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Risk Assessment due to Environmental Exposure to Fibrous Particulates in Taconite Ore Richard Wilson Harvard University Cambridge, Massachusetts RP Nolan & CW Axten Environmental Sciences Laboratory Brooklyn College of The City University of New York Brooklyn, NY Problems with Risk Assessment Direct data at present levels impossible to attain. Historical cohorts had risk ratio ≈ 5 Present estimated risk ratio ≈ 1.002 If Risk Ratio < 2 in epidemiology studies are not believed, unless same material gives higher Risk Ratio with a higher dose. Then RR ~ 1.3 is often believed (air pollution; second hand cigarette smoke; Childhood leukemia's caused by in utero X ray) But RR < 1.05 would NOT be believed Origin of the Problem Map of N. E. Minnesota Disposal of Taconite Tailings in Lake Superior 67,000 tons in 700 million gallons of water each day 15,000 - 20,000 lb/hour of Particulate Matter Initial Concern Ecological Impact Fiber Size Distribution for Duluth Drinking Water Samples Mean Length 1.98µm Range 5-10µm ≥ 10µm Mean Width 0.3µm 6.3% 0.8% Cook et al. 1976 June 8, 1973 Grunerite Fibers in Drinking Water leads to a Potential for Asbestos-Related GI Cancer Exposure to Asbestos among insulation workers have increased risk of GI Cancer (Dr Gamble’s presentation puts this to rest) Talc -Treated rice might be etiological in Stomach Cancer Mesliss 1971 Japanese have higher stomach cancer incidence EtiologicalAmphibole Asbestos in Talc ? Public Health Cancer (1970) Latency Period for Asbestos-Related Disease may lead to an unnoticed build-up of the carcinogen in the Environment This has not happened Dr. Arnold Brown, the Principal Court-appointed expert opined: “…that no adverse health consequences could be scientifically predicted on the basis of existing medical knowledge.” If the distribution of fiber type, size and shape is identical in the occupational epidemiological studies and in the environmental samples of interest, extrapolation to low doses is comparatively simple The Length and Diameters of the Taconite fibers are not Consistent with the Population of Respirable Amphibole Asbestos Used in experimental animal studies Question that should be answerable What is the concentration at the place of interest? What is the carcinogenic potency ( at high concentrations) For the taconite fibers? (or other postulated agent?) Question that are hard to answer Are some asbestos fibers worse or better then others? What is the relative potency of a cleavage fragment? How does one extrapolate to low doses? What indirect data can be used? Animal Data In Vitro Data Surface Chemistry Biopersistence in Target Tissue (including such issues as splitting) DNA Tests Our subject is Interdisciplinary “Definitions are important” If it moves – it is Biology If it stinks – it is Chemistry If it Doesn’t work – it is Physics If it sends you to sleep – it is Statistics Pathogenicity of Long Vs. Short Fibers Samples of Amosite Asbestos in Rats Davis et al. Br. J. Exp. Path (1986) (see also Dr. McConnell’s discussion for ingestion in animals) Experimental Animal Study 12 Months of Inhalation Exposure Long: Widespread Pulmonary Fibrosis Short: No Fibrosis Amosite Tumor Type Long Short Controls Lung Cancer 27% 0% 1.7% 5% 2.5% 0% 2.4% 0% 0% Mesothelioma Pleural Peritoneal Experimental Animal Study Size Distribution Short and Long Amosite Concentration at Site No 7 (Oct-Dec 1998) (Nearest to community) By TEM 178 liters measured 19 taconite fibers > 5µm 61 taconite fibers total Mean Concentration 0.00034 f/mL Total 0.00011 f/mL > 5µm ± 0.00003 Lower end of Axten’s list This concentration is small and I could stop here. But I will underline the issue. Risk Coefficients. (K) (Continuous Exposure) Effect = K x C Where C is in (f/mL) – yrs Which is the concentration in f/ml for an 80 yrs exposure Low Dose Behavior Slope in Measurable Range depends on internal or external control. Evidence for Non- Linearity depends using external control for lowest point (Limited). Problem comparing asbestos workers & rest of population (different smoking habits) Low Dose Linearity Lash et al. allow the intercept ( ratio of internal to external control) to vary & find linearity fits. Hodgson does not allow intercept to vary and finds nonlinearity (also Brown & others earlier) Risk coefficient K ml/f-yr OSHA NAS 0.01 MS 0.0022 NAS MNS 0.001 IRIS 0.0033 LASH 0.0026 CAMUS (Chrysotile) 0.0003 HODGSON (Amphibole Asbestos) 0.0025 Site No 7 / Risk (Lifetime) OSHA 7.5 x 10-5 IRIS 2.5 x 10-5 NAS (smoker) 1.8 x 10-5 NAS (non smoker) 0.8 x 10-5 LASH 2.3 x 10-5 CAMUS 3 x 10-6 HODGSON 0.23 x 10-5 Mereweather (1938) asked: Is it asbestos Itself that Causes Lung Cancer Or Is it the Asbestosis that is the Proximate Cause? (cf. Benzene – Pancytopenia; Arsenic – Dyspigmentation or keratosis) Still not definitely answered (Dr Kane yesterday). Julian Peto raised the linearity issue in 1988 Richard Doll accepted it (even in Sept. 2002) General argument by Guess, Crump, Peto (Richard) If medical outcome is indistinguishable from a naturally occurring outcome (& the asbestos acts at one stage in the process similarly to natural agents) then Taylor’s theorem says there is low (incremental) dose linearity Effect Incremental Effect slope assuming linearity datum Natural Effect Conc. Incremental Conc. Why not do a DNA matching analysis on: Asbestos Lung Cancer Natural Lung Cancer Smoking Lung Cancer Are they really indistinguishable? (cf. Janet Rowley compared DNA of AML naturally occurring and as a consequence of radiotherapy) US EPA (simplified) 1980: tried to regulate risks of 1 in 1,000,000 per lifetime calculated pessimistically. This can not be done consistently. Attempts are inherently arbitrary and capricious. 1990: EPA back off to 1 in 10,000 per lifetime. 2000: Spend $ 5.1 million to avoid a “statistical death” (arsenic rule). Other Lifetime Risks > 10-4 Smoking 0.3 Obesity ≈ 0.3 Car accidents ~ 0.02 Particulate Air Pollution ~ 0.01 Nuclear War ~ 0.01 Worst case Natural Outcroppings of Cleavage Fragments ~ 0.0001