Document 8bgpwxm0xneDKnx46OZLxOZk

February 22, 1962 Memo to; Dr. Robert A. Kehoe From: T. Sterling Subject: Analysis of California TMJL Study The changes observed in the excretion of lead and in the blood picture o workers (who switched from handling TED containing products to those containing TML) are of such consistency and magnitude as to preclude any chance factors. The pattern of results would ordinarily force only one conclusion on the investigator; namely, that underlying changes in physiology or body chemistry had taken place during the period subjects handled TML. It is true that the data were collected in a somewhat haphazard and cavalier fashion. However, the most important findings are based on laboratory analyses of urine and blood samples and may be above reproach. It is a great misfortune that the medical follow-up data turned out to be useless. The results available now would make it appear desirable to complete tire collection of all the data and do it in the form originally planned as well as to extend the follow-up on the laboratory analyses for an additional year. Lead hovels in Urine and Flood 1. Data on lead in blood and urine were almost complete. Five urine samples were obtained during the year of study while two blood samples were taken, one in the beginning the other at the end of the study. These data are presented in a series of tables at the end of this memo. Consecutive examinations are identified as wRounds'* one to five. The number of samples are given in the second column of each table. Statistical evaluation of differences observed between consecutive rounds are based on Analyses of Variance. The statistical analysis is rna.de extremely complex by the fact that, while most measures were made repeatedly on the same subjects, not the same number of subjects was tested each round. The analyses are not reproduced here. When the probability of finding, by chance, a variation among means as large as the one # 2 observed was smaller than . 05, asterisks were placed on the table. (For example, the means on Tables 1, 2, 3, and 4 differ with acceptable statistical reliability. This is indicated by placing asterisks on each side of * Table in, * Table 29 , etc.) . Levels of lead in urine and blood as well as urine volume and spe cific gravity are given in Tables 1 to 5 for all workers combined, in Tables 6 to 10 for workers in San Francisco, and in Tables 11 to 15 for workers in Los Angeles. There is an obvious, consistent and statistically significant decline in the lead content of blood and urine. This conclusion is reinforced by the progressive decline in urine lead, over the period of the study, toward a new stable state. Cuch a progression would be expected, on basis of the lead chamber studies, whenever the burden of environmental lead decreases, istatistical significance among urine volumes for "All Eata" is not accompanied by