Environmental exposure to arsenic and chromium in an industrial area
Environmental exposure to arsenic and chromium in an industrial area
Luigi Vimercati 0 2
Maria F Gatti 0 2
Tommaso Gagliardi 0 2
Francesco Cuccaro 0 2
Luigi De Maria 0 2
Antonio Caputi 0 2
Marco Quarato 0 2
Antonio Baldassarre 0 2
0 Interdisciplinary Department of Medicine, Occupational Medicine BB. Ramazzini
1 , University of Bari Medical School , Giulio Cesare Square 11, 70124 Bari , Italy
2 Health Local Unit of Barletta-Andria-Trani , 76121 Barletta , Italy
Arsenic and chromium are widespread environmental contaminants that affect global health due to their toxicity and carcinogenicity. To date, few studies have investigated exposure to arsenic and chromium in a population residing in a high-risk environmental area. The aim of this study is to evaluate the exposure to arsenic and chromium in the general population with no occupational exposure to these metals, resident in the industrial area of Taranto, Southern Italy, through biological monitoring techniques. We measured the levels of chromium, inorganic arsenic, and methylated metabolites, in the urine samples of 279 subjects residing in Taranto and neighboring areas. Qualified health staff administered a standardized structured questionnaire investigating lifestyle habits and controlling for confounding factors. The biological monitoring data showed high urinary concentrations of both the heavy metals investigated, particularly Cr. On this basis, it will be necessary to carry out an organized environmental monitoring program, taking into consideration all exposure routes so as to correlate the environmental concentrations of these metals with the biomonitoring results.
Arsenic; Chromium; Carcinogens; Environmental exposure; Biological monitoring; Public health
Arsenic and chromium (Cr) are widespread environmental
contaminants that affect global health due to their toxicity
and carcinogenicity (Centeno et al. 2006; IARC 2012a,
2012b; Tsai et al. 2003; Lai et al. 1994; Lee et al. 2002;
Chakraborti et al. 2003). Both exist ubiquitously in the
environment and they are commonly present in air, water, soil, and
sediments and could find their routes into the human body
through inhalation, ingestion, and skin absorption (ATSDR,
Agency for Toxic Substances and Disease Registry 2007).
Arsenic exists in organic and inorganic forms and in
different oxidation or valence states. The valence states of arsenic
compounds relevant to human health are the trivalent (AsIII)
and pentavalent (AsV) states. These arsenic species include
Responsible editor: Philippe Garrigues
arsenates (compounds containing AsO43−), arsenites
(compounds containing AsO33−), and the mono-methyl (MMA)
and di-methyl (DMA) metabolites. Arsenic species in the
trivalent (III) state including arsenous acid (commonly arsenite),
dimethylarsinous acid (DMAIII), and monomethylarsonous
acid (MMAIII) are estimated more toxic at lower doses than
those of other arsenic species (ATSDR 2007; Drobna et al.
2009). Results from animal and epidemiological studies have
shown that inorganic arsenic (iAs) compounds can be
categorized as carcinogens (group 1) or potential carcinogens (group
2B) such as DMA and MMA, while arsenobetaine and other
organoarsenicals have not been categorized as carcinogens
(group 3) (IARC 2012a, 2012b).
The primary source of arsenic exposure in human is
drinking water (NRC 1999; NRC 2001; Smith et al. 2002;
Watanabe et al. 2003). Organic arsenic compounds (e.g.,
arsenobetaine) are mainly found in fish, which thus may give
rise to human exposure, whereas inorganic arsenic is found in
groundwater used for drinking in different areas of the world
(such as Asia and South America), although it has been long
recognized that arsenic exposure from drinking water is
causally related to cancer in the lungs, kidney, bladder, and skin
(WHO 2001). Water reservoirs can be contaminated by oil
refining wastes: indeed, conventional waste-treatment
techniques are not effective in the removal of the same arsenical
species contained in crude oil (e.g., As(III) and As(V))
(Tonietto et al. 2010). In addition, contaminated soils are a
source of arsenic exposure (WHO 2001). Soil can be
contaminated by arsenic-rich steel plants’ emissions, due to the
melting of metal scrap containing this metalloid in blast furnaces to
obtain recycled iron. Neighboring land may be polluted for
decades after plant closure (Lambert et al. 2011).
