[Federal Register Volume 76, Number 38 (Friday, February 25, 2011)]
[Notices]
[Pages 10591-10592]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2011-4250]


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ENVIRONMENTAL PROTECTION AGENCY

[EPA/100/R-11/001; FRL-9270-7]


Notice of Availability; Recommended Use of Body 
Weight[bds3][bdsol][bds4] as the Default Method in Derivation of the 
Oral Reference Dose

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice of availability.

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SUMMARY: This notice announces the availability of ``Recommended Use of 
Body Weight3/4 as the Default Method in Derivation of the 
Oral Reference Dose'' (referred to hereafter as BW3/4). This 
document was developed as part of an Agency-wide guidance development 
program by a technical panel of the U.S. EPA's Risk Assessment Forum, 
composed of scientists from across the Agency. Selected drafts were 
peer reviewed internally by EPA scientists and externally by experts 
from academia, industry, environmental groups and other government 
agencies.

DATES: The document will be available for use by EPA risk assessors on 
February 25, 2011.

ADDRESSES: The Guidelines are available electronically through the EPA 
Web site at http://www.epa.gov/raf/publications/interspecies-extrapolation.htm. A limited number of paper copies will be available 
from EPA's National Service Center for Environmental Publications 
(NSCEP), P.O. Box 42419, Cincinnati, OH 45242; telephone (800) 490-9198 
or (513) 489-8695; facsimile: (513) 489-8190. Please provide your name, 
mailing address and the title and number of the requested publication. 
Additionally, copies of the document will be available for inspection 
at EPA headquarters and regional libraries, through the U.S. Government 
Depository Library program.

FOR FURTHER INFORMATION CONTACT: Dr. Michael W. Broder, Risk Assessment 
Forum, Office of the Science Advisor (8105R), U.S. Environmental 
Protection Agency, Washington, DC 20460; telephone (202) 564-3393 or e-
mail: [email protected].

SUPPLEMENTARY INFORMATION: In order to assess the toxicity of a 
particular chemical in the absence of human data, EPA relies on the use 
of animal models as surrogates. EPA endorses a hierarchy of approaches 
to derive human equivalent oral exposures from data from laboratory 
animal species, with the preferred approach being physiologically based 
toxicokinetic

[[Page 10592]]

modeling. As a default method to account for differences in dosimetry 
between the animal models and humans, EPA previously applied a direct 
body-weight conversion from the model to humans (i.e., 
BW1/1) for non-cancer endpoints, in the absence of chemical-
specific data. In contrast, EPA applies a dosimetric adjustment factor 
(DAF) based on body weight raised to the three-quarter power 
(BW3/4) for cancer assessments. By adopting the adjustment, 
this document moves in the direction of harmonizing the approach for 
assessing cancer and noncancer endpoints.
    In addition to laying out the computational method for interspecies 
extrapolation, the document also addresses the issue of changes to the 
interspecies uncertainty factor (UFA). The document 
recommends a reduced interspecies UFA (with a default value 
of 3) in lieu of a default of 10 for the reference dose (RfD) 
calculation. The quantitative significance of this procedure with 
regard to the magnitude of an RfD will depend on the body weight of the 
species (as well as the value assigned to the UFA) and may 
be more or less than the current procedure of dividing by the default 
composite UFA of 10.
    BW3/4 scaling for derivation of the human equivalent 
dose is recommended as the default approach for RfDs for remote, as 
well as portal-of-entry effects. It is noted that this scaling is not 
inclusive of lethal or frank effects for which maximum concentration 
(Cmax) may be the most appropriate dose metric and that such 
effects are not among those effects recommended for use in deriving 
RfDs (USEPA, 2002). This default approach generally applies to 
different durations of exposure. The reader is encouraged to read the 
document carefully, however, in order to fully understand how to apply 
the policy appropriately. Additionally, although non-oral RfDs can be 
estimated (e.g., a dermal RfD), this document focuses only on oral RfDs 
and for this document the acronym refers only to RfDs for oral 
exposure.
    It is recognized that this procedure, as with all default 
procedures, may not always predict oral exposures associated with 
precise toxicologically-equivalent doses for specific chemicals. It 
should be emphasized that other biological information not discussed in 
this document may inform interspecies adjustments. As a general default 
procedure, however, it may be anticipated to provide a reasonable 
description of average behavior of many chemicals much of the time.
    Even though this document is not a binding rule, EPA is issuing it 
in a manner consistent with the procedures in the Administrative 
Procedure Act that are generally applicable to rulemaking, including 
providing opportunity for public comment. EPA considered and responded 
to all significant public comments as it prepared the document.

    Dated: February 16, 2011.
Paul T. Anastas,
EPA Science Advisor.
[FR Doc. 2011-4250 Filed 2-24-11; 8:45 am]
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