any systematic increase or decrease and may be discarded as spurious.) Three occupational subgroupings were singled out, who would have relatively uniform exposure. These were service station attendants in San Francisco (Tables 16 to 20), service station attendants in Los Angeles (Tables 21 to 25) and Blenders (Tables 26 to 30 - all slenders are located in San Francisco). Again lead in urine and blood decreases for all occupations. It is interesting to note that the decrease appears to be most pronounced for Blenders. Blood Analyse A series of laboratory tests on red and white blood cell counts were made. Not all counts were repeated so that comparison data are lacking for: Hematocrit - Per Cent Reticulocytes - Per Cent M. V.C. M.C.H. M.C.H.C. Polys - Hetamyelocytes Morphology Platelets Comparisons of the counts listed above could not be made 3 The data were complete for comparisons on the following blood cell counts: Red Blood Count Hemoglobin - grams Color Index White Blood Count Polys - Neutral Total Per Cent Polys-Filamented Per Cent Polys-Nonfilamented Per Cent .Lymphocytes Monocytes Easinophiles Basophiles (Table 31) (Table 32) (Table 33) (Table 34) (Table 35) (Table 36) (Table 37) (Table 38) (Table 39) (Table 40) (Table 41) The blood cell count increases consistently (except for Lymphocytes) ^irn -n tn hr oxrtrrfrrh*), Not all increases are statistically signi ficant; however, since all increases are in the same direction, there can be no doubt as to the over-all change in the blood count. One very interesting fact emerges from the inspection of cell counts. In each case the change is from a low normal tjo the mean of the distribution which defines normal blood cell count. In the case of Lymphocytes the change is from a high normal to the mean. The blood data are too fragmentary to permit further breakdown by city or occupation. Some Conclusions The consistent changes demonstrated by the data lead, without dispute, to the conclusion that they reflect fundamental changes of physiology or body_chemistry engendered by the change in leaded gasoline. The total pattern of results is such that even if none of the changes would have reached an appreciable magnitude of statistical significance the former conclusion would have to be reached. There is no question, therefore, of statistical magic or manipulation on which conclusions are based. Two basically divergent interpretations of these findings appear to be possible. (The alternatives were derived through discussions with I-Iorton, Cholak and Grupp.) ^ ^P^tLfjLjUj^J V A. TML provides lead which is deposited in soft tissue in excess of excretion. The rise in blood cell count may be a compensatory lii Ud)T'i O'^hi) J ut jik -rP 1 j> ih? uiiuity^ fW*jc '' 5 --( U eMuLL KfT ir ~b-<> reaction as for example, to interference with blood oxygenation across the lung tissue 3.3 3 reaction to organic lead deposited