Document ZnGv8B8agRxQyBwbwx5x327w7

l e a d p a ;:.t :::c s s t t o s s t v o y '*' W ' - w V I FINAL REPORT 14 Sopuobor 1973 Contract So. 62-tf-62GOkSPC MR! Projocr So. 3729-B *-. > i * -f 3 ii For National Paint and Coating* Aatoelatien 1500 Rhode Xiland Avanua, S.W. Waihingcon, D.C. 20005 Aten: Mr. Royal A. Brown 0007--SWP--03 6972 o ?xsrac e This report was prepared at Midwest Research Institute, tli Volker Boulevard. Kansas City, Missouri 64110, under Contract No. 62-W-62CCANPC, J3U Project No. 3729*8, "Lead Paint Ingestion Study." The research was sponsored by che National Paint and Coatings Association, 1500 Rhode Island Avenue, N.U., Washington, O.C. 20005. Dr. John P. Frawley, Chief Toxicologist, Hereules, Ine., Wilmington, Delaware 19899, was the project monitor. The research was conducted in the Biological Sciences Division, under the direction of Dr, W. 8. House free 1 December 1972 through 31 July 1973. Dr. Thomas X. Castles, Principal Pharmacologist, was the principal investigator, assisted by Dr. Jsios L. Senyer, Aesoeiatt Pathologist, and Mrs. Jane Koch, Biology Research Assiecant. Dr. Jamas L. Splgsralli, Senior Chemist supervised the lead analysis with the assistance of Mrs. Hope >!. Millar, Assistant Chemist. m Approved for: o MIDWEST RESEARCH IXSTTTLTE w, S. House, Director Biological Sciences Division 14 September 1973 igg; eStete 6Hg Wik iv `A ' '"X -------- 0007-SWP-036973 0007-SWP-000115541 '3 ' :ac ix or c o k t s ht s I. Introduction II. Methods . . Psee 1 A. Preparation of Paint Files Containing Different Cancan* traciona of Lead............................................. B. Preparation of Diets ....................................................................... C. Experimental Procadura .................................................................. D. Analyaaa.............................................................. E. Pathology............................................................................................ T. Statistical ........................................................................................ III. Results........................................................................................................... i 2 2 3 j 6 6 A. Concentrations of Laad in Paint Filaa ................................. e B. Laad Analyaaa of Olata Containing Different Paint Filaa. c. Fraliainary Feeding Studies .................................................. . 6 9 D. Croat Observations, FeedConauaiption and Body Weights . 9 E. Weakly and total Land Consuaption .......................................... 14 r. Kasaoology of Hats Fed Paint Filaa Containing Different Concentrations of Lead............................................................ 14 Tissue and Fluid Chaaistry of Kata Fed Paint Files Containing Different Concentrations of Lead ................. 14 H. Lead Content in tissues of Rats Fed Paint Flint Containing Different Coneancraciona of Lead ................. 36 I. Pathology of Rats Fed Paine Filaa Containing Different Coneaneraciena of Lead ............................... 51 :v. Discussion 58 V. Conclusion 59 References 60 'mil Sfi? E.'feair r&y m k-s. 3 iii 0007-SWP-036974 0007-SWP-000115542 I. INTNODUCTIOH Few parsons will disagree that old laad-basad paint praaenta a^ ftSeJut d ................... iiwlrh hJ'.il awg imiaicn. At a result of forts ay Kehos,i> Chisholm,!*1 and King,-'' aiadical raaaarchars, paint menu- icurars and legislators hava recognized the aariouanaaa of tbit problem j acting co iscabliah aafe concantraciona of lead in paint, to do this, ,JL ly have voluminous reports on clinical observations and aniaial research from ich to draw. Unfortunately, moat of chia information ia based upon eha aid i*'r"i* tn;i Jf ti.-o.a.-aad u.:s^ mien not tMUuUc: cn name rar- 2?mu TETST on toaav ' t aia V. ' Tslifl ill! loneantraclone of load in paint can ba intalligantly established, we must evaluate the cexlelty of the lead as it exists currently + in modern paints. l_uat_tht puroosj of thla ttudyj to evaluate eha toxicity in_raea produjed__,by modern paints containing lead octoacajplaad chromata_?r iwod' eaweawsesjindj^o^ottparsthai^ommol^painc^jotgilationjibyfc^e^f N chosi^ras^^^i^T^^^^^S^^^^ST^p^'lbrTe'tuTTs ar* presented in cue following pages. ' |sU t--* # **. ^fW iz. MEimpg A/- Q/ A. Preairatiof! of Paint Films Containlnt Different Concentrations ef Laad Paint filmsij without added lead and^addodX[aaid eompounda ir. the jfe form of lead octostt. laad chromate, or lead"carbonate ware supplied by mam* bars of tna National Paint and Coatings Association. Paints which contained laad octoate.*lead chromate (medium yellow) am*^rti>m*aibmmjgwe were Pr*Par,<* using e flat elkvd enamel formula baaed upon M'TttTTwTjtwil Class I alkyd. The flat elkyd paint without added laad was used for control^ The percent of lead ia aaeh aampla was calculated on tha beats of tbepsfnvoletila matsrial. Dispersion waa accoapUahad with a Cowlea DlaspJdar and eha pigment volume concentration was held at one level. TheinjKfita ware placed In pana fb TZ**' and allowed to air dry. Tbit was fallowed by^Mfrcsd air drying at 120*r to volatilize any remaining solvent. Peine Qm were ground^sieved, end chips ranging from 0.5 to 1.0 mm in alas wKr^usad for this study. Ihlc chip sire was saltotad on tha basis of a preliminary rat feeding study which aatablisbad :r.at rata would selectively eap/round larger aisad chip*. , lr*Jr i> Misled 'Whd fcWO Tha concentratStfns of lead in the different paint fllma wars datar- r.inae indapasdantly b//DaScto Incorporated, the Shetvin-Wiliians Company and Kicvest Research Ipdcituca, using Atomic Absorption Spectrophotometry. '3 .H-jpmw, .iiu 0007-SWP-036975 0007-SWP-000115543 Sample^ of old lead-based psinc.iS^ obtained frroomn eh* uU.S. Dsparcnone of Commerce, Sac ion* 1 Bureau of Standards, Washington, O.C. Thi* paint had bean pulvtntad and aiavad through 323 M*h seratn (0.06-0.OB i sis*J and contained 11.872 lead by vitight. Thi* sample will b* rafarld to aa "J'BS lead pain:" in chit report. B- f-*Jra_e-.on_ofi.O:ecs , CW* . Oieta u*r* prepared by mixing paint tela* with Purina Rat Chow each in the concentration of 0ilt (weight/weight). thi* wa* aceompllined by first preparing a 102 conctncraca (paint film/feed, w/w) in a high-speed twin ahall aixar. This concentrate was ehan added to the appropriate amount of Purina Rat Chou mash to give a final concentration of 0.11 (paint flla/fnnd, w/w) and mixed for 10 mm'in a bulk mixer. lech diet was prepared three times during thn experiment and samples of tech of these preparations were assayed for lead content. C. Experimental Procedure ^g_tmgdred weanling (40-60 fa) Charles River rati (100 mslas and 100 female ret*) were used far thia a tody. Upon arrival rets were housed individually in air conditioned quarter* in polycarbonate cage* containing' hardwood bedding and filter topi. After 3-7 days of equilibration, all rats were assigned ons of the following diets. 1. Rat chow plus paint f*4m without added lead (control) 2. Rat chow plus paint fA* eeneainlng 0.082 lead AS lead ACCOAtt 3. Rat chow plus paint . Rac chow plus paint concainlng 0.331 laad AS laad OCCOACS * containing 2.052 laad AS laad octeAti 3. Rat ehow plus paint ila containing 0-422 laad AS laad ehrooACA i 6. Xac chow plus paint fila containing 1.952 laad AS laad e.SroesiCA 7. Rat chow plus paint film containing 12.432 lead as lead chrosace I. Rat chow plus paint film containing 66.051 lead as laad csrbenata 9. Rat chow plu* KBS lead paint containing 11.922 lead stedte 2 'Sliw. >' .r'*. ' -vV..., s ' ''v.* '' "r r '*........-5 0007-SWP-036976 0007-SWP-000115544 Twenty ih U end 20 female rats were assigned to the control diet, and 10 males aha 10 fcsiala rats were assigned to each ef :ne remaining discs. Seen diet was fad in a 9-os widc-mouth glass jar which was secured to the cage. Tap water wee available acv libitum during the entire experiment feed consumption was measured twice each week and calculated on a daily basis. The animals were weighed once a weex. All rats were observed twice or more each week for toxic signs. Afeer A, 6 and 13 weeks, a selected number of male and feaiale rats from each group were placed in mseabolisai eages for ehe collection of 2A-hr urine samples. A portion of the collected urine wee used for urinelysis and che remainder frosen for assay of delta.aminolevulinic acid and coproporphyrin. After urine collection each rat was anasehetixad with ether, exsanguinated vis the abdominal aorta and bone marrow smears were prepared. Blood samples ware heparixined, cooled and ueed imaedlacely fogp hametelogy and enzyme sxsayz. Aliquot* of the resistning blood were cakan for protoporphyrin and laid assays. Afcar urine and blood sample# were obtained, each rat was necropsied and tissua taken for lead analysis ft microscopic examination. 