Document NEor0gEJqoz6EXpyRmx99GyMR

Federal: Register / VoL 51* No. 119 / Friday* June 20, 1986 ./ Rules and- Regulations; 22645 Aapointed outbyDr.. Weill in his written testimony* "Exposure-response relationships, havebuen reported using, as the biologic response indicator either a constellation of clinical hidings to. define asbestosis,.or certification.by a worker's compensation panel or board" [Ex. 99, p. 24J1. but such.approaches have "varying.degrees 0flimUation"'[Ex. 99,. p. 12]. Because of the many possible combinations, and'therefore "definitions" of asbestosis given by different'groups, the quantifi'cation.ofa' single risk associated; with.asbest'osi's is' difficult. As'Dr. Weill'noted' during cross examination:. * * * The problem is, with asbestosis,. the quantification is not'exactly the same as it is with malignant disease; because one is dealingwith'a'different set'of rules in the ascertainment' of this health effect: And no two studies have exactly'lKe same:scheme for making:a decision, that this-individual has asbestosis and'this individual doesn't- fTr. 6/ 19, pp. 205-208]. In his prehearing1.testimony, Dr. Weill explained further: Mortality date'are not useful in'quantifying the risk ofasbestos-induced liing'libroBi'a (asbestosis): Affected- workers may die with asbestosisbut.notsof iti in whichcasedt is not likely to appear on .the death certificate; as the primary causeddeath. In contrast; sensitivity of. detecting.eariy evidence-of asbestosis In a living exposed population has increased substantially in recent, years. . . . Since much of the asbestosis being seen now is- theresultof lower dusf levelh in the past two decades, the fllma are likely1 to be classified in the lowsrcafegoriee-of profusion' of small opacities, (fewer shadows.meaning' less severe disease). As ia.frequently the case with biological measurement's*!!, is at:these lower.iimitis of disease,detection, that Interend Intra-observer variabilityis greatest. Again, it-is gratifyi'ng to know that in-spite of these'recognjzed'problems; excellent exposure-response'relationshipshave resulted1 from the.radiographic classification described [Ex. 99.23], Quantitative studies' exist,, primarily for the disabling- forme of tlie disease: specifically, two- separate studies provide informationTo develop at doseresponse relationship: between- asbestos exposure andincidenceof asbestosis [Ex. 84-254 and-84-44.]' Detail's1 of the data-were reported'at 48FR 51130. It is clear that material' impairment bom asbestosis occurs' prior to the; onset ofits disabling stage. As discussed: in: the1 November proposal, Berry etal. [1979i Ex: 84-20]; studied: a- group of 379'rhen> who worked atan-asbestos textile factory for at least 10 years:. Dust measurements: were available:and'were correlated: to'each, job, performed' for. each:year under study. Health; effects- were-correlated- tocumulative exposure.,Using prevalence data, Beery et-al. found a dose-response A similar conclusion is-dea-wm in. the relationship, with, cumulative exposure, report: of the-- British. Advisory/ Committee (f-y/cc) for three endpeiritsi, crepitations-, on Asbestos,, when- the committee-noted- possible asbestosis, and: certified, that: "The-present-authors-come: down In asbestosis* In. addition* these: data, also1 favorof.a, dose-response relationship- support the'hypothesis that, there is. a [asbestosis] without' at threshold for low,, or possibly no, threshold for chrysolite within the range experienced asbestosis, since, there- is increased' risk in industry'"[Ex*84-218;.volume:2*p: 38]. at cumulative, exposures: as low as-37 Based; on: this- recommendation. OSHA fiber-years/cc.. did.employ a, linear model in the: Berry and- Lewinsohn' [1979, Ex. 84- prediction of risk from asbestosis,.but 254]' have reported the incidence, of made no-uttemptin.the proposal to- asbestosisin this same'asbestos textile- extrapolate the data below the 0.5>f/ec, factory:. The population-was divided into level or above-the-10.f//cc-level using two- cohorts:, those: first- employed- before this: model.. 