EPA/600/A-97/043
I
EPA'S UPDATE OF THE CARCINOGENIC RISK ASSESSMENT
ON BENZENE
-OFFICE OF MOBILE SOURCES
-NEW DATA SINCE EPA'S 1985 ANALYSIS
EPIDEMIOLOGY
MODE OF ACTION
REANALYSIS OF EXISTING
EPIDEMIOLOGIC DATA

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WHAT WAS DONE BY EPA IN 1985
-WEIGHT OF EVIDENCE = A
-DOSE RESPONSE/RISK EXTRAPOLATION
LINEAR MODEL ON EPIDEMIOLOGIC
DATA
WONG, 1983, UNPUBLISHED
OTT ET AL., 1977
RINSKYET AL., 1981
GEOMETRIC MEAN OF MAXIMUM
LIKELIHOOD ESTIMATES

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U.S. EPA, 1985
RISK DUE TO LIFETIME 1 PPM BENZENE EXPOSURE BASED UPON
COMBINED OTT ET AL., 1977, WONG, 1983, UNPUBLISHED, AND
RINSKY ET AL., 1981 COHORTS FOLLOWED FROM 1940 TO 1978.
UNit msK = 2.6 x 10(-2)/PPM
MLE

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QUESTIONS FOR EPA'S 1997 UPDATE ANALYSIS
-WOULD WE DO DOSE-RESPONSE ANALYSIS
DIFFERENTLY?
BECAUSE OF NEW EPIDEMIOLOGIC DATA
BECAUSE OF BETTER UNDERSTANDING
OF MODE OF ACTION
BECAUSE OF PROPOSED NEW CANCER
RISK ASSESSMENT GUIDELINES

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BENZENE EPIDEMIOLOGIC STUDIES
Bond et al., 1986	Leukemia in chemical workers exposed to benzene
Wong, 1987	Leukemia in chemical workers exposed to benzene
Rinsky et al., 1987	Leukemia in Pliofilm workers
Yin et aL, 1989	Leukemia in Chinese factory workers exposed to benzene.

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LEUKEMIA CASES IN CHEMICAL WORKERS EXPOSED TO
BENZENE (BOND ET AL., 1986)
CASE NO.
YRS. OF EXPOSURE
CUMULATIVE EXP.
EST. IN PPM-YRS.
AVERAGE EXP./YR.
(PPM)
1.
10.7
54
5.0
2.
1.5
1.5
1.0
3.*
5.0
25
5.0
. 4.
19.5
350
17.9
5.
23.3.
28
1.2
~Underlying cause of death listed as pneumonia

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RELATIVE RISKS OF LYMPHATIC AND HEMATOPOIETIC CANCER COMBINED
AND LEUKEMIA SEPARATELY BY SELECTED CUMULATIVE EXPOSURE
CATEGORIES OF CHEMICAL WORKERS EXPOSED TO BENZENE (WONG, 1987)
CAUSE OF DEATH
CUMULATIVE EXPOSURE
(PPM-YEARS)
DEATHS
RR
CHI-SQUARE
FOR TREND
Lymphatic and
Less than 15
5
2.1

hematopoietic
15-60
5
2.95

cancer
Over 60
¦ ' 5
3.93
5.42*
Leukemia and
Less than 15
2


aleukemia
15 -60
1
Undefined
6.46*

< Over 60
3

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LEUKEMIA CASES IN CHEMICAL WORKERS EXPOSED TO
BENZENE (WONG,1987)
CASE NO.
YRS. OF EXPOSURE
CUMULATIVE EXP.
EST, IN PPM-YRS.
AVERAGE EXP./YR.
(PPM)
1.
9.9
43.7
4.4
2,
14.9
113.4
7.6
3.
5.8
10.0
1.7
4.
12.2
61.0
5.09
5.
1 *2 ^
0.6
0.5
6.
29.2
70.8
2.4
7.
1.4
N.A.
N.A.
4 cases-lymphatic; 2 cases-chronic myeloid; 1 case-acute leukemia

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RELATIVE RISK (SMR) AS A FUNCTION OF CUMULATIVE
EXPOSURE (ADAPTED FROM RINSKY ET AL., 1987)
CUMULATIVE EXPOSURE (PPM-YRS)
SMR
0-40
I-1
40 - 200
3.2
200-400
11.9*
Over 400
66.4*
^significant 95% confidence

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STANDARD MORTALITY RATIOS FOR CANCER
MORTALITY IN CHINESE WORKERS FROM
HEMATOPOIETIC MALIGNANCY BY CUMULATIVE
BENZENE EXPOSURE (HAYES ET AL., 1996)
CUMULATIVE
EXPOSURE
(PPM-YEARS)
NO. CASES
RELATIVE RISK
<10
9
¦ 2.5 ¦
10-39
8
2.1 : ••• ;•
40-99
10
2.9
100-400
18
3.1
>400
9
2.0
Total	54 x

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DEATHS FROM LEUKEMIA BY CUMULATIVE
EXPOSURE IN CHINESE BENZENE WORKERS
(YIN ET AL., 1989)
CUMULATIVE EXPOSURE
NUMBER
(PPM-YEARS)

Under 40
7
40 to 200
4
Over 200
19
Total
30

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RANGE OF UNIT RISK ESTIMATES CALCULATED ON PLIOFILM
WORKER COHORT BASED ON EXPOSURE ESTIMATES BY
PAUSTENBACH AND CRUMP, LINEAR VERSUS NONLINEAR
(CRUMP, 1992).
EXPOSURE	LINEAR	NON-LINEAR
ESTIMATES	(1 ppm)	(1 ppm)
Crump/Allen
l.lxl0(-2)
to
2.5xl0(-2)
5.4x10(-3) to
2.5xl0(-2)
Paustenbach
7.1xl0(-3)
to
1.5xl0(-2)
8.6x10(-5) to
6.5x10(-3)
U.S. EPA 1985a
1.8xl0(-2)
to
4.1xl0(-2) (Crump/Allen)

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METABOLISM
GENOTOXICITY
-CHROMOSOMAL EFFECTS
-POINT MUTATIONS
-DNA ADDUCTS

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CONCLUSIONS
-UNCERTAINTIES IN DOING DOSE-RESPONSE
ANALYSIS,
.SHOULD THE UPDATED EPIDEMIOLOGIC
DATA BE USED?
.MODE OF ACTION
.SELECTION OF APPROPRIATE RISK
ASSESSMENT MODEL
-COMPLEX NATURE OF RISK ASSESSMENT
-NEXT STEPS

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I
TECHNICAL REPORT DATA
(Pleat rtod initru(tk>ni cm the nvcn* before comple/tnt
	—t
. 			 i
1 WW6I0O/A-97/O43
3, *f
4, TITLE AND SUBTITLE
EPA1s Update of the Carcinogenic Risk Assessment on
Benzene
8 «€PORT OAT f •
March 1997
e. MS'OIMiNfl 0*0»MI2ATION COOf I
EPA/600/021 |
7. AUTWOrt(S)
David Bayliss, NCEA-WA, ORD, USEPA
«. PfiRfOR^INO ORGANIZATION X£>OHT MO.
NCEA-W-0253
6, PtHFORMINC ORGANIZATION NAM! ANO ADDRESS
NCEA-WA, ORD, USEPA (Mail Code 8623)
401 M Street, S.W.
Washington, D.C. 20460
10. fROQHAW ELCMt^t NO
1 1 €
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