3. Analyses (WiM 1. laid analyse* of osinc films sad diets containlns saint Me: a. Paint film: Tn.ailligrsmf samples ef paint fUae con taining no lead or O.OflZ lead oetoate were eharrtd with 3 ml of concentrated nitric acid and dry-ashdd at 500*C for 2 hr. The ash was dissolved in 1 ml of ecus regie, diluted to 5 ml with dlseillad water and this final dilution mtasurad fer lead content by atomic absorption. All other peine M4me (10 mg samples] wars digested in 15 el of a mixture of concentrated nitric acid and 37& perchloric acid (2:1, V/'V], evaporated end ehe remaining perchloric acid solution diluted eo 25 ml with distilled water. This final dilution wae used for atomic absorption spec trophotometry. b. Diets: One-gram samples of feed were digested in a eixture of concentrated nitric acid and 371 perchloric acid (2:1, V/V) end their final dilutions adjusted eo make their lead concentre cions within the detec tion limits of che atomic absorption technique. i\>v* u i -1.0-f 3 0007-SWP-036977 Z. ArsIvi> r>rfsrrtd uoor. each rat: t. Haaatolcev: (1) Hematocrit: Hematocrit was deticninad in capillary cubes using * microcapillary centrifuge (International Equipment Company, Model MS). nechenogisbin.i' (2) Ksmoclobin: Hemoglobin was measured as evano- (3) Smhrocvce end leukocyte counts: Total erychroeys# and leukocyte were counted using e Coulter Electronic Particle Counter with 100-u spareture.l^ (4) Reeiculocvtee; Reticulocytes were counted by the aetnylene blue method using the Miller disc.-^ (5) Differential leukocyte counts; Wright's stain use ! used to stain the leukocytes for examination. i (6) Ervthrocvte osmotic fragility; Osmotic fragility of erythrocytes was quantitatively determined by subjecting heparlmted whole blood to sodium chloride solutions of different Osmelerieioe.2^ The concen tration of sodium chloride vhieh hemolyted 301 of the o$chroeytes wee obtained oi from a plot of percent hemolysis versus sodium chloride eoneentretion. b. Body fluid end tisaue chgriitrv: tl) E,;emjr^|^p,,t}(|p^OBj}lffXii^ rotil plasma proeain w h dacerained using che dyes l Biuret Reagent (Hycal, Inc., Houston, Texas). The quantity of each plasms protein vas dtcernir.ed aieetro- pnoretically on ca'.luloia aettaca end expressed ea a percentage of tho total plains protein. (2) Irvthrocvtc-6-amlnolevulinic acid dehydrate fAlAD): b-Amicolevulir.ic acid dehydraae activity waa dateimmad by tna method of -- ch tsan and .reismao.i/' This eroeaduta vas a carted 30 min aftar each blood sampit was taken. (3) Ervchrocvta orotooorohvrin; Protoporphyrin in erythrocytes was ossturad by the method of Heller, ee el.2/ This analysis was performed the day after blood wee wiehdrewn. (!) Urinary i-tminolevulinic acid fAIJll: Urinary 4-aminolevulinic acid was measured eccerding to the Davis end ndelaar.2/ modification of Maui trail't and CranicU'e Method.22/ Thcet ana lye ea were perforret :n subdued lignt. -J- ><r s.,V 0007-SWP-036978 0007-SWP-000115546 <e* (3) Urinary codjsabnornhvrin: Orinarv^eeproperphyrins vers determined by chs method o Sehlenker and KitctieLl. Thasa analyse! vara performed in subdued light. e. Urinalvs is: (1) Urinary nrocein (albinini: Urinary protein vas measured with "Uriaeix" reagents strips (Ames Company, Elkbart, Indiana). (2) Microscopic examination of urine: Urina samples vere centrifuged, the residues resuspended, and explained microscopically for the presence of erythrocytes and leukocytes under high power field end for caste under leu power field. d. Tissue lead! (1} Blood: One milliliter of blood wee mined with 1 ml of a mixture of 5Z trichloroacetic aeid:37X perchloric ecld (3:1 v/v). The temple wee centrifuged end the tuperneceac filtered through an AAWJ 0.8 u Killipore filter. The tupernace wae analysad for load with an aeomie adsorp tion tpactrophotomaear uaing atandarda prepared in control rat blood. (2} Other tiatuea: Bone, liver, kidney, end brain ware digeited in eoncencreead nitric acid, evaporated to dryneea and reconaeltutad to the lowest possible volume with 2OX nitric acid. These aotutlons ware... analysed for lead by atomic absorption spactrophotometry, (3) Atomic absorption analysis': Lead concentrations were measured using e Varlin-Teehcron AA-5 atomic absorption spectrophotometer. Sample solutions were aspirated into an air-eceeylene flame end the absorbance was measured st 2B3.3 nm. Background interference wae determined wieh the use of a hydrogen concinuta lamp at 283.3 nm and subtracted from the absorbance obtained at 283.3 nm wieh the ?b hollow cathode lamp. E. Pathology 1. Gross pathsloev: At necropsy, rets were examined for grots abnormalities, chsir livers, kidneys, spleens, hearts, gonads, thyroids, orair.s, and adrenals weighed, and tha relative organ weights calculated. After weighing, a portion of tha liver, kidney end brain ware taken for microscopic examination and the rut of each organ van measured for lead content. A (aw wee removed to be used for the measurement of lead in bone. 2. Microscopic oathoiocv: So d s marrow smears were prepared for a cyeicid/srytnroid call count. The following tisauos were fixed in buffered neutral 102 ioraalin: brain, liver, spleen, steewch, small intestine 3 tSLlihi'in j-W*? .. r* v Ks *g*; "b- m 38. :v. >SS?: ! 'Vjr I /n'' 0007-SWP-036979 0007-SWP-000115547 (duodenum, jejunum, ileum), colon, pancreas, kidney*, urinary bladder, adrenal*, Chymu*, gonad, enyroid (with parathyroid atcacned), reseneerlc salivary (land, lymph nod**, heart, lung*, diaphragm, skeletal ru*ele, and pro*cate or uterus. Tissue* from all 13 week rat* led tna control. 2.057. lead octoat*, IZ.uj?. lead entoeate, 66.03" lead carbonate, and t.nc 11.92* SBS lead pain; dices were embedded in paraffin, section te * thickness of 6 u, stained with hematoxylin and eosin and examined far histopathoiogy. F. Statistical Analysts Control and craatment value* were compered statistically using Dunnect's multiple-comparison cast with P < 0.05 ss tht criteria of signifiesnes. III. ttSCLCT Cl. im A. Ccncencrstions of Lead in Psir.c Prta* The eonetntroeiens of lead in the paint two* supplied by th* Members of tho National Paint and Coating* Association wort analysed for lead content by S*5oto Incorporated, the Shatvin-Uilliaae Company, and Midwest Research ln*ti tutaO*l). Tha result# of the** analyst* or* shown in Table 1. Th* control f*Hri which did noc contain l*ad octoat* or chromate was found to contain approximately 0.01% lead. Thor* wo* a reasonable agrees*.-.; beewt'es the different analyses, so an average ppm of lead wa* computed and used for tho actual lead concentration of oach paint film. Load concentra tion* of the lead paint obtained from the National Bureau of Standards wort averaged in a similar manner. B. load Ar.elvsj of Siets Contelnine Siffarent Paint Film* table 2 shows the lead contone of tach diet. Purina Rat Chew -as-, was found to contain approxiaiataly A ug/gm of load (assuming 0.1 ug/ga cf lead was contributed by th* control paint). 7h* ug of lead/gm of food which was attributable to each added paint filsi was reasonably elos* to its respective theoretical value, the average total ug of laad/gm of feed for each dice wis used for th* calculation of weekly end total load consumption fir seen rat. r_ ST v*oRw ~ "_ . ?. i 6 : * 0007-SWP-036980 0007-SWP-000115548 Paint Tils Control Paint Lead oetoat* Lead oetoaee Lead oeeotce Ltad chranaca Lead chromate Laad chromate Lead carbonate SIS laad paint TABLE l COSCENT'LVHP: OF LEAP IN PAINT PILM Theoretical Load Concentration f".'i Veaeured lead Cercentratinn Paint Companies "HI r-,\ /pi Average,*/ /> 0 0.06 O.SO 2.00 0.30 2.00 15.00 64.12 0.01 0.08 O.SO 1.90 0.42 l.BO 12.37 62.20 , 11.87-' < 0.32 0.07 0.36 2.20 0.41 2.10 12.30 68.90 11.98 0.01 0.38 0.53 2.05 0.42 1.95 12.43 66.05 11.92&' */ Maaaurad by V.S. Departnant of Ceauaarea, National Bureau of Standard*, Vaihlngcon, a.C. bf Avri|* of paint coapante* and MBI value*. / Average of Bureau at Standard* and MRI value*. ; 0007-SWP-036981 0007-SWP-000115549 or r:rrs-ad as al y s s s c o s t a tvryn n:rr;--T ?a ::.t Diet Control paint plus rat chow Theorottcali' 0.1 Lead octoate (0.081) plua rat chow o.a Lead oetoata (0.537.) plua rat chow 5.3 Lead octoate (2.05.) plua rat chow Lead chromate (0.62L) plua rae chow o Lead chromate (1.95L) plua rat chew Lead chTsrata (22.43-) plua rat chow 20.5 4.2 * 19.5 224.3 leae carbonate (66.057.) plua rae ehow 660.5 NBS ; cad ammmd paint (.11-92%) plua rat chow 119.2 Measured TocalS' ?elnt laaei f-js/sm) -.Carr.? - 4.1 (6) 5.2 i.i (6) (6) 12.0 (6) 7.9 (6) 27.2 (6) 11.0 (6) 23.1 (6) 6.9 (6) 23.5 (6) 19.4 (6) 140.2 (6) 136.1 (6) 516.0 (5) 511.9 (5) 124.0 d> 119.9 (3) */ 7'ii-orecieal concentration of lead in Iced contributed by indicated paint film. b' waan sig of load/pm feed for number of am|ilo* aiiown in iiarunchuaia. c/ ".can ug of lead froa paint fllms/gm feed for number of sample* shown in parenthetis. 3 a i jdw'ii " .j"! t V-.. 0007-SWP-036982 ... . -V- r. iv.-? 