Document vB5mp5bn1Kpm19pdq2wM73vZY
*'2*'j* *'*'' ."-;-1`tJiat threshold _ a t '-^vv* *.<dii*"4sisfe>ie.U 'substances* even, the most.potent^v
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the mechanism or at.crude v. . _,.------------ ------ ---------a^and does^document {ftet> . ''lat?high-'dosapi::^'^(l?iebuldJfind no studies of ,* - ' asbestos-related healtheffeets^testing for no
offset dose levels in humans. *ven very strong carcinogens such as sethyleholanthrene,a polycyclic aromatic hydrocarbon, have been shown in animal studies to have levels below which no carcinogenic . effect occurs. [Bayes *751 nils and several .. . othersubstances tested inanimalsahov s-'shaped .
?$4da7*t*pona.curves, which is;hlso:;'cohtiii*ht-^ith^ " the known .toxicology of chemicals whirhi'Sve toxic
effects other than carcinogenesis [e.g. ,\ead, cyanide,
etc.l,
`: ... - .... '
One reason for; the-' lack of studies testing the. no effect level for low incidence cancers such asasbestos related pulmonary ,cancer or meso> thelioma is as .follows. vlf at cancer occurs at the rate of 1 per 10*000 or*1`person*, million as a result of an aabestosexpOsure.inorder to test"
047
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l>bttw*Vhil^' ftoV^mne^ouia'.occur [with -->.f/ , - 1
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iiibitively
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dose-response data do have an S-shaped dose. response
curve with a definite safe level, [see Figure For such substances the body's normal netabolic ana
other defense mechanisms are capable of handling small quantities of toxins. Pathologic effects occur only when the body's defense mechanisms are
overwhelmed quantitatively. Such common toxins as
.ctharibsonprminocniopxaidler*epcyeaanteiddelya.ndClyeaandidhea, vefodreemxoanmsptrlaet,ed _
begins to exert pathological effects .only when the quantity absorbed into a human system.is greater than that quantity which the cyanide metabol'c hway
, is ablevtoJtandleran even more common exempt is our (
. exparieneefai/individuals with alcoholic beverag
1
Although thequantity varies somewhat,,all healthy human
beings e^n' tolerate low to moderate?,levels.of alcohol
ittaxe without feeling or developing .any;toxicologic
Efecto The mm li true of silica [sand].
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v>:
n n aWm.
CRMC-M&S-002977
Iiiifili!
Mr. Jamie B.W. St*eh*r
P. ag* three
Oetobii
1
tl^,jiliu*4'V0ff4*t*rninVt/o%o*f a safe level
.:*_x_p__b_s^u12."r*Va__re_ Ua_e_v-4e--rai;proble,f'mUas..* f Mfoil s' t- -
lurements .of."suspected effects/of ;asbestos rely
Si on verycru_d_e_._i_n_d__ic_a__to_rs^. auch aa. group,mortality
-
.ft.. by cause. Also, diagnosis ofvsiesothelioma is not uniform^ Various studios ofAagr**m*nfa-b*tween path-,
Ss*'>U
Sill
wortalityrelatedtoasbestosexposure/there, is no i way at presentto separate out effeets duo to other types of exposures.:/ Investigations, relating axeass : .morbidity...and/or aorta1ityto asbaatos-exposure are --^wt^wtl^^g^rejgau-g^otheg.
'i
contr6iled:>direUiBscaneasfto alimi'hatafothar/carein
genic .agents,;; human epidemiologic studies have no
such assuranceyespecially in the involved industries
where other^earCinogens such as arsenic," haxavalant
, . ehrooium,fhi*ckl*,^ beryllium, and cadmium .are known
rto^oecuriat^retftively high levels. Similarly, many
mmm
" /^hinah^tudi^Sido^nbt':even attempt.toaceount forthe obviousconfoundingfactor of,cigarette.smoking, ,, ,
a*n*lyffalt to. aceountjfor.far and away -
st"proportionof human cancer deaths.'
' *"
ling.with a .substance, the toxicologic
loot'**}completely,known,,when a
^am*W*<Mi^S5to|b*j in' excess' b s" > in-m|%*^pi*3TOs*d^tbasb*'stoSr.ithis.baanganarally
entirely attributbd^to'asbestos; Man&such associations
may eventually be shown to be indirect, that-isassoci
ated with both asbestos and the pathologic outcome, but-,
in fact caused by a third factor common to both.