Cr(0), Cr(III), and Cr(VI) are used commercially and are
present in the environment. Cr(0) is mainly in its metallic form
as a component of iron-based alloys such as stainless steel.
Trivalent chromium (Cr(III)) is primarily of geological
origin and hexavalent chromium (Cr(VI)) is derived mainly
from industrial processes (Zhitkovich 2011), but can also
originate from the oxidation of naturally occurring Cr(III) by
minerals containing Mn-oxides (Oze et al. 2007).
Inter alia, since 1960s, Cr(0) is mainly used in its metallic
form by steel factories as a component of iron-based alloys
such as stainless steel and tin-free steel, less expensive than tin
steel. During these processes, metallic powder containing
chromium ions and chromium oxides is produced and, despite
the presence of particular filters, it is poured into the air.
Moreover, factories’ blast furnaces melt metal scrap
containing chromium and other ions to obtain steel. Due to high
temperature, Cr(III) and Cr(VI) evaporate and are output via
the furnaces’ chimneys (Nicodemi 1994). Chromium also is a
waste product in oil refining processes (on average, 27–80 mg
per kg of oily sludge): a wrong waste management could lead
to a substantial soil pollution around the refinery plant
(Bhattacharyya and Shekdar 2003). Finally, cement factories
produce dusts during raw material processing, grinding of
clinker, and packaging of finished product: this matter is
composed of several elements, among which different species of
chromium and arsenic and it is deposited to many hundreds of
meters from the site of release (Gbadebo and Bankole 2007).
In food and dietary supplements, chromium is mainly
Cr(III) and is considered to play a key role in human
metabolism, otherwise in drinking, water is primarily Cr(VI).
In contrast with arsenic, is not so clear if chromium can
cause cancer following ingestion via drinking water.
According to this hypothesis, two ecological studies
conducted in China (IARC 1990; Beaumont et al. 2008) and in Greece
(Linos et al. 2011) estimated lung and stomach cancer
mortality associated with prolonged oral consumption of water
contaminated with Cr(VI).
Like for arsenic, it has long been established that inhalation
of chromium, in particular hexavalent chromium (CrVI), can
cause human lung cancer (IARC 1990).
The specific mechanism of chromium carcinogenicity
remains unclear; however, there is an abundance of data
supporting the genotoxicity and mutagenicity of Cr(VI)
in vivo and in vitro. Particularly, chromium in its hexavalent
form is considered to be a pro-carcinogen. Cr(VI) manages to
enter the cell through molecular mimicry mechanism as an
oxyanion followed by its metabolic reduction to Cr(V),
Cr(IV), and to the final reduced trivalent form. These reduced
forms have been shown to induce a wide range of genomic
DNA damage, which may lead to DNA replication inhibition
(Salnikow and Zhitkovich 2008; Alexander and Aaseth 1995;
O’Brien et al. 2001). Moreover, Cr(VI) is thought to be able to
induce DNA double-stranded breaks selectively on
euchromatin and to accumulate ubiquitinated forms of histone H2AX:
these two kinds of damage lead to suppressed upregulation of
inducible genes and help to explain the high genotoxic
potential of this metal (DeLoughery et al. 2015).
As for chromium, the precise mechanisms that acute or
chronic exposure to arsenic performs to induce cancer are
not yet understood. Recent studies have shown that the
toxicity of arsenic depends on several factors: exposure amount,
length, and frequency, biological species, age, sex, individual
susceptibility, genetics, and nutrition (Abernathy et al. 1999).
Different hypotheses regarding the toxic mechanism
behind arsenic have been suggested, including induced
chromosome abnormalities, promotion/progression, oxidative stress,
suppression of p53, altered DNA repair, enhanced cell
proliferation, altered DNA methylation patterns, altered growth
factors, and gene amplification (Hong et al. 2014).