0007-SWP-000115550 .: v. C. Preliminary Foedinc Studies Cl>T Before beginning this study, a pilot experiment was perfersee to see if tne rite were consuming tax iced peine fTT> along with tne:r toed. Three rets each were, pieced an (lie concrol diet end the 66.03% lc-J ceroor.ece diet. After AS hr^*tece were collected and lead content measures. ?cces tram rets on tne control diet concerned 11.5 eg of lesd/gn faces vnile (sees from rate ted the 66.05% Iced cerhoneee diet concerned 5,683 eg of leadiga fsees. Thus, rats etc esnsume tne peiot * along with tneir feeo. w i :*."** 4: 0. Cross Observations Feed Consunoeione and Sodv U'alehts Duri^eth^jntir^jtudvjj^jjagji^Jie^jgjejl^ig.siymm. One female ret on 2.05% iceo oeeoete developed an aoysT'w^isrjj^jjjygg^^j during the ninth ereaemenc week end one female on 66.0& leeo carbonate developed abcessed hind feet in the 10th veek end chewier toes off. ............ ' 1 The feed eonsumpeientof male and female rats m* shown la Figures 1 end 2, respectively. Ixcept for the rats fed the diet containing 11.82% lead as KSS lead peine, all groupe conaumad feed at the tame race as tne con* tool group throughout the entire experiment. The reaaon che 11.82% KBS lead pair: group ate aignificantly lass initially, wa* that they ware started a 0 month after the other rats and war* initially smaller. Since this group css consuming faad ae tha saaa rata at eha control group by 4 weeks, we consider tneir initial food consumption normal also (for their site). ^ fir-' ir v'v -: . >>- .* The body weight gains for each group of rets are ahown in Figures 3 snd i. as mentioned above, the rata on che 11.92% KBS lead peine diet were small initially but bteamt similar to controls by either tha 4th (females) or Sen cask (males). Throughout she entire period the male rats in the other treatment groups gained weight at e normal rate. The female rats did snow a enanga m booy weights during tns first S weeks of fseding which appssrs related to the concentration of laad oeeoete. After 4 weeks of fseding, rats in tne T.C5% lead oeeoete group weighed significantly lass then concrol. Tha pattern was the same at 8 weeks. After 12 weeks chair average body veignss sttll exhibited the seme peccern, but the 2.05% lead oeeoete group vet not significantly different from control. This was due to fewer animals end a slight increase in variability. *0 *-- - t e*' " w h ;-i'i Fwir'i.'- +***- T * mth i * i ^ 1 U-t. %. mG . , xr 0007--SWP-036983 0007-SWP-000115551 I - J v^V*.'<*** '> . >* -** * < w ii Q s^ !rt .: _"' :. '=\'..-*li^aL;;.. v-s.r/sr.K'.f ...*..'*. -< ? i3 ^Igtfjag^^ytv:'gaafiMsaggl au J*>i_L. mini] ]]11 ]I ]i fs ____ sites?: ~ " 2 3 = . []' ffg.*w?aai.a' -g- u l m s-v-e-^Jl^X^a aa **$' ' ' . .: ?[- ^ JJ -u--------------------------------- i--; ' frrz^=pL V ;-y vwif. ......... . -. .^.v k-. ; cv- v. .. '*%*:-. r. , ."V .* - -.1 .3. ) ."IJJ/.V. .; : '.0 fM*. M - C-'^-r.; ;--=- 5: -. . 0007-SWP-0369B4 0007-SWP-000115552 .r* 5<t*; i * ij it ^s 11 s* it iiiliils { M i . i I i ad i 4*'/* - I} i (*/*./-*> 'Otjtf.'tf'WCS :}3> n j 'Tr; ^ ^ ... p ,, I 0007-SWP-036985 I 0007-SWP-000115553  =! Figure I*1 ' - Cl* ' J ~nr 0007-SWP-036986 0007-SWP-000115554 I -* i--J ______ _________________ * 7"! .". '-** ' ~A7 "n'` IEs " *_! T3 ' ^ ^WA\ = ta-t .......... '.*. "t _____ pj *--1 .. ,. . c .......................................... . v .,. - -a : ; vE ' -- ..... . ... ...... . . a k_\. / . k^;vr- Ji -v~" * . . . W-9*.: *>: ' ?> 32 -n . n___ ___ 1 . .... ............ . . ' # o Ilf !! rv` Ili]1 <5 ids nw j; I7 1 7 1 1 1 5 i *i % s s i a oo N s3r CCG CIj O ID SSESE3 1------H I*-5 1 n 0007-SWP-036987 0007-SWP-000115555 '-'ttk jv and Tata i a Corsur^ticn The weekly and total, leas consumption djring th experiment were eaieuiaced sn the basis of the tetel iuad/diet and amount of each diet eaten by each rec. These calculations are snsun in Tables 3 and a. During the 13th week period, the control group consumed approximately 1C3 ug of lead/da while rats eating 2.:sr. lead octoate, 12.4311 lead chromate, 66.03!; lead careonace, and 11.92". MS lead paint eonsunad an average of 786.5, 3,391.1, 13,435.8. and 3,184.3 ug of lead/dav, reapeeeively. I'aing the average body weights of rats surviving 13 days, the rats m the control, 2.035 lead octoate, IT-431 lead chromate, 66.051; and 11.927. KBS lead paint groupl coneumad 245.2; 1,957.5; 8,469.6; 34,430.8! and 7,804.7 ug of lead/kg/day, raapeceivaly. F Hegatoloay of Bata Fed Palr.c Swims Containing Oiffsrent Concentrations o \ ,!TS The results of the hematology of rats fad paint films containing different concentrations of lead are shown in Tablas 3*13. No differences were observed in the erythrocyte count, reticulocyte count, hasatocric, leukocyte count, differential leukeeyte count, and the erythrocyte oamotie fragility. C. Ttn. and Fluid Chemistry Concentrations of letd Rats Ted Psint 6 cx-r Tables 14-22 show the tissue end fluid chemistry of rats fed paint ms* containing dlfferant concantraclona of laad. The serum proteins, crytnrocytt protoporphyrin, urinary coproporphyrin, and urinary dalta-asmo- iavulin;: acid ware not altered by any of the diets. The activity of ehe arythroeyta aasyma, dalta-aainolevulinie acid cenydraja fAlAD). is thi control, laad octoata (0.085, 0.335, and 2.035) and '.sad enrsraea /l.-111. 1.537. and 12.35) irouoa am not diifdr tnrouchout tna axnar'.r.snt -Taolas 13). aIAP scttvicv was eoBresaad in rats fed 66.03% laad carOngy,_gjg>ii^^2%K^ At 4 weeks thara was a depression Of 36% and 39% in thaaa two erouos, ratesdttvsiv. At 8 wteka tna ALABactivicy was -^ffSnara hug in* ALAD activity in tna MS laad paint group was not significantly different from control. At this time a sex diffaranca waa observed in both of theso groups. The AIAS activity m the male rats remained depressed it the 4-waek>laveIs while the r.L/O activities of the fssnale rets returned to control levdls. This sex difference say be liniied to Che fact that these female retsNttad matured and wore prruaoly Beginning chair mensArul cycles. (TsUglinv) lea it . - '*i 1P*- sk ;fcr'W; 7> %C revi>t p* 7#0 0007-SWP-000115556 zu *> = i. = * ; .2 : - >m * ? X ;; i ' \i r A ;: i ;t i" mi = a* i * X il t t ;i* .*2 * 7 i4 - zX s * * i*: * V iXs 5 Vx - 8X * X i.1 il l Asl s = i* !* is s* X i* vi> it i* i-* xi Is i5 s Ii s r i! Ai* i 35 j* j</: i5 z i;: : <* H Is im 5 Is i5 i` s* * :z ii Is V V i5 i* 5 r V z ii si I lin * 3X i= H A* i? ii u i n* s ii :s* i- : -- i H i' j;i ii x 7 li ii * n ll ii ii !3 ii ii :* i xx A75 < i! 2 r * n ? * 5= ii*i s 4r ;] ;ii ' t'iiv > - y~- - > .... x. 13 i; - ?zzrrr?r. i, - 0007-SWP-036989 0007-SWP-000115557 - '* t -5 5 ^ s o I s ; i t Lk- =i P P p r*s s -s rI :*7 'i Zi ii :> - ::* :;* 'i r *j r ! 'i f i* !* A-.-.' j* rP P P I s* - 5* * ; J ;i ; * s= = ! . p i5 5 1 5: * 5I * 5s * a SI *' 5= "; i- *; S- p* -p *. s s* - *s 5 s S* 5 5: * Q - 5 Z71i ti:! Ii !S`s a ^ -3 ji ;s =5 i! p .* i* j* 1! p P :* 7 - Is :**7 s Is s 5 s U*-'' s^C*. ^7 { ` r.. * E:^ I *2 I i*- i.*- i* P i5 r is i5 -5 i j i* i* Is1 j-* i! ^ P i5 - 3` i!* `-J i? 5? s* - si I1- II !M Pr -3 if j! i! P P P - a * a M i 1i *i ?* if l |'3 i- ?i \l j* j* a ?= '5 5= il is V iU s <71 Ji;4 rt\* 55 il P a it il n ;* i1 -T *= i*:: , , & & I T j? 5 I: ! !, iili .r> 5 V* 2r 16 r. `**V ? 0007-SWP-036990 0007-SWP-000115558 *- TABLE 5 HEMATPTOCY TM ATS TE" ?A?*:T coxTA::.ir:c n o l e a d Treat-tnt Veck 6s i9 ) 13 irythroeyte* (x 106/r 3) 6.17 O.iiS^ 6.33 0.19 6.42 x 9.29 Reticulocytes, " 1.5 0.7 0.8 = 0.3 1.4 s 0.1 Hematocrit, vol.^T. 66.1 0.6 44.6 1.2 44.6 * 0.3 Hemoglobin, ga, L 14.0 s 0.3 14.6 a 0.3 16.0 * 0.1 Leukocytes (x 103/os3) 5.0 * 0.5 7.6 * 1.3 8.0 x 0.6 Seu cropbill, 7, 11.a * 2.9 21.7 a 5.6 13.1 x 1.5 Lyaphocvtei, ' 86.3 x 3.3 75.4 * 5.3 84.1 s 1.6 Benda, 7. 0.3 i 0.2 0 0.1 = 0.1 Eosinophils, " 0.9 0.4 1.3 a 0.4 0.3 = 0.2 Basopnils, * 0 00 Monoeyres, ?, 1.1 s 0.6 1.6 0.6 2.1 * 0.4 Atypical, T. 0 0 0 Nucleated BBC, " 0 0 0.1 x 0.1 o irymrocytt o ieio c ic fragility [SaCl]> 0*311 * 0*004 0.391 * 0.008 0.400 x 0.004 i Nusoar of race par parted, b/ Mean s icandard error. SJ Concentration of XaCl that hetnolyred J0& of tho erythrocytes. ; .\ . 3 ' ' X:' * ' " ./V -' 1 * H:5: m ? *.* 0007-SWP-000115559 0 o TABLE 6 HEMATPIOGY C? 3-ATS 7E0 PAINT ?*-- coNTAir.'t::; r.'vy. '.t a p as '.t ab o c t o at e A.-s Iv s b s Trucr-enf Vk 4S Ervihroeyt** (x iO/B^) Baclculoeytts, % Kraatotrit, vol.j T. Hemoglobin, gry % laukoeyta* (x 103/(0x3) Neutrophil*, *. Lvnphoeyti*, * Bond*. ~ Eoiinophils, \ Saaophils, * Manoeyt**, X Atypical, * Nucleated %BC, * Eryehrocytt osnocic fragility [SaClZ-/ 5.14 0.32-1 0.9 = 0.5 41.3 * 0.9 14.1 s 0.4 5.1 a 0.S 24.5 a 1.6 74.3 * 1.8 0 0.8 a 0.3 0 0.5 = 0.5 0 0 0.381 a 0.005 6.33 = 0.09 1.0 a 0.5 46.0 a 0.7 15.4 a 0.2 5.5 a 0.7 20.3 a 4.7 76.3 a 6.7 0 1.3 a 0.6 0 2.0 a 0.8 0 0 0.410 = 0.007 13 r;;.12> 5.92 a 0.39 1.4 a 0.2 43.0 a 0.5 14.7 a 0.8 7.7 a 0.9 16.3 a 1.7 SO. 9 a 1.8 0.3 a 0.2 0.7 * 0.3 0 1.9 a 0.5 0 0 0.395 a 0.005 / Numbtr of :s:s par period* b/ Mean = ie*ndird arror. c,/ Concentration of Nad chic htmolyred 50" of Che tryth?oeyc S**X-` >V V-y-VA"' ;v **%*... .VAf * l ' r-.