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