Mortality for chronic-degenerative diseases in Tuscany: Ecological study comparing neighboring areas with substantial differences in environmental pollution

Abstract

Objectives. Environmental pollution is associated to morbidity and mortality for chronic-degenerative diseases. Recent data point out a relationship between proximity to industrial plants and mortality due to neoplasms.
The aim of this study was to compare mortality due to chronic-degenerative diseases in an area of Tuscany (Bassa val di Cecina) characterized by the presence of two neighbouring municipalities similar for size but with substantial differences in industrial activities: Rosignano (site of chemical, energy production and waste processing industries) and Cecina (with no polluting activity). Materials and methods. Standardized mortality rates for the 2001 - 2010 decade were calculated; data of the whole Tuscany were assumed as reference. Environmental levels of pollutants were obtained by databases of ARPAT (Tuscany regional agency for environment preservation). Maximum tolerated pollutant levels settled by national laws were assumed as reference.
Results. In the whole Bassa val di Cecina, significantly elevated standardized mortality rates due to mesothelioma, ischemic heart diseases, cerebrovascular diseases and Alzheimer and other degenerative diseases of nervous system were observed. In the municipality of Rosignano, a significant excess of mortality for all these groups of diseases was confirmed. On the contrary, the municipality of Cecina showed only significantly higher mortality rates for ischemic heart diseases. Elevated levels of heavy metals in sea-water and of particulate matter PM10 and Ozone in air were detected in Rosignano.
Conclusions. The present study shows an excess of mortality for chronic-degenerative diseases in an area with elevated concentration of polluting factories. Proximity to industrial plants seems to represent a risk factor for those diseases.

Full text

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ORIGINAL PAPER
International Journal of Occupational Medicine and Environmental Health 2017;30(4):1 – 13
https://doi.org/10.13075/ijomeh.1896.00972
MORTALITY FOR CHRONIC-DEGENERATIVE
DISEASES IN TUSCANY: ECOLOGICAL STUDY
COMPARING NEIGHBORING AREAS
WITH SUBSTANTIAL DIFFERENCES
IN ENVIRONMENTAL POLLUTION
CLAUDIO MARABOTTI1,2, PAOLO PIAGGI3,4, PAOLO SCARSI5, ELIO VENTURINI1, ROMINA CECCHI1,
and ALESSANDRO PINGITORE2
1 Bassa Val di Cecina Hospital, Cecina (LI), Italy
Cardiovascular and Coronary Care Unit
2 National Research Council (CNR), Pisa, Italy
Institute of Clinical Physiology
3 National Institutes of Health, Phoenix, Arizona, USA
Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases
4 University of Pisa, Pisa, Italy
Department of Endocrinology and Metabolism
5 National Research Council (CNR), Pisa, Italy
Institute of Geosciences and Earth Resources
Abstract
Objectives: Environmental pollution is associated with morbidity and mortality for chronic-degenerative diseases. Recent
data points out a relationship between proximity to industrial plants and mortality due to neoplasms. The aim of this study
has been to compare mortality due to chronic-degenerative diseases in the area of Tuscany (Bassa Val di Cecina), Italy,
characterized by the presence of 2 neighboring municipalities similar in terms of size but with substantial differences in
industrial activities: Rosignano (the site of chemical, energy production and waste processing industries) and Cecina (with
no polluting activity). Material and Methods: Standardized mortality rates for the 2001–2010 decade were calculated;
the data of the whole Tuscany was assumed as reference. Environmental levels of pollutants were obtained by databases
of the Environmental Protection Agency of Tuscany Region (Agenzia Regionale per la Protezione Ambientale della Tos-
cana – ARPAT). Maximum tolerated pollutant levels set by national laws were assumed as reference. Results: In the whole
BassaValdiCecina,signicantlyelevatedstandardizedmortalityratesduetomesothelioma,ischemicheartdiseases,cere-
brovascular diseases and Alzheimer and other degenerative diseases of nervous system were observed. In the municipality
ofRosignano,asignicantexcessofmortalityforallthesegroupsofdiseaseswasconrmed.Onthecontrary,themunici-
palityofCecinashowedonlysignicantlyhighermortalityratesforischemicheartdiseases.Elevatedlevelsofheavymetals
Received: March 20, 2016. Accepted: June 28, 2016.