The aim of this study was to assess arsenic and chromium
exposure in the general population with no occupational
exposure to these metals, resident in the municipalities of
Taranto and Statte, site of a large integrated cycle steel
foundry, a refinery, and a cement factory, and in the municipality of
Laterza, 54-km driving distance from Taranto, considered as a
non-polluted area because no significant industrial plants are
In fact, the land close to Taranto industrial plant is polluted
by many heavy metals, as well as PAHs (Campo et al. 2012):
the water samples also taken from aquifers contain high
arsenic and chromium concentrations (ARPA 2009). The steel
plant in Taranto, for 2005, has emitted into the air 3800.8 kg
of chromium and compounds, into the water 20,407.3 kg of
chromium and compounds, and 1172.1 kg of arsenic and
compounds (APAT - INES 2005). Moreover, in Taranto Gulf, soil
contamination is partially linked to air pollution and both
could be not homogeneously distributed in closer sites (e.g.,
Paolo VI, Statte) due to meteorological conditions (Mangia
et al. 2013).
Materials and methods
Between January 2010 and April 2012, a cross-sectional study
was conducted to measure the urinary excretion of inorganic
arsenic and its methylated metabolites monomethyl arsenic
acid (MMA) and dimethylarsinic acid (DMA), chromium as
well as urinary creatinine, which was used both to confirm the
acceptability of urine samples and to adjust the metal
The analysis of the urine samples was performed by atomic
absorption spectrophotometry (PerkinElmer Corp.—Model
5100 PC—PerkinElmer Inc.—Wellesley, MA, USA),
employing the hydrides (arsine) generation technique for
determining As and the graphite furnace method for Cr
according to the NIOSH analytical methods (NIOSH 2003); an
automated kinetic Jaffe technique using alkaline picric acid was
used to measure creatinine. Urine samples were not processed
for metal concentrations if the creatinine excretion was not
within the range of 0.3–3.0 g/L (ACGIH 2010).
An internal quality control (IQC), according to
manufacturer instructions, was used systematically to verify the
reproducibility and the repeatability of the data that were obtained
using the standard curve prepared by the operator.
The research was conducted with 350 subjects residing in
Taranto and the surrounding area for at least 10 years; they
were randomly selected from the Regional Assisted Care
Registry to reduce the possibility of bias in self-selection.
The response rate was high (93.1%).
All of the subjects were contacted in accordance with
procedures agreed upon by local general practitioners, who had
previously been invited to a dedicated meeting at which they
were fully informed about the aims of the study and asked
whether they would be willing to collaborate. All subjects
agreed to the processing of their personal data and understood
that this information was categorized as Bsensitive data^. All
subjects were informed that data from the research protocol
would be treated in an anonymous and collective way, with
scientific methods and for scientific purposes in accordance
with the principles of the Helsinki Declaration.
After obtaining informed consent from each participant
qualified health staff it was administered a standardized
structured questionnaire. Each questionnaire included personal
data of the study participants and information of lifestyle habits.
In particular, the questionnaire has investigated the residential
history, housing exposure (intensity of car traffic, the presence
of fireplace inside their home, proximity to industrial areas),
environmental exposure (use of pesticides, paints, wood
preservatives), and occupational exposure (company, type of job,
use of PPE). In addition, they were investigated regarding
eating habits especially if they had consumed seafood in the
last 48–72 h before urine collection and were evaluated with
other confounding factors including quantity and type of
water consumed (tap or bottled mineral water) and smoking
habits (type, cigarettes/day, years of smoking, use of cigars,
pipe). The questionnaire also investigates the presence of
diseases and use of drugs.
First-void urine (FVU) was sampled from each participant
into clean conical 50-mL polypropylene tubes, which were
then immediately sealed with O-ring screw caps and packed
into coolers with frozen ice packs. Samples were sent to the
laboratory and then stored at −20 °C and analyzed within
After analysis, we excluded 47 (13.4%) subjects from the
study because of creatinine excretion values <0.3 g/L or
After these exclusions, the final sample consisted of 279
subjects, including 135 males and 144 females aged between
18 and 77 years (mean age 46.0 ± 13.12 SD). Of the 279 study
subjects, 179 resided in the city of Taranto; they were
subdivided into three district areas: BPaolo VI^ (N 39),
BTamburi—Old Town^ (N 50), or BNew Town^ (N 90). A
total of 55 subjects were residents of the nearby Statte
municipality and 45 resided in the Laterza municipality (Table 1).
