Risk Assessment dose-incidence relations

This option does not appear to be advantageous for either radionuclides or chemicals that cause stochastic responses. In radiation protection, total detriment is used mainly to develop the tissue weighting factors in the effective dose (see Section 3.2.2.3.3), but ICRP and NCRP have continued to emphasize fatal responses as the primary health effect of concern in radiation protection and radiation risk assessments. Since total detriment is based on an assumption that fatalities are the primary health effect of concern, the same difficulties described in the previous section would occur if this measure of response were used for chemicals that induce stochastic responses. Other disadvantages of using total detriment include that detriment is not a health-effect endpoint experienced by an exposed individual and the approach to weighting nonfatal responses in relation to fatalities is somewhat arbitrary. Furthermore, total detriment is not as simple and straightforward to understand as either incidence or fatalities. 

The treatment of rats, both male and female, for two years with tamoxifen revealed a dose-related increase in malignant liver tumors (Table 7.2). Thus, the table indicates that liver carcinomas caused by tamoxifen show a dose-related increase in both sexes, with a similar incidence, and metastases showed a slight but similar incidence. Research by various groups on the mechanisms underlying the carcinogenicity of tamoxifen has been extremely important in assessing the risk from this important drug and has allowed it to continue to be used. 

The 1994 report of the Institute of Medicine concluded that the evidence was inadequate to accept or reject a causal relation between MMR and encephalopathy, and it is known that the incidence of encephalitis after measles immunization of healthy children tends to be lower than the observed incidence of encephalitis of unknown cause. Two large studies have been negative. In a study analogous to the British Childhood Encephalopathy Study there were no increased risks of either encephalopathy or neurological sequelae after measles immunization (19). A retrospective case-control study through the CDC Vaccine Safety DataUnk assessing the risk for 300 000 doses of MMR found not a single case of encephalitis/ encephalopathy within 30 days of the administration of MMR (20). In contrast, the review mentioned above (18) reported an association between measles vaccine and encephalopathy. However, the conclusion of the report of the Institute of Medicine is still valid, namely that evidence is stiU inadequate to accept or reject a causal relation between measles vaccine and these diseases. 

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