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