Assessment of Exposure-Response Functions for Rocket-Emission Toxicants (1998) / Chapter Skim
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Exposure-Response Functions for Rocket-Emission Toxicants
Exposure-Response Functions for Rocket-Emission Toxicants
Pages 67-83
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From page 67... ...
is provided in Appendix F HNO3 can produce respiratory damage because it is a strong acid, it is an excellent oxidizing agent, and it reacts immediately with any tissue it contacts.
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From page 68... ...
If the probability of an observable effect is 0.067 at 0.2 ppm for 4 hr. and if Haber's rule applies, an exposure at 0.S ppm for ~ hr implies the same risk of 0.067, or an incidence of 67 per 1,000 individuals.
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From page 69... ...
for ~ hr implies a risk of 86%, which could be used as a second point to establish an ERF for sensitive individuals. This assumes Hat hypersensitive sheep and sensitive humans respond similarly to HNO3.
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From page 70... ...
However, as indicated for healthy individuals, the subcommittee believes that an ERF for respiratory resistance for sensitive individuals based on only two data points (with small sample sizes, using Haber's rule, and with the second point based on animal data) is too uncertain to estimate the ~nciclence of effects associated with exposure to HNO3 from rocket launches.
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From page 71... ...
(1976) have similar results, the 5- and 30min mortality results are plotted in Figure 6-2 as a single ERF for percentage dead versus cumulative (total)
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From page 72... ...
Some mortality might have occurred in those groups if more animals had been tested per group. That possibility is particularly true for the 5-min exposure at 9,551 mg/m3, because deaths occurred In other groups exposed at lower concentrations.
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From page 73... ...
That percentage is a conservative adjustment for the ERF at low concentrations of HCI, because it lowers the slope of the ERF and, in turn, increases We incidence of effects et the low exposure concentrations. Such adjustments provide a conservative correction for potentially unlikely results that are due to small sample sizes.
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From page 74... ...
, where Cis concentrationinm~lligrams per cubic meter and Tis duration of exposure in minutes. The exposure estimated to correspond to a risk of corneal opacity in guinea pigs of 10- (1 in 10,000)
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From page 75... ...
Therefore, the subcommittee examined Me possibility of constructing an ERF for mild effects in sensitive humans by using a NOEL for humans as a lower anchor point and the slope of an ERF from animal data. However, the true incidence of maid effects In sensitive humans at the NOEL is unknown.
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From page 76... ...
Of those, the subcommittee attempted to develop ERFs from the most promising data sets: exposure-response data for animal mortality and for human airway responsiveness.
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From page 77... ...
However, guinea pigs are more sensitive than other laboratory animals to mortality from exposure to high concentrations of an irritant because the guinea pig's airways tend to completely constrict and occlude the passage of air (Azoulay-Dupuis 1983; EPA 1993~. Therefore, the mouse data were used here to construct ERFs.
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From page 78... ...
air quality criteria document for NO2 summarizes the results of several studies investigating airway responses of asthmatic subjects exposed to NO2 at concentrations of 0.1 to I.0 ppm for 20 to 120 men. Results were erratic, and airway responsiveness tended to be somewhat less severe In exercising subjects than in resting subjects.
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From page 79... ...
t herefore, the difference in the proportions of individuals showing positive and negative airway responsiveness was used as a measurement of the effect of exposure to NO2. The subcommittee concluded that the data, listed In Table 6-l, are too erratic to model.
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From page 80... ...
For example, suppose one wishes to estimate the exposure at which an additional 10% of the sheep will experience an abnormal level of lung resistance. Because ~ % of sheep are by definition in the abnormal range, an excess risk of 10% means the total risk is If%.
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From page 81... ...
Similar calculations for other levels of excess risk are shown In Table 6-2. If sheep and humans are equally sensitive to NO2 when expressing dose on the basis of milligrams per kilogram of body weight, then a dose of 0.86 mg/kg corresponding to an excess risk of 10% is 0.86 x 60 = 51.6 mg total of NO2 for a 60-kg adult.
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From page 82... ...
Based onits analysis, the subcommittee concluded Hat the paucity of exposure-response data for nonle~al end points makes it impossible to construct ERFs for most of the TABI E 64 Excess Risk of Increased Lung Resistance in Sheep Exposure Excess Risk mg/kg mg mg~min/m' ppm~min 0.056 3.4 310 165 0.01 0.24 14.4 1330 710 0.1 0.86 51.6 4750 2530
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From page 83... ...
The magnitude of the uncertainty could be determined by calculating the expected number of individuals at risk with the ERFs shifted higher and lower; however, there are additional uncertainties if ani~nal data are used to estimate effects for humans and if the slope of the dose-response relationship for one end point is used to estimate the slope of dose-response relations for another end point. Given the limited dose-response data available for the rocket-em~ssion toxicants, Chapter 5 recommended that either an expert elicitation process be used to estimate ERFs or the hazard-quotient-hazarci-index approach be used to characterize risks.
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