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Issues in Risk Assessment (1993)

Chapter: DATA

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Suggested Citation:"DATA." National Research Council. 1993. Issues in Risk Assessment. Washington, DC: The National Academies Press. doi: 10.17226/2078.
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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.)

Suggested Citation:"DATA." National Research Council. 1993. Issues in Risk Assessment. Washington, DC: The National Academies Press. doi: 10.17226/2078.
×

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

Suggested Citation:"DATA." National Research Council. 1993. Issues in Risk Assessment. Washington, DC: The National Academies Press. doi: 10.17226/2078.
×

 

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

Suggested Citation:"DATA." National Research Council. 1993. Issues in Risk Assessment. Washington, DC: The National Academies Press. doi: 10.17226/2078.
×

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.

Suggested Citation:"DATA." National Research Council. 1993. Issues in Risk Assessment. Washington, DC: The National Academies Press. doi: 10.17226/2078.
×
Page 177
Suggested Citation:"DATA." National Research Council. 1993. Issues in Risk Assessment. Washington, DC: The National Academies Press. doi: 10.17226/2078.
×
Page 178
Suggested Citation:"DATA." National Research Council. 1993. Issues in Risk Assessment. Washington, DC: The National Academies Press. doi: 10.17226/2078.
×
Page 179
Suggested Citation:"DATA." National Research Council. 1993. Issues in Risk Assessment. Washington, DC: The National Academies Press. doi: 10.17226/2078.
×
Page 180
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Issues in Risk Assessment Get This Book
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The scientific basis, inference assumptions, regulatory uses, and research needs in risk assessment are considered in this two-part volume.

The first part, Use of Maximum Tolerated Dose in Animal Bioassays for Carcinogenicity, focuses on whether the maximum tolerated dose should continue to be used in carcinogenesis bioassays. The committee considers several options for modifying current bioassay procedures.

The second part, Two-Stage Models of Carcinogenesis, stems from efforts to identify improved means of cancer risk assessment that have resulted in the development of a mathematical dose-response model based on a paradigm for the biologic phenomena thought to be associated with carcinogenesis.

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