Corresponding author: C. Marabotti, Bassa Val di Cecina Hospital, Cardiovascular and Coronary Care Unit, via Montanara 1, 57023 Cecina (LI), Italy (e-mail:
c.marabotti@alice.it).
Nofer Institute of Occupational Medicine, Łódź, Poland

ORIGINAL PAPER C. MARABOTTI ET AL.
IJOMEH 2017;30(4)
2
Rosignano Solvay, situated in close proximity of the in-
dustrialsite(Figure 2). In1999,theWorldHealthOrga-
nization(WHO)identied thecommunityof Rosignano
Solvay as a “priority pollution hotspot in the Mediterra-
nean”[6].Ontheother hand, Cecina(12kmsouth)has
an economy prevailingly based on tourism, agriculture and
trade. An epidemiological evaluation of pollution-related
mortality in this area seems particularly interesting, since
inhabitants may be differently exposed to pollutants:
from the maximum, represented by people who are both
workingand livingin proximity ofpolluting factories,to
the minimum, represented by people who are neither liv-
ingnear, norworking in polluting industries. Bothcom-
mutingindustrialworkersandnon-industrialworkersliv-
ing in the proximity of polluting activities may represent
intermediatelevelsofenvironmentalpollutionrisk.
A retrospective evaluation of both mortality rates due to
chronic-degenerative diseases and environmental expo-
sure to pollutants in this area has therefore been designed.
The aims of this study have been:
– to evaluate the possible excess in mortality due to po-
tentially pollution-related diseases in the whole Bas-
sa Val di Cecina and in the 2 main municipalities of
the area (Rosignano Marittimo and Cecina) with dif-
ferent industrial impact,
– toinvestigatethepotential links betweenthepossible
excess in mortality rates and environmental release and
detection of pollutants,
– to discuss the pathophysiological mechanisms linking
environment pollution to the diseases responsible for
the excess in mortality.
INTRODUCTION
The relationship between ambient pollution and morbidity
and mortality due to neoplasms and chronic respiratory dis-
eases has been demonstrated by a large number of epide-
miological observations [1,2]. More recently, an association
between environmental pollution (particularly due to heavy
metals contamination of water) and cardiovascular diseases
has also been reported [3]. The residential proximity to po-
tentiallypollutingindustriesisaknownpowerfulriskfactor
for mortality due to pollution-related diseases [4]. In par-
ticular,workerslivingin contaminated areas(i.e.,inclose
proximity to polluting industrial activities) may have both
professional exposure during working hours and environ-
mentalexposurewhileoffduty[5].Onthecontrary,com-
mutingworkers, travelling onadailybasisfromtheirresi-
dence (somewhat far from polluting industrial activities) to
theirworkplace,shareonlyprofessionalexposurewithresi-
dentworkers[5].Thedistrictnamed Bassa ValdiCecina,
including 10 municipalities with approx. 82 000 inhabitants,
issituatedonthecoastofTuscany,Italy, afew kilometers
south of the towns of Leghorn and Pisa (Figure 1).
The particularity of this district is the presence, just in
the middle of the area, of 2 neighboring mid-sized mu-
nicipalities (where majority of population is concen-
trated), similar in terms of the number of inhabitants
(about 30 000 each) but with considerably different eco-
nomic background. In the municipality of Rosignano
Marittimo an important industrial site is located, includ-
ing several factories, dealing with chemical production,
disposal and recovery of hazardous and urban wastes,
energy production. About a half of the inhabitants live in
inseawaterandofparticulatematterwhichcontainsparticlesofdiameter≤10mm(PM10) and ozone in air were detected
in Rosignano. Conclusions: This study shows an excess of mortality for chronic-degenerative diseases in the area with el-
evatedconcentrationofpollutingfactories.Proximitytoindustrialplantsseemstorepresentariskfactorforthosediseases.
