TABLE 12

Dose-effect relationships of carcinogenic hydrocarbons in mice with chronic and acute exposure: an analysis by the median-effect equation Reproduced from Chou TC, “Comparison of Dose-Effect Relationships Following Low-Dose Chronic Exposure and High-Dose Single Injection: An Analysis by the Median-Effect Principle,” Carcinogenesis, 1980, volume 1, pp 203-213, by permission of Oxford University Press. Table also used by permission of Oxford University Press in Chou and Talalay (1987).

Experiment and Source of Data Carcinogen Weeks of Treatmenta Cumulative Fraction of Tumorless (1 – fa)b Slope (m)c Median-Effect Dose (Dm)c
Chronic exposure (Peto et al., 1975)d
   Starting age: 10 weeks Benzo[a]pyrene 42 0.99216 4.5693 ± 0.0630 (r = 0.9981) 39.469 weeks
44 0.98425
46 0.96851
48 0.95276
50 0.93701
52 0.88977
54 0.87402
56 0.85040
58 0.77166
60 0.70867
62 0.66862
64 0.65212
66 0.57060
68 0.51354
70 0.43841
72 0.37033
74 0.30933
76 0.30037
78 0.26339
80 0.22507
82 0.19507
84 0.13265
   Starting age: 55 weeks Benzo[a]pyrene 42 0.99024 4.6225 ± 0.1337 (r = 0.9917) 41.120 weeks
44 0.98010
46 0.97316
48 0.96597
50 0.95489
52 0.95109
54 0.92644
56 0.88793
58 0.84308
60 0.78719
62 0.71539
64 0.66450
66 0.60643
68 0.53731
70 0.46268
72 0.40959
74 0.36449
76 0.35503
78 0.28518
80 0.18780
82 0.17147
84 0.17147
Experiment and Source of Data Carcinogen Dose Fraction Affected (fa)e Slope (m)c Median-Effect Dose (Dm)c
μg/mouse
Acute (point) exposuref (Bryan and Shimkin, 1943)
   Starting age: 6–13 weeks 3-Methylchoanthrene 125 0.973 1.9330 ± 0.040 (r = 0.9992) 20.663 μg/mouse
62 0.881
31 0.668
15.6 0.379
7.8 0.146
3.9 0.036
Dibenz [a,h]anthracene 62.5 0.912 1.7720 ± 0.0502 (r = 0.9984) 16.208 μg/mouse
31.2 0.748
15.6 0.494
7.81 0.242
3.90 0.083
1.95 0.019
Benzo[a]pyrene 2000 0.988 1.3879 ± 0.0455 (r = 0.9973) 98.857 μg/mouse
1000 0.960
500 0.888
250 0.756
125 0.565
62 0.358
31 0.186
  • a Weeks of exposure minus 28 weeks (the latent period from initiation of tumor to tumor growth of 10 mm diameter) to obtain the effective exposure period of carcinogen as indicated by Peto et al (1975)

  • b Cumulative incidence of tumorless (i.e., cumulative 1 – fa) is calculated by the life-table procedure as used by Peto et al. (1975) See original study for details

  • c The median-effect plot was carried out by plotting log [fa/(1 – fa)] vs. log D, where m is the slope and log Dm is the intercept of the plot at the median-effect axis (i.e., at log [fa/(1 – fa)] = 0). Both m and Dm are obtained from least-square regression analysis and Dm = antilog (–y-intercept/m). The range of m values is given as mean ± S.E. and r is the linear regression coefficient

  • d Benzo[a]pyrene was applied twice weekly to skin of Swiss albino female mice. Animals with epithelial tumors of 10 mm diameter were scored

  • e Statistically calculated values obtained by Bryan and Shimkin (1943) are used. Tumor incidences of 100% and <1% have been excluded from analysis

  • f Carcinogenic hydrocarbons were injected s.c. into C3H male mice. Animals with spindle cell sarcoma during life-time were scored