there. inhaled in smaller or exhaled in larger amounts. The body burden of load being decreased the amount found in urine and blood declines to a new stable state and the increase in blood cell count represents the reaction of the bone marrow to the decreasing amount of lead in surrounding tissue and blood supply and a return to a more normal {if such an expression can be used) state of the blood cells. Since hypothesis A would indicate heightened toxicity to relatively small occupational exposure one would expect that this increase in toxicity -would have been spotted during the manua.cture of TML, where workers arc exposed to much higher concentrations of lead in the atmosphere than are the occupations present in this study. However this was not the case in the plants of the .Tthyi Corporation. Hypothesis 3 appears more reasonable and Caere is then substance to the conclusion that TML pre sents less of a lead hazard than uses TSL under normal procedures of 0 \J (; v S 9 9 Uria* Toluas in aftr Air Pstn " ~ - * v ' * v . . Wt;- : . :- - .'*. ? .<*.' :-' ;'. ; .* . ^` .: : .# : .`p Round of Testing .. - 7-7.,. V- ;'y; x . - .7777.. . 'V"7 ;: a .- V7 f'> C* v .* % ? _ ', t ; , . . * * ^. . * * , *. r .-j, < ' ' T.r , V- V* 7 ... '" ' '.. . , * %' KtodMr ,J; of-. Observations Jtean : 99 88.98.- > ".. - .- 8.9. 38.88 91. V 108.82 33.77 3 m 113.46 29.39 .4 , , `* s ' 80 . 7 w. 107.96 99.47.;, 31.94 33.16 " , ' ** ^ 9 7: V 7- ;. . ' /' . ; . ' 4` . * 't ': * l . r* ,*> . * .>' '. * . *r ` !' . *, * * ^ ; , ,. ' ",/. ` . *'/ . 4- *.*T7 * 7. - '/-"v ' V ', '* ,y-7; ; f:*: ^ `; 7-^:7 ' 1 .. IT.l' ** . ^ . . . J ` ""T v`. ;' -V-'-C ' - , ;> V*. ,. ' ' *' . . / " <.' - v'V'<>:i v*' .'..V\ -V ^ *' t 4 * * ^ ^ * . ' " > *, % * T ..*' ,`*`^"Vv V' `v'.' ' - -ir r, **'. ` * : 'V^t1-V:?'C* A * V, .: 1 _ '* '  Table 2* Lead in Urine- (ng. Pb/H#P Liter): All Data Round of Testing 1 2 3 4 5 Kiunber of Observations 99 91 89 80 85 Mean $> .0307 .0275 .0238 .0243 .0232 S.D. .0181 . .0163 .0118 .0123 .0104 ,i Frf-t; -H' If ,' *.ik$^., >!> "iBafS + ' k S . * Va. 3.K-- ^ C;< * ` *T*ble 3* Lead in Blood (Spect. mg. Pb/IOQ grc) : All Data ' 5 Round of Testing Number of Observation* 96 84 Mean .0335 .0289 t 3. S,,D. .0120 .0077 1 Oryt'/^O.pO: MS ^^xT** *S-> "''J '* * ...W..' J `jl'v * ~, V>V ^ ^% ^ '-* *V* V . ; . . . v '*. _,.: : '7 . -. ..... - ' " . '" '-T-"-=< ' v- -'' - - ^ ' ;4~ - ;'.^ ., . ' .-' * ' *f- Vj "*-i rt.vi' s. . 4 > ,, ^ **< -'. ...' **' . .. ,. .->, - Boundof Testing 1 * * " V'1'- , ; ' ' ' ' ; 7 '*/ '..' . . Busbar : of . Observation* ' 97 Mean .0272 5 87 . .0228 ' S.D. .0363 .0231  Table 5* Specific gravity .of Urine: All Pet* Round of Testing 2 3 A Jfua&er of On ti e.rv a fcl ods^" - - 87 .. 88 : !.'. 77 Mean ' S, 0, 1,0147 1.0159 1.0167 .0076 .0073 .0084  Table 6* Ine Volume In ;San Fraudb c o Round of Tea t ins 1 2 3 4 5 Humber of Observations 53 51 43 50 Mean 100,5785 103.0754 117.8627 108,4883 104.6800 s :d . 