IntJOccupMedEnvironHealth2017;30(4)
Key words:
Heavy metals, Particulate matters, Environmental pollution, Mesothelioma, Ischemic heart disease,
Neurologic degenerative diseases

CHRONIC-DEGENERATIVE DISEASES IN POLLUTED AREAS ORIGINAL PAPER
IJOMEH 2017;30(4) 3
All-cause mortality, mortality for chronic-degenerative
diseases and mortality for respiratory diseases potentially
pollution-related were evaluated. In particular, the follow-
ingInternationalStatisticalClassicationofDiseasesand
Related Health Problems, 10th revision (ICD-10) codes
were investigated: malignant neoplasms (as a whole, C00–
C75, and the single codes of each neoplastic disease), dia-
betes mellitus (E10–E14), ischemic heart diseases (I20–
I25), acute myocardial infarction (I21), other forms of
ischemic heart disease (I20, I22–I25), cerebrovascular
MATRIAL AND METHODS
Demographic and mortality data source
Mortality rates for the years 2001 to 2010 were obtained by
les elaborated by the Institute for Oncological Study and
Prevention (Istituto per lo Studio e la Prevenzione Onco-
logica–ISPO) for theareaof BassaValdiCecinaand for
the municipalities of Rosignano Marittimo and Cecina. Stan-
dardized mortality rates in the whole area and in the 2 largest
municipalities were compared to the corresponding rates of
Tuscany as a whole, assumed as a reference.
Bassa Val di Cecina
Val di Cornia
Livomese
LIVORNO
Collesalveti
Santa Luce
Rosignano
Marittimo Castelle
Marittima
Riparbella
Castelle Marittimo
Guardistallo
Montescudaio
Cecina
Bibbone
Castagneto
Carducci
Monteverdi
Marittimo
Sassetta
SanVincenzo
Suvereto
Campiglia
Marittinea
Piombino
n – Bassa Val di Cecina area
l
– the 2 largest municipalities in the area of Bassa Val di Cecina: Rosignano Marittimo (with high degree of industrial concentration) and Cecina
(with very low level of industrial concentration)
Fig. 1. Studied area of Italy in the study of association of environmental pollution with morbidity and mortality
for chronic-degenerative diseases

ORIGINAL PAPER C. MARABOTTI ET AL.
IJOMEH 2017;30(4)
4
N
STREAMS
S
WE
NE
NW
SW SE
WINDS
chemical factory
energy production factory
urban and industrial waste disposal plant
monitoring stations for sea-water and sediments sampling
monitoring station for air quality
Drain channel
Fine river
Cecina river
Fig. 2. Studied area – Bassa Val di Cecina, Italy

CHRONIC-DEGENERATIVE DISEASES IN POLLUTED AREAS ORIGINAL PAPER
IJOMEH 2017;30(4) 5
residential area; the other 2 were “background” stations,
one placed in the urban area, the other – on the top of a hill,
afewkilometersawayfromboththecitycenterandindus-
trial plants. Data was available for the years 2002–2010.
Levels of particulate matter (which contains particles of di-
ameter≤10mm(PM10)anddiameter≤2.5mm(PM2.5)),
ozone,nitrogendioxide(NO2),nitrogenoxides(NOx), sul-
furdioxide(SO2)andcarbon monoxide (CO) weremoni-
tored. It is relevant to note that PM2.5 were monitored only
byoneofthe “background” stations,farfromboth urban
area and industrial plants.
Due to the low potential exposition to ambient pollution,
no permanent air monitoring system is active in Cecina.
In the years 2013–2014, a mobile monitoring station was
placed within the residential area of Cecina [11]. Even
if this period does not correspond to that of the study,
that data could be useful to have a comparison with data
obtained in the neighboring municipality of Rosignano
Marittimo, with higher industrial exposure.
Quality of air was evaluated according to the criteria of
the Directive 2008/50/EC of the European Parliament and
of the Council of 21 May 2008 on ambient air quality and
cleaner air for Europe [18].
Pollution of the sea in front of Rosignano Marittimo was
evaluated by a system of monitoring stations located in
theareaoverlookingthedrainchanneloftheonlychemi-
cal factory declaring pollutants release to water [12].
