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OCR for page 177
Issues in Risk Assessment
DATA
Twelve of the candidates were already included in the CPDB and in Krewski's study (upper portion of Table G-2). For two other agents (benzo[a]pyrene and 1, 3-butadiene), the committee identified dose--response data that could be analyzed quantitatively (Tables G-3 and G-4). For another agent (vinyl chloride), the committee identified an ingestion study that gave results (Table G-5) markedly different from those of the inhalation study included in the first part of Table G-2. The ingestion study (Feron et al., 1981) appears to have met the inclusion criteria of the CPDB, and it is not clear why it was not included in the CPDB. The data in Tables G-3, G-4, and G-5 were analyzed by Krewski with the same methods as those used in his workshop paper, and the resulting estimates of TD50 are tabulated in the lower portion of Table G-2.
For four agents listed in Table G-1, comparable numerical estimates of carcinogenic potency could not be obtained, for the following reasons:
Dimethyl sulfate. The only reported studies are unsuitable for quantitative analysis, but show tumors at the MDT and MDT/2 (IARC, 1974).
Dibenz[a,h]anthracene. The only reported studies are unsuitable for quantitative analysis (ATSDR, 1990).
Methyl bromide. Data purporting to show induction of forestomach tumors within 90 days (Danse et al., 1984) have been discredited (EPA, 1986; Reuzel et al., 1991).
Plutonium. Dose data on this and other radionuclides are not commensurable with those customarily applied to chemical carcinogens. For plutonium, the radiation dose that causes early death (within 1.5 years) due to radiation pneumonitis and pulmonary fibrosis in animals exposed by inhalation is about 45 Gy (Scott et al., 1990), whereas the TD 50 for animals similarly exposed is 3.3 Gy (Diehl et al., 1992). (In this case, early death is used as the measure of toxicity for the purpose of determining the MTD.)
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Issues in Risk Assessment
TABLE G-2 Deviations from Krewski's Regressions
Gold's Estimate (one-stage, time-corrected)
Krewski's Estimate (one-stage, time-corrected)
Krewski's Case No.
Chemical
MTD
log MTD
TD50
log TD50
Predicted log TD50
Difference
Standardized Difference
TD50
log TD50
Predicted log TD50
Difference
Standardized Difference
2
2-Acetyl-amino-fluorene
10.0
1.00
3.78
0.577
0.835
-0.318
-0.582
3.83
0.583
0.895
-0.312
-0.572
3
Acrylonitrile
5.69
0.755
5.31
0.725
0.647
0.078
0.144
5.61
0.755
0.647
0.102
0.187
1
Benzidine
80.0
1.903
8.99
0.954
1.811
-0.857
-1.571
9.10
0.959
1.811
-0.851
-1.561
3
C.I. Direct Black 38
60.0
1.778
0.945
-0.025
1.684
-1.708
-3.132
0.99
-0.002
1.684
-1.688
-3.095
6
C.I. Direct Blue 6
60.0
1.778
1.18
0.072
1.684
-1.612
-2.955
1.17
0.068
1.684
-1.616
-3.962
8
C.I. Direct Brown 95
75.0
1.875
2.07
0.316
1.782
-1.466
-2.688
2.62
0.418
1.782
-1.364
-2.500
3
CCl4
1650
3.217
114
2.057
3.143
-1.086
-1.991
115.12
2.061
3.143
-1.082
-1.983
3
EDB
28.1
1.449
1.26
0.100
1.350
-1.250
-2.291
5.60
0.748
1.350
-0.608
-1.103
1
ENU
0.429
-3.68
0.904
-0.044
-0.491
0.447
0.820
0.94
-0.026
-0.491
0.464
0.851
2
Ethylene
6.11
0.786
7.43
0.871
0.678
0.193
0.354
7.69
0.786
0.678
0.208
0.381
9
MOCA
34.0
1.531
20.8
1.318
1.434
-0.116
-0.212
21.07
1.324
1.434
-0.110
-0.202
13
Vinyl chloride (CPDB)
0.279
-0.554
14.2
1.152
-0.681
1.833
3.360
33.52
1.525
-0.681
2.206
4.044
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Issues in Risk Assessment
Gold's Estimate (one-stage, time-corrected)
Krewski's Estimate (one-stage, time-corrected)
Krewski's Case No.
Chemical
MTD
log MTD
TD50
log TD50
Predicted log TD50
Difference
Standardized Difference
TD50
log TD50
Predicted log TD50
Difference
Standardized Difference
Chemicals or studies not in the CPDB or in Krewski's analysis
Benzo[a]-pyrene
32.5
1.512
11.70
1.068
1.414
-0.346
-0.634
1,3-Butadiene ()
380
2.580
20.81
1.318
2.496
-1.178
-2.160
Vinly Chloride (CRAM)
14.1
1.149
4.89
0.689
1.046
-0.357
-0.654
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Issues in Risk Assessment
TABLE G-3 1,3 Butadiene*
Dose Rate (mg/kg-d)
Tumor Incidence
Males
Females
Lymphocytic lymphoma
0
2/70
2/70
3.8
1/70
4/70
12
2/70
6/70
38
4/70
3/70
120
2/70
11/70
380
62/90
36/90
*Inhalation exposure, 6h/day, 5d/wk for up to 2 years. Most animals died in high exposure groups by 65 weeks because of high tumor incidence.
Source: Melnick et al., 1990.
TABLE G-4 Benzo[a]pyrene*
Dose Rate
(mg/kg-d)
Tumor Incidence
Male and Female
Stomach, squamous cell carcinomas and papillomas
0
0/289
0.13
0/25
1.3
0/24
2.6
1/23
3.9
0/37
5.2
1/40
5.85
4/40
6.5
24/34
13.0
19/23
32.5
66/73
*Oral exposure in diet. Mice, CFW, male and female. Duration of exposure: 110 days. Duration of experiment: 183 days.
Source: Neal and Rigdon, 1967.
