. The existence of matrix interfer- 2.41 1.50 3.89 99.5
ences was checked by comparing the plotting of No. 36 0.75 0.00 0.75 100.0
the calibration graph wabsorbance s y0.0014q 0.75 0.50 1.26 100.8
0.0463 ŽAs, ppb.x and the addition calibration 0.75 1.00 1.77 101.1
0.75 1.50 2.66 118.2
method wabsorbance s 0.0157q 0.0231 ŽAs, ppb.x.
No. 53 13.28 0.00 13.28 100.0
Consequently, As determination was undertaken 13.28 1.50 14.39 97.4
by the addition calibration method } adding As 13.28 6.00 19.56 98.8
amounts ranging from 0.0 to 4.0 m grl to four 13.28 12.00 25.03 99.0
sample aliquots of 1.5 ml. 13.28 18.00 32.25 103.1
58 M.L. Ruiz-Na¨arro et al. r The Science of the Total En¨ironment 216 (1998) 55]61

Table 2 Table 3
Precision of method for determining arsenic in urine samples Arsenic levels in urine from healthy subjects classified accord-
ing to sex
Sample Mean As R.S.D.
concentration a Ž%. Sex n Mean " S.D.a 95% Confidence Range
Ž m grl. Ž m grl. intervals Ž m grl. Ž m grl.

No. 8 3.59" 0.06 1.73 Women 30 3.40" 1.99 2.57]4.23 0.53]8.85

No. 29 1.51" 0.09 6.27
No. 33 1.69" 0.18 10.48
No. 40 0.78" 0.08 9.87
a
All values are the mean of seven determinations " S.D.
2.5. Statistical analysis
Results obtained are expressed as mean and
standard deviations. To determine the influence
of sex, geographical location and type of pathology
on arsenic urine concentrations, we performed an
ANOVA analysis, using the Student t-test, when
the variables fulfilled parametric conditions, and
the Kruskall]Wallis test when these were non-
parametric. Linear regression analyses were used
to determine the relation between individuals’
age and urine arsenic. The statistical study was
carried out using Statgraphic Statistical Software
6.0.
3. Results
Urine As concentrations in healthy subjects are
shown in Table 3. The average level is 3.68" 2.27
m grl. Men did not present any statistically dif-
ferent urine As mean to women Ž P) 0.05., nei-
ther did patients with diseases studied Žhepatopa-
thy, diabetes or myocardial infarction. to As lev-
els to the control group Ž P) 0.05, Table 4.. Addi-
tionally, no influence of the various health zones
on urine As concentration from healthy subjects
was observed ŽTable 5. Ž P) 0.01.. Urine As con-
centrations were not correlated with age Ž P)
0.05..
4. Discussion
Men 19 4.12" 2.65 3.07]5.16 0.50]9.31
a
No statistically significant difference Ž P ) 0.05..
that found in female subjects Ž3.40" 1.99 m grl..
This result coincides with the findings of other
researchers Ž5.8 and 4.2 m g Asrg of creatinine in
healthy boys and girls, respectively ŽAndren et al.,
1988.; 9.6 and 8.1 m g Asrl in healthy adult men
and women, respectively ŽPolissar et al., 1990..
This fact can be explained considering that en-
ergy requirements for women are approximately
20% lower than those for men and, therefore,
their food intake is also lower, in particular the
intake of seafood which supplies the highest As
intake in the daily diet ŽNavarro et al., 1992b..
Consequently, taking into account that As excre-
tion in urine is the main via to eliminate this
element from the human organism, this should be
20% lower in women than in men Žin our study
As excretion in men was 17.48% higher than that
in women..
Table 4 includes mean As levels determined in
patients with different pathologies considered.
Those suffering from hepatopathies show levels
ranging from 1.25 to 6.61 m grl, with a mean
value of 4.24" 1.98 m grl. After applying the one-
way ANOVA to results obtained and comparing
them with those found for the control group
Žhealthy subjects., we observed that patients with
Table 4
Arsenic concentrations in urine from patients with different
pathologies
Pathology n Mean " S.D.a Range
Ž m grl. Ž m grl.