Comparisons among groups were made employing
nonparametric techniques (rank sum Wilcoxon-Mann-Whitney
test and Kruskal-Wallis test). We also performed a
multivariate analysis through a linear regression model, investigating
the association of the urinary concentrations of As and Cr with
the explanatory variables obtained by questionnaire. The main
variables included in the model were age, sex, body mass
index, drinking water, smoking habits, city of residence,
Table 1 Flying distance
from the industrial site
dwelling site, consumption of fish, crustaceans, and shellfish
in the 48–72 h before collection, presence of dental fillings,
and use of fireplaces in homes.
A p value ≤0.05 was considered significant. Statistical
analysis was conducted using packages SAS (v. 9.0) and
STATA (v. 11).
Table 2 shows the urinary levels of iAs + MMA + DMA, and
Cr measured in the overall population of 279 subjects residing
in Taranto and neighboring areas.
It was carried out a comparison of the urinary Cr and As in
study groups with the range proposed by the Italian Reference
Values Society (SIVR).
Table 3 shows the urinary levels of iAs + MMA + DMA,
and Cr measured in the different districts of Taranto (Paolo VI,
Tamburi-Old Town, New Town).
The median value was 0.3 μg/L, which was comparable to the
upper limit of the range proposed by the SIVR. The 95th
percentile was significantly above the reference value limits
The differences in the measured median values among the
municipalities were significant, with the highest values found
in Statte (Table 2). In the different districts of Taranto, the
highest median values of urinary concentrations were found
in the Paolo VI district (Table 3).
The median values of urinary chromium were comparable
in both sexes, in all age classes, among smokers and no
smokers, regardless of whether they drank tap or bottled
mineral water, and seafood consumption (Table 4).
In our study, we investigated the association between
having a fireplace in home and the urinary excretion of Cr,
without finding any association.
The multivariate analysis showed the following results. For
Cr, we found an association with the city of residence;
specifically, we found a higher concentration in the people living in
Statte vs Taranto (p = 0.001), and this analysis is not
influenced by principal investigated confounding factors (Table 5).
Urinary inorganic arsenic and methylated metabolites
The median urinary concentration in the entire study
population was within the SIVR reference limit whereas the 95th
percentile was higher than that of the upper limit (Table 2).
Considering the municipalities, the 95th percentile was higher
than the reference value only in Statte (Table 2). Moreover, the
median urinary concentration of iAs + MMA + DMA was
significantly higher in Statte than that in Taranto or Laterza,
although it was still within the range limits (Table 2). In the
different districts in the city of Taranto, the 95th percentile and
median urinary values remained within range limits (Table 3).
When analyzing the urinary excretion of iAs + MMA +
DMA in relation to the variables considered in the study
population, similar median values were obtained in both sexes. In
subjects who drank tap water, urinary iAs + MMA + DMA
values (3.6 μg/L) were higher than in those who drank bottled
mineral water (2.5 μg/L). Slightly higher values were found in
smokers (4.1 μg/L) than those in non-smokers (3.8 μg/L).
Statistically significant differences were found when comparing
the urinary concentrations in those who had eaten shellfish and/
or seafood in the 48–72 h before sampling (9.8 vs 3.8 μg/L)
In our study, no association between the use of pesticides and
urinary concentrations of As was found. Moreover, we
investigated the association between having a fireplace in home and the
urinary excretion of As, without finding any association.
The multivariate analysis showed the following results. For
As, we found an association with the city of residence;
specifically, we found a higher concentration in the people living
in Statte vs Taranto (p = 0.001) and this analysis is not
influenced by principal investigated confounding factors (Table 5).
Whole study population
We also found a lower concentration in the people living in
Laterza vs Taranto (p = 0.037) and a statistically significant
association with the consumption of crustaceans in the 48–
72 h before collection (p = 0.019).
To date, few studies have investigated exposure to arsenic and
chromium in a population residing in a high-risk
environmental area such as Taranto, Apulia Region (Southern Italy)
(Iavarone et al. 2012). Many years have passed since the
WHO first included the Taranto area among those at high
environmental risk and underlined the increased mortality
rates, as compared to Italy as a whole, for bladder, liver, and
lung cancer, as well as cancer of the pleura and non-Hodgkin
lymphoma (WHO 1997).
