1. Chinese Benzene Cohort Study
74,828 exposed and 35,805 unexposed workers
Leukemia deaths: RR 2.3, 95% CI
Malignant lymphoma deaths: RR 4.5, 95% CI
No deaths from multiple myeloma in either population

5. Wong and Raabe, 2000

6. Meta-Analysis of Risk of Multiple Myeloma in Petroleum Workers
22 cohort studies of >250,000 workers
deaths expected; 205 observed
SMR 0.93; 95% CI
Bergsagel et al; Blood, 1999
Metr

7. Nested Case Control Study of Multiple Myeloma and AML
>18,000 petroleum distribution workers
Up to 5 controls for each of 11 cases with multiple myeloma and 13 with AML
Cumulative mean exposure (ppm-yrs THC):
MM 672; controls 800
AML 773; controls 837
Wong, Trent & Harris, 1999

8. Why is it harder to find an elevated SMR for MM than for AML in benzene-exposed cohorts?
Benzene does not cause MM
Benzene is a relatively less potent myelogen than it is a leukemogen
Benzene is as or more potent a myelogen than it is a leukemogen, but the background incidence of MM is less than AML
The latency period for MM is longer than for AML

10. Healthy Worker Effect: Reasons Specific to Hematopoietic Cancer
Acute Myelogenous Leukemia
Down’s syndrome, Fanconi’s anemia, etc
Status post cancer chemotherapy
Non-Hodgkin’s Lymphoma
HIV AIDs
Immune suppression diseases or therapies

11. Exposure Dose Relationships in Determining Causality
Is this a useful approach when there are only small numbers and borderline statistical significance?

12. Challenges to Epidemiological Identification of Environmental Causes of Cancer
Cancer as a final common pathway
Unknown susceptibility factors
Uncertain exposure levels
Powerless negative
Cluster fallacy

14. Different Levels of Certainty Required for Decisions
SCIENTIFIC (p < .05)
TORT (p < .50)
REGULATORY (p = whatever)

15. Is Relative Risk Greater Than Two Required for Proof of Causation
Is Relative Risk Greater Than Two Required for Proof of Causation? (Carruth and Goldstein, 2001)
Threshold: Required to support inference of causation 12
Threshold: Determinative of ultimate issue 2
Not required for inference of causation 14
Sufficient for inference of causation (not clear if required) 1
Total # of published decisions 29

16. Total # of published cases 11 10
Is Relative Risk Greater Than Two Required for Admissibility? (Carruth and Goldstein, 2001) 21
Total # of published cases 11
Not required for admissibility 10
Required for admissibility

17. Required 10 Not Required 5 6 Not Considered 9 1
Cases Before and After Daubert II Addressing Whether Relative Risk Greater Than Two is Required for Admissibility of Causation Opinion
Before
Daubert II
Daubert II
and After
Required 10
Not Required 5 6
Not Considered 9 1

18. Inadequate exposure data Dilution of high risk group
Shortcomings of Occupational Epidemiology for Establishing an Odds Ratio for a Specific Risk
Healthy worker effect
Inadequate exposure data
Dilution of high risk group
Appropriateness of time period