Water and sediment sampling was extended north-
ward, according to the direction of prevailing streams.
The only southward monitoring station is situated
about12 km southof Cecina. Bothwater and sediment
analyses were available for the years 2002 to 2010. More-
over, in the years 2004 and 2005, a study of metals bioac-
cumulation in water-ltering animals (mussels – Mytilus
galloprovincialis) was performed in the shoals in front of
Rosignano Marittimo [13].
Pollution of groundwater was evaluated during sampling
campaigns performed between 1995 and 2008, in the area
diseases (I60–I69), hypertensive diseases (I10–I15), dis-
eases of arteries, arterioles and capillaries (I70–I78),
Alzheimer and other degenerative diseases of nervous
system (G30–G32), other forms of dementia (F00–F03),
motor neuron disease (G12.2), multiple sclerosis (G35),
chronic lower respiratory diseases (J40–J47), lung diseases
due to external agents (J60–J70).
An indicator estimating the proportion of workers pro-
fessionally exposed to pollutants (in the whole area and
in the 2 largest municipalities) was obtained by relating
the number of subjects employed in industrial activi-
ties with the number of inhabitants. Demographic data
was collected by 2011 Population Census [7]. The num-
berof industrial workerswas obtained by 2011 Industry
Services Census [8]. Both datasets were elaborated by
the National Institute for Statistics (Istituto Superiore di
Statistica – ISTAT).
Pollutants release and detection
Data about the presence of polluting industrial activities
and about the amount of pollutants release (in air, water
and soil) was collected from the European Pollution Re-
lease and Transfer Register (E-PRTR) [9]. Data was avail-
able for the years 2001, 2004 and from 2005 to 2013. Since
development of pollution-related diseases requires time,
emission of pollutants in the same decade of mortality
analysis may be considered as only a general indicator of
pollutants exposure.
Data about air and water contamination was collected
from databases of the Environmental Protection Agency
of Tuscany Region (Agenzia Regionale per la Protezione
Ambientale della Toscana – ARPAT) [10–13] and reports
of the National Research Council (Consiglio Nazionale
delle Ricerche – CNR), Institutes of Geosciences and
Earth Resources and of Biophysics (Pisa, Italy) [14–17].
Air pollution was evaluated, in Rosignano Marittimo,
by 4 permanent monitoring stations [10]. Two of them were
located at the border of industrial plants, neighboring to the

ORIGINAL PAPER C. MARABOTTI ET AL.
IJOMEH 2017;30(4)
6
industrial workers (2.42%). As previously mentioned,
the majority of population (73.12%) was concentrat-
ed in the 2 largest municipalities: Rosignano Marit-
timo had 32 494 inhabitants (15 759 males, 16 735 fe-
males), Cecina had 28 864 inhabitants (13 292 males,
15572 females). Thenumber of industrialworkers was,
respectively, 1199 (3.76% of municipality population)
and285(1.01%ofmunicipalitypopulation)(Figure3).
Mortality rates
Totalmortalityratesinthestudiedareaswerenotsigni-
cantly different, as compared to regional data.
When compared to the Tuscany region, the area of Bas-
sa Val di Cecina showed signicantly higher standard-
ized mortality rates due to mesothelioma (C45), ischemic
heart diseases (I20–I25), other forms of ischemic heart
disease (I20, I22–I25), cerebrovascular diseases (I60–I69)
and Alzheimer and other degenerative diseases of nervous
system (G30–G31) (Table 1). In the municipality of Ros-
ignanoMarittimo, asignicantexcessofmortalityforall
thesegroupsofdiseaseswasconrmed.Onthecontrary,
themunicipalityofCecinashowedonlysignicantlyhigh-
er mortality rates for ischemic heart diseases (I20–I25)
and other forms of ischemic heart disease (I20, I22–I25).
of Bassa Val di Cecina. Sampling of water and sediments
from both the Cecina River and from wells located in
the coastal area were analyzed [14–17]. Pollutants bioac-
cumulationwasalsoassessedinfreshwatershcaughtin
the Cecina River [14].
Quality of the sea and groundwater was evaluated
according to criteria settled by Italian national
law (DM 260/2010) [19].