The median value for chromium (0.3 μg/L) was the upper
limit value of the relative SIVR range, while the 95th percentile
was actually higher than the proposed SIVR upper limit. There
were no significant differences in urinary excretion by sex, age,
type of water drunk, and number of smoked cigarettes, unlike
in other reports in literature (EPA 1984; SIVR 2011; Zhitkovich
2002). Moreover, our study found higher urinary levels of
chromium and arsenic in people living close to industrial plants.
It has been generally accepted that low or moderate doses
of orally ingested Cr(VI) are non-carcinogenic, but, more
recently, the potential risks of Cr(VI) exposure by ingestion in
drinking water have come under increased scrutiny (Nickens
et al. 2010).
The chromium concentration limit in drinking water
applied both in Italy (Legislative Decree no. 31/2001) and in
the USA. (US Environmental Protection Agency—EPA) is
50 μg/L (ATSDR 2007). However, in a study conducted in
California (USA), 38% of municipal sources of drinking water
reportedly showed higher levels of chromium (VI) than the
detection limit of 1 μg/L (Sedman et al. 2006).
Tobacco smoke is known to contain chromium (VI), and
indoor air polluted by cigarette smoke can contain hundreds
of times the amount of chromium (VI) found in outdoor air
(IARC 2012a, 2012b). However, other different exposure
routes, such as transdermal way (as well as inhalation and
ingestion), are possible but their contribution to overall
chromium intake is not clear and cannot be investigated in this study.
The subjects who had eaten seafood and/or shellfish 48–
72 h before urine collection had higher levels of urinary
excretion of arsenic (9.8 vs 3.8 μg/L). In fact, diet is the main
source of non-occupational exposure to arsenic (Vimercati
et al. 2009). Foods with the highest content of arsenic include
some marine organisms, such as shellfish and crustaceans
(Argese et al. 2005; Fattorini et al. 2004; Lopez et al. 1994;
WHO 2001). However, some authors did not find a positive
association between the consumption of seafood and/or
shellfish and the urinary concentrations of As. In particular,
Hsueh et al. (2002) found no differences in the urinary
concentrations of the various As species before and after
refraining from eating seafood for 3 days, respectively.
Moreover, despite the notorious toxic effects of arsenic in
humans, it is still used in both agriculture and industry (Park
et al. 2010; Kumaresan and Riyazuddin 2001). This large
Table 5 Urinary excretion of As
and Cr metals (μg/L) in relation to
the variables listed in Statte
() = n value
amount of inorganic arsenic-based pesticides has led to serious
environmental arsenic contamination (Datta and Sarkar 2005).
Given the notorious adverse effects of arsenic exposure in
humans, the US Environmental Protection Agency (EPA)
banned the use of many inorganic arsenic-based pesticides
during the late 1980s and early 1990s (Quazi et al. 2013).
Although some countries have issued documents to phase out
organo-arsenical pesticides from the market, large agricultural
sites contaminated by years of organo-arsenical pesticide
application still exist. These agricultural lands might pose significant
health risks in the present and in the future (Li et al. 2016). About
that, contribution of transdermal route in overall As intake is hard
to estimate and thus cannot be investigated in this study.
In our study, no association was found between the use of
pesticides and urinary concentrations of As. There were
significant differences between those who drank tap water and
those who habitually drank bottled mineral water. The
contamination of the main water supply remains a major source of
exposure to inorganic As in many parts of the world (IARC
2004), despite the fact that in 1993, the WHO recommended
that levels of As in drinking water should not exceed 10 μg/L
(WHO 1993). On the other hand, a recent analysis of 40
different labels of bottled mineral water on sale in Italy
demonstrated higher levels of total As than the legal limit in five of
them (Signorile et al. 2007). In contrast, in the surveys of
water in the Apulian aqueduct over the period 2004–2006,
total As values were consistently below 1 μg/L.
