Health Assessment Document for Diesel Emissions - NSCEP | US ...

1 12.3.2.1. Derivation of an Inhalation Reference Concentration
2 The derivation of an inhalation reference concentration (RfC) for DE is a dose-response
3 approach used by EPA for noncarcinogenic, threshold chronic effects. An RfC is defined as an ,
4 estimate of a continuous inhalation exposure to the human population, including $ensitive
5 subgroups, with uncertainty-spanning perhaps an order of magnitude, that is likely to be without
6 appreciable risks of deleterious noncancer effects during a lifetime. The RfC approach is based
7 on the assumption that a threshold exists for the human population below which no effect will
8 occur.
9 As an alternative to using a no-observed-adverse-effect-level (NOAEL) in the RfC
10 methodology as a dose-response marker, this assessment examined a benchmark
11 dose/concentration (BMC) analysis approach, a newer approach that EPA has used to derive the
12 RfCs for carbon disulfide, chlorodifluoromethane, and several other chemicals (U.S. EPA, 1995).
13 The BMC refines the ascertainment of the NOAEL.
14 The database EPA chose to work from for RfC derivation consisted of 10 long-term
15 (greater than 1 year) studies of inhalation of diesel engine emissions in laboratory rats. The
16 available human studies, as discussed earlier, were qualitatively suggestive of adverse effects but
17 were inadequate for RfC consideration. The selected rat studies were conducted by the Inhalation
18 Toxicology Research Institute (ITRI) and the Japanese Health Effects Research Program (HERP).
19 These studies were selected because each identified respiratory effects after chronic exposure and
20 provided good information about pulmonary histopathology. Further, the selected studies
21 spanned a wide range of exposures, from 350 to 7,000 J.lg/m 3 with three exposures in the 350-960
22 J.lg/m 3 range. Human equivalent concentrations were calculated using a dosimetry model
23 developed by Yu et al. (1991) that accounted for species differences in respiratory exchange rates,
24 particle deposition efficiency, differences in particle clearance rates at high and low doses, and
25 transport of particles to lymph nodes.
26 The adopted RfC comes from the HERP study, which showed a NOAEL of 460 J.lglm 3
27 (human equivalent concentration, HEC, = 155 J.lg/m 3 ). While particle overload is thought to be
28 still present at 1,000 J.lglm 3 to some degree, at 460 J.lg/m 3 the overload is thought to be much less,
29 if not minimal. Consistent with standard RfC practice for a good chronic animal study, two types
30 of uncertainty factors were used to further lower the NOAEL-HEC to a value having a sufficient
31 margin of safety for humans. An uncertainty factor of J out of 10 was used to account for
32 interspecies sensitivity; that is, humans could be somewhat more sensitive than rats. Out of a
33 possible factor of 10, credit is given to the dosimetry adjustment procedures used. We would also
34 ·note that some researchers believe rats could be more biologically sensitive than humans to DE
35 particles, but we do not know whether rats are more or less sensitive to the organics. A second
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