ERRATA—Replaces page 29  of EPA/630/R-00/002
2.6.1.2.  User Fact Sheet: Relative Potency Factors

       The user of this guidance document can follow  ?
Figure 2-1 to determine that the data available are on the
components of the mixture of concern and that there is
evidence of toxicologic similarity of the components. Then
a procedure is suggested for estimating risk from exposure
to the mixture by using Relative Potency Factors, as
encapsulated in the following user-information fact sheet.
Approach:
Type of Assessment:

Section(s):
References:
Data Requirements:
Strategy of Method:
Ease of Use:
Assumptions:
Limitations:
Uncertainties:
Relative Potency Factors
Dose-Response Assessment for
Any Toxic Endpoint
4.1,4.4
New Procedure
Method requires both toxicity and
exposure data on the mixture's
components. Toxicity data are
missing for some components.
Scale component exposure
concentrations relative to potency
of an index chemical (typically the
best-studied component) following
expert committee consensus.
Add scaled concentrations.  Use
dose-response curve of index
chemical to generate response
estimate for sum of scaled
concentrations.
Complicated to use. Requires
some statistical modeling and
judgment of relative potency
factors.
Based on dose addition which
carries with it assumptions of
same mode of action and similarly
shaped dose-response curves
across the components.  The
"common mode-of-action"
assumption can be met using a
surrogate of toxicologic similarity,
but for specific conditions
(endpoint, route, duration).
Limited by data quality and
similarity. May not have data
from all routes of exposure of
interest. Same mode-of-action
across components may not be
known.
Judgment of relative potency
factors.  Similarity of toxicologic
action. Missing data on some
components.
2.6.2.  Independence and
Response Addition
       Response addition may apply
when components act on different

systems or produce effects that do
not influence each other. Under
response addition, the chemicals in
the mixture are assumed to behave

independently of one another, so that
the body's response to the first
chemical is the same whether or not
the second chemical is present.
Mathematically, response addition
can be described by the statistical
law of independent events, with
"response" measured by the
percentage of exposed animals that

show toxicity or the proportion of
the population responding.
Response addition is particularly
useful when the effects of concern
are thought to be present at low dose
levels for each of the component
chemicals, even though it is highly
unlikely the effects are capable of
being observed at these low levels in
the environment.  When interaction
data are available on any of the
components in the mixture, the risk
assessor may provide a qualitative
discussion of the likely effect of
these data on the outcome of the
mixture risk assessment under
response addition (see Sections
2.2.4, 4.5.4).
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