Statistical analysis
The Chi2 test was used for comparing the mortality rates
for each ICD-10 code between each area and the whole
Tuscany region. For diseases resulting in the excess of
mortality, a post-hoc analysis to evaluate the statistical sig-
nicanceofdifferencesbetweenthe2areaswithdifferent
pollution level was performed.
The95% condenceinterval forthe mortalityrates was
calculated and rates were compared by the z-test. Analy-
ses were performed in the whole population and then
stratiedbygender.Nocorrectionwasmadeformultiple
tests because all analyses were preplanned and of inde-
pendent interest.
Data is presented as count and percentage. Analyses were
performed using SPSS (v. 21, IBM Corp., USA).
RESULTS
Geographic and demographic data
Most of Bassa Val di Cecina is occupied by a coastal
plan crossed by 2 rivers, Cecina and Fine, owing near
the 2 largest communities (Cecina and Rosignano Solvay,
respectively).TheFineRiveris22kmlong;itscourseisall
inside the Bassa Val di Cecina area and no industrial plant
issituatedalongitscourse.TheCecinaRiveris73kmlong;
most of its course is outside the Bassa Val di Cecina terri-
tory. A geothermal power plant and a chemical factory are
located in the upper course of the river.
The area of Bassa Val di Cecina is inhabited by 82 023 peo-
ple (39 404 males, 42 619 females); 1986 subjects were
REST OF BASSA VAL DI CECINA
ROSIGNANO CECINA
industry workers
Areas are proportional to the number of inhabitants.
Fig 3.Inhabitantsandindustryworkersinthearea
of Bassa Val di Cecina, Italy

CHRONIC-DEGENERATIVE DISEASES IN POLLUTED AREAS ORIGINAL PAPER
IJOMEH 2017;30(4) 7
Table 1.Standardizedmortalityratios(SMR)inTuscany,BassaValdiCecina,RosignanoandCecina,Italy,in2001–2010forthediseasesshowingsignicantexcess
in comparison to the reference population
Respondents and area
Standardized mortality ratio
[deaths/100 000 population×year]
(95%CI)
mesothelioma
(C45)
ischemic heart diseases
(I20–I25)
other forms of ischemic
heart diseases
(I20, I22–I25)
cerebrovascular diseases
(I60–I69)
Alzheimer and other
degenerative diseases of
nervous system
(G30–G31)
Total
Tuscany (reference) 1.21 (1.12–1.30) 55.34 (54.81–55.87) 30.96 (30.59–31.33) 53.32 (52.84–53.8) 7.97 (7.79–8.15)
Bassa Val di Cecina 2.51 (1.66–3.36) 65.72 (62.03–69.41) 40.13 (37.4–42.86) 57.16 (53.85–60.47) 9.66 (8.37–10.95)
Rosignano 3.69 (2.11–5.27) 62.40 (56.84–67.96) 36.47 (32.46–40.48) 60.22 (54.9–65,54) 12.36* (10.1–14.62)
Cecina 1.93 (0.59–3.27) 72.95 (66.22–79.68) 45.31 (40.36–50.26) 55.13 (49.63–60.63) 7.57 (5.55–9.59)
Males
Tuscany (reference) 2.11 (1.93–2.29) 79.04 (78.03–80.05) 43.31 (42.59–44.03) 79.04 (78.03–80.05) 7.41 (7.12–7.7)
Bassa Val di Cecina 4.64 (2.9–6.38) 88.33 (81.49–95.17) 52.46 (47.38–57.54) 63.80 (58.16–69.44) 8.38 (6.43–10.33)
Rosignano 6.87 (3.59–10.15) 83.24 (72.94–93.54) 46.97 (39.56–54.38) 66.67 (57.71–75.63) 10.55 (7.2–13.9)
Cecina 3.64 (0.87–6.41) 99.01 (86.24–111.8) 58.59 (49.16–68.02) 61.14 (51.58–70.7) 6.32 (3.26–9.38)
Females
Tuscany (reference) 0.49 (0.41–0.57) 37.77 (37.24–38.3) 22.42 (22.04–22.8) 48.59 (48.01–49.17) 8.20 (7.97–8.43)
Bassa Val di Cecina 0.63 (0.21–1.05) 48.43 (44.59–52.27) 31.51 (28.56–34.46) 51.54 (47.59–55.49) 10.56 (8.81–12.31)
Rosignano 0.94 (0.18–1.7) 46.09 (40.4–51.78) 28.83 (24.5–33.16) 54.60 (48.21–60.99) 13.65 (10.56–16.74)
Cecina 0.52 (0–1.27) 54.38 (47.39–61.37) 36.80 (31.37–42.23) 50.66 (43.99–57.33) 8.21 (5.55–10.87)
ICD-10–InternationalStatisticalClassicationofDiseasesandRelatedHealthProblems,10threvision;CI–condenceinterval.