-rir Ir? ,. / ...du. 0 8 0007-SWP-036992 0007-SWP-000115560 * "ABLE 7 tJU*HEMATOJWY OF HATS FFO ?a :n t s-9 CONTAINING -IS}''. LEAD AS LEAD OCTOaTS Analyses reatment 'Jack A 8 13 fS.il Erythrocytes (x 106fsm3l Reticulocytes, Z Hematocrit, vol.y % Hemoglobin, gm^ Z Leukocyte* (x ioVam^) Neutrophils, Z Lymphocytes, % Banda, Eosinophils, Z Sisophils, Z Monocytes, Z Atypical, * Nucleated BBC, 7. Erythrocyte osmotie fragility [NaCli^ 6.27 = 0,7 0.9 = 0,7 42.3 * 0.7 14.2 * 0.2 5.0 a 1.4 15.8 a 3.8 83.0 * 4.4 0 0.8 * 0.3 0 0.5 0.5 0 0 0.383 a 0.006 6.04 s 0.31 0.9 * 0.4 43.8 a 0.5 14.9 a 0.3 7.5 * 2.8 19.3 3.8 77.3 * 3.8 0 1.0 0.4 0 2.3 a 0.5 0 0 0.388 a 0.012 3.6 s 0.4 1.6 a 0.2 43 s 0.7 15.3 a 0.3 8.3 s 1.0 16.2 s 1.9 81.4 a 1.3 0.1 a 0.1 0.8 a 0.3 0 1.6 a 0.3 0 0 0.401 8 0.006 a/ Nursbar or rata par period. Jb/ Mean a acandafd error. t/ Concentration of SaCl that heaolyaed 507. of Che erythrocytes. I v; y ,> 1 !- k -y-;- 19 0007-SWP-036993 0007-SWP-000115561 o TABLE 8 HEMATOLOGY g? RATS F~0 PAINT c o x t a in in c g;*" l e a p Ai aaraefsstt ! Ay Ivifi Treatment Votk 4 8 13 CN-41 n:i2' Erythrocytaa (st X06/r *) Retlculocytaa, Heaaeocrit, vol.a X Heaojlobin, ga .. leukocyte* (x lO^/W) Neutrophil*. % lynpheeytea, Band*, T. Sotinophils, * Basophil*, X Monocyte*, S Atypical, " Nucleated RBC, 7. Erythrocyte otaocic fragility 'SaCl'^ 6.30 * O.li7 1.1 = C.6 AX.8 * 0.3 14.4 a 0.2 3.1 * l.X 13.3 a 3.0 83.8 * 3.2 0 0.8 * 0.5 0 0 0 0 0.381 a 0.006 6.46 s 0.08 0.7 a 0.1 43.0 * 0.4 15.3 * 0.2 6.7 * X.7 13.0 * 2.1 83.0 = 2.3 0 0.3 0.3 0 1.8 * 0.9 0 0 6.72 = 0.42 :.o = c.6 43.4 * 0.8 13.6 a 0.3 8.1 0.7 14.1 a 2.6 82.8 a 2,3 0 0.9 a 0.3 0 2.2 a 0.7 0 0 0.399 s 0.008 0.393 a 0.006 f*; Sft- I'dcfc- a/ :.'uso*r of rat* par period. b/ Mean a standard error. ' Concentration of SaCl that hemolyied 50* of the erychr ocytu. *' Ki* V-* 1P&L"*s5*,frif-*>U^A'!W.r*f!* #4?&&&*S!? {Sss^ W0$- yj/i" ;5":V-} -?h\ s 20 ** 0007-SWP-036994 0007-SWP-000115562 ms 9 HEVATOIOCY 7? EATS &L*r* b a t -?- r-u. An lvsas fSW.i' 7 reatment Vick a Erythrocytes (x 10/m*31 Reticulocytes, % Hematocrit, vol./ % Hemoglobin, gm^ 7. leukocytes (x lO^/ax^) Seucrophlls, % lyupnocytts, 7. Banda, % Eosinophils, % Basophils, % .Monocytes, % Atypical, 7. Nucleated RBC, 7, Erythrocyte osmotic fragility, CsaClji' 6.71 x 9.16^ 0.9 0.8 63.3 * 0.6 14.7 0.6 5.1 x 0.6 8.5 * 1.7 90.3 X 2.0 0 0 0 1.3 x 0.8 0 0 0.383 x 0.003 6.16 x 0.16 0.8 x 0.2 65.0 X 1.1 15.1 0.3 5.1 x 0.5 19.0 x 2.0 79.5 x l.J 0 0.8 * 0.8 0 0.0 X 0.8 0 0.3 * 0.3 0.395 X 0.12 13 f*ei >' 6.6 s 0.3 1.6 x 0.2 43.6 x 0.7 15.6 x 0.3 6.9 x 0.7 16.3 x 2.1 83.6 x 2.0 0 . 1.2 x 0.4 0 1.2 x 0.4 0 0 0.392 = 0.007 */** a/ Number of rata per period, except where indicated otherwMr. b/ Mean X standard arror. c/ Concentration of NaCl that heaolyied 50% of :ha erythrocytes. &&>: m * * i/a.-* t-pt.'*-*c**.* ^ n 4 r^'.r* '***:-.*4 0007-SKP-036995 0007-SWP-000115563 I 3 7AS1Z 10 l**Y.VT0Lf *v HATS r-t) u' CflT.TA "C :.-5* -Jha' as mm2 crsnv.vr- Aralvees * Erythrocytes (x 106,rp) Reticulocytes, \ Hcnatoeric, vol.jZ Hanot lob in, tv ' Leukocyte* <x 10^/=a3) Neutrophils, ". Lymphocytes, 7. Sand*, % Eosuiopnils, 7. Basophils, X Monocycaa, Z Atypical, 7. S'uelaattd RBC, Erychrseyti osmotic fratiUcy, CSsCl# 6.17 s 0.0j' C.S s 0.4 40.8 z 0.6 13.9 z 0.2 4.9 s 0.8 10.0 3 2.4 92.0 z 1.8 0 0.5 * 0.3 0 0 0 0 0.383 = 0.007 B r:;.4t 13 6.21 = 0.13 0.8 * 0.3 44.3 s 0.3 15.3 s 0.3 6.1 3 1.2 18.3 s 6.6 80.3 s 6.6 0 0.3 s 0.3 0 0.8 0.3 0 0 0.383 * 0.007 * f' II . 6.37 s 0.52 1.2 3 0.2 44.1 s 0.7 16.2 s 0.4 8.2 z 1.0 85.9 s 2.2 0 1.3 s 0.5 0 1.2 s 0.3 0 0 0.404 z J.003 / .`.'unbar oi rat* pr period. V .".aan s standard error. c/ Concentration of I'iCl Edit htnolyted SC7. of Cho arythroeyct*. >cr~ -i\r* ' UrS^v.j* Lv.^;- | S'T.i-V ***,\--"% r-'-; Af>T- 22 0007-SWP-000115564 o o t abl e u , HEJWTe'.ocv or bat s ~o **~r CONTAIVINC: i;.-3*T LEAD AS LEAD S!3eVATS AnaK'sea Treatment "ck A6 /?r4i Erythrocytes (x 10/ni^ ftetieuioeyte^jfc Heaatoerie, vol./ 5 Hcaeglobin, jiy 7. '.aukoeytei (x lOVsm^) Seutrophils, 7. Lymphocytes, % Bands, 7. Eosinophils, T, 3asophils, * Monocytes, % Atypical, 5 Nucleated BBC, T. Erythroeyee osmotic fragility L-VaClI-7 6.32 = 0.14^ 1.95 a 1,28 41.3 * 1.1 13.9 = 0.4 4.6 a 0.3 21.3 a 6.3 73.0 a 6.0 0 0.5 * 0.3 0 0 0 0 0.384 a 0.007 6.23 s 0.18 0.9 a 0.1 43.8 * 0.5 15.2 a 0.1 5.3 a 1.8 15.0 * 2.1 B2.8 a 2.0 0 1.0 a 0 0 1.3 * 0.3 0 0.3 a 0.3 0.385 a 0.010 13 'S-12' 6.61 a 0.33 1.6 a 0.2 44.1 a 0.7 15.8 a 0.2 7.6 a 0.6 12.8 a 1.6 34.8 a 1.7 0.1 a 0.1 1.0 a 0.4 0 1.3 a 0.3 0 0 0.396 = 0.006 a: NueSer pi rats par period. 6/ Mean a icandard error. 0/ Coneantratlon of NaCl chat hemolyred 305 oi the erythrocytes. SS . L"!*-^4a r i*' f ' . * . W'.*r:i q*nMt' !*rf; *v*vS o 23 I g! 0007-SWP-000115565 3 TABLE 12 ., nEMAToiosy gy r at s rsn ?A?vr r^T. CONTAIS'rS'G LEAD AS LEAS CARBONATE Analyses A 'S3'l/ TreitncnC Ve*' 8 13 t"..\ v Erythrocytes (x 10*/TM*) Reticulocytes, % Hcautocrit, vol.y 7. Kaaoglobin, gay % Leukocytal (x I03/soi3) Seutrophill, r. Lyapnoeycei, % Banda, X Eoi inophill, 7. Baaophila, X Monocytes, X Atypical, 2 Nucleated RBC, X Erythrocyte osmotic fragility [NaCl'- 3.94 * 0.36^ 0.4 s 0.2 41.3 0.9 13.9 * 0.3 4.3 s 1.2 14.3 s 4.1 82.0 x 3.8 0 0.7 4 0.7 0 3.0 s 2.0 0 0 0.388 3 0.009 S.13 3 0.06 1.1 s 0.3 44.0 * 1.3 13.0 * 0.2 3.0 * 0.9 13.0 3 4.1 14.0 * 4.2 0 0.3 s 0.3 0 0.3 3 0.3 0 0 0.394 * 0.012 n o 1* Oh o 6.60 3 0.37 2.9 s 1.3 44.7 m 1.2 15.6 s 0.6 7.7 s 0.3 13.2 3 2.6 82.7 s 2.7 0.2 s 0.1 0 1.0 s 3.3 0 0.1 3 0.1 0.397 = 0.003 */ Xuobtr of rats per period. V Mean s standard error. c/ Concentration of NaCI chat hamolysed $0% of the arythrocytet. psag i-e .*! ?:2?C sS8 *3r v---* 1 4 * b Me TajyaB'f 2. 0007-SWP-036998 0007-SWP-000115566 TAIC.E 13 roLC'r or r\t s r*o ::ss l s /o :sr ctwiwjfsss K.r :ead 6 {Smi.'li1 Treatnenc Waat" a rv4i U 3.72 s 0.15^ 2.5 * 0.3 39.7 x 0.8 13.6 * if 9.7 1.4 9.5 s 2.X 90.2 * 2.3 0.3 * 0.3 0 0 0 0 0 0.389 0.006 4.49 0.83 1.0 e 0.6 42.8 * l.l 16.7 * 0.3 6.7 * 1.2 7.0 * X.7 92.0 * 2.1 0 0 0 1.0 0.7 0 0 0.412 * 0.006 5.63 = 0.36 1.3 s 0.1 62.9 s 0.4 14.7 * 0.1 -- 4* 7.0 X 0.5 14.2 * 2.1 83.6 = 2.2 0 1.4 s 0.4 0 0.8 0.3 0 0.1 X 0.1 0.408 x 0.005 :iriod, excapc vhara indicaced oehcrvise. chat hamolyia* 50% of eha arychroeytaa. :s ^TV^rT,; > '` 0007-SWP-036999 0007-SWP-000115567 TABLE 14 c !mv t is s u e a s p r-vin oitirrsisy o f mt s TE3 ?Ai:rr c Sn t a i:::^ k >, l e a p ................... Analyses Traarr-artc 4>k 48 r:.g> '.3 <>24) Serum *lc:rophor*i* Albumin, % Alpha l globulin, % Alpha 2 globulin, T, Bara globulin, 5 Gamma globulin, % Total prorain, fa X Albuain/globulin ratio 43 28 s 1 Ja 1 20 * 1 6s l 5.4 3 0.1 0.76 0.03 43 * 2 23 * L 5*1 20 * l 10 x 1 6.2 s 0.2 0.77 * 0.07 48 x 1 21 3 l 5s 1 21 3 A 63 1 6.3 s 0.1 0.93 s 0.94 Erythroeyte ALAO, umol. PBS/ Hale*: 23.2* 2.3S7 100 ml ABC/hr Female*: 16.6 x 3.1*' Total: 19.9 x 2.2 Protoporphyrin, 19.6 * 1.6 ug/100 ml RBC 15.1 * 16.3 s 2.2&' 15.6* 1.5 23.5 * 1.9 14.5 * l.if 13.4 x o.-i' ..15.0 * 1.0 29.2 x 2.0 L'rina Copreporphyrir., ug/24 hr ALA, ug/2A hr 2.5 * 1.2 78.0 s 7.4 3.3 * 7.4 83.3 * 11.0 6.0 * 1.9 43.4 * 5.0 a/ Cushat oi ran par period, except where indicated oeharviaa. .`lean = standard arror. 3/ Four rasa. it Twelve rac*. 26 0007-SWP-000115568  .................TABLE 15 .............. ..............>......... t is s u e a:.'p firu cvr.v:sTBY o f s at s rsi COKTAWta i. 25". tljiAi AS '-ini' OCTOATE Artlv*s Treacrent :.*eek 4a iiil 13 Sarua electrophoresis Albumin. *. Alpha 1 globulin, X Alpha 2 globulin, 1. Baca globulin, X Camma globulin, X Total pretain, ft X Albumin/globulin ratio 40 ii' 26 * 1 531 21 3 1 8*1 5.9 * 0.1 0.66 * 0.02 44 -- 3 20 3 2 4* 1 20 * 1 12 * 1 6.3 * 0.2 0.79 3 0.08 48 = 1 20 3 1 ..... S3 1 22 3 1 7*1 6.2 3 0.1 0.93 s 0.04 Erythroeyces AUO, uaol. PBC/ .Ha lac 26.8 * 7.7i' 100 ml RC/hr Famalaa: 19.5 * 4.iSJ Total: 22.2 * 3.9 Protoporphyrin, 28.4 x 2.4 ug/100 ml BBC 14.9 s 1.3' 18.7 * 0.3&' 16.8 3 1.2 24.2 3 1.6....... 12.0 = o.ci/ 16.1 3 1.3^ 14.0 s 1.4 22.8 x 2.5 Jrint Coproporphyrin, ug/24 hr AtaAg ug/24 hr 1.2 * 0.2 86.4 * 16.6 4.8 * 2.4 107.6 3 34.1 2.9 = 1.4 35.0 3 6.7 4/ Musbcr of rata par period, except where indicttad othtruiae. / Maan * acaadard error. :/ Two rata. i! S ix ra ca. n c * . .' :sv-Jfr p' aKir: feSs.- h TL_> : "TiX, 0007-SWP-037001 0007-SWP-000115569 TAS1* 16 Ana!-.-*** T.ISSCE ACT K03V =*s :<:s t Y OP PATS *?D PAT' COSTA':*:2N0 \53*- MV0 A< errOATT CW^e rsai'i' Traacnanr Weak 6 ('^41 ......... ' ........... 13 Serum alectrophoreiia Albumin, r; Alpha l globulin, a Alpha 2 globulin, T. lata globulin, * Cana globulin, X Total protein, dtg X Albuain/globulin ratio 41 * ' 26 * 1 5* 1 21 s 1 6=1 3.7 = 0.1 0.66 * 0.04 Erythroeyta* ALAD, uaol. PBC/ lUlaa: 100 nl RBC/hr rasalei. Total; Protoporphyrin, Hg/100 ml X3C 21.4 x 6.