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I
Measurements of-airborne levels of asbestos which
occurred proximal to individuals who later developed
pathologic effects attributed to asbestos exposure
are poorly, if at all, documented. The airborne trposure
levels which are recorded are consistently well above
the levels which are now accepted as legally safe, which
arc in turn 1000 to 100 times higher than the levels associated with Garlock product usage. Investigation
of relationships between airborne levels of asbestos
fibers and pathological outcomes have often been separated
049
"iV,
CRMC-M&S-002978
JS&$.
, :s
*. - v'. {*-y'*+*(?'
Nr. Jamie B.w. Stecher Bag* four October 13, 1980 , > * ' ' ' \ * -r ' >v,, t \\, *r:. ^ ^ 5 >'*,a
'. into
^ *'. >4S3
for'asbestos, in cancer infeidenS*T^thi^spMeiii61dgi< investigations show, a > clear trend.of increasing
incidence of .pulmonary xancerin trades : and groups i with the highest expected and demonstrated levels of asbestos exposure tasbestos^miners, millers, asbestos production workers, and insulators]. iSelikoff '73, Newhouse *73, Wagner *60, Rubino *72, Elmes *71, Enterlixe *73, McDonald *74, Cochrane *78 and Basan'78].
l*"*fs<. ' \ * z*?z+ .V 1 Zs there a safe or threahold level for asbestos exposure
\fJ-r
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v'' f:'
.> 5- f
good
data
to
r*Ma. a' safe level of 'asbestos exposure assess numerically what.that level is.
There is significant data suggesting what the level is
not. There is a large amount of data suggesting a.
strong association between mesothelioma and relatively
high levels or levels above where Z would.expect that
threshold to occur. .Human.epidemiologic studies _indicats
mesothelioma related:lifelong asbestos exposures ranging
upwards from 5 fibers per cubic centimeter to as high
as 100 fibers per cc [Nicholson '79, McDonald *?0.
Berry '79, Selekoff '76]. Such studies also dio.ee
a trend of increasing mesothelioma incidence associated
with increasing duration as well as increasing intensity
of exposure [Newhouse '79, IARC' 79]. Because MM has
such a long latency period (average 30 years] and
because asbestos exposures which occurred 30 to SO
years ago were not generally or precisely recorded,
there is essentially no precise data correlating airborne dust levels and MM incidence.
. ..
0o0
CRMC-M&S-O02979
vl-i i'\\*S "-i *
Mr. Janie B.M. Stachar Page five October 13* 1980
iilpl
The literature which ia available on mesothelioma attempt! to measuredoae interna of length of employ' ment or veara aince^firatemployment [Selikoff '79, Seidman *79]. Nevertheless, this data does auggeat a threshold relationship, aineefor example Seidman's study showed no mesothelioma incidence in males with . less than 8 months employ in an amosite asbestos factory. Many other studies combine all pulmonary .cancers, including bronchogenic carcinoma and mesothelioma in one.category, so itisvimpoasible to, Jinterpretfsuch.data in terns of, mesothelioma., incidence ;'alOM.^t|&esafdfrdct^im9ieitoraiWexpoaurea'.sueh^aa [ duration ofemplOymentandhypeiOf work are available' .and lndlcate that oceupational MM eaaes have occurred
iwlttefibeEeMK9iutia4fthighiintensity,- arrincla^^^iiffi^aod^{Hcl)tihifldMfjji^jtilklmats-i
lofldeatha&duffit^MMiihice^iiHi,.--
77i * -^*v-vr ;
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The few long term studies of highly exposed groups such as insulators [Selikoff *79] asbestos factory workers (Newhouse *79) show similar findings. There have been no comparable studies of MM incidence in groups with exposures at very low levels consistent
with those levels generated in the use of Garlock
froducts. Further complicating the threshold issue s a suspected difference in the carcinogenicity of different.fiber types. Xn decreasing order, carclnogenie poteney (the lesser amount of asbestos fiber causing^tbe same effect is considered the most potent] may be crocidolite, chrysotile, amosite and antbopholyte
as shbwn in.some human and animal studies (Wagner *77, Meurman *74, XARC* 77]. Although the order of potency may vary, according to different studies, it isi generally accepted that carcinogenic potency does vary with fiber type. Unfortunately, many epidemiologic human studies or MM have either mixed or unknown fiber type exposures. Recent studies have shown differences in carcinogenic potential mccording to fiber length; the longer thinner fibers being more potent carcinogens [Davia.,79, Stantu* *73]. Xn support of this hypothesis. Stinger. -Jound no significant difference in carcinogenic potency if different fiber types administered to animals were all reduced to the same size. Such findings suggest that not fiber type of asbestos but rather fiber length is the critical factor in tumorogenesis.
