Lo stato attuale delle conoscenze sugli effetti sanitari dell amianto. Rodolfo Saracci. CNR- Istituto Fisiologia Clinica Pisa

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1 Lo stato attuale delle conoscenze sugli effetti sanitari dell amianto Rodolfo Saracci CNR- Istituto Fisiologia Clinica Pisa

2 A Effetti cancerogeni dell amianto B Tre specifici punti : - la relazione amianto-mesotelioma - i meccanismi della cancerogenesi - il ruolo di possibili cofattori

3 The IARC Monographs Consensus evaluations of the weight of the evidence that an agent can increase the risk of cancer in humans Approximately 900 agents evaluated since carcinogenic to humans 110 2A - probably carcinogenic to humans 64 2B - possibly carcinogenic to humans 243 National and international health agencies use the Monographs As a source of information to identify potential carcinogens As scientific support for their actions to prevent cancer

4 IARC Monographs on Asbestos Asbestos Serpentines Chrysotile (White asbestos) Amphibole s Actinolit Amosite Anthophyllite Crocidolite Tremolite (Brown asbestos) (Blue asbestos)

5 IARC Monographs on Asbestos Actinolite, amosite, anthophyllite, chrysotile, crocidolite, tremolite Vol 2, 1973: sufficient evidence in humans, sufficient evidence in animals (1) Vol 14, 1977: sufficient evidence in humans, sufficient evidence in animals (1) Suppl 7,1987: sufficient evidence in humans, sufficient evidence in animals, 1

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7 IARC Monographs, Volume 100 A Review of Human Carcinogens Scope of volume 100 Update the critical review for each carcinogen in Group 1 Identify tumour sites and plausible mechanisms Compile information for subsequent scientific publications The volume was developed over the course of 6 meetings A. Pharmaceuticals (23 agents, Oct 2008) B. Biological agents (11 agents, Feb 2009) C. Metals, particles and fibres (14 agents, Mar 2009) D. Radiation (14 agents, June 2009) E. Lifestyle factors (11 agents, Sept 2009) F. Chemicals and related occupations (34 agents, Oct 2009)

8 Asbestos: Mesothelioma and lung cancer, V100C The epidemiologic evidence has only strengthened over time and there is currently overwhelming evidence that all commercial forms of asbestos fibers are causally associated with an increased risk of mesothelioma and lung cancer. There are still current controversies about the extent to which there are potency differences for the particular forms of asbestos (i.e. chrysotile versus amphiboles) and sizes (i.e. long and thin fibers). However, these issues do not alter the fundamental conclusion that the epidemiologic evidence indicates that all forms and sizes of commercial asbestos fibers are carcinogenic to humans.

9 Chrysotile and cancer recent epidemiological evidence Cohort of 5782 workers of 4 textile plants in NC, USA, followed-up Lung cancer SMR 2.0 (95%CI ), mesothelioma SMR 11.1 (95%CI ); RR increased with time since first employment and duration of employment (Loomis et al, 2007) Cluster of 14 mesothelioma cases among workers who were active in the Balangero mine, Italy, and 13 among other people exposed to Balangero chrysotile adds further evidence to the carcinogenicity of tremolite-free chrysotile (Mirabelli et al, 2008). Cohort of 3072 workers of 1 textile plant in SC, USA, followedup Lung cancer was most strongly associated with exposure to thin (< 0.25 μm) and longer (> 10 μm) fibers (TEM) (Stayner et al, 2008)

10 crocidolite crocidolite & chrysotile chrysotile amosite mixed

11 Exposure to asbestos and mesothelioma mortality in UK Adapted from Hodgson et al, 2005

12 Relazione esposizione-mesotelioma

13 La relazione tra rischio di mesotelioma ad un tempo t (eta o tempo trascorso dall inizio dell esposizione) e caratteristiche dell esposizione : 4 Risk ( t) = 1 exp{ t exp[ 4( a + b1 x1 + b2 x b n x n )]} x 1 x 2 = intensity of exposure = duration of exposure x. =.

14 4 Risk ( t) = 1 exp{ t exp[ 4( a + b1 x1 + b2 x b n x n )]} ln( ln(1 Risk )) = 4ln t ( a + b x + b x b x n 1 n ) ln (Risk) ln t

15 Rischio di mesotelioma nella popolazione di Wittenoom, Australia (de Klerk NH et al.,2012) RISK yrs. since start of exposure

16 Accelerated Failure Time (AFT) : accelerazione del tempo dell evento (comparsa del mesotelioma) RISK anticipation of cases increase in risk yrs. since start of exposure

17 Il rapporto causale individuale: attribuire una causa a un caso In generale (Greenland S & Robins JM, 2000) si puo considerare che la frazione attribuibile (% calcolato di casi attribuibili all esposizione) rappresenti un limite inferiore della probabilita che l esposizione sia effettivamente causale nel caso in esame, ma non un limite superiore, che puo essere 100% come, ad esempio, nella situazione in cui tutti i casi osservati tra gli esposti sono stati accelerati

18 Meccanismi della cancerogenesi

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22 Possibili co-fattori

23 Table 4. Observed and predicted familial mesothelioma cases

24 Conclusioni

25 Gradi dell evidenza di causalita Evidenza scientifica in linguaggio corrente 1. Definita e [praticamente] certo che. 2. Consistente e probabile che 3. Dubbia e [forse] possibile che 4. Lacunosa/inesistente e stato suggerito che

26 Gradi dell evidenza di causalita per il mesotelioma 1. [Praticamente] certo : ruolo causale di tutte le varieta di amianto 2. Probabile : forma e coefficienti della relazione del rischio con intensita e durata di esposizione e latenza dell effetto ; relazione con la geometria delle fibre [Forse] possibile : diminuzione del rischio a molto lungo termine ; ruolo/i delle proprieta di superficie delle fibre; 4. Suggerito :co-fattori (?) ; una varieta di natura speculativa di meccanismi

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