* p < 0.05 as compared to Cecina.
BoldedissignicantexcessinmortalityratescomparedtoTuscany(reference).

ORIGINAL PAPER C. MARABOTTI ET AL.
IJOMEH 2017;30(4)
8
situated in the municipality of Rosignano Marittimo: 6 of
them in the close proximity of the urban settlement, while
theremainingone(theurbanwastelandll)issituatedin
avalley10kmawayfromtheurbancommunity.
Pollutants release
Mean yearly pollutants releases in the municipality of
Rosignano Marittimo (as obtained by E-PRTR database)
are reported in the Table 2.
Release to air: chemical factories released, yearly,
large amounts of carbon monoxide and carbon di-
oxide, ammonia, non-methane volatile organic com-
pounds, hydrochlorofluorocarbons and nitrogen oxides.
For 3 years (2001, 2004 and 2007) one chemical plant
declaredthe release of84kg,48kgand16kgofmer-
cury to atmosphere, respectively.
The analysis of data disaggregated by gender showed, in
RosignanoMarittimo,asignicantexcessinmortalityfor
mesothelioma in males and for ischemic heart diseases,
other forms of ischemic heart disease and Alzheimer dis-
easeinfemales.InthemunicipalityofCecina,asignicant
excess of mortality for ischemic heart diseases and other
forms of ischemic heart disease was observed in both gen-
ders (Table 1).
Polluting activities
Seven polluting industrial activities are included
in E-PRTR database for the area of Bassa Val di Ce-
cina: 3 chemical production factories, 2 plants for en-
ergy production from fossil fuels (natural gas), 1 plant
for disposal and recovery of industrial and hazardous
waste, 1 landll for urban waste. All polluting sites are
Table 2. Yearly release of pollutants in Rosignano Marittimo (Italy), 2001–2010, as reported in the European Pollutant Release
and Transfer Register (E-PRTR) [9]
Substance
Substance release into environment
(M±SD)
air water soil
Carbonmonoxide(CO)[t/103] 87.83±212.01 0 0
Carbondioxide(CO2) [t/103] 2099.78±249.0 0 0
Ammonia (NH3) [t] 257.11±83.41 0 0
Hydrochlorouorocarbons(HCFCs)[t] 9.31±10.15 0 0
Nitrogenoxides(NOx) [t] 733.56±208.41 0 0
Nitrogenoxide(NO)[t] 25.32±14.92 0 0
Non-methanevolatileorganiccompounds(NMVOC)[t] 197.78±118.21 0 0
Arsenic (As) [t] 0 1.94±0.56 0
Mercury(Hg)[kg] 16.44±29.96 88.09±49.07 0
Cadmium(Cd)[kg] 0 108.44±49.66 0
Lead (Pb) [t] 0 4.17±1.89 0
Chromium (Cr) [t] 0 2.82±1.17 0
Nickel(Ni)[t] 0 1.79±0.83 0
Copper (Cu) [t] 0 2.21±0.82 0
Zinc (Zn) [t] 0 12.97±4.02 0
M – mean; SD – standard deviation.

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IJOMEH 2017;30(4) 9
to the period 1940–1970, when mercury cell electrolysis
was used in chemical industries of the area [12]. High level
ofnickelin sedimentswasthe onlyabnormalparameter
found in the monitoring station located South [12].
Highlevels of chromium,arsenic andnickel were found
in mussels gathered in front of Rosignano Marittimo [13].