: s 05i
CRJVTC-M&S-002980
U MVm <?* ** st9eh0T
!"agm si*' '
-- .*'*
>*JV.OV c' to'b' er -1~3, 1a*98a0t ^ ^*w *"* ;rn^&mi
if e- */' -sji-a * ' , . T*,.vi O,,\V* * i
Zf so, the length of th fib*r generated by the particular industrial process may be more critical than the actual duration, intensity or total dust exposure. . A^strong association.has; been shown between high asbestos exposures and`NN. mostly on the basis ,o occupational histories ehlehiShow; employment in or around a very " ..... tredeA Most mesothelioma eutopay
i. cases witha^likellhood :ekp6sur*;;lpng|Srior4`t'
is-li
*tion:( live!;
'^f^it^sIi^Sfectiat
verylovfiberievelinasmaHSri
|of-subjects;
is not .supported- by known toxicologic^principals,
laboratory.investigations, or human-experience.
Cases have been -reported in which exposure to asbestos
was by supposition or history,apparently lower than
in highly exposed occupational groups. Such cases
have occurred in children or.spouses of asbestos
h:-j
workers-or in occupations having*casual asbestos exposure or in'neighborhood contacts (Anderson '79,
Viano *78, Mostert '79]. - Yet .the environmental
sampling data which'exists for homer, and asbestos
factory or min* neighborhood exposures shows levels ;
10 to 1000 times the levels in ambient urban air
(ZARC 77]. Also the likelihood of a short but intense
exposure during clothes washing at home is high
considering that in those years dusty clothing was ;
worn.and washed at home. Most of these studies
either indicate amoslte, mixed or unknown fiber
types.
estimates of asbestos incidence during and prlr<r i.c the present MM epidemic ranged from .07% of autvipsies between 1910 and 1943 to .24% of autopsies between 1950 and 1970 in general populations -(McDonald *771. This shows a substantial increase in MM occurrence but does lend support to the observation that approxmately 1/3 of the MM cases may have no relation to asbestos exposure sine* they would, have occurred .
CRMC-M&S-002981
I .. "
, r*
k. , .v-
^Kh --* ,
r:,y >*, > '
V > ' '^' ' - * , , ' , .
Hr. Jamie B.w. Stecher
Fiji seven
V-w"*-
r
4*1.
during periods when asbestos was not used heavily. This observation has been borne out in most recent autopsy series where history of asbestos;exposure ranges from 40-87% of MM eases [McDonald *77, Sines *67,Viano *78, Hasan *77, Borov '73, Oles *71. The .International Agency for Research on Cancer has"suggested that., approximately 851,of MM cases.are
* investigations reported in the literature iveldonefilCtWMivehifor^any^reaote indlcationl of' ' ..igeriite|4xpbstfresIandyil^artyliuchM*b4jfo ioxpc*ufif|i3^tascribeitA^causati6i^@hSPteaseltpji ,, asbestos wxpoS^ref^Sibilarlyi:?som^|W^i^rtslinSvhic ; novobviousi asbestos exposure has*' beeh'Jfouhd5iay|bep| implied to be due .to exposure to anbient asbestos "" without any other basis in fact. In-ether words, because MM,occurs due to high exposure levels. it has > been assumed with very weak supporting evidence that it similarly occurs due to low levels of airborne fiber exposure. Mo control studies of low doses in either hunans or animals have been done. Animal Investigations of MM resulting;from inhalation as well as intrapleural administration of asbestos fibers clearly support a dose response, threshold i relationship with increasing rate of MM occurrence in association with increasing levels as well as duration of asbestos administrations. Wagner's rat studies [1974] of asbestos inhalation exposure did however have 2 eases of MM. at the lowest dose level, one each related to croeidolite and amosite exposure respectively. However, the dose administered over a 7 hour period for one time only was 12 mg per cubic meter. Although this dose is not directly convertible to human dose measurements in fibers per cc. Z suspect it is roughly a thousand to a million times the dose found dally in heavy human asbestos exposures fVreu on a comparison with data from Nicholson and Sewtscxan* p,34 XARC]. Zt is not unlikely that even one such massive dose could overwhelm the carcinogen defense mechanisms of rats. Other animal studies involving oral inhalation and intrapleural administration of various asbestos types have involved doses far in excess of what would be expected to occur over the lifetime of a worker exposed exclusively to Oarlock
053
-*
I
1
C.RMC-M&S-002982
A?*>*<!. '
/**
*. ~ Jisit
BW
Stwcher
eight
^ '
i- .<% v ; y +
fiiipl
1 f ^ 'AcodoetB.' Althoughltisstrictly,conjectural to
iSS*,1 ..' >U.<i
compare doses.In milligrams-per;eubiCiweter,.to fibers per 'CCf based, on what little comparison data is
available l suspect that thedoaesgiven in most of
khei*ii8liiiii^^
iprOdUCtS iafe;
'The existence of a threshold-is- further/supported -Whitwell's.studies of fiber, content in /lungs from MM
%.i^,s.;r.&.,
ml
iPa^ients. o99fOf ^MH;'.caaes,>with, a ^.significant ssbestos
IV
IS',
x. X*V\* /*4M
SiiSSlI
1...
