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result sql = Relationship between dose and risk reduction: statistical evaluation of a combination experiment with three hepatocarcinogenic N-nitrosamines in rats.
Relationship between dose and risk reduction: statistical evaluation of a combination experiment with three hepatocarcinogenic N-nitrosamines in rats.
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char = e;code = 101
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char = ;code = 32
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char = e;code = 101
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char = f;code = 102
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char = ;code = 32
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char = v;code = 118
char = e;code = 101
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result sql = Data from an experiment on the single and combination effects of very low doses of N-nitrosodiethylamine (NDEA), N-nitrosopyrrolidine (NPYR) and N-nitrosodiethanolamine (NDELA) in 1800 male Sprague-Dawley rats were analysed for age-specific incidence (time to death with liver tumour) by Cox's proportional hazards model. THE MODEL REVEALED A LINEAR RELATIONSHIP BETWEEN DAILY EXPOSURE TO LOW LEVELS OF N-NITROSAMINE AND TIME TO DEATH WITH LIVER TUMOUR WITHIN THE DOSE RANGE INVESTIGATED: an increase in individual dose resulted in a proportional decrease in liver tumour-free survival. The finding was established for the three individual carcinogens as well as for their combination. NDEA was 40 times more active than NDELA. Extrapolation to N-nitrosamine exposure levels lower than those used in the experiment revealed only a minor reduction in age-specific liver tumour incidence compared to that achieved by an equivalent reduction within the experimental dose range. In rats at advanced age a further reduction in carcinogen-induced liver tumour incidence did not contribute to longer overall survival, due to competitive, probably independent causes of death. The data thus support the idea of a quasi-threshold in terms of a 'no observed effect level'.

Publication: IARC Sci. Publ. 1991 ;(105)::311-7.
Publication Date: 1991
Study Author(s): Berger, M R;Schmähl, D;Edler, L;
Institution: Institute of Toxicology and Chemotherapy, German Cancer Research Centre, Heidelberg.
Shortcut link to this study:
Data from an experiment on the single and combination effects of very low doses of N-nitrosodiethylamine (NDEA), N-nitrosopyrrolidine (NPYR) and N-nitrosodiethanolamine (NDELA) in 1800 male Sprague-Dawley rats were analysed for age-specific incidence (time to death with liver tumour) by Cox's proportional hazards model. THE MODEL REVEALED A LINEAR RELATIONSHIP BETWEEN DAILY EXPOSURE TO LOW LEVELS OF N-NITROSAMINE AND TIME TO DEATH WITH LIVER TUMOUR WITHIN THE DOSE RANGE INVESTIGATED: an increase in individual dose resulted in a proportional decrease in liver tumour-free survival. The finding was established for the three individual carcinogens as well as for their combination. NDEA was 40 times more active than NDELA. Extrapolation to N-nitrosamine exposure levels lower than those used in the experiment revealed only a minor reduction in age-specific liver tumour incidence compared to that achieved by an equivalent reduction within the experimental dose range. In rats at advanced age a further reduction in carcinogen-induced liver tumour incidence did not contribute to longer overall survival, due to competitive, probably independent causes of death. The data thus support the idea of a quasi-threshold in terms of a 'no observed effect level'.
PMID: 1855870

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