& 15.5 x 2.T&1 18.4 s 3.3 23.1 = 1.0 41 * 4 ' 23 x 3 6x2 20 x 1 11 x 2 6.3 x 0.1 0.70 0.13 50 = l 20 x 1 4x l 20 X 1 7xi 6.0 s 0.1 1.00 X 0.07 10.3 x 0.8/ 15.3 x 0.2> 12.8 x 1.5 21.7 * X.l 12.5 * 0.7&' 17.0 x 1.2$/ 14,7 X 0.9 27.7 x 3.3 Urine Coproporphyrm, Pg/24 hr AU, ug/24 hr 10.7 x 5.9 97.4 s 19.2 1.1 x 0.6 101.6 x 30.1 4.9 x 2.4 50.5 x 6.6 V .^unoer oi rata period, axeape wnert indicated otharviie. b/ V.aan r *tandard error. SJ Two rat*. e/ Six rat*. an?sj^: 23&i- ' VIA.:- ... {& *?& m?**>;! e***V*V^%C*^4.*--1 **> 4- .- r - :s 1 ' nnna.03D.naanaa 0007-SWP-000115570 AM lviai TABLE IT TTSSl'S AND BORY fU'Tn c v e v t s w f'T SATS rr*> . S*T* C3.\Ta :v T-.'G 2.05'. LEAD AS LU.`.0 0CT3ATE ftk* rracsent "ask i* 8 .\Va4> "" ' " 13 Sana electrophoresis Albumin, T. Alpha l globulin, X Alpha 2 globulin, X Seta globulin, X Casons globulin, X Total precaln, tl X Albumin/globulin ratio 41 * 3^ 27 * 2 4a 1 20 a 1 9x 1 5.7 a 0.2 0.70 x 0.07 Erythrocytes AiAD, unol. ?BC/ Malta: 24.1 a 4.0*' 100 ml XBC/hr Females: 18.7 a l.o> Total: 21.4 a 2.3 Protoporphyrin, 29.5 a 2.8 ug/100 ml BBC 46 a 2 22 a l 4al 19 a i 9ai 6.0 a o.l 0.85 a 0.07 48 a 2 20 a 1 6xi 21 a l 6x 1 6.2 x o.l 0.96 x 0.07 12.1 a 1.7S' 11.3 a o.z4; 11.7 a 0.7 30.8 a 2.5 11.4 a 0.8^ 16.3 a 3.9^ 13.8 a 2.0 24.0 2.2 "fine Coproporphyrin, ug/24 hr ALA, ug/ 24 hr 1.6 a 0.6 80.7 * 17.3 3.0 a 0.8 82.7 a 10.4 7.7 a 2.9 64.5 x s.8 a.- : -xbar of rot* ptr poriod, except vhart indicated otherviee. b/ Moan a standard arror. c/ Tuo rat*. ' fix rats. 29 w " 0007-SWP-037003 0007-SWP-000115571 TABLE IB TISSUE AND BODY fr.CIP CHEMISTRY ffr RATS rso ?a :?.t XW* COmiKISS 0.;r, LEA3 AS LEAP CHROMATE An !' 'rtatncnt Vcak 48 <41 13 OM2) Albumin, X Alpha l globulin, * Alpha 2 globulin, X Beta (lobulln, X Cima (lobulln, % Total protein, g X Albuain/globulln ratio 42 * & 28 * l 4* i 19 * i 8* 3 3.8 X 0.2 0.71 * 0.06 Erythrocyte AUO, pool. PBS/ Male*: 23.4 * 3.5fJ 100 ml MC/hr Pi ulet: 13.4 A 0.9^ Total: 18.4 A 3.3 Protoporphyria, 27.3 A 2.8 uj/100 al TBC l'rtn Coproporphyria, u|/24 hr AU, Ht/24 hr 8.2 * 6.7 69.3 * 6.6 44 s 2 2Q * 2 4X 1 19 X 1 12 X 2 6.0 X 0. 2 0.80 X 0. 08 47 X 1 22 X 1 3X1 21 X 1 6X 1 6.1 X 0..1 0.90 A 0..03 ".... ' 14.1 X 0. 6*/ 17.6 X 0. & 15.7 X 1. 0 28.3 X 0. 6 15.7 X i .,s*i 16.3 X i. 16.1 X i. 0 27.9 X 2.,1 rHl 90 1.3 * 0.7 65.2 * 17.4 2.2 85.3 a 31.4 */ Buaber of rat* par period, except whtra Indicated otherwie. b/ Mean = (tandaid error. cl Two rat*. i/ Six rat*. i'l: V ^ <mk L.Vo j H. *Vi .V 7 rfvC^Tvdi-#j?:4 30 4* v-Tr:* 0007-SWP-037004 0007-SWP-000115572 9 3 TABU 19 Ana!vse* TISSUE AMD WHY n.n-' CHEMISTRY or r at s reco p a !; *W COSTA! S'ISC' 1.95". ! CAO A.s ma d cakot'ArE"' CUro 4 Oil*/ I rcat-ent ,..'etk 6 12==1 13 Scrum al*etrophore*i* Albumin, % Alpha l globulin, X Alpha 2 globulin, 7, Baca globulin, ", Casna globulin, 7. Total protein, ft % Albuain/flobulin ratio 41 i 2&/ 25 a 1 4Sl 20 * 1 9* 1 5.7 * 0.1 0.73 0.06 45 a l 19 * l 4a i 20 * 1 11 * 1 6.20 * 0.04 o.si a 0.04 47 a 2 19 a 2 5*1 23 a l 6* l 6.4 a o.l 0.94 a 0.08 Erythrocyte ALAD, Uol. BBC/ Mala*: 100 al RBC/hr Females: Total: Protoporphyrin, ug/100 al BBC 29.5 * 3.& 20.4 a 4.3S/ 24.9 * 3.4 26.5 * 4.7 12.3 a 1.0; 14.7 a 0.6/ 13.5 * 0.8 26.8 a 1.8 13.3 A l.id/ 12.9 a 2.34' 13.1 * 1.3 27.4 a'1.5 trine Coproporphyrin, Ug/24 hr A1A, Ug/24 hr 0.9 * 0.1 S0.B a 7.2 7.0 = 6.4 67.7 = 6.8 4.4 a 1.9 66.5 * 17.5 */ Suober at rare par period, except when indicated otherwise, h/ Mean * icmdard error. Two race. i/ Six rat*. >* .Tj -'? fev p; v'y-v I ******<;*< -vvr* 3 31 V .. . 0007-SWP-037005 0007-SWP-000115573 TABLE 20 TISS11 AN5 BOW r VtS C^SMISTB? 0" -ATS *ST'PAT.'.T 1 ccs?Arnsg "::.^r LEac *^'LX5". :^t:aT- Anaivss* Treat-ant *>'< 6 ....... iSl) :3 Strum tlettrophortsis Albumin, X Alpha 1 globulin, * Alpha 2 globulin, * Seta globulin, X Gama globulin, 7. Total protein, ^g 5 Albumin/globulin ratio AO * / 27 a l 3a1 22 a 1 8* 1 5.6 a 0.1 0.68 a 0.03 Erythrocyte ALAO, uaol. PSG/ >!alea: 100 ml RBC/hr Famalat: Total: Protoporphyrin, ug/100 ml BBC 26.4 a 7'4=/ 14.2 a 3.2-; 20.3 a 4.9 25.3 * 1.6 Irina Coproporphyrin, ;s|/24 hr ALA, ug/24 hr 2,6 * 1.6 as.7 a 19.3 47 * 3 21 a t Aa 1 18 a 1 ** 2 S.l a 0.1 0.90 a 0.12 46 = 2 21 a 1 5a 7 "2 a 9A. 6a X 6,4 a 0. X 0.88 a 0*36 16.5 a 1.4*' 13.4 a 3.8--^ 15.0 * 1.9 24. 2 a 2.6 Uii12.6 a 13.7 a l.i13.1 = l.G 24.6 a 2.3 0.9 a C.l 78.4 a 6.8 2.6 a 3.3 49.7 a Suaber of ra:a par period, exeepc vhara indicated otherwise. / Mean a standard error. ' Two rats. ' Six rats. i&f*. j-fc'*;. `3$. rfafcrfA Vv t: LV'-? ** 4 V rt-.Buwipr 32 r".i .... ................. .. >7 u n^aplBp 0007-SWP-037006 tM l* l* 0007-SWP-000115574 TABLE 21 A:i*vses t is s u e A`;r r.mv rt.:*T9 CKEWSM* or aa-v t t o : ?*: SU rc.NTAIS: :s -j0.051 LEAD A S ISAS CAKOVATt UMf* Tresc-cnr '.t** am ! ^y4i s 5erua alaccrophorasia Albumin, T. Alpha 1 globulin, " Alpha 2 globulin, % Bata globulin, * Cacma globulin, % Total protain, fg % Albumin/globulin ratio 41 s 6 27 * 1 3*1 21 * 2 a 12 5.4 a 0.2 0.73 * 0.17 45 a l 21 a 2 19 a 1 10 s 1 6.0 a 0.06 0.12 a 0.04..... 47 z 2 22 = 1 5* 1 20 * l 7z l 6.3 r 0.1 3.56 s 0.06 Erythroeyta A1A0, uaol. PBS/ Miles: 12. & 100 ml ABC/hr females: 9.1 * 2.11/ 10.2 = 1 .blf Protoporphyrin, ug/100 ml ABC 23.2 = 0.9 4.4 * O.li7 12.4 a 0.4J/ 6.4 z 2.3X' 20.4 s 2.1 3.4 a l.Ofi/ 7.4 a 0.5*/ 6.4 z O.rP 27.2 z 6.8 Trine 4HJA Cooroporphyrtc, ug/2A hr AUA > ug/ 24 nt 2.0 * 0.7 90.3 * 27.7 0.S z 0.3 72.3 = 13.4 6.7 s 2.2 42.2 *5.8 , Sumoar of rats par period, except utiara indicated otherwise. ' >'.an a standard error. Ona rat. ! Two rats. / Six rats. / Significantly different iron control (? < 0.03> as shown by Synnett's nulcipleeoeparisoB test- following an analysis of variants. .e^r- t *...' * * v. if sags At*** 23 0007-SWP-037007 to* t> |i 0007-SWP-000115575 :a u TtSSrE vry ' 1AD ?. a fV^rT!6??::? ST EATS ??2 ' SS .* ii.r is.\o....... Anjlvsis < Sarum alectropnoresis Albumin, " Alpha 1 globulin, * Alpha 2 globulin, * beta globulin, 7. Caiaoa globulin,' Total protein, f.g % Albumin/'globulin ratio 52 = :i = i i= i 20 * 1 3=1 5.4 * 0.2 1.1 * 0.03 Erythroeyta ALAD, nmol. ?SC/ Males: 8.5 si 5.0i/ 100 ml UC/hr Females: 10.1 * o.i--/ Total: 9.3 s 2.1*/ Protoporphyrin, 14.8 a 4.3 ug/100 ml sac Treatment .'oek 8 '.W> 44 = : 21 si 2 8*5 21 * 3 6a1 6.0 a 0.2 0.78 * 0.06 5.0 * 0.3*/ 15.0 * 5.1--/ 10.0 * 3.6 24.5 * 1.8 13 /w::- 44 s : 24 s 1 7* 1 21 * 1 5=1 6.1 = 0.1 0.82 = C.26 4.9 a 0.61/ 8.8 a l.C^/ 6.9 s O.S--' 26.3 a 1.2 Trine Cop roporphy rir., ug/24 hr a ia . ug/24 hr 2.0 = 0.8 nc.i * :i.5 6.8 * 4.9 72.0 * 13.6 4.6 a 2.1 51.3 a 3.6 i' N'usber of rats per period, axeapt unsrs indieatad otherwise. 1 Mean = standard arror. I Two rats. Six rats. i Significantly diffaranc from control C? < 0.05) as ir.dicacad by Ouanttt's ajlsiplecot?ariaon test following aa analysis of variants. rs- . ?*** . '4 '. * ' f,. \ ' '7 ' a *' 1 E&s.-. -r-7* r -,v. i r.-> * *' '** ;v*`' * r'-. Si.-.-- i 34 0007-SWP-037Q08 I<t lii. (n 0007-SWP-000115576 ' v! m ?iv <;:.'ia :51? # :V1 ,.** ,).? * * ***V1. |i iM ;M 1n 2 Vi o0 TABI.E 2 I . e*>r~ SIIHHAHY OK rilKrilYtlH HKIAMUI.ISH 1H BATS FEU FAINI.FOB >1 WEEKS CONTAIN INK DIMERENT CONCENTBATIONS OF TJAI) M yllirocvte__________________ ___________ AIAI)S*7 III unify Diet J ( mil. l'BC/100 oil KMC/lir) lBfi/100 1 BMC) * (1`g Control 24 15.0 4 1.0^ 29.2 f 2.0 6.0 4 1.9 41.4 0.U8Z l.end Oct oatc 12 14.0 4 1.4 22.8 4 2.5 2.9 1.4 15.0 II.VJl l.cml Octoate i/S.QYL U'ol Octoate 0.421 leal Chromate 1.951 l.ead Chromate 12 12 12 12 (ft. 2 4 0.9 u. a t 2.0 16.1 1.0 11.1 f t.l 21.2 i 1.3 24.0 t 2.2 22.9 i 2.1 22.4 * 1.5 4.9 4 2.4 2.2 4 2.9 4.3 i 2.2 4,4 4 1.9 50.5 64.5 85.1 66.5 I2.4U CliriMate 12 11.1 * 1.0 24.6 1 2.0 2.6 t 0.8 49.2 66.U5Z la`d Chromate 12 - 6.4 t 0.// 22.2 4 0.8 0.2 4 1.2 42.2 11.721 IMS l.ead Faint 12 - 0.9 4 0.8"/ 20.1 1 1.2 4.6 4 2.1 51. af 6-Anliioleviitlitic acid ddiyilMsc. b/ 6-Aminolevulinic acid, c,/ Ntiwb.r u( rnta |>ar diet. d/ Avi-race i standnrd error of nuaber of rats indicated. e/ Si|>ol(lcant ly dlfteren) Iron control (F < 0.05) as shown by Ounnett** Hull Ipte-comparison tes on analysis at vatlaorc. o o 0 -j CO $ "10 o o o tn on -d -vl By 13 vaoks the tax difference had disappeared and the ALAD activity in 66.05* -caa caroonacc trevp a.-.c ;TT. ;.'3S -Jg oai-.t ;::j depressed 5b:. and 53. respectively. l U> Urinalysis of rats fd paint Mb * containing different concentra tions of lead are shown in labia 24-31. No marked difference* in urinary protein or sediment (erytnroevee, crystals. tuts. etc.). Thu*. urinaiysia can be considered within normal rangea for all traatmant groups. tXtf H. load Contant in Tlaauaa of !Uti Fed Paint ^er.tdinjr.g.piffaran^ Concantrationa of laad i^|. '/ft Tab lea 33-37 show the/iiad contant of^lood, brain, livar, kidney, ( and bona from rata fad paint mu containing /iffaranc concaatrationa of laad. \Zlfea valuaa for tha laad eoncantratlona in bl^d at 4 and 8 weak* vara omxttad^P^ I from Tab la 23 bacauaa it waa diaeovarad that/cheat templet had baan eontaiy/' LiaateC by thair atsraga containara. Atl3^aki_thj^bloodleadleve3j^ thajtafadlaa^otoataand^h^rtafaa^i^Kaodl^5^1aa?