ml
'-KH'VcSses$hSid of dried It:
fc>Ki^fiJdjtil|&5&ii
levelsland ihigh,occupational expoiure?levels . .
women^in^tbis^study^who had KM, who had a history i
ahortduration exposures, had greater*:than 250,000
S grams of dried lungtissue suggesting
ryjintense axpoaures. Khitwell also found
tjmesothelioma control patients. from urban
h'ghexsppeected ambient* asbestos ^exposure
Nholdl thaye.highlungfiber^counts.V
itwell'finterprets^tbis. data^as^CirmvSupport'Of
aponsejfethresholdrelationship between asbestos //
.IjAshcrbftSj findings.;are_-similar;`and' add support
?hS^thesiMt^t|,S':;thre'shold.: exists rand/ it may be a:
l-;not|heceisafilyitol/lSngth'Sof/.exposure but .to the
totar-lifelg/cOSMiatlvo''dose.'-ji%^.^
V ,;
A possible explanation for MMoccurrence! in individuals
with .minimal asbestos exposure "[assuming a threshold
exists] is related to the animal and human studies
showing MM to be due to exposure to other non-asbestos
form materials (as well as asbestos] many of which have
similar fiber characteristics (manganese dust, silica,
polyurethane, diatomaceous earth, beryllium, fiberglass,
and avian leukosis virus (Stanton '73,
Sorows '73,
Wagner '62, Bueper '64, Chabot'70,and Weh#tvr '65].
Baris'('791 investigation of a MM epidemic .n Turkish
villagers having negligible asbestos exposure shows
an association between MM and seolite fibers which
he suggests may be the cause of some other non-asbestos
related MM. Obviously, many of the above mentioned
substances are encountered In the industrial and
urban environment and could be the cause of MM in
054
m6*to--\-3tr-Sh &
'^1
CRMC- M&S- 002983 (
f 1s
Mr. Jamie B.W. St*char Pig* nine
October 13, 1980
' -V
k-; /' .. .5* n *,, < ** `5'.*
. persons with minisalor negligible asbestos exposure
\ ^4;V(!<a
uhistory.Xdoubt'.if many of the inv*stigstors inquired
. l?,~5 ^Ijss.^Mply^inte^pohsibl*;history, of^exposuro; to, thiH i
J?>f.^VvV*^IM 1
<*1-5`*4yJVijV" *i?.
mu
only asbestos oxposar* would'result'frbm useof Garloe
products?'
- ,, rr v, r,. -
- -o V .V,.* t""* *v`^ V
*#.- .< ,,
Because do data exists for exposures'of *006 to *05 fibers per cc, [the levels encountered during Garloek
produet usage] estimates of risk are purely speculative. Crunp states that the effect on carcinogenesis will be
proportional to t.i* amount of the carcinogen added if r
the subject resides in an environment with multiple
carcinogenic processes. , At very low doses and in
the presence of other possible carcinogens also
'commonly/eneountered",,in ^shipyard and other asbestos '
related industries [seolita,: manganese,' .fiberglass] , i
'the role of low levels of asbestos in MM occurrence
could possibly be completely overshadowed by these
other mesotheLlioma producing agents.