AMI 29 3.64" 1.85 1.12]7.68

As concentrations in urine of the healthy indi- Diabetes 38 3.44" 2.36 0.32]9.82
viduals are shown in Table 3. Male subjects pre- Hepatopathy 10 4.24" 1.98 1.25]6.61
sented a mean concentration of 4.12" 2.65 m grl, Healthy subjects 49 3.68" 2.27 0.50]9.31
which is not statistically higher Ž P) 0.05. than a
No significant difference Ž P) 0.05..
 M.L. Ruiz-Na¨arro et al. r The Science of the Total En¨ironment 216 (1998) 55]61 59

Table 5
Comparison of urine arsenic concentrations found in non-exposed Žcontrols. and exposed individuals and arsenic contamination
determined by other authors

Mean As in non- Mean As in exposed Sources for Reference

exposed subjects subjects Ž m grl. arsenic
Ž m grl.

4.4 0.2a Glass factory Farmer and Johnson Ž1990.

4.4 238.0a As chemical plant Farmer and Johnson Ž1990.
4.4 245.0a As chemical plant Farmer and Johnson Ž1990.
4.7 ] Ingestion of sodium Buchet et al. Ž1981.
metaarsenite
5.6 20.5a Glass factory Foa et al. Ž1984.
6.0 ] Environmental and Vahter Ž1986.
occupational As
57.2 120.0a As acid plant Yamamura and Yamauchi Ž1980.
50.1 238.0a Copper smelter Yamauchi et al. Ž1989.
9.6 19.6b Living near smelter Yamauchi et al. Ž1989.
17.5 25.7b Living near smelter Smith et al. Ž1977.
10.1 11.7b Living near a copper Polissar et al. Ž1990.
smelter
10.1 9.4b Living near a copper Polissar et al. Ž1990.
smelter
a
Occupationally exposed population groups.
b
Environmentally exposed population groups.

hepatopathies showed higher As levels in urine,
although they were not statistically significant Ž P
) 0.05..
As chronic intoxication can cause hepatic in-
jury which eventually progresses to cirrhosis
ŽBoudene, 1990.. Taking into consideration that
the most important route of As elimination from
the human organism is urine, these high and
constant As contamination indices, related with
the development of cirrhosis, will cause an in-
crease in As levels in urine, as a detoxification
path. Nevertheless, in our study this result was
not observed. Although As concentrations in urine
in patients with hepatopathies are slightly higher
than those found for healthy controls, these dif-
ferences are not statistically significant Ž P) 0.05..
Moreover, mean arsenic levels found in patients
are the same to those observed in individuals
living in areas with low As environmental levels
ŽTable 5.. This result establishes that hepato-
pathies were not caused by dietary consumption
of As Ža low intake., and that the As metabolism
in the human organism, given the As hepatic
accumulation among several organs, was not af-
fected by the pathologic state of patients suffer-
ing from hepatopathies included in this study.
The group of patients who suffered from my-
ocardial infarction showed mean As levels in urine
of 3.64" 1.85 m grl ŽTable 4.. After applying the
one-way ANOVA statistical study to the results
obtained and comparing them with those found
for the control group Ž3.68" 2.27 m grl. signifi-
cant differences were not observed Ž P) 0.05..
This result establishes the non-influence of this
pathology on As body regulation in the human
organism because mean As levels are very similar
to each other.
Other authors found that a continuous expo-
sure to environmental As contamination from
AsH 3 in the workplace caused a number of car-
diovascular disorders related with an increase in
As elimination in urine ŽChen et al., 1988b;
Benowitz, 1992.. Moreover, it has been indicated
that the ingestion of inorganic As is associated
with peripheral vascular diseases ŽChen et al.,
1988b.. Nevertheless, this relation does not occur
in patients with myocardial infarction because, in
this case, the As environmental and exposure
60 M.L. Ruiz-Na¨arro et al. r The Science of the Total En¨ironment 216 (1998) 55]61

levels in subjects from the area under study are ment of As in the urine of adjacent populations
low. ŽKalman et al., 1990; Polissar et al., 1990; Chat-
Mean As concentration obtained for patients terjee et al., 1995; Das et al., 1995.. Taking into
with diabetes was 3.44" 2.36 m grl ŽTable 4.. This account the low As concentrations measured in
result was not significantly lower to that found for urine from inhabitants of the most industrialized
healthy controls Ž P) 0.05.. Consequently, it was Mediterranean coastal area, it has been shown
also observed that there was no incidence of the that industries Žpaper mill, power station, petrol
pathologic state of diabetic individuals on As tanks and oil refinery. from this area do not
metabolism in the human organism. produce significant As contamination. This fact is
Table 6 summarizes urine As concentrations also observed when our As values are compared
from healthy individuals grouped according to with those determined by other researchers in
their basic health zones. The ANOVA analysis urine from individuals not exposed to the As
showed that there were no significant statistical sources included in Table 5.
differences in As concentrations between the dif-
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