|c^S*S*JMt hot ceewenanc control.Tntht rata^eaTTjj^iaae cnroaatifrjb6.0521 ad ' 11.92* MBS load pmCfft, blood. 1 avals waraTound to bo ilavacao ncty ------- -------.---------------------------------fi'y2...... ' " ..-- & SpAb ?"*U * St. <%}* ky-et. K? b!&. At 4 waaka, tiaaua laad lav*la livar and kldnay vara balm* tha dataetioa limit* of our assay.^Tbo rasults vara Che aamt at 8 waaks with tha exception of chtJjBS<>leedjlncjreu. All four rats in this group showed dataetabla lead in chair kldnaya^ tCs^e A^-Wjjaok*jdataec*blj^iavjl|^MjM^Binilliehj^bralrMtg|jjd_on^ injjherac^ednjj^&jjU^E^et^m'IjtSCiSOy^SSSiSii.iSiSiS-im lead vara found .nTwora^r'TedbijaTl laid csrbonatV and nlni rics fed 11.52* SBSlaadsaint, So load waa dataecad in tha kidneya of tn_so8trol group at 13 wtaaa. in centralt, load waa ootaecod in tha-kidneys of onartvo rats in ~ tseh laad aecoata group) and thd 0.421 and 1.9JZ laad ehroaata groups, laid was dsttecsd in tha kldnay* of three rats, eight rats and 12 rats in tha 12.431 laad chromate, 66.051 laad earbonaca and 11.95* NBS laad paint group*, rtspeetivsly. ? Ths_ femurs of rat* fed the control diet, load oeto*e*_or_lft*d_ chromate exnibi ttj^!eryTrcsIe*?Bp'T?y weans However. tne iaauts of rata [*aj__trBonate or l.L^&21_HSS_liAd-ai.,--nr eon gained 13.0 and 1.$ -S of laad/gu of bene, raapactively. r-:i- 36 *: ' 0007-SWP-037010 TABU 24 D--11 L'aiNALv<rs or r a t s .rsf p a in t ONTAINL'.C ':'? Uao Protein: < 100 Dig m _ > 100 mg r. Microscopic Examination HiCi' : Normal Moderate _ _ Excaniva UBCi': Normal Modaraea Excessive Epiensliaaic': Normal Nod arata Excessive Crya ta1si': Norma 1 Modaraea Caat*: Negative _ oiiriva Treatment Vrlfk 4 1 i2 7 6 20 12 4 75 l2 l *7 2 ______2_ . aa 23 1 2 7 4 4 2 -i. 8 a a 23 * 24 Kuaors andicaca number of rats at response level. / Normal, 10 or lass calU; moderate, 10*100 call*; excess:ve, >100 cails/fiald (x 440). b/ Normal, or laaa call*; modaraea, J-23 ceils; excessive, > 23 cells/fiald (x 100). c/ Normal, nona; modaraea, 1*3 crystals; excessive, > 3 crystals/field (x 100). 37 "rS -* v 0007-SWP-037011 0007-SWP-000115579 TABLE IS isimvsis o f s a t s f t p f a in t -aw con ?a :n :;;o 0.0HL LSAO AS ITA.0 OCTOAIE ___ L:,gU3 -Cjak 1A Proeain: N'acaeiva < 100 mi H _ > 100 >51 Microscopic Examinecion RBCi/: Normal Medaraca 43 8 4 3 10 12 -------- ; . WCi': Normal ____________ 3 3 "IT" Modsrace 21 2 __________ Exeats^vj_____________ -- -- EpieneliucE^: Normal _ 4 ' " a" 12 Moderate _ _______ ________ txcfiiivi_____ __ _ _ _ _ ________ _ _ Cryscals/: Normal 2 4 11 Hodarata 2. 1 -------------------------- _______________ Caaca: Negative u 4 12 Numbers indicate number of race at responds level. / Normal, 10 or Its* call*; eedsrste, 10*100 cells; excessive, > 100 eells/field (x 440>. b/ Normal, 5 or lass calls; moderate. 5*25 calls; excessive, > 25 calla/field (x 1001......... / Normal, none; moderate, 1-5 crystal*; excessive, > 5 cryatala/fiald (x 100}. .. /, y.vv.. 1 3B 0007-SWP-000115580 'ABU 26 VKiSALYSIS OF RATS FE3 PAINT ?4W CONTAINING 0. j 3* UAO AS IlAO OCTOATS ....... Preccr.: Najativa < 100 r ib r. __________ > i0 r.:_%_ _ _ , Microscopic Examination RBCi^: Normal Moderate _ _**l*iv WBCi': Normal Moderate __________ Exeats Wa _ _ _ ^ picnelius&/: Normal Moderate ________ _Excsiv Cry seal si'': Normal Moderate _Exessiye_ _ Caaca: Na(aciva ___ ?os:c1va ___ Treatment Weak, 4 8................ 13 43 l _ __ __ 10 1 _1. 22 10 12 1 1___________________ l. 4 19 33 4 12 34 1 12 4 4 12 Numbers indicate nunbar of rata ac response laval. a/ Normal, 10 or laa* eetla; aoderata, 10-100 calls; axcaasiva, > 100 cella/field (x 440). ....... ......... / Normal, 5 or lass calls; moderate, 5-23 calls; excessive, > 23 cells/field (x 100). c/ Normal, none; moderate, 1-3 crystals; axcaasiva, > 3 erystaia/field (x 100). r j-saii itr-rt i sKw 39 v0007-SWP-037013 0007-SWP-000115581 TABU 27 t>'vT4 jRiXALvsts o f Bat s rso pain t w ai 2.05*; LEAP AS UA3 QCTvATE Trcscrcnt Week *8 ;3 Frotum: Negative 44 < 100 mg u > 100 t..K X Microscopic Examination RdCi': Norasl 4 <* Moderate Excessive UBCS': Norms l 33 Moderate 1 * ___________________ Epitasliusti': Sternal 4 7 U Modarsco llCiliiVO ___________ _ _ _ Crystal*^; Normal 24 Mod*roc* * Casts: Negative Positive 4* 11 l 12 8 4 r+ ______ 12 12 Kunbera indicate number of me * at rospons* level. */ Normal, 10 or l*i* call*; moderate, 10*100 culls; excossivo, > 100 eolU/fiold (x 440). b/ Normal, 3 or 1ms colls; moderate, 3-23 colls; .................................. excessive, > 25 eells/field (x 100). ................. e.` Nora* l, none; u.-dorno, 1-5 cry* to Is; excessive, > 5 crystels/iield (x 100)................................................... -' 4a-:: ' -i.'1' \ l-.i ~v-'' 40 0007-SWP-037014 0007-SWP-000115582 TABLE 2B Tt r in a l y s is or r a t s p t d PAINT CONTAIN e*.oiwm 0.42', LSAO AS '_TAD CMM5KA Protein: Negative < 100 mg X > 100 ra X Microscopic Examination HBCj> ; Normal Moderate Excessive VBCi'; Normal Moderate cpitneluc--': Normal Moderate Crystalsi.': Normal Moderate Casts: Negative Positive Treatment Week 48 4 2 :o 2l % 31 13 23 21 8 3 1 8 1 1* 4 12 2 4 12 1 4 4 12 Numbers incicace number of rats at response level. / Normal. 10 or less cells; moderate, 10*100 cells excessive, > 100 calli/field (x *40). >/ Norm*!, S cr less calls; moderate.. 5-25 cells; excessive, > 25 celle/field (x 100). / Normal, none; moderate, 1*5 crystals; excessive, 5 5 erystala/field t* 100). r k t :.r. 41 < 0007--SWP-037015 0007-SWP-000115583 o o TABLE T9 (klP* l 'r is a l y s is o f r a t s f e d ?a :?.t HtM c c n t a :n :n s l.?sr. LA3' AS LEAP CHROMATE .............. Procter.: Negative < 100 sig 1 i2 SSj^__________ Microscopic Examination RBC1': Normal Moderate WBCi': Normal Moderate Epithelium-'; Normal Moderate _________________Exejsiive Cryittlsi'; Normal Moderate ------- _EtJsiive_ _ _ Casts: Negative Positive Treacnenc Week kS i 3 1 __ 3 1 1 ' 1 A 3 9 *9 l 23 2 _____ 1 _ AA B 3 9 *fc 4 A 12 A A 12 Numbers indicate number of race at response level. J Normal, 10 or lea* cells; moderate, 10-100 cells; excessive, > 100 etlls/fieid (x 4A0). b/ Normal, 5 or less cells; noderace, 5>25 cells; excessive, > 25 eells/fielo (x 100). e/ Normal, none; eoderste, 1-5 crystals; excessive, > 5 erystals/field (x 100). . *. ... ,, *9 * ... * ' * ;.r . * v; i i >, . -'.'-V; -.-..a "ffr}-' ............................ i'.'f'':'' *7 .2 . ' . ' --: rC ---* v-v--.--.'. irt .v-.wi;;- 0007--SWP-037016 0007-SWP-000115584 TABU 30 tktr1 CR1NAIYSIS Of RATS FE3 PAINT rUE CONTAINING 12.-3'. LEAD AS LEAS CHROMATE Protein: Negative < 100 mg 2, Microscopic Examination RBCi'': Normal ......... Moderate Excessive WBCi': Norma 1 .Moderate Epitneiiums' : Normal Moderate ___ ______Excessive Crystals^: Normal Moderate Excessive Casts; Negative Posicive To eatment week i H ^3 i1 32 9 3 41 3 11 31 2 44 24 2 44 11 1 11 1 11 1 12 12 Numbers indicate number of rats it rttponii level, a/ Normal, 10 or lass cells; moderate, 10*100 calls; excessive, > 100 cclls/field (x 440). ........ b! Norms 1, 3 or lest cUs; moderate, 5*25 cells; excessive, > 23 cells/field (x 100). i! Normal, none; moderate, 1-3 crystals; excessive, > 3 cryseals/fiuld (x 100). r.0st>v- m cs i*. : r* j 43 0007-SWP-037017 0007-SWP-000115585 :a 2L 31 ~ VRIN-Airsis cr .h at s F-3 pain t c ***"* . ............................... --.o .- MXi c ax ;j :;a~s Protein: Negative < 100 e.t 1 Microscopic Examination RiC/: Normal Moderate *BCi': Normal Moderate Excessive Epienaliuat-': Normal Moderate ________ _Exeassiva Crystals^': Normal Moderate Casts: Negative Positive Trotffanc l'ocx a* 13 3' 1 4 ^ i: 1 42 2 2 22 a 4 u * 10 2 12 34 12 4 4 12 Numbers incicste number of test at response level. *,! Normal, 10 or lass calli; moderate. 10*100 calla; excessive, > 100 cslls/fULd (x 440). b/ .Normal, 5 or laai call*; moderate, 5*23 calls; excessive, > 25 cells/fleld (x 100). e/ Nonas!, nona; moderate, i-5 crystals; excessive, > S erysiais/field lx 100). spar- I*KXV. It* '* * I----- 'T k>~? S^SK t ?-"- a. 0007-SMP-037018 0007-SWP-000115586 :a b i2 * % "RINA .vs is or s.ms 7zo ?,u: Trticnep.c V.u k -- 3 13 Protein. Ngaciv < 100 nB r. > *.00 ag *. .Microscopic examination RBCi'; Normal Moderate 23 2 7 5 2 4 12 2 im________ waci-: Normal 2 "3 Moderate Excessive 1 2 Spittle! uni': Normal *4 11 *1 12 Modaraca _ -- _ _1x c ij ii_ _____ _ _ ______ _ _ Crystal si' : Norms 1 4 4 .2 ModarJta Excessive Cases: Negative * 4 12 Positive Nye^cri ineicar* number of rats at response laval. a/ Sorisal, 10 or laaa call*; moderate, 10-100 cell*; excessive, > 100 eallsffield (k 440). b/ Kansal, 5 a; last calls; moderate, 3*25 calls; excessive. > Zi ealli/ileld (x 100). ' Normal, non*; moderate, 1-5 crystals; excessive, > 5 cry*tai*/fi*ld (x 100). - - .. 'v *-.. - ** v />V i *^. L.* i . ii-r-js-. ; .* . ; i*,'.. * 1 .* H ;* P _ k ..* ~ ,.v: . . N`.a , t *\.c. ' :. *, 1.