Pete ['79] reasons that if an exposure is reduced by a given proportion, the outcome [MM] will be reduced similarly. Zf we assume-an average proportionate mortality [% of all deaths] due to mesothelioma of 7% in insulation workers exposed to approximately IS J fibers per cc, on a time weighted average, an estimate of proportionate mortality at .03 fibers per ec iivetage Garlock product usage level] should according to Peto's model equal .03 divided by 15 x 7% which equal .014%. This is certainly less than the .031 proportionate mortality found in the United States prior to heavy . asbestos use [McDonald '77].
055
CRMC-M&S-002984
ji , v!' "V
Mr. Jamie B.W. Stecher Fag* ten October 13, 1980
. '*=' >
life 'h1 > * '
SSI
4. .... ...
Thai* crude calculations show that avan if a linear dose response relationship exists, it includes a KM asbestos exposure threshold above the levels encountered by individuals whose only asbestos exposure Is useof
" 'lt>vthereore.v8uggestsn:that-exjposurs ,one at no greater risk for,MM ^ than
wit theIiiMsfis:;`iclehsimrrmipsimi,'s 1'8d]\
f-^study... of, ambientasbestoi ''lii^lWlbJspprbxioatelyrjlO T.3t9*newX^oficefsnd:,(s__r_b_o__fib. md&as^n^ininigi '
,.4
la: products would be;at'theisame\rI5b?ot^bestos^Tllhtei disease as Garloek product users.Zn fact, approxi mately 25% of the cumulative life long asbestos exposure of persons whose only asbestos exposure would be through the use of Garloek products and attending school would have occurred during the 12 years of attending primary and secondary schools.
IV. Is there a safe level for lung cancer [exclusive of mesothelioma) and what is the likelihood of pulmonary cancer duetto exposure at garloek product user levels? Although ,-Xbelieve a threshold for asbestos related pulmonary carcinoma exists, as in-the case of MM,1 data has not beeh produced to determine where that levellies.,Existing data is based upon the asbestos
-.exposure levels indicated in the previous section; ' (malignant mesothelioma) which range from.approximately
lOO to 10,000. times that encountered with exposure to garloek products.-. Existing data does indicate a -strong association, probably-causal, between high, level asbestos exposure and bronchogenic carcinoma. . . Becklake [76] summarises these studies; which i^^cate relative risks, for lung cancer in -association !*-. asbestos exposure ranging from 1.5;to,17.6 with -a; mean of approximately 5.0 (relative risk is determined by dividing observed cases by expected and has decreasing significance as it approaches 1.0].
056
CRMC-M&S-002985
Mr. Jamie B.W. Stecber
Pagellevan
,V;
October 13, 1980
-
I ''*!
A< * ^ t **V-* * ^*- >`v .* -r^* i
* * * 4 14 * ^7-rrf" # H 1 . V*' `f ' -
f,V , '
I wm.
Complicating this issue is the finding that smoking -cigarettes and asbestos exposure act together to ; increase one's risk of pulmonary cancer in either an additive [Enterline '79] or multiplicative fashion, such that the risk of pulmonary carcinoma in the 1 preaenee of both smoking cigarettes and asbestos exposure may ,er may not exceed the sum of their ' individual-risks^[Sellikof *79* Wagner *80* Martischnig
*771.kSmoking.can affect the findings of studies; ;'^whicii|do|ia%a$lat^tbeiranalyses?iforS8mbking'haDitsr .
Iff--
Itsf!
_______ ;-havifbelifprfS^ exposure; levels*ith lung eancer^
..Also
in
some
of,
the human studies * it swears that KM ere' included j. in
the lung cancerstatistics* the effect of which would
be to artifleally amplify the relationship between asbestos and lung eancer [McDonald 1979, Henderson
*1
1979]., Nevertheless, McDonald's data supports a linear
dose response relationship and:, threshold level for
asbestos and pulmonary canccr at approximately 90:
fiber years of cumulative-exposure [fiber years are
determined by-multiplying the mean fiber concentration
per cubic - centime ter tiaes.the total number of years
of exposure at that, level]. " Garloek product users
would be estimated to have from ,3 to 2.5 fiber years
with an expected mean of 1.5 fiber years total cumu
lative asbestos dust exposure, if their asbestos ,
exposure was due solely to the asbestos generated
from the use of Garloek products and assuming a 50
year work life with an average of 240 work days per
' year.' : Similarly, Henderson and,Enterline [*79] ;!
suggest a good correlation between cumulative exposure
+.
and risk of pulmonary cancer mortality. Boweverj the
lowest exposure level which they had correlr..*jC '
between pulmonary carcinoma mortality and asb?-tds
exposure was 62 million particles per cubit foot/years
[approximately 120-180 fiber/years] which, like <
McDonald's data, is approximately 100 times that of
expected cumulative Garloek product user exposure.
