Download Risk Assessment due to Environmental Exposure to Fibrous

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