-T5 itr `v1* ai.. :&r:P -'V* 0007-SWP-0370I9 0007-SWP-000115587 \i3Li 33 LEAD CrXTEN" :c d Tiet Control"^ 0.03% Lead Cctoate 0.53% Lead Occoaca 2.05% Lead Oecoaca 0.42% Lead Chromate 1.95% Lead Cbrosata 12.43% Lead Chrooata 66.05% Lead Carbonate 11.92% KS5 Lead Paint 4' Tru fon c Ve<t Si' d- (3)-' 13.1 = 0.9 (16)*/ 12.3 5 :.s (3) -6< z 2.* (?>!' 14.5 - 1.5 (8) 13.2 : 1.0 (S) 12.0 : 1.4 (8) I 19.4 - 2.2 (S)i' I 24.9 = 2.2 Wi/ ^3.9 = 1.3 ciiiiii/ a/ Values dtlatad due to contaminecion. b/ Four value* dilated du* eo contamination. e/ Number of rat blood* analysed par group unit** indicated otbarvis*. it Sixteen blood samples war* analysed. &t Average ug of ltad/100 ml blood - standard trror of number of rat* in parenthesis. it On* blood sample lost. fi/ Significantly diffarar.t from control CP < O.CJ) as shear. by Ou.nnett's eulcipls-cempariion cast following in analysts of variance, n/ Twelve blood sampla* analvzed. ......................... ........................... %* / v* t t< .v \.j . *"5 *. -J * -'yy ` '?:' rfsJ . - SvOlSS'*J.' H5P3C 46 ir *r J 0007-SWP-000115588 2;*= Control^ 0.08Z Lead Oetsata 0.53* Lead Oetoata 1.051 Lead Oetoata 0.42Z Lead Chromate 1.95X Lead Chromate 12. A3* Lead Chromate 66.051 Lead Carbonate 11.92X N8S Lead Paint TABLE li LEAD CONTENT C? liV.TN a* (A)-1'' n.d./ n.d. n.d. n.d. n.d. &ad. n.d. n.d. n.d*......... ' "ek 9 (A) n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. ' 13 r.:> n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. 0.2 g Q.li/ (7) a/ Nuaoer of braina analyzed par group unlaaa indieaced otherwise. b/ Eight brain# ware analyzed at A and B week#. Twenty-four brain# war# analyzed at 13 weak*. e/ Not detectable. Below sensitivity of 0.07 ug/gs of brain. it Average ug of laad/ga brain - atandard error number of rat# shown in oarenthaiis. ........................... * -* * f.r .i ' ' ?. ' at mi : N T T :i ru. i.'i-L'i.i.'.' `> a .(.ir'^'JaS*. t*< *J.^aT Jyibear S'**.'? c*-^ . * **' - :\ o4**y ' : 0007-SWP-037021 0007-SWP-000115589 Ttet Control^ 0.091 Lead Oetcate 0.531 Lud Octett* 2.051 Lead Oetoate 0.421 Lud Chromate I, 951 Lud Chromate LI.431 Lud Chromate 66.051 Lud Carbonate II. 921 KBS Lud faint TABLE 35 i cr:m:.T c f (4)*'' n.d.-S' n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. Treatment Keek 9' ;-) 13 (12) n.d. n.d. n.d. n.d. , . . . Red* ........... n.d. r..d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. 1.1 g_0.6j/ (1) n.d. 0.4 sjl.l (9) a/ Kumber ot 11vara analyzed per group unleaa indicated otherwise, b/ Cighc livari were analyzed at 4 and B waaka. Twenty-four liven were analyzed at 13 waaka. / Not dacaetabla. Below sensitivity ef 0.07 ug/ga liver. / valuer are average ug of lead/gn liver s standard error ef number of rati anown in parentherii. B& r>/ v5v V .'r life gfe ISSr? . 30saa>* i *y* - "* v\* .9 0007--SWP-03 7022 0007-SWP-000115590 ZABLE 36 LEAD CCNTIST Of VlONSV Jit* (I)i' Trcatnent '->< a (-) Control-^ 0.087. Lead Octeats 0.53% Lead Octoats 2.03% Lead Ottoace 0.42% Lead Chromate 1.93% Laad Chromate 12-43% Lead Chromate 64.03% Lead Carbonate 11.92% XBS Laad faint n.d.^ n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d* n.d. n.d. - it o r..d. :.3l C) 0.31 (1) 0.** -0.1 C) '*.5i (i) 0.4 = 0.....0....(..3..) 2.3 - 0.2 (8) 1^ = 0.1 U2) /* xx*. a/ Number of kidneys analyzed par group unlaaa otherwise indicated. .b/ Eight kidneys vara analyzed at 4 and 8 weeks. Twenty-four kidneys vara analyzed at 13 vaaka. e/ Not dataecablt. Balov sensitivity of 0.07 ug/ga kldnay. d/y Values ar* ug of lead/gn kidney or average of lead/gs kidney : standard error ef number of'rata in parenthesis. -I . N. p* ,fM C`Srr*'&& ma: m* ? *&.: iV:: h""iX r\ i:. - & * .. V" - ^r--ov *' 0007-SWP-037023 0007-SWP-000115591 s - ?; `ABLE 37 t-A3 ecxTsrr or s q n e ^7:3) W*' rraatsarc yaak (4> Z-7yii\ >V- Us.1 3 Concrol-/ O.OB Laad Oetoact o.jji Laad Occoaec 2.05. Laad Oetoaca 0.42S Lead Chrooace I.95S Lead Chraaac* 12.437. Lead Chresata 66.057. laad Carbonaca II.5:7. N3S laad Paine 1.6S/ (1) 3.1 (1) n.d.i/ n.d. 2-9 (D 0.9 (1) 3.3 (1) U.O - 4.1 (4) 14.9 i 2.5 (4) 3.9 * 0.4 ce) 4-2 > 0.6 (4) 3.9 s 0.2 (4) 3.0 s 0.7 (4) 2.6 r 0.9 (4} 1.8 r 0.2 (4) E`l 6.0 5 1.1 2.1 8* 1-4 S 0.4 wf 3.2 = 0.2 C4) 3.3 = 0.3 (.3) 3.1 r 0.2 (12) 3.9 s 0.5 (12) 3.8 = 0.6 (12) 4.1 r 0.5 (12) 3.5 s 0.5 21.7 (12)^ 20.9 r C.9 C22>/ If*.>a*r.-. *aA . r*.. a; .'.ueetr si bonts analyzad par group unlati indicated otherwise, b/ Sight bonaa wara analyzad ac 4 and 8 uaaks. Twanty.four bonai ward analyzad ac 13 uaaka. cl Valuta ara ug of taad/ga bona or avaragt ug at lead/gw bona - standard arrot of number of rati in paranchasia. i! Net datactabla. Balow sensitivity of 0.4 ug/ga of bona, a ^ Significantly difftranc iron control (9 < 0.5) aa shown by Ounnett's sail c ip la ccrpiruon cast following an analysis of variance. t -1Wi%4a^ta->. X 9 S3 0007--SWP-037024 0007-SWP-000115592 At 8 weeks, the femurs ef rat* id tne control, lead oetoste or lead chromate diets contained similar quantities of lead, ranging from l.- 4.2 ug lesd/gs bone. Ladccrn^nth^femu^^rcneJj9J?!iZiiJ1e*d>^aroo^^e andJ11ij^>2J>35jCTOuo^>uer^h^janel^^jjyl-j^Ci-jmi_^lljig-- 3otn*:cr.it ;car;.y coh-Js control. , ``' After 13 weeks, the rats fed lead Detract or lead chromate had r.o more lead in their femurs than at 6 weeks ana then tnose in tne control group. TheJo.P5% lug csrhonatt grous exmaited ntgntr .svtisotTaUPin their ftmurs i21.7 ug ieia.ga eons; tr.ar. at 8 weeks. ThelLJJ2Zj<BS lead paint group had leas lead in their femurs (10.9 ug leed/ga bona) man at 6 weeks. Ihj_laid_Iiy b Is in both of these groups wore s--*tsignificantW greater than those qbaaryta in tat ta5tr5TTnlT {Mr1 1. Pstholotv of Rats Fed Paint P*lm Containing Oifferent Concentrations sLiss* " "" '............. "............... ........ The relative organ ueighca of the thyroid, spleen, heart, kidneys, liver, adrenals, brain and gonada are shown in Table 38. The 3unnect`s........... multiple-comparison test showed that nohe of the relative organ weights dif fered from control veluee. Ihe pathology of rats fad the control, 2.03Z lead octoate, 12.43Z lead chromate, 66.03 lead carhonaca or 11.92* BBS lead paint diets for 13 vsaks it shown in Tables 39-43.^Tj^s control rats had a few naturally occurring lesions. Fourteen of thepm rafiKaS mild to moderate lymphoid hyperplasia m tha lungs, characteristic of early minuet pneumonia. One of these rats had a sodtraet pneumonia and another one a mild mnphysema.^ Other lesiona included en unspecific myocardlcds in no rscs; foci ef subeeute ir.fUnsacion in the liver of two rats; a cross-section of a parasite (roundworm) in the colon of one rat; and foci of mononuclear cell infiltration in the kidneys ef two rats. Tha bona marrar myeloid/crytnroid cell ratioe (M/I) of ell rata war* within normal lisiti. Tha lesions observed in rats fad the 2.33Z lead octoate diet ware, sieilar to the lesiona saan in the control rsea. Sevan out of tha 12 racs^s-*-* hae slid to moderate lymphoid hveerplaeia in the lungs and one had slid pneumonia. Four rats had mild s^S^Bf subacute inflaraiation in tno liver......................... charstcerited by e leas of aaveral hepatic cord call* which were replaced by aecropnagea and lymphocytaa. Another rat had a foeb^&f inflance cion in the..... intcrscieiel tissue of the panereas. Tha K/E ratios of meat rats were norms 1. ... v,i _. Oh 0007-SWP-037025 0007-SWP-000115593 0 m SB# *** * 9 5 -:v:E WK&: sifijiaiir "rji*** ' ?rr^ti*. c-fv-: i i i i|i.irJ * w ia'S ia o iin lS _ iiiD t jiilM ij li M lM TTS i -tiiamaai in il Viai a#i ji _ tiMMim mv imi fc lm ij & 2 0 o SI| s Si *1 2 *1 r * ii 1 sa i =1 * r *t Sa i .. s; " *.1i A ;. 1t l> >4 lj i, -?1!1| ms t11d ; a* :I ii 3 in # -i i! ? li fc a ii ii S3 r ?. ?*> t:icA. ri *it:-*.. * i'-s & r?#5S5 1VAJ. raSEb. SsSr X&X-' m -a-vi; gi&ST&sf*t P e *;t -V-vV 53p*{N .--'-T*. , i1 *-* A T.''UV? srts. >'JiCCj J^u w iu j u . J5HJ * * . * -'.* fc'rt"yr 0007--SWP-037027 0007-SWP-000115595 0007-SWP-037028 0007-SWP-000115596 -3 TM 0 <m $ >* 4wftTl Ki IN *51 i J f mi ll ll ll 1to IN 8 :i o -*8 *-* S8 O a*h> M> 4a1 (OA U !- <ll v \ _"T*s.C 1 '.Va-,`n* #fmm. ms .A#:vy.; - r 0007-SWP-000115597 0007-SWP-037030 0007-SWP-000115598 I o o o -n | GO "0 o o o cn cn CD CD .` TABLE A) rATimXBiY or MTS tEU fM 11 WEEKS WITH MBS ITS.. c o u t a ih ih g 11.921 l e a d ' C.^ at Bo. 1S2 114 1*5 15* JL5 190 191 J9A JJl J9B laMa Lynphold hyperplasia Pneuoonla 2' 2 2 I2 Heart Myocarditis .} liver Tocl of Inflaaaiat Ion Bone Marrow M/E ratio 1.2 1.4 1.3 1.2 1.5 1.2 1.2 l.| 1.5 1.3 Tisanes not listed were noroal. -/ Severity of le.loo,: 1-.I-I.mI; 2-ood.r.te; j-sev.re; |(V(r( * /* The rats fad_lht--12*A3% lud chromate diet haia lesion sin Ui-i? A s,v*n bf"T2 rets/hid mils to'moderate ^ lymphoid hyperplasia, and ona had mild pneumonia..... Onlf'tone rac had a moderate . unspecific myoearditi*. Tha M/E ratios were normal. Tha iaaiona seen in cha raca fs_d tha 11.927. 35 lead paint die*ct .