Impatto dei metalli pesanti sul sistema nervoso: dal neuro- sviluppo alle patologie neurodegenerative Prof.Roberto Lucchini Medicina del Lavoro, Universita’ di Brescia [email protected]Icahn School of Medicine at Mount Sinai, New York [email protected]
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Impatto dei metalli pesanti sul sistema nervoso: dal neuro-
sviluppo alle patologieneurodegenerative
Prof.Roberto Lucchini Medicina del Lavoro, Universita’ di Brescia
Ferroalloy production (Si-Mn, Fe-Mn, Fe-Cr) Exposure ⇒ Mn (MnO2, Mn3O4), Fe, Pb, Zn, Cu, Cr, Cd
Luria Nebraska Motor Battery
Recent 5 Year Average Respirable Exposure (ug Mn/m3)
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Figure 23: Dose Response Relationship between LURIA Thumb and Fingers and ExposureSubgroup: Workers That Consume More Than 23.75 Grams Of Alcohol Per Day
Adjusted For Average Number of Cigarettes per day and Number of Children
LinearPowerWeibullLog-logistic
Lucchini et al. Long Term Exposure To “Low Levels” Of Manganese Oxides And Neurofunctional Changes In Ferroalloy Workers.
Long Term Exposure to “Low Levels” of Manganese OxidesAnd Neurofunctional Changes in Ferroalloy Workers
Roberto Lucchini, Pietro Apostoli, Carmine Perrone, Donatella Placidi, Elisa Albini, PieraMigliorati, Donna Mergler, Marie-Pascale Sassine, Silvana Palmi, Lorenzo Alessio
BMCL05’s & NOAELsARE ARE5
HealthCanada 2010 RfC
HealthCanada 2010 RfC
0
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SPES finger t
appin
g/DH
LN thum
b-fingers
/NDH
LN sum
LN sum
LN thum
b-fingers
/NDH
LN thum
b-fingers
/DH
LN hand c
lench/D
H
SPES dig
it sp
an/mea
n
LN
hand c
lench/N
DH
SPES additi
ons/m
ean
SPES dig
it sp
an/hig
h
SPES finger t
appin
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serum
pro
lactin
bm
cl0
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bmcl minimum estimatebmcl maximum estimateNOAEL estimate
HealthCanada 2010 RfC
HealthCanada 1994 RfC
0.05
0.11
Prevalence of Parkinsonism
15
Sellero plant (1950-85)
Breno plant
(1902-01)Darfo plant (1930-95)
GardaLake
(ref area)
Bagnolo M plant
(1970-present)
Mn exposure from ferroalloy emission
Study site Cases Population Stand prev
Bayesian SMR
Valcamonica 324 77,708 492 1.25
Rest of the Province 2,353 826,289 321 1.00
Total Province 2,677 903,997 407
Average ITA-EU 150
SMR = 1.58; CI=1.41-1.76
Lucchini et al., High Prevalence Of Parkinsonian Disorders Associated To
Manganese Exposure In The Vicinities Of Ferroalloy Industries.
Am J Ind Med 2007; 50: 11: 788-800
SMR Parkinsonism vs. Mn in dust p=0.005
Parkinson’s Disease
Pathological hallmarks:
1. degeneration of dopaminergic neurons of pars compacta of the substantia nigra
2. accumulation of alpha-synuclein protein in the form of Lewy bodies
Wirdefeldt et al Epidemiology and etiology of Parkinson's disease: a review of the evidence
Eur J Epidemiol. 2011 Jun;26 Suppl 1:S1-58
Fibrils of α-synuclein deposited in the neuronal body form round lamellated eosinophilic cytoplasmic inclusions, Lewy bodies cause neuronal degeneration and death