As far as groundwater pollution is concerned, high lev-
els of chromium (of natural origin) [14], organic nitrates
(due to the use of organic fertilizers) [17], boron and
mercury [15,16] (both released by chemical and geother-
mal plants situated in the upper course of the river) were
found in water and sediments of the Cecina River basin.
Elevated organic mercury concentrations were also docu-
mentedinseveralshspeciescaughtintheriver(particu-
larly in eels – Anguilla anguilla) [15].
Soil pollution: since industrial plants do not release pol-
lutants to soil, no data has been collected. Partial data is
available only for asbestos contamination; in 2007, the En-
vironmental Protection Agency of Tuscany Region (AR-
PAT) took a census of the sites containing asbestos in
Tuscany. Unfortunately, the resulting database is limited
to public buildings and industrial plants (no informa-
tion is provided about the presence of asbestos in private
buildings) and is only a list of sites, with no indication of
the amount of asbestos in each site [20].
DISCUSSION
This retrospective study reports a signicant excess in
mortality due to ischemic heart diseases, cerebrovascular
disease, Alzheimer disease and mesothelioma in the area
of Tuscany coast with a high concentration of industrial
plants. In the same area, reports of E-PRTR pointed out
the release of considerable amount of pollutants both in
seawater (mostly metals) and in air (nitrous and nitrogen
oxides, ammonia, carbon monoxide and dioxide). Envi-
ronmental monitoring showed critical levels of several
pollutants: PM10 and ozone in air, mercury and other met-
als in seawater and sediments. All pollutants but mercury
Urbanwaste landll releasedlarge amountsof methane
to air on the annual basis. Electric power plants released
carbon dioxide, nitrous oxide and nitrogen oxides.
Release to water: one out of the 3 chemical plants declared
releases of pollutants to water, particularly concerning
heavy and transitional metals. Yearly releases (mean (M)
± standard deviation (SD)) of potentially dangerous met-
als in the evaluated period are reported in the Table 2.
Release of pollutants occurs directly into the sea, through
a drainage sewer, in close proximity to the residential area.
Release to soil: No industrial plant declared pollutant re-
lease to soil.
Environmental pollutants tracing
Air pollution: when compared to European parameters for
ambient air quality, high levels of PM10 (from 2003 to 2006)
and ozone (from 2007 on), expressed both as average an-
nual levels and as absolute number of exceedances, were
detected in Rosignano Marittimo, in the 2 monitoring sta-
tions placed at the borders between industrial and urban
area [10].
No exceeding was reported during the temporary monitor-
ing of air pollution performed in Cecina in 2013–2014 [11].
Water pollution: the analysis of the seawater column
showed, in front of Rosignano, levels of Mercury higher
than the limits settled by national regulations [12]. Simi-
lar values were found in all the sampling stations north-
ward (in the direction of prevailing currents) as well as in
the one situated southward [12].
Thesedimentanalysisintheareaoverlookingtheindustri-
al plants in Rosignano showed levels of mercury, cadmium,
arsenic,chromiumandnickelhigherthanlaw-determined
limits [12]. High levels of metals in sediments were also
found in northward sampling sites, according to the direc-
tion of prevailing sea currents [12]. In 1982, a core sam-
pling study performed on sediments 1.5 nautical miles off-
shore the drain channel showed highly elevated concentra-
tions of mercury at a depth approximately corresponding

ORIGINAL PAPER C. MARABOTTI ET AL.
IJOMEH 2017;30(4)
10
air pollutants were detected in Rosignano Marittimo.
Moreover, in one cohort study, Norwegian men exposed
to nitrogen oxides showed signicantly higher mortality
for ischemic heart disease [28].
AcausallinkbetweenmetalpollutionandAlzheimerdisease
has been hypothesized many years ago, since aluminum de-
posits were detected in neurons of affected patients show-
ingneurobrillarytangle[29].Moreover,prospectiveepide-
miological studies showed that chronic aluminum exposure
wasassociatedwithahighriskofcognitiveimpairment[30].