27; i4 39,65 27.3i 3fc , 55 32,94  ' .'li* /*- *Tabl 7* ^*-1ln Urine (ng.Pb/lgg liter); San Francisco . . ^ **S"^*T'V Round of Testing Kuraber of Obsorrationa Mean . S,,D. *1 58 .0299 .0200 2 53 ;- 4-K$h'.V ' . .0313 .oise 3 t 51 .0233 .0130 ,4 1 5 , 43 50 .0255 .0224 - .0129 .0110  Table 8* i^lio^loojLispect.eg. Pb/IQQ ); "to 'V "' - '' - ' -r v-`. - Sound of Teating . . . . .>-'* : :.: Jfuuttber ' ' *'" of Observation* Kean 1 5 tOo 86 . .0318 ' .0374 Ld . .0090 ' . 0073' * rssF&#s v?v'?: ?.v, ; 4 *' ' Lead i- Bound of Testing '1 . '; 5 'f^k.4$002 ZgtA ----'-.:IWf`^bM4'K`*Ig Nt:Vl3Usv%AS.yS.;' in Rlood (Pith.an. Pb./lOO g) ` Francisco " *** "" '" 'w"|ir !. h i _ .......... - .j, * ?' 4, SMsy-WS ,,' - 'CffSfS?* sfeiA'S'*' *' -v'",. f ->r 4^;'5>* ' _ -* if ,,-r "" -V <* * * ^ **. * > ...... T 1- .* dumber '* &&*&-*&*' *, *i'^VjrilJj4r. '" J^iS*V '*<*'" * 4 " -cggirsj rMllimeatt .*.-. :w.i.^ r B.D. '*.$$** of UDSsrriviwu ; -r v.' J t. B5 1J.3T * t , 'V t4 K 1 -\k/ v "'t* * ' * <r *r " .0859 ` " " 'V t' *'*< * i ^ k 50 t , r T * *.* > 1 ** -1 .0830' .. .0077 . v .` > ---------------------` .0085 /J^f ,, . w*!? ^ss%igg - -." 'i-il'/ v : .>! .' 'r& -r ` * , ' .--S' i.' '. - - "!l " k ; a . V ..:* V ^ .* . _ :--r^.-^M-:i.; ' ' ' . 4*--1iS toSki. *.=Sa 0 ,- -^ * - steen. -*f- *-J<- 'M. ^`C*.;. ;A5d'*pi'24>t^tu-*". . * C.`*f *** T*ble 10 *, ~ *_: ^.4'_:_ r ..wS .- .:..Ti\ijV <Jirf-'v--,T^-'T'..'4l^ Specific gravity of Urine:4 ^ -"T^v 4/W^'*-T)!- v~ s^' i,. 4*t *-^? .- >* .^ -V >9* ^ ... ." ~ .....y...*. ...- **** ,i>..... 3. .1 i LL__lX_i_S____ i'^r;- o '&**&***#''. .... ...a...s...s...i.s...t..... '~ iMyes^ ;:., mmh -J6&S.D. - - -a s r- /- *, *% K-^er -u*J,jT4' "*^*' C* l-W"' ' m* - *: ; -" , -- r; V* ;;' Round of Testing ;1 2 3. 4 5 Table 11* Urine Volume wl* Los Angolea Nujaber of . \ Observations 43' 38 38 37 35 Mean 95.1182 109.8578 105.2105 107.3513 02.0571 S.D. 30.38 23.38 30.13 26.OS 32.40 ;s:S. I'/ .3B&.V 7 * V* 1" v 4 * '3&anu\ ** 7 i- v * wtJ ^ a. u- wife -*.,* .,,.--*J^i('!***4^*.?>-yjif-....'....' *..v*"*4-** v Viable IS* * * Href'S#***>" v ,*-w > .**<> * * * & '*- - ' ~'~a * ** *,***-. s-TV'-j U ** V*s j ^ ^ W *4,^ ^ j Lead In Blood (spect-.fltg. Fb./lOO gm)i Lo Angeles ' "\t k S <f ' " V . . ^ i sj.V: t. -*'41Sin>7* - -* .* ,.^-.04 ^ J.*^.,._'/ - *r -r- ?7t**c r.* sfeiw ^........ 'Te <?* $ .r * '^AiS*S ^ 5t^ .,.w. -Vi r ,4.-- ' -^i of " 1 'rj Observations Mean /fe 5*~ " ^ . 0362 ' ' 44'-/ i ? :v *>**- r, 35 * - A3 ' . K .0306 * ;J.^'^S.4<4S'r'' ^ <*t -` * * A i17; r. 8.D. 0145_ .'.. .' 0274 >- 4? ......^:*fSmEi$pmS -.' iA'.v V Hs-iWf s;j*i??sii^^^;- S4M';S?;v'; .. .. SSSEfiSfek '-is^C: ?j*r- J ;n . 5"*^Ci+- - . ;. ',..i>- vt^- ; ^ `JiStSS^Tj ` .;4' ' 44g>3ilii7'' ' ?W> ' *-*' * ^ r ' -T< v ' r, V^^. ..)>*7-^;-'v;?fc*&i8c* -a. aSMS as $AA- #Se*s ^ -S' '^'T ... ~A--: ,: '' ** , -ASS. - ^f.r =%.,... .., .;..;-. gMafc^ . 