Document JNED6Lvo3oZZjq7M7Ere2vRdZ

Federal Register / Vol. 51. No. 119 / Friday. June 20. 1986 / Rules and Regulations 22639 :,A ' !* ;| - K s; . r. f. L V V; RL/RE)-l = KLxfd,-,0 (Eq- Z) which when extended downward to levels of exposure below, which observations are showing, on the left-hand side, the excess relative risk (excess SMR] as a function of KL and total dose (Fibers times years). II is.lhis form of the available, are not inconsistent with linear low dose extrapolation (Ex. 99. p. 13). And. in his testimony, Dr. Weill concluded: equaiion that is used to derive the Now, as far.as the shape of the curve for individual Kt's for each of the eight the important malignant consequences of studies. These eight KL's are used to asbestos exposure. I think we are all in derive one overall Kt for lung cancer. Then the excess risk is computed for each five-year age interval; the overall lung cancer risk is then computed as the sum of the risks in each of the five-year' intervals from age 25 to age 70. The agreement so far today, that the evidence does not permit us, nor does concern of public health or prudence permit us for the conditions that we are concerned about, to develop on any basis other than linearity of exposure and response in'.a no threshold model (Tr. 6/19. p. 154J. excess risk is expressed as the number of additional lung cancer deaths per . 1000 workers exposed for a specific time period. Evidence or the linear dose-response relationship for lung cancer is found in Dr. William Nicholson of the Mount . Sinai Environmental Sciences Laboratory elaborated on the rationale for the choice of the linear model for lung cancer; several well-conducted epidemiologic studies that examined lung cancer mortality in relation to cumulative asbestos exposure in the workplace (for example. Henderson and Enterline. 1979, Ex. 84-10; l.iddell et al,, 1977 Ex. 84-59. and Dement et al.. 1982, Ex. 84-35). In the three studies cited above, workplace asbestos air concentrations were available from measurements made in the worksite studied. Although the In three studies in which it (the linear dose'response curve) has been demonstrated (see above Exs. 84-46, 84-59, and 84-35| the range of exposures is targe, over a tenfold range of exposures, that linearity has been documented over a tenfold range of dose. Further, it has biologic plausibility [Tr. 6/19. P- 75). This biologic plausibility was also discussed by Dr. Kenny Crump, testifying on behalf of the AiA/NA: studies differ in the magnitude of the risk found (discussed later in this section), all three demonstrate a linear relationship over the entire range of. observation. As stated in the November proposal, other scientific and scientific groups There is.a theoretical argument (Crump et al.. 1976) that suggests that cancer incidence should vary approximately linearly with dose for low doses particularly when there is an appreciable background of carcinogenesis in unexposed-populations. ... If asbestos induces cancer through the same mechanism as smoking, then there is reason to believe who have aitempted to estimate risk that the response should be approximately -from asbestos exposure have used the linear at low'dose . . . just as assumed in linear model Tor lung cancer (Crump, Ex. the OSHA model (Ex. 237A, pp. 8, 25|. 85-22, British Advisory Committee on Though Dr. Crump noted in his Asbestos. Ex. 84-218. Acheson and Gardner. Ex. 84-243, Selikoff. Ex. 82-2. EPA,. Ex. 84-180. CHAP, Ex. 84-256, National Research Council/National. testimony that the linear model for lung cancer "is a hypothesis which is by no means proven" (Tr. 7/9, p. 90], he stated during cross-examination that "all of the Academy of Sciences, Ex. 3211. The estimates I have' made in the testimony model is generally accepted and OSHA were based upon a linear model for lung believes use of the linear.model for cancer" and that the linear model for predicting lung cancer due to asbestos . asbestos and lung cancer "has been exposure is reasonable, and well- widely used" (Tr. 7/9, p. 118]. supported. Although participants in the Thus. OSHA feels confident in its . rulemaking pointed to the uncertainty ' adoption of a linear model to predict the associated with the use of the linear risk of lung cancer from asbestos ' mode), no one suggested another model exposure. The model has wide support for computing the lung cancer risks. because of its scientific plausibility and Dr. Hans Weill elaborated on this reasonableness and its prudence for use point; in public health decision-making. ' "* ' As regards the shape of the dose- B. Data Used in the Calculation of response slope, and operational judgment is . Individual AL's. In the November based on the conclusion that there is proposal (48 FR 51125], an estimate of currently no available evidence.that convincingly proves that the slope is not linear, crossing the |excess| risk axis at the origin. This assumption (as made in the OSHA risk analysis) is justified from the observations at moderate and high levels or exposure that generally indicate linearity. lung cancer potency (KJ was calculated for each of 11 studies using equation 1. For studies with individual exposure data. Ki was the slope of the regression equation fit to these points: for studies having only an overall risk estimate and average estimate of exposure, this single point was used in the calculation of KL. For each study, the best estimate of Kt is indicated along with a range of. uncertainty. The ranges given are the result of uncertainties in estimates of exposure, methodological uncertainties that led to alternate evaluations of risk or exposure, or, in some cases, statistical uncertainties associated with the use of small numbers. The differences in-the KL`s among the various studies result from a number of different factors. There do appear to be actual differences in risk depending upon the nature of the asbestos exposure. One potential explanation is that workplaces differ with regard to fiber size distribution (long finer Fibers appear to have greater carcinogenic . potential than coarse fibers). For ' example, as several participants in the rulemaking acknowledged, there appears to be a distinct difference in the risk from mining and milling and other processes. As Dr. Nicholson summarized: 1 think 1 staled this morning. . . the possibility that the mining work environment may demonstrate a different pre-unit risk. That Is. there's three studies showing somewhat lower risks. At least two of them show, with fairly substantial data, lower risk, . that that [lower risk) may be a function of the fiber size distribution in the mining environment. One may have a much greater number percentage, of long curly fibers, which are readily counted, but are not inspired. And. thus, the Fiber counts are proportionately high in that environment relative to the amount of asbestos Inspired. It seems to be consistently so for chryBotile and also for amosite. For example, one finds very few cases of mesothelioma associated with amosite mining but a considerable number associated with amosite manufacturing. And so there is perhaps a difference in the mining environment, where they are working with different type of fiber composition (Tr. 6/19. p. 127). Thus, where airborne fibers are relatively coarse, the Kc's are lower than the Ki values found in studies of textile operations where fibers are fine. Differences may also be explained by variations in study design and other factors influencing the ability to define the dose-response relationships. One of these is the limited knowledge of past fiber exposures of those populations whose mortality was later evaluated. Prior to 1970, few measurements were. made in facilities using asbestos fibers. Further, those measurements that were done usually quantified all dust present in the workplace air and not just fibers. Current techniques, which involve use of membrane filters and phase contrast GLEASON-000881