Xn extrapolating to lower [as yet: unstudied] exposure
levels, Henderson and Enterline developed the following
057
CRMC-M&S-002986
.... ./.;
--.J
____ ________ ...................
.............................................................
fcr"''".'....... * ~
i 'V
1 Nr. Jami* B.M. Steeher
Pag* twelve
October' 13, 1980 tf ,5^<" , .
v\4, . ,
formula for standardised mortality ratios (1.0 Is
the "normal* basslins SNR]i 100 plus .858 times the
cumulative exposure in million particles per cubic :
foot, For Garlock product users this would be approx
imately 100.658* a negligible changes Similarly
McDonald's formula for. relative risk of pulmonary car
cinoma due to asbestos exposureis 1.0 plus .0014 times
the cumulative-dust exposure;. >- For. garlock product users
/it?
-this would be approximately 1.006 and indicates that out of every 10*000--cases..of lung, cancer, occurring in
Garlock product users* 6 would be due: to/asbestos '!
exposure. Using 1976 statistics* this would result!
in a total of approximately 55 deaths or an annual >
/rate of approximately 1 per 4 million persons exposed
` nig* that, far ..less /than 4
Lon^re>/exposed/to^arloc)c|P^uCtt7Sthisarist
/
`for*/ even wit&iuiHi^^^4boldl^^^^^^^^S5
at Garlock levels appears very low. If we accept t Peto's hypothetical model which.indicates a 1.8% rate or proportionate mortality of pulmonary carcinoma with
50 years of exposure at approximately;! fibers pereci
Garlock exposures of .03 fibers per cc would correspondently yield .00027% or 3.7 asbestos cancer related deaths per 10*000 deaths or approximately !/to 2 per million exposed per year.' As low as -thse.:estlmates are*vthey probably over estimate the impact of asbestos albner because smoking was not taken into account in either study. Unless otherwise stated* it is impossible to know whether exposed persons smoke more* less or the same as unexposed persons.
Several studies have demonstrated [Schneiderman '79*
Enterline '76* Newhouse and Berry *79] that pulmonary
carcinoma is related to intensity and duration of
dust exposure as well as length of time from first
exposure (latency]. If in fact there is .lo safe
level but instead very low level exposures result in extremely long latency periods which would well
exceed the lifetime of the individual exposed, such a risk due to low exposures would then be virtually
sero. Schirrlpa's analysis of exposure in school*;
office and general purpose buildings supports tnis
concept of extremely low risk of carcinoma during
present expected life times due to the very low
[comparable to Garlock] exposures presently encoun
tered in office* school and other general purpose
buildings.
*
n~ ~ UoS
tr i>/(
CRMC-M&S-002987
r *'**
*
4
PPf /r
**V" **&' <1'*?*t\'r^i?vs v,
^ '- ' s> , v+,fatt '-> wm^
. Mr. Jamie B.W. Stecher >*Page^irteen .;55y? J ^ S' ' v '*
/iSvIlMOV^1 \r*^-* v; ^*-w* '
#A';h
|*Tf J ^ Martisehnig I* 793 supports a dost responsa, threshold ' relationship between asbestos and pulmonary carcinoma
in his study of..asbestos bodies found,in autopsies , ofpulmonarycarcinoma eases. ' Be observed a statistically signifleant e relationship between asbestos > IflSIfbodiesvand;.khowti,r,hiat6ry:'.of^:asbestos:ixpQisure i^&Ba also found a ,higher rate of anaplasticcarcinoma in patients with, asbestos bodiesthan in patients i without, suggesting a specific tumor cell type rtla:. tionship to asbestos exposure. Weiss ['77] cohort of workers in a chrysotile manufacturing plant had , lover exposures.than.most other studies and found , !poXso^ryi4circih&standirdlaortalltygratios^below.