1 j*d in Biood'<1)1 tK-rfe-4 Pbf. /100 CT; ' "r % Je^, Xs;..::,f rs^ .y *5Jv /' ,* -v *r '^ ^r-X "^ \. ! ', 1' - '5''/* 'ft J ---- * -V * ** ;" * y I?* .. Vuibery of' ~ Observfttic - *- -.V. .... tnpfy* r '&Xr*Z' ' /^uU* * <..v...^..^ Ssfofk..*&*.._ : .- y ;* r .. v.>. . '"Z'1 f ,->*>' -f- - , ^ ^^'tv' ...`-O'- V- -.v . ..* , *-'** J .* jfliS ` *' f ?v * ` "v*<* . - 3& '$*2 + . ,/ri^i - *- - T,.-,;;. iM<tS-aV'>K <->>l >' ..- rri'~.- .1. v>T^ - ^^- -u'-1 JrW_~ ' y*~ *4fr=%'1 > ~J,V*3 '*f, - lisp '' '443^*''' ,-j *- ..**.. : --.' ? f~ X.- ,fV'' t/- I ~ -* ^ . `--'sV?1- t * % ~J &' > *? r 3 ^v^rlU^r- /`.ix^v , SoD. ' __*...... * * V'i *-: 3fe& l?,s ^ ^ s *a ;M ........ Tx^yxM-:^ l^f.: .... &zm 9^ /K;` *: *>- - * ''## mmm-: -- ',x'. '' 0-''V,'"-'iV:*3^'?',^^S x %iv I SsSS iy&?? ..uS... - :CS3& - fS.^K mm 1V- x-:-****& `W- Specific gravity.of Urine; Los Apgeles C&sorvatioE..'! *+' ; -^ A s X* * -38 * * .38 37 1.0144 1.0126 1.0168 1.0170 S. D. .0030 !0079 0070 .-:o-;;  Table 16* Urine Volume in 1.: Service Station Attendants, San Francisco . ' "Number . of . Observations 30 28 2? 21 : 25. Mean 95.0333 95.7857 106,9999 ice.7619 -104.5200 S,D. 23,85 41,21 3?.41 35. M 33,88 yw apaB Attendants i.D. * * --*--- .0262 .9150 .0164 .0114 .0112  Table 18* ! Lead in Blood (Spect. &g. Fb/100 gn.)i gsrvice Station Attendants San Francisco Hound of Testing 1 5 llvueb&r , of : Observations 30 23 Maa .0329 ,0282 - S,B. ,00*4 .ooas { v Hv*!? *> .-:r'" Kr K *TJ. 5^1 <- r*> '4I& Zi^ * r* * J*-* A ' *Ai? - * tVV*1ilyrS>^ ,, >V & 7 S-f - ' ^.. * '. V. '-is;* . " **/< : . j*r Kr * 4. tW..**.^r r. r*<fr 5 * s S|tt.*' - IV */*>< - ` * ^ ` fs?r- STs S.' ,, v - ^ J* * $?> * r,, ; . ' ;$$; ', . -*#**' .: -i --....*4 ^ ^ fi ': ' 4 -/ ':--- i' v--v^;V'^ --* ' ^, * <V - ' ^ . <- G0f8-0A.7.:., .; ..: - . .'' ;-;'r-W'-:;.i.'ii:- .: ' / ' ^V - ':.' . k ,-v- 'r - ^:' f* - i--; - 'lltf} Wf 5|b| /- Jg V ..SO^Vr. r*9 A"f ;fvwrV*, 3?*- "i ~ * '"gj <, ` ' "* *'* ,,r ,T^' , * * f ' Table 20* ru '. *-;*"-* * C ~\ { > - *'?,j -'-v - *' ^ * Specific Gravity pi Urine: V-r.1 Service Station Attendant* '* -.'. '. '. 7 San Francisco ;;.. '"S\ Round of Testing 1 2 3 4 Number of Obaertationa 29 26 2e 20 Kean 1,0127 1.0157 1.0138 1.0160 S,D, ,0079 ,0070 .0080 ,0068 :r- Round of "eating 1 2 3 4 .e. / S'uiaber of Observe t 1 orss 34 29 , 29 >. 4 ' " ' ... 29 ; 27 Mean ..... 98.2947 113.4137 108.1379 107.7241 89.2592 s,n 25.07 22.04 25,07 23.93 28.24 .. \\& cocooiy .Round % of Testing 1 2 3 : / .4 5 -;\.. ;V'- ;':' '-<;X. y'iy-y " ' `^ ':\v^;-\\'\f,'':i' . ' ^ 4? - * ~ Nuaber of ., ' Mean Observations 34 29 -. 29 29 27 .0322 .0224 .0241 .0232 .0244 S.D. .0136 ,0088 .0087 .0089 .0093 ' ;* * .*# `v#/ ; *J ' < V. 'y 03Off020 *5- ., .. -...* - ' '; Z-. ' ,f>:. AJJ- *-Sr - , *- .- *-:vJ ,*f ' ' ' ~'-"^-<;' '"%TX' -- ---._Y Jt,-: ** -J*' 4S&3B '1, i.f!