\ wara 2E-ii*2^ES!lSS^ZiSi Eigne oi 12 ra t (fct-i'V had different degrees of lymphoid hyperplasia in the lungs. In one rat pneumonia uat evident. Unspecific myocarditis occurred in 2 rats while foei of inflaaaaation in tha liver were observed in only one rac. The M/E ratios ware normal. In conclusion. e^* fthologyjtonin the control and traatedrati were characteristic! of chose in a notaaT'pooulatia^ailrttr^No evidence of lead-induced resjOn^^eBtouBTTM*"**'*"^^^^^................ -- IV. DISCUSS Tha levels of lead fad to rata in cha study ware sufficient to pro * duce significant elevation of body lead burden if cha lead ia in tha fora of lead nitrsta.il'' If wa equate cha amount of lead consumed by tha average rac Q fad the 2.051 lied'ocroeta, 12.43% lead'chromete, 66.05% lead earbonaca, and 11.92% ms laad paint diets to a 14.6 kg (3-year old) child, wa find that eh# laad conaumpcion would oqual 28.6, 123.7, 303.0 and 113.9 mg of lcad/day, respectively. On tha baaia of a 2% laad paint, tha total gaint intake would / ba 1.5, 6.2, 23.0, and 5.7 ga/day. Daily ingestion of chess quantities of / old psint havs bean reported to produce laad poisonlng.il/ There ware no changes in hematology, urinalysis or sarua pretsins throughout Cha entire study. However, chare was one effect on porphyrin socaholism. As sarly as 4 wsaks, rats fad either cha 66.05% laad carbonate diet or ths 11.92% KBS laad paint diet exhibited 50% depression of erythrocyte A1AD activity. This affect appeared to ba directly related to the concentra tion of blood laad aa has bean reported by others.iiuii/ However, chars was ona axeaption, blood laad la cha 12.43% laad chromaca group became tlevacad by tne 13th week, but there waa no depraaaion of A1AD activity. This dis crepancy eeuld ba related to tha duration of alavatad blood land or tna age of tna animal when blood lead becomes alavatad. _ Evan though erythrocyte AUD waa depressed 50%, tha overall affect on porphyrin metabolism must be considered mild, since theta was no concoainant change in cha levels of protoporphyria (erythrocyte), dales-aminolevulinic ' acid and coproporphyria. These observations ere consistent with reports chat blood load lavals greater than 40 ufi/100 ml UC are needed before serious w charges m porphyrin mttaoolism occur.I*' 58 ' V** &**..V*' SapBy!>4 ".-w*. Av-^2y>' .... .. . 0007-SWP-037032 0007-SWP-000115600 Thi bad* Usd burden at rscs ftd rr.rt ewtuaiM leed octoite or lcad_chraate_tfer no-different :r~~ cartrcL .umJ '.3 At trul tire lead was found in the kidneys of one to three rota on asen of tha load octoace ind lead chromate ditts. and chc blood lead levels ir. tnc '.2,417. lead chromate ' group wart significantly elavatad. Sines rata fed lead nitrate show elevated lead levels in blood, kidneys, bone and liver within 2 weeks.i27 it^eooears that the lead octaate and lead chroma ee_wee_ni_li_lg^ill^bgil_r euaTTSSTa tor sosorption/^^^................................... ... ...... ... . ,, Pathology was performed only on the rats that ware fed the control, 2.OS* lead oceoate, 12.43% lead chromate, and 11.92% KBS lead paint diets for 13 weeks. 411 of these rata were relatively free of lesions, and those lesions which were observed, oecur naturally in rat colonies. V. conclusions 'CWsjjtjjdviijhoj!i^ha^Mitafed^iJ^^|t|iJjjaint/feed2oc^dj^int containing 11.92% lead andjS^paTnt^ontalnlni bfeToi^Taad'^NrTearTsrPonrca amuaitaa early si|ns of lead poiaonin|. these nans consisted at arvthrocvte ALAO depression (30%) and significant increases in blood, kidney, bona, liver and/or brain land. katf_Jf4_t_>iat consisting of 0,1% new paint Ilia contalnint I2.i32_lcad as lead chrawate exhibited only elevated blooa lead_elter 13 ~ weeks of leadini. 4 nailar^aiet oi. new oaijtconteum?g"r^%ladaa*TeeT~ oceoete produced no signs of lead poisoning. Tha lack of any marked change in the body lead burden in these rats suggests that very little lead was absorbed from the gastrointestinal tract. Since there is considerable evidence that the rat can absorb lead in several forms, one muse conclude chat the lead in the paint used in this anparimene was r.ot readily available for ebaorption. In conclusion, tha raaults reported nereis support the contention that 1 tad is not readily aosoroed from tha hewer otir.it. ..........................'... ..................................... .V 39 n.i >l"<s;y^ 0007-SWP-037033 0007-SWP-000115601 REFERENCES o 1. Khec, R. A., "The Metabolism of Lead m Man in Health and Disease,'' ; Lecture II, J. Rov. Inst. Rub lie Health Hug,. 26;101 (1961). 2. Chisholm, J. S., fed. Clin. March Amor,. 17:591 (19*0). 3. King, B. G., Amer. J. Pis. Child., iii:337 (1971). 4. Selagson. D.. Standard Methods of Clinics! Chemistry. Academic Press. Inc., New York. Vol. 2, p. 52 (1958). ................ 5. Brother, C., M. Schneidarnan, end C. Z. William, An. J. Clin. Path.. 26; 1639 (1956). .............................. ................... 6. Breeher, 5., and H. Sehneidemen, Amti-Slaai-SiStLi' 20:1079 (1950). 7. Faulkner, W. R.. and J. W. King, Eds., Manual of Clinical Laboratory Procedures. 2nd Ed., p. 178 (1970). ..... ...... . 8. Lichtman, H. C., and F. Feldsan, J. Clin. Invest.. 6:830 (1963). ^ 9. Heller, S. R., R. F. Labbe, and J. Nutter, Clin. Chan.. 7:525 (1971). 10. Pavia, F. R., and S. L. Andelnan, Arch. Envir. Health. 13:53 (1967). 11. Kauzerall, and S. Cranick, J. Biol. Cham.. 219:635 (1956). . 12. Schlenker, T. S-, and C. L. Kicehell, Am. J. Clin. Pathcl.. 29:593 (1938). 13. Casa, J. C.. and K. H. Litchfield, J. Oil. Col. Cham. Assoc.. 52:236 (1969). li. Coldvatar, 1. J., Induct. Mod.. 41:13 (1972). 15. Killer, J. A., V. Betti*tint, R. L. C. Cusaaing, F. Carayell, and A. Goldberg 4**et. 3_:695, October 1970. A*ent*+ * e- t W * *. *.*>% :>/ fi60 sew cc\zv:s:y: Older paint formulations contained sol uble lend salts. Two samples of paint chips representative or these fomulstisr.s were fed to rats at 0.1% of their diets. One was supplied by the Sational Bureau of Standards and was removed from interior walls o: alder hares. It contained 11.92% lead. The other was a cejAa formulation containing 66.OS', lead carbonate. Both of these samples produced classical signs of lead poisoning in the rats. These signs consisted of erythrocyte ALAD depression (0%) and significant increases in blood, kidney, bone, liver and/or brain lead. Newer paint formulations contain insoluble lead pigments and low levels of lead driers. Several samples of paint chips containing us to 12.43% lead chromate pigment and up to 2.0% lead octoate drier were also fed to rats at 0.1% of their diets. Tht only evidence of toxicity or effect or. body burden appear in the rats fed the paint esntiinir.g 22.13% lead chromate. This consisted of an increase in blood lead, withouc ether sips of poisoning. Paint containing 1.95% laad ehrsaata and pair.t j. containing 2.05% lead octoate produced no detectable changes in the rats. *3 These studies show a marked difference in the toxicity of lead in paint formulations depending on the nature of the salt form and its > solubility. The lack'of toxielty with paints containing 2.0% lead chromate or lead octoate undoubtedly it due to the lack of sipiflcant absorption from the gastrointestinal-tract. -r.- Y> h-im W ' . IBJ % s Tj iEe ?? v\V-V' ! *- %> r. V**i tv. - >.:-1 f V mfc r< 4 :W- ... 0007-SWP-037035 0007-SWP-000115603 1 4 MODincvr:ov CrCisrirs* :rs:'-'ss:ov r ?*-' The levels of lead fed to rats in the study were sufficient to pro* duce significant^e'evation of body lead burden if the lead is in tr.e fern of lead nitrate.ii' If we equate the amount of lead consumed oy the average rat fed paint chips containing 3.05% lead cotsate, 13.43* lead chromate, 66.05% lead carbonate, and 11.93% XBS lead ratal ditts to a Id.6 kg ;3-ytar old) child, we find that the lead consultation would equal 3S.6, 135.3, 503.0 and 113.9 ng of lead/day, respectively. On the basis of a 3*. lead paint, the total paint intake would be 1.5, 6.2, 25.0, and 5.? gm/day Daily ingestion of these Quantities of old patnt.hsvs been reported to produce lead poisoning.!" ir L+J- PJtSS.V There were no changes in hematology, urinalysis or serum proteins throughout the entire study. Hqa/iyy, porphyrin metabolism was affective w as early as J weeks in rats fed either the 66.05% lead carbonate diet or the 11.93% XBS lead paint diet as evidenced in a 50% depression of erythrocyte ALAD activity. This effeet appeared to be direstlv related to the concentre* tion of blood lead as has been reported by others.iitii/ !ie eeeri there was one exception; blood lead in the 12.45% lead ehrpaate group became elevated by the 13th week, but there was no depression of AUD activity. This dis* crepancy could be related to the durttion of elevated blood lead or the age 1 of the aniaal when blood lead became elevated,..... .....'...... .................... - f.- * ` *"SL Ner r%. V * ,. . *' * 3 Even though erythrocyte ALAD was depressed 50%, the overall effeet on porphyrin metabolism must be considered mild, since there was no concomitant change m the levels of protoporphyrin (erