PRINCIPLES OF TOXICOLOGY

466 RISK ASSESSMENT
The RPF values for chemicals in the group may vary depending on the toxic effect of concern and
perhaps the exposure circumstances. There are a few examples where all of the toxic effects of concern
share a common mode of action and a single scaling factor is applicable for all effects and exposure
conditions. This represents a special case of the RPF method termed the toxic equivalency factor (TEF)
approach. An example of the use of the TEF approach is the risk assessment of polyhalogenated
aromatic compounds. Most of the adverse health effects of concern for these compounds are thought
to arise from a common mode of toxicity: Ah receptor activation. In this example, the index chemical
is 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD), which is assigned a relative potency of 1.
Based on studies of comparative potency in terms of Ah-receptor-mediated toxicity, comparative
potency factors (termed TEFs) have been determined for other polyhalogenated aromatics (e.g.,
PCDDs, PCDFs, PCBs). TEFs for PCB congeners relative to 2,3,7,8-TCDD are listed in Table 18.3.
In assessing risks from exposure to a mixture of PCB congeners using the TEF approach, the TEF
equivalents for all congeners present in the environmental sample are summed to derive a risk estimate
for the PCB mixture.
Another means of adding chemical effects is the hazard index approach. This approach does not
require the assumption of a common mode of toxicity, only that the chemicals share the same target
organ or effect. In this approach, the dose of each chemical is compared with some representation of
a threshold dose for toxicity. In practice, that may be a reference dose or a benchmark dose (see Section
18.4 for a discussion of reference and benchmark doses and their derivations). The dose for which a
risk estimate is sought is divided by the threshold dose for that chemical in the target organ of interest
and the result is termed the hazard quotient. For example, if exposure to a chemical is predicted to
result in a dose of 1 mg/kg⋅day, and the threshold dose for the toxicity of concern is 10 mg/kg⋅day, the
hazard quotient is 1 / 10 or 0.1. Hazard quotients for each chemical affecting the target organ are then
summed to obtain the hazard index (HI). The interpretation of the magnitude of the HI is similar to
that already discussed.
Yet another way in which effects can be added is through response addition. This differs from dose
addition methods in that the chemicals and their effects are assumed to be completely independent.
For this approach, the percent of animals or humans expected to develop toxicity from each of the
individual chemicals at their respective doses is estimated. These percentages are termed the “responses.”
The probability that a toxic event will result from a combination of two chemicals can be
expressed as follows:
TABLE 18.3 Proposed Toxic Equivalency Factors (TEFs) for PCB Congeners Relative to Dioxin
IUPAC No. CongenerTEF
2,3,7,8-TCDD 1
77 3,3′,4,4′-TCB 0.0005
105 2,3,3′,4,4′-PeCB 0.0001
114 2,3,4,4′,5-PeCB 0.0005
118 2,3′,4,4′,5-PeCB 0.0001
123 2′,3,4,4′,5-PeCB 0.0001
126 3,3′,4,4′,5-PeCB 0.1
156 2,3,3′,4,4′,5-HxCB 0.0005
157 2,3,3′,4,4′,5′-HxCB 0.0005
167 2,3′,4,4′,5,5′-HxCB 0.00001
169 3,3′,4,4′,5,5′-HxCB 0.01
170 2,2′,3,3′,4,4′,5-HpCB 0.0001
180 2,2′,3,4,4′,5,5′-HpCB 0.00001
189 2,3,3′,4,4′,5,5′-HpCB 0.0001
Source: Ahlborg et al. (1994).