-'.4` -! Lead in Blood (speet. mg. Fs>/100 ga)r Service Station Attendants . Los Angeles Hound of Teeing 1 5 .. Nussber ' of ' Observe U. on* 32 . A 2h Mean G365 ,0315 S-D. ...~.015* Round of Testing ' 1 `5 Table 25* Specific Gravity of Urine; Service Station Attendant a Lo b Angeleg Round * Testing 1 2 3 4 Kinaber ' of Observe dons 32 29 29 29 Moan V 1.0140 1.0134 1.0182 1.0179- S.D. ' .0050 .0077 .0073' . OC ' 7 Table 26 I 1 as 104.CCXX) 40.8' 2 05 127,,8000 12.92 3 .. 05 115,4000 17.. 1 ; 4 OS 102,6000 36.11'' 5 '05 ' . 11S.SOOO 14 OO fO i A A f. U U U. S3|>^{ *3^&u-csvi^si^z'.C ^2**VV7''%*v",v2-"v r * ;i--'SvK^^:x?_,^':^- * .**W* -- _ _i-K1' r'-'- -,. ________ a~V?*~ .j %gmm........... V '*~*sfer >&$* * Wiv-'.-: A*TTa^>bil1m>' 27* ?-s * * ? -SM ** ,, ^ ; ^fS&SF* "j. ,,,.,jps^ y. -.......4^... .. -/'.>V^>V?-t*;^>-A&4S^a4&S*SMS/S''<'s&^yte< *. - \ >''X^'^s*-Mmf'7.'#K ,,,-. ,,-... ^nre^iV^vSSg^ " < w *- w-, m .#v?srA ***<*?y^* j ~ -s-.* -j-~* `<- * . < - *'ts *. Tfc**^ ^***S*SK----- *_ r. - '*1 *<-c r-Vi-;^;- *^ ,,e,C`vV*"t ' $' >. - j^Sht offf * iVs ^ ,-jV'i <f. %3h !tft&W- " ^ ! - .... ~ _ Blenders *. V ?* `V vfetSfrZ ;= S#- * ^ -~ - - ' ' *-? `` ' *~*i. s - ***. - ^"Ssa'-'f Sound . _ .......... .. . ^ Kusber *" < *, ; * V. *!* .. Mean A .  Table 28* -*d in Blood (epect ^Pb./IOO yiXt? Blende Round of Testing 1 5 `. ' Number;^'"'"' of: "' Obs et\ aiiss 05 05 # Mean ':'y.- a 0300 . 0230 s ,d : .0079 .0CV:7 . 'e " : ' ,' /V.-;, ;;: : '.;* "Table 29* Lead In Blood (THth , mg, Pb,/10Q- g,) ; Blenders Bound of Tasting-. 1 5 Kuasber of . 'ObSO^TAtiOtt* - ' 05 \ ' OS . - t^rnw , .0240 .0180 ' S.D. ; > ' .0065 ,.0045 :-f 000ou>V  Table 30' Spectflc Gravl*y of irrlna;' Blenders Round of Test 1 eg 1 3 4 ^ Number . of Observations 05 05 05 05 Mean. i.oieo 1.0120 1,0140 10220 S. D. .0089 GOST .0055 . ,004 4 & O^GoO^o ' ' ' -V - * i -15 < 1 "*" 'w Table 31+ i*.^d,ij-IOQd Count: All-Data Round of Testing -Vumber of lb*-:* nr* flouts 98 ' '43 M*an 4.9323 5.2974 ,B. .3493 .4339 t Round of 1 s . Table: 32*;;-\ / Herae^lobin - gms. All .Data Number ^ of Observations 98 44 Mean 14,378 . 15.735. sr t . S.D. 1 !l44 1.082 . ' Hound of Testing 1 5 *7abl 33* Color Index: All Data Nuabar of Observations 21 ' IS * Mean , S.D. *9833 . . .9750. .,0382 .0310 0008031 Round of Testing 5 a" < "**'' 'l K ' *' TV **- 'b*"l-'J' ^ Table 35* Polye-aautral (Total Per Cent.); All Data . Round " Of Testing_________ Number -*' Oi^y-':' v:C.:;':' Obaeryatlona 1 18 5 12 . Mean ' '; : . 55.5655 . 81.8688 s.D. 22.33 8, mo Kt 0008033 \j r' 00u 8034 ,,r ^ 'Table 37*/' Polys-NonYilamented (Per Cent.): All. Data iJT' Hound of Testing 1 3 Number of,-' Observations 98 28 Mean .0028 .1249 S ,, D, .1450 ,12sO 000 oo3 o <. ,^r ` -! - Round of 'Testing ' Table 38* Lymphocytes: All Data dumber Of....... Observations . 98 44 Kean 33,0102 28.4090. S,D, 8, fSO S. 89 3 i Monccytes: All Data Hound of Touting 1 5 Kuabor ' of Ob servant ion 9 98 41 Een 4.33*-7 4.8341 8,D 2..727 2. :;o<