1951- and- those- employed after 1950; A Based on1 the threecohorts-discussed dose-response relationship is- apparent above; OSHA calfcul'ated estimates of for the ineldfencedaia* though it is not the lifetime incidence of asbestosis for quite as consistent as-for the- prevalence the Finkel'sfein, Berry and Lewinsohn data. pre-1951 cohort, and the Berry and1 In a second study,. Finkelstem [1982,. Lewinsohn posf-1950'cohorts, Ex. 84-44] looked! at- the development of respectively; The-estimates from the compensable (.certified;)! asbestosis- 'three cohorts differ By an approximate among 201 workers at an asbest'os- factor of three. This may be indicative of cement factory in-Ontario: A.dose- some of the methodological differences response relationship wBsdeveloped among the studies'. For example; ibis- using estimated cumulative-exposures possible'that'the estimates made from based- on plant: dust measurements' and Berry and Lowinsohn"s data' maybe using medical, information'from the- underestimates. The'maximum duration Ontario- Workmen's Compensation. of follow-up in that study was'23 years, Board. with an'average follow-up of'Iff years. As-noted by Dr.. Weill; "A fina-l Observations' from Finkeisfein's'data complicating'aspect ini the'development' (his Table 1)!demonstrate' that only 41% of exposure^responee- information: on (23/56 casesj'of total incidence'wbs> asbestosis is that it is a slowfy progressive disorder which- may (-and! experienced in the first 24 years: since first'exposure, That is; 59% of'the frequently does), continue to worsen after exposure ceases" [Ex. 99* p, 1'2).. OSHA soriginal estimates of risk, were-derived from- a simple linear regression' of the- incidtence of asbestosis on the midpoints ofths cumulative exposure dhta of Berry and Lewinsohn and of Finkel'atein. A linear, relationship was assumed, at least for the point estimation-of, 0,5 fibers/cc for 45 years (or 22.5. fiber-years/cc). As Dr.. Weill stated: While the shape of the dose-response curve for osbestosis cannot be determined with " cerlainty, it is clear that this fibrotic effect is dose-related, perhapslinearly,and whether a' asbestosis' incidence was not'expressed until at.least 25 years from onset of exposure; Thus, it is likely, that the low incidence rates in tlie Berry and. Lewinsohn. studies (and', thereforethe low estimates of. risk predicted from these data) are reflective of the short' follow-up-period, for this group of workers. On the other hand, Finkelste.in's (-1982), observations may overstate-tiiei incidence of asbestosis because at . autopsy there, was histologic evidence of silicosis as well as asbestosis in many, men. Finkelstein states that "we have* nevertheless, chosen to call their threshold exists may very well depend,on the disease 'asbestosis^as we Believe-that'is response indicator chosen-[Ex: 99, p.ll). the pathologic process of most- The assumption.of risk linearity is consistent with-the fact' that early stages of the disease are observedat low . exposures. This point was reiterated1 by Howard Ayer on behalf of the Organization Resources Counselors, Inc. when he1 noted that: It does appear clear that there is a simple linear relationship bet'weentKe frequency and degree of asbestosis-and' die cumulative exposure toasbestosidust, Time is'merely a' factor in that'it takes a certain-amount of time--at.least a matterof years--to develop significance. Most of the parenchymal radiographic abnormalities- were'smallirregular opacities, and the mortality . - pattern among the men was,consistent with the toxic-effects of asbestos" [Ex; B4-44. p. 5001- More importantly;, it.is indeed possible that all of these: investigators may haveunderstated- asbestosis risk, by examining.only, certified! disability from asbestosis!.which: istam advanced- stage of the- disease:. As: noted; in- the' Novemberproposal* there was'evidence the effect on the lung |Ex. 91-10-2. pp. 4-.r,j. of the early-signs of-asbestosis at levels GLEASON-000893