Risk Assessment due to Risk Assessment due to Environmental Exposure to Environmental Exposure to

Fibrous Particulates in Fibrous Particulates in Taconite OreTaconite Ore

Richard WilsonRichard WilsonHarvard UniversityHarvard University

Cambridge, MassachusettsCambridge, Massachusetts

RP Nolan & CW AxtenRP Nolan & CW AxtenEnvironmental Sciences LaboratoryEnvironmental Sciences Laboratory

Brooklyn College of The City University of New YorkBrooklyn College of The City University of New YorkBrooklyn, NYBrooklyn, 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 Origin of the ProblemProblem

Map of N. E. MinnesotaMap of N. E. Minnesota

Disposal of Taconite Tailings in Disposal of Taconite Tailings in Lake SuperiorLake Superior

67,000 tons in 67,000 tons in 700 million gallons of water 700 million gallons of water

each dayeach day

15,000 - 20,000 lb/hour of 15,000 - 20,000 lb/hour of Particulate MatterParticulate Matter

Initial ConcernInitial ConcernEcological Ecological

ImpactImpact

Fiber Size Distribution for Duluth

Drinking Water SamplesMean Length 1.98µmRange 5-10µm 6.3%

≥ 10µm 0.8%Mean Width0.3µm

Cook et al. 1976

June 8, 1973June 8, 1973Grunerite Fibers in Drinking WaterGrunerite Fibers in Drinking Water

leads to a leads to a

Potential for Asbestos-Related GI Potential for Asbestos-Related GI CancerCancer

Exposure to Asbestos among Exposure to Asbestos among

insulation workers have increased insulation workers have increased risk of GI Cancerrisk of GI Cancer

(Dr Gamble’s presentation puts this (Dr Gamble’s presentation puts this to rest)to rest)

Talc -Treated rice might be Talc -Treated rice might be etiological in Stomach Canceretiological in Stomach Cancer

Mesliss 1971Mesliss 1971

Japanese have higher Japanese have higher stomach cancer incidencestomach cancer incidence

Etiological-Etiological-Amphibole Asbestos in Talc ?Amphibole Asbestos in Talc ?

Public Health Cancer (1970)Public Health Cancer (1970)Latency Period for Asbestos-Related Latency Period for Asbestos-Related

DiseaseDisease

may lead to an unnoticed build-up may lead to an unnoticed build-up of the carcinogen in the of the carcinogen in the

EnvironmentEnvironment

This has not happenedThis has not happened

Dr. Arnold Brown, the Principal Court-appointed expert opined:

“…that no adverse health consequencescould be scientifically predicted on thebasis of existing medical knowledge.”

If the distribution of If the distribution of fiber type, size and shape fiber type, size and shape

is identical in the is identical in the occupational occupational

epidemiological studies epidemiological studies and in the environmental and in the environmental

samples of interest, samples of interest, extrapolation to low extrapolation to low

doses is comparatively doses is comparatively simple simple

The Length and Diameters of the Taconite fibersare not

Consistent with the Population ofRespirable 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 Pathogenicity of Long Vs. Short Fibers Fibers

Samples of Amosite Asbestos in Rats Samples of Amosite Asbestos in Rats

Davis et al. Br. J. Exp. Path (1986)Davis et al. Br. J. Exp. Path (1986)

(see also Dr. McConnell’s discussion (see also Dr. McConnell’s discussion for ingestion in animals)for ingestion in animals)

12 Months of Inhalation ExposureLong: Widespread Pulmonary FibrosisShort: No Fibrosis

Tumor Type

Lung Cancer

Mesothelioma

PleuralPeritoneal

Amosite

Long

27%

Short

0%

Controls

1.7%

5%2.5%

0%2.4%

0%0%

Experimental Animal Study

Experimental Animal Study

Size Distribution Short and Long Amosite

Concentration at Site No 7(Oct-Dec 1998)(Nearest to community)

By TEM

178 liters measured19 taconite fibers > 5µm61 taconite fibers total

Mean Concentration

0.00034 f/mL Total0.00011 f/mL > 5µm± 0.00003

Lower end of Axten’s list

This concentration is small andThis concentration is small and I could stop here.I could stop here.

But I will underline the issue.But I will underline the issue.

Risk Coefficients. (K)(Continuous Exposure)

Effect = K x CWhere 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 non-linearity (also Brown & others earlier)

Risk coefficient Kml/f-yr

OSHA

NAS MS

NAS MNS

IRIS

LASH

CAMUS(Chrysotile)

HODGSON(Amphibole Asbestos)

0.01

0.0022

0.001

0.0033

0.0026

0.0003

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

Lower if non-linear at low concentrations

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

slopeassuming linearity

Conc.

NaturalEffect

datum

IncrementalConc.

Why not do a DNA matching analysis on:

Asbestos Lung CancerNatural 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 perlifetime calculated pessimistically.

This can not be done consistently. Attempts areinherently 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 ~ 10-4