Cancer risk assessment 790 INDEX

Lipsett MJ, Carmelli D, Winship-Ball A, et al. 1982. Quantitative cancer risk assessment for occupational exposure to ethylene dibromide. Govt Reports Announcements Index (GRA I). Cincinnati, OH Robert A. Taft Labs. NTIS/PB83-184325... 

To assess tlie overall potential for noncarcinogenic effects posed by more dian one chemical, a liazard index (HI) approach has been developed based on EPA s Guidelines for Healdi Risk Assessment of Chemical Mixtures. This approach assumes that simultaneous subtlu eshold exposures to several chemicals could result in an adverse healtli effect. It also assumes tliat tlie magnitude of the adverse effect will be proportional to tlie sum of the ratios of the subtlireshold exposures to acceptable exposures. The non cancer hazard index is equal to tlie sum of the hazard quotients, as described below, where E and tlie RfD represent the same exposure period (e.g., subclironic, clironic, or shorter-term). 

It is clear that patients with febrile neutropenia represent a heterogeneous group. Some patients are at lower risk and potentially could be treated as outpatients, thereby avoiding the risk and cost of hospitalization. The Multinational Association for Supportive Care in Cancer (MASCC) has validated a risk-assessment tool that assigns a risk score to patients presenting with febrile neutropenia7 (Table 96-3). Patients with a risk-index score of 21 or greater are identified as low risk and are candidates for outpatient therapy (discussed under Treatment ). 

The cohort was assessed by questionnaire for incidence of new cases of prostate cancer from 1989 to 1994. Higher levels of selenium in toenail clippings were significantly associated with a reduced risk of prostate cancer. After controlling for factors such as a family history of prostate cancer, body mass index, calcium intake, lycopene intake, saturated fat intake, vasectomy, and geographical region, the odds ratio (OR) was 0.35 (95% 0=0.16-0.78, P for trend=0.03). 

Risk Characterization. Once a quantitative exposure assessment has been made, Risk Assistant allows the user to automatically calculate lifetime excess cancer risk and/or a hazard index for toxic non-carcinogenic effects of chronic exposure for any agent included in the toxicity databases which currently include about 300 compounds. The appropriate hazard values (slope-potency factors and reference doses) for the relevant routes of exposure are automatically retrieved from the databases. The uncertainty calculations in the exposure assessment can also be retrieved to assess the range of risks associated with a given exposure situation. 

The chronic daily intake (CDI) estimated in the analysis of exposure, the second step of the risk assessment, is used to calculate the risks of both noncancer health effects and cancer. Risk calculations are also referred to as quantitative risk assessment, a term that is somewhat misleading because the word quantitative implies a high degree of accuracy, which is clearly not the case. In the first risk scenario described in Section 8.3, future residents drink arsenic-contaminated water from the aquifer beneath a former Superfund site. Their CDI by this pathway is estimated to be 0.0I6I mg/kg/day of arsenic. The oral reference dose (RfD) for arsenic is 3 x lO"" mg/kg/day, according to the EPA s Integrated Risk Information System (IRIS) (U.S. EPA 2009). The hazard index (HI) for noncancer health effects caused by this chemical of concern by this exposure pathway is calculated using Equation (8.3) ... 

Bradbury et al. (2004), however, recently reanalyzed the relation between tamoxifen and cataracts and described it as a null association, They used a nested, matched, case-control study design and data collected in the General Practice Research Database. They identified all women 30-79 years old who were diagnosed with breast cancer and treated with tamoxifen within 6 months, or with bladder cancer, colorectal cancer, or nonmelanoma skin cancer between January 1991 and December i999. From this population they identified all newly diagnosed cases of cataract and matched four female controls to each case on age, index date, and study entry data. They assessed the risk of cataracts for current, past, and sometime users of tamoxifen... 

However, be aware that in spite of the usefulness of the MIB-1 antibody in assessing the rate of cell proliferation, the classification of cancers (e.g., breast cancer) by the size of the primary tumor and the presence and extent of lymph node metastases does not adequately explain differences in the clinical outcome of individual patients. Cell proliferation indices are commonly used, along with other diagnostic parameters, to estimate the risk of recurrence of a cancer for individual patients. Therefore, it is important to understand the relationship between various indices of proliferation such as MIB-1 labeling index and detection by either in situ hybridization or polymerase chain reaction. This approach will lead to quality assurance in diagnosis. 

The exposure scenario described in the previous example of domestic uranium mill tailings was used to classify the high-radium residues. The risk and dose assessments indicated a probability of radiation-induced cancer incidence of about 0.6, potential doses in excess of 10 Sv, and a risk index between 50 and 100. Thus, these residues would be classified as high-hazard waste, even under conditions of perpetual institutional control over near-surface disposal sites, and they would require some form of greater confinement disposal well below the ground surface. This conclusion is consistent with recommendations for disposition of these residues (NAS/ NRC, 1995b). 

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