Moriske et al. found higher concentrations of heavy metals
in indoor air pollution in houses with coal burning and open
fireplaces than those in homes with central heating (Moriske
et al. 1996). In our study, we investigated the association
between having a fireplace in the home and the urinary excretion
of heavy metals, but did not find any association.
Overall, the biological monitoring data reveal high urinary
concentrations of both heavy metals investigated, above all in
However, in our study, it was not possible to correlate the
biological monitoring data with the environmental data because
the information collected by the official institutions and/or
those in the literature were incomplete and only provided by
the European Monitoring and Evaluation Programme (EMEP).
For the whole province of Taranto, the value of emissions of
Pb into the atmosphere in 2009 was 38 tons, one of the highest
in Europe, and the emissions of Hg in the same year was
510 kg. There are no available data concerning the emissions
of the other metals. In the future, therefore, we believe it will be
necessary to carry out an organized environmental monitoring
program, taking into consideration all exposure routes to
correlate the environmental concentrations of these metals with the
biomonitoring results. However, our study suffers from some
limitations due to the small population sample and data
analysis. In fact, the questionnaire results could be influenced by
subjects’ personal replies. Moreover, chromium analysis could
be affected by redox reactions interference, during the ions
determination (Jiang et al. 2013). Furthermore, for arsenic
speciation, best sensitivity was shown for As(III) with respect to
MMA, DMA, and As(V) (Moreno et al. 2000).
In any case, the data we obtained, which may be further
confirmed by larger population studies, are sufficient to
warrant the expectation that local and national institutions should
be required to adopt preventive measures to reduce the
environmental exposure of the general population to heavy metals,
especially lead and chromium. Such actions could help to
reduce the health risks, including those of a carcinogenic
nature, posed to populations residing in areas with a known high
The importance of investigating the exposure of the general
population to As and Cr lies in their ubiquitous nature, since
they are also widely distributed in nature, as well as in their
harmful effects on human health. We conducted a study to
evaluate the exposure to heavy metals in the industrial city
of Taranto and the surrounding area in Southern Italy through
biological monitoring techniques.
We measured the levels of chromium, inorganic arsenic,
and its methylated metabolites in the urine samples of 279
subjects residing in Taranto and neighboring areas.
Our study results showed high urinary concentrations of
both heavy metals investigated.
It would be appropriate to search the causes of this finding
and deepen the impact of industrial plants present in that area.
This is important in developing a comprehensive risk
assessment and management program in order to adopt preventive
measures to reduce environmental exposure of the general
population to As and Cr, considering their toxicity and
Further epidemiological studies with larger samples and
including environmental air quality data will be necessary to
confirm our results.
Acknowledgments The authors thank the general practitioners who
participated to the study (Dr. Basile, Dr. Carone, Dr. Catucci, Dr.
Colucci, Dr. De Sabato, Dr. Dell’Aquila, Dr. Guarino, Dr. Mancino, Dr.
Ostillio, Dr. Perrone, Dr. Poretti, Dr. Zizza) and Dr. Michele Conversano
and Dr. Giovanni Caputi of the Department of Prevention—Taranto
Health Local Organization.
Authors’ contributions LV is the principal investigator, planned and
designed the study, and drafted the manuscript; MFG is the principal
investigator, administered questionnaires, and helped to draft the
manuscript; TG carried out analysis of urine samples and measured metals’
concentrations; FC performed statistical and epidemiological analysis;
LD performed statistical and epidemiological analysis; AC carried out
the data entry; MQ carried out the data entry; AB is the principal
investigator, performed statistical and epidemiological analysis, and helped to
draft the manuscript. All authors read and approved the final manuscript.
Compliance with ethical standards All of the subjects were contacted
in accordance with procedures agreed upon by local general practitioners,
who had previously been invited to a dedicated meeting at which they
were fully informed about the aims of the study and asked whether they
would be willing to collaborate. All subjects agreed to the processing of
their personal data and understood that this information was categorized
as Bsensitive data^. All subjects were informed that data from the research
protocol would be treated in an anonymous and collective way, with
scientific methods and for scientific purposes in accordance with the
principles of the Helsinki Declaration.
Informed consent Informed consent was obtained from each
participant of the study.
Financial supports None.
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