I
* * '! * .
mmmi
| the lungs of. patients with pulmonarycarcinoma regard-'
lessofvhethertheylived in ;an:urban or rural envir-
...nmerit^prloirStd- their death. Goff [*?2] ridentified v'
asbestosjrelated disease in an individual whose expo-
'' aure was inthe manufacture of 'asbestos, cigarette :
filters; [X am wondering if the increase 'in pulmonary
carcinoma in smokers could be related-to asbestos in
the cigarette fliters rather than.other intrinsic
'. > N^^tigittWbiologiea^interactions?!,^,
'
Animal"data, although shewing a clear, dose response
relationship, has not really tested for threshold
levels. Leong 1*78], Lynch 1*57], Gross ['74], Beeves
['74, '76], Wagner ['74], and Noordman have conducted
inhalation animal studies using exposure levels 100
to 1000 times in excess of Garlock product users'
exposure, and these exposures were administered
within a very short period in comparison to the i
working lifetime of a Garlock product user. In mice
; and rats pulmonary tumors have occurred with exposures
as short as 1 day [Wagner *74). Wagner's one day
dose, however, was approximately equal to the same
amount a Garlock product user would encounter
a 10 year period. Beeves ['74] study of rabbi**, guinea
pigs and gerbils found no pulmonary tumors. Goldstein
1*78] found cancer in one out of 12 baboons who were
;' subjected to approximately 166 fibers per cc for 266
days [approxmately 100 times the total lifetime
dose of Garlock product users].
05;
CRMC-M&S-002988
v
rc
Mr. Janie B.W. stecher Pag* fourteen October 13, 1980
it*
f *' * t > i'.Zn summary, the animal and human data ia strong evidence, i' X' , for a causal dose response .relationship.between asbestos * ; :
and pulmonary carcinoma, but it has not yet tested for " 1 carcinoma^outcomes at sufficiently low levels to determine whether or not a threshold exists. Furthermore, even . v -v .-iJt no safe.,thresholds, exist, the risk, for pulmonary . earcinomaduetoexposuresjconslatent withGarlock > . product use appears extremely low;. Cigarette^ Booking confounds and increases the risk.of asbestos niated pulmonary carcinoma and appears to have a multiplicative relationship.
athreshold levelforasbestosis and what is. ibeatoala.afetheilevelasfoundJln^Carlockl
tersl
As with' asbestos indiu'ced^pulmonary carcinoma, airborne asbestos exposure levels which have been associated with asbestosis [diffuse interstitial fibrosis] have been in the order of 100 to 10,000 times that expected for Garlock product users, whether expressed as cumu lative lifelong exposures or average daily exposures. . Asbestosis incidence rises with both intensity and duration of asbestos exposure (Enterline '79, XARC '77, Sellikof 78] Although a few family contacts}; have developed, x-ray or:clinical signs of asbestosis or other possible causes thereof were not addressed and no exposure data was available. Neighborhood proximity to asbestos plants may have caused additional and measured asbestos exposure in these patients. i Zn attempts to define a threshold Berry noted no signi ficant x-ray findings in asbestos exposed persons with less than 25 fiber/ years of exposure [Garlock product users have approximately 1.5 fibsr/years exposure]. Berry ['79] estimates however that; to assure a 1% prevalence of asbestosis, exposures should be in the range of approximately 1 fiber per cc or 55 fiber/years, but this projection is based on cases occurring as the result of much hicher exposures. Berry states that'it is not pfr^ibie to assess effects of relatively low doses [2 /ibers/cc] with today's data. Berry also found normal lung function tests in Individuals whose cumulative dust exposure was approximately 35 fiber/years [20 times that of Garlock product users]. Merewether and Price [1930] report of examinations of textile workers
0oG
CRMC-M&S-002989
--,}* j `yt-
` *,.
