Exposure adjustment factor

To adjust for uncertainties in assessing potential cancer risks for short-term exposures under the multistage model, the 24-h exposure is divided by an adjustment factor of 6 (Crump and Howe 1984). 

It is also noted that there is overlap in the individual UFs and that the application of five UFs of ten for the chronic reference value (yielding a total UF of 100,000) is inappropriate. In fact, in cases where maximum uncertainty exists in all five areas, it is unlikely that the database is sufficient to derive a reference value. Uncertainty in four areas may also indicate that the database is insufficient to derive a reference value. In the case of the RfC, the maximum UF would be 3,000, whereas the maximum would be 10,000 for the RfD. This is because the derivation of RfCs and RfDs has evolved somewhat differently. The RfC methodology (US-EPA 1994) recommends dividing the interspecies UF in half, one-half (10° ) each for toxicokinetic and toxicodynamic considerations, and it includes a Dosimetric Adjustment Factor (D AF, represents a multiplicative factor used to adjust an observed exposure concentration in a particular laboratory species to an exposure concentration for humans that would be associated with the same delivered dose) to account for toxicokinetic differences in calculating the Human Equivalent Concentration (HEC), thus reducing the interspecies UF to 3 for toxicodynamic issues. RfDs, however, do not incorporate a DAF for deriving a Human Equivalent Dose (HED), and the interspecies UF of 10 is typically applied, see also Section 5.3.4. It is recommended to limit the total UF applied for any particular chemical to no more than 3000, for both RfDs and RfCs, and avoiding the derivation of a reference value that involves application of the full 10-fold UF in four or more areas of extrapolation. 

When there is evidence of signihcant potential for bioaccumulation and/or cumulative injury with prolonged or repeated exposure, a larger adjustment factor is required. 

IPCS (2001b) Guidance document for the use of data in development of chemical-specific adjustment factors (CSAFs) for interspecies differences and human variability in dose/ concentration-response assessment (draft). Prepared as part of the IPCS project on the Harmonization of Approaches to the Assessment of Risk from Exposure. Geneva, World Health Organization, International Programme on Chemical Safety. 

Refinements of the RfC have utilized mechanistic data to modify the interspecies uncertainty factor of 10 (Jarabek, 1995). The reader should appreciate that with the inhalation route of exposure, dosimetric adjustments are necessary and can affect the extrapolations of toxicity data of inhaled agents for human health risk assessment. The EPA has included dosimetry modeling in RfC calculations, and the resulting dosimetric adjustment factor (DAF) used in determining the RfC is dependent on physiochemical properties of the inhaled toxicant as well as type of dosimetry model ranging from rudimentary to optimal model structures. In essence, the use of the DAF can reduce the default uncertainty factor for interspecies extrapolation from 10 to 3.16. 

If the extrapolation factor (ratio of the mouse dose to the expected human exposure adjusted for stage sensitivity, dose rate, and other relevant factors) is taken to be 1,000, the 95% upper confidence limit on the mutation rate for the lower human exposure is 0.000003. 

The technical support document (TSD) is the compilation of all relevant data and information from all key studies and references and the most important supporting studies and references for both human exposures and laboratory animal exposures. Additionally, this support document addresses all the methodologies used in the derivation of the AEGL values and presents the rationale and justification for the use of certain data in the derivation and for the elimination of certain studies or data. The TSD addresses why specific methodologies and adjustment factors were or were not used, the scientific evidence supporting the rationale and justification, and the appropriate references to the published scientific literature or sources of unpublished information. 

ADI is derived from NOAEL or other starting point, such as the benchmark dose (BMD), by the use of an uncertainty or adjustment factor. In contrast, for non-threshold effects a quantitative hazard estimate can be calculated by extrapolation, usually in a linear fashion, from an observed incidence within the experimental dose-response range to a given low incidence at a low dose. This traditional approach is based on the assumption that there may not be a threshold dose for effects involving genotoxicity. Alternatively, for compounds that are genotoxic, advice may be given that the exposure should be reduced to the lowest possible level. 

A subset of the cohort (N = 332) was tested at 4 years of age using the McCarthy Scales. By this age, the smelter group mean PbB had risen to 40 pg/dl (rounding) versus controls mean of 10 pg/dl (rounding). GCI scores were statistically inversely associated with all postnatal exposure markers and with prenatal values > 20 pg/dl (Wasserman et al., 1994). At 7 years of age, children (A = 301) were tested using the Third Edition, Wechsler (WlSC-III) IQ scales and various exposure markers (Factor-Litvak et al., 1999). Adjusted for confoimders, there was a statistically significant inverse association of Performance IQ on the WISC-III tests with an integrated exposure measure, the lifetime Area-Under-the-Curve measurements, at 5—7 years. 

Ty = Turbulant adjust factor Tc = fetch factor for adjustment Pcont-ANSI A58.1 for exposure C Fig. 2 of the code To Load based on 100-year recurrence wind,... 

There are several limitations to tliis approach that must be acknowledged. As mentioned earlier, tlie level of concern does not increase linearly as the reference dose is approached or exceeded because the RfDs do not luive equal accuracy or precision and are not based on the same severity of effects. Moreover, luizm-d quotients are combined for substances with RfDs based on critical effects of vaiy ing toxicological significance. Also, it will often be the case that RfDs of varying levels of confidence Uiat include different uncertainty adjustments and modifying factors will be combined (c.g., extrapolation from animals to hmnans, from LOAELs to NOAELs, or from one exposure duration to anoUier). 

Used to derive an intermediate inhalation Minimal Risk Level (MRL) of 5 x 10 ppm dose adjusted for intermittent exposure and divided by an uncertainty factor of 100 (10 for extrapolation from animal to humans, 10 for human variability). 

Regulations and recommendations can be expressed in not-to-exceed levels in air, water, soil, or food that are usually based on levels that affect animals then they are adjusted to help protect people. Sometimes these not-to-exceed levels differ among federal organizations because of different exposure times (an 8-hour workday or a 24-hour day), the use of different animal studies, or other factors. 

The majority of people who smoke never develop lung cancer. Genetic risk factors may predispose certain smokers to lung cancer. After adjustments for age, smoke exposure, occupation, and gender, relatives of a lung cancer patient have approximately a twofold risk of developing lung cancer. The... 

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