Similar evidences have been reported also for other metals,
largely released in the area of the study. An altered cerebral
zinc homeostasis is associated with generation of extracel-
lular β-amyloid plaques and neuronal neurobrillary tan-
gles [31], while an increase in non-ceruloplasmin-bound cop-
per has been reported both in animal models and in humans
affected by Alzheimer disease [32]. Finally, both groundwa-
ter arsenic levels and chronic low-level cumulative exposure
to lead (as assessed by bone lead content) appears to be as-
sociated with cognitive decline humans [33,34].
Afurther, althoughindirect, possible link between envi-
ronmental pollution and Alzheimer disease could reside
in the effect of the above reported circulatory abnormali-
ties, potentially responsible of vascular dementia.
A few differences have been observed in mortality rates re-
ported in the 2 largest municipalities of the studied district.
In particular, an increased mortality for mesothelioma, Al-
zheimer disease and cerebrovascular diseases were observed
only in Rosignano Marittimo, while both municipalities
shared an increased mortality due to ischemic heart disease.
Acausal link betweenproximity toindustrial plantsand
mesothelioma seems conrmed by the presented data,
showing increased mortality for mesothelioma only in
the industrialized area of Rosignano Marittimo. In this
area, almost 4% of residents is employed in industrial
activities and may represent a subset at the highest risk
of contracting an asbestos-related illness. As known,
mesothelioma may develop after a long latency after
(both in the sea and freshwater) were more elevated in
the industrialized area of Rosignano Marittimo.
Several mechanisms could support a possible pathogene tic
link between environmental pollution and the increased
mortality rates for these illnesses.
On the one hand, the wide use of asbestos in industry,
as a component of tools for thermal insulation, is a well-
known strong risk factor for mesothelioma, so that this
type of pleural cancer has been recognized as an accurate
indicator of asbestos contamination [21]. On the other
hand, pollution due to transitional and heavy metals (re-
leased in large amounts in seawater by chemical plants
situated in Rosignano Marittimo, and objectively detected
both in water and sediments) could contribute to explain
the increased mortality from both Alzheimer disease and
cardiovascular diseases.
The hypothesis that metal environment contamination
mightrepresent acommon risk factor for thisheteroge-
neous group of diseases deserves a few comments.
Strongepidemiological studies supporta causal link be-
tween chronic environmental exposure to xenobiotic
metals (arsenic, lead, cadmium and mercury) and cardio-
vascular morbidity [22,23]. All heavy metals may reduce
antioxidant cellular pool, increasing the intracellular con-
centration of reactive oxygen species and promoting lipid
peroxidation and both cell membrane and DNA damages.
Moreover, some heavy metals may also affect tradition-
al cardiovascular risk factors. For instance, chronic lead
overload (both evaluated by its blood and bone levels) is
associated to arterial hypertension and dyslipidemia [22].
Asaresult,anincreaseinvascularinammationanden-
dothelialdamage markers[24] and early carotid athero-
sclerotic changes [25] have been reported in chronically
exposed subjects to heavy metals.
A possible role of air-released pollutants may also be sup-
posed. Actually, previous studies showed that cardiovas-
cular morbidity and mortality are related to both particu-
late matter and ozone [26,27]; high levels of both these

CHRONIC-DEGENERATIVE DISEASES IN POLLUTED AREAS ORIGINAL PAPER
IJOMEH 2017;30(4) 11
bescrutinizedinfuturestudies, signicant differencesin
socio-economic status (as expressed by the Social and Ma-
terial Vulnerability Index), calculated by ISTAT [36] have
not been observed between the 2 municipalities of Rosig-
nano Marittimo and Cecina.
ACKNOWLEDGMENTS
Authors wish to thank Antonio Lombardi and Maria Gloria
Marinari (Prevention Department, AUSL 6, Leghorn, Italy)
andSalvatoredeMasi(EpidemiologyUnit,OspedalePediatri-
co Meyer, Florence, Italy) for their support in collecting epide-
miological data.
Authors particularly appreciated the invaluable contribution of
Fabrizio Bianchi (Environmental Epidemiology, CNR Institute
of Clinical Physiology, Pisa, Italy) to the interpretation and dis-
cussion of results.
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