h&> 'Me. Jamie S.W Stecher r"' Pag* -fifteen ;
October 13t 1980
I formedthe basis for the exposure levels during ithe . .50*s ,,and, 0!c. Csing duration of employment aa an ' xposureCindicator, they fo--und no.evid e-nee^ofAddisdeainseg een.| 1 high asb*stos,*xposure;;and asbestosis;developedjdue - to-the appearance, of > thisdiseasealmost excli .in only the. heavily exposed work*raj. ISmithera *t `* The lowest cumulative doaea related to asbestos"
aratfiplliiiibi
rAJ / 1
- aabeatoais 'nortality-did>'tbd'eurlinfi<i^ht`piutil'oSi-r:i! high intensity category. This aupportc the concept of a cumulative dose response mechanism. McDonald further implies that at cumulative exposures of leas than approximately 100 fibr/years[or 2 fibers/cc] there is no increase in risk. Murphy's data t'71I shows evidence of asbestosis only above 60 million perticiespercubic foot/years [approximately 120 to 200^fib*r/y*ars) Animal studies.have supported a doae response relationship but have' not adequately v - testedjffor/avthreshold level.. Wagner's ['74] rat inhalation.studies shows minimal evidence of asbestosis ,,in rats subjected to 12 mg per cubic meter of. asbestos for'up to 6 months. The'mean cumulative.dose of asbestos J,, to which these animals were exposed was 8400 mg per > -cubic meter which is moughly;5 to 10 times that expected ' .over the working lifetime of'a Carlock product.user.
1 Although the'data for'a' dose response relationship is strong, data establishing a safe lev*, has not'been developed. However* there does appear to be afconsensus in the medical literature that low exposure levels do not result in the risk of asbestosis occurrence and do not merit the concern that is found in ri*ilon to similar issues surrounding: pulmonary and wu'sochelial
malignancy [Sellikof '78]. It is the recommendation of the National Institute of Occupational Safety and Health [*78] that a time weighted average of .1 fiber per ce would protect workers from the occurrence of asbestosis.
061
CRMC-M&S-002990
(
Mr. Jamie B.W. Stecher Page sixteen
October 13, 1980
As of July 5, 1980, the State of California Department
of Occupational Safety and Health (Cal OSHA] established
0.1 fibers/ec as its action level (General Industry
Safety Orders seetlon 5208(J)(1) p. 442.2.1]. In
the medical literature I reviewed X could find no j
. evidence in support.of a lower.standard.- l>ased on
the meager data-*above>t X suspect that the probability : <
- of asbestosis occurring due to exposure to Oarlock
froducts only'would be-in the order ofxero to 1 per
oo,ooo.-\-;
,|
&V2.x^en> should Oarlock have suspected La hazard due to
'Administration'standard"'contin^ei|?it?:2fO|fiberS0;||^|tpg)-l per cc, because most other industrialized nations' have a recommended asbestos exposure standard between 5.0 and .1 fibers per cc, because there is no good data showing toxic effects at levels lower than 2.0 fiber per cc and because Garlock product user; exposures are and previously have been well below: that,;I do not feel that Oarlock should have ever; suspected a hazard and X don't believes hazard exists for persons whose only occupational exposure to asbestos occurs as a result of the use of Garlock products. Even if it were ever shown to exist that a pathological effect could occur at this low level of exposure, the Garlock exposure levels are com* parable in many instances to those found in nonoccupational environments, and it would be very dif ficult to determine the relative contributions of the occupational vs. the non-oeeupational exposures. Because of the existence of natural asbestos deposits and man made non-occupational exposures (general purpose buildings].asbestos exposure occurring as a result of Garlock product usage barely exceeds that which could be encountered InvoluntarilLyy in the nonoccupational environment. Please be advised that the preceding statements, analyses and conclusions are based on the assumption that the environmental measurements of asbestos generated by use of Oarlock products are accurate and valid.
062
CRMC-M&S-002991
V*
r ,,k 1 *-. yt \^.
Mr. Jai* B.M. Stecher Pag* a*v*nt**n
October 13# 1980
r
*-aettad la a list of th* r**r*nc*a cited and 1 hav* additional * : f!2nc*saJdticl*s in efflet obtained during the process
Sf oSthHinS this data! X will be glad to forward to you all or arenyp9oprat.rt oOfnftohr*turneafeterelyn,cebe*cXauhseawe*oonb* taoifnethdeinreferences are in ;
Abi^iira ot fortisn loumalSf I have not boon able to review ail - of the articles I have requested, but will continue to attempt r< I / .' to cet. these articles, ^his has been a laborious yet most > enloyabl* experience and X am greatly looking forward to your
nsrm*n*of this report. r Xf you have any further questions, i can be of any further service pleas* do not
Cchaid"?oh*n, M.D.# M.P.H.# P.h.C.P.K.
RC/bw
' 1 'I
063
I
CRMC-M&S-002992