Reference dose INDEX

For each clironic exposure padiway (i.e., seven years to lifetime exposure), calculate a sepmate clironic hazard index from die rados of the clironic daily intake (GDI) to die clironic reference dose (RfD) for individual chemicals as described below ... 

The cumulative risk index (CRI), also referred to as the aggregate risk index (ARI) has been suggested by the US-EPA (Whalan and Pettigrew 1997) to combine MOEs for chemicals with different AFs. The risk index (RI) of a chemical is the MOE divided by the AF or simply the reference dose divided by exposure, and is the reciprocal of the HQ ... 

Non-carcinogenic risk is normally characterized in terms of a hazard index defined by the ratio of the estimated intake dose from exposure to the reference dose (RfD). Reference doses depend on the exposure route and may be used with its exposure data. The hazard index is calculated as... 

If the acceptable level of intake is deemed to be equal to the reference dose, then a hazard index smaller than unity is acceptable. 

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 term dose—response in environmental epidemiology is typically understood to mean that quantitative relationship in which adverse effect severity and multiplicity increase in proportion to the intensity of exposure or dose indexed externally (intake/uptake quantities) or internally (exposure biomarkers). In the case of experimental animal exposures, reference is often to the administered dose, but biomarkers can also be available. Dose—response has also been employed to denote impacts at some selected effect level of a toxicant in terms of increasing affected fractions of some population as exposure increases. In this case, a dose—population response label is more precise. 

The reference dose for a toxic chemical—an equivalent term is the acceptable daily intake (ADI)—is taken to represent the threshold level of exposure above which a noncancer health effect can result in humans. The hazard index (HI) indicates... 

Airborne toxic chemicals may pose a risk of toxic effects directly on the lungs as well as toxic effects on other organs and tissues after entering the bloodstream through the lungs. The reference dose for an air pollutant is termed the reference concentration, or RfC. The reference concentration differs from the reference dose in that it is the actual concentration of a chemical in the air, not the average daily dose of chemical that enters the bloodstream. The air qnality index (AQI) is an estimate of the risk of effects from air pollutants, particularly in people with preexisting conditions such as asthma. The air quality index is calculated as the ratio of the concentration of an air pollutant to its reference concentration multiplied by 100 ... 

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) ... 

The hazard index (HI) is used to assess the risk of a noncancer health effect in an exposed population. The hazard index is calculated by dividing the chronic daily intake (CDl) by the reference dose (RfD) HI = CDI/RfD. A hazard index equal to or greater than 1 indicates significant risk. The higher the hazard index, the greater is the risk. 

Calculate the chronic daily intake and divide it by the reference dose to obtain the hazard index ... 

For the non-cancer effects of chemicals, risks or probabilities of effects are not estimated. This is because, unlike the assumption of no threshold used for cancer chemicals, there are doses below which no adverse effects are expected from chemical exposure for non-cancer effects of chemicals. Instead of generating a risk, the estimated dose is divided by the reference dose, which is considered a safe level below which toxicity is not expected to occur. The result of this division is a ratio that will either be above or below one. This ratio is referred to either as a hazard quotient, if only one chemical is considered, or a hazard index, if multiple chemicals are included. If the ratio is below one, this means that the estimated dose is below the threshold dose, and no toxicity is expected. If the ratio is above one, the estimated dose is above the threshold dose, and toxicity may result. Ratios above one do not mean that toxicity will resnlt, but that there is a chance of this occurring. The higher the ratio is above one, the greater the chance that toxicity can result from exposure. 

If there are specific data germane to the assumption of dose-additivity (e g., if two compounds arc present at the same site and it is known that the combination is five times more toxic than the sum of the toxicitics for the two compounds), then tire development of the hazard index should be modified accordingly. The reader can refer to the EPA (1986b) mi.xiure guidelines for discussion of a hazjird index equation that incorporates quantitative interaction data. If data on chemical interactions are available, but arc not adequate to support a quantitative assessment, note the information in the assumptions being documented for the risk assessment. 

Since GABA-ergic synapses are confined to neural tissues, specific inhibition of central nervous functions can be achieved for instance, there is little change in blood pressure, heart rate, and body temperature. The therapeutic index of benzodiazepines, calculated with reference to the toxic dose producing respiratory depression, is greater than 100 and thus exceeds that of barbiturates and other sedative-hypnotics by more than tenfold. Benzodiazepine intoxication can be treated with a specific antidote (see below). 

The long-standing interest in the properties of L-ascorbic acid is manifested by the fact that 1146 references related to vitamin C are listed for year 2000 in the PUB MED index in the Internet. The most popular use of L-ascorbic acid is for prevention and treatment of the common cold, but this role remains controversial. In a recent review, the authors conclude that the long-term daily supplementation with large doses of vitamin C does not appear to prevent colds, but there is a modest therapeutic effect on the duration of cold symptoms.369... 

Formulation of the risk index for mixtures of substances that cause deterministic effects is considerably more complex than in the case of substances that cause stochastic effects discussed in the previous section. The added complexity arises from the threshold dose-response relationship for these substances and the need to keep track of the dose in each organ or tissue at risk in evaluating whether the dose in each organ is less than the allowable dose in that organ. For substances that cause deterministic responses, the index T can refer not only to a specific organ or tissue (e.g., the liver or skin) but also to a body system that may be affected by a particular chemical, such as the immune or central nervous system. 

Concentration (or dose) addition (CA) and response addition (RA) both apply algorithms that combine the results of single substance evaluations to produce an estimate of the mixture risk. The uncertainty in the estimate is a combination of the uncertainties in the individual components. The hazard index (HI), which is a specific case of CA, adds the ratios between the exposure and reference values of the individual substances ... 

Intravenous deferoxamine can be indicated in gross iron overload, serious cardiomyopathy, or intolerance of or non-adherence to subcutaneous administration. The results of continuous 24-hour deferoxamine infusion via indwelling intravenous catheters in 17 patients (25 intravenous lines) have been presented (154). The doses of deferoxamine were calculated with reference to the serum ferritin concentration, with a view to maintaining the therapeutic index (mean daily dose in mg/kg divided by the serum ferritin concentration in ng/ml) below... 

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