Human Equivalent Dose

The inhalation RfD is derived from the NOAEL by applying uncertainty factors similar to those listed above for oral RfDs. A UF of 10 is used when e.Ktrapolating from animals to humans in addition to the calculation of the human equivalent dose, to account for interspecific variability in sensitivity to the to. icant. The resulting RfD value for inhalation c. posure is generally reported as a concentration in air in mg/m for continuous, 24 hour/day c. posurc, although it may be reported as a corresponding inhaled intake (in mg/kg-day). A human body weight of 70 kg and an inhalation rate of 20 nv /day are used to convert between an inhaled intake e.xprcsscd in units of mg/kg-day and a concentration in air e. pressed in mg/m. ... 

If an inhalation study in animals, list conversion factors used in determining human equivalent dose ... 

If an inhalation study in animals, list the conversion factors used in determining human equivalent dose Va male Wistar rat = 0.23 mVday, BW = 0.217 kg Va human = 20 mVday, BW = 70 kg... 

Convert the NOAEL to the human equivalent dose (HED) using the data from Table 5.3 (calculations are based on body surface areas). 

No factors were used to convert to a human equivalent dose, since the data obtained from this study was obtained from human exposures to chloroform. 

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. 

Extrapolation of data from studies in experimental animals to the human situation involves two steps a first step is to adjust the dose levels applied in the experimental animal studies to human equivalent dose levels, i.e., a correction for differences in body size between laboratory animals and humans. A second step involves the application of an assessment factor to compensate for uncertainties inherent in toxicity data as well as the mterspecies variation in biological susceptibility. These two steps are addressed in the following sections. 

It was also noted, in the 2002 review of the RfD and RfC processes (US-EPA 2002), that currently, no procedures parallel to the inhalation RfC methodology exist for deriving either oral or dermal human equivalents from animal data. Default factors (usually of 10) are routinely applied to address the issue of animal-to-human extrapolation. Thus, no parallel to the HEC, i.e., a human equivalent dose (HED), is derived nor are other adjustments applied to the animal oral or dermal dose. Instead, assumptions are made regarding the comparability of ingested or applied dose, based... 

Data from epidemiological studies, of sufficient quality, are generally preferred for estimating risks. When the evaluation is based on animal studies, the estimation of a human-equivalent dose should utilize toxicokinetic data for cross-species dose scaling if adequate data are available. Otherwise, a default procedure should be applied. The aim of the cross-species dose scaling is to define exposure levels for humans and animals that are expected to produce the same degree of effect, taking into account differences in scale between test animals and humans, such as size and life span. 

The benchmark dose method and MOE analyses are essentially the same for substances that cause stochastic or deterministic effects. For both types of substances, the point of departure in the dose-response curves for purposes of protecting human health is a dose at which some response is expected, either LED10 or some other human equivalent dose or concentration as the data support. For stochastic responses (e.g., cancers), the point of departure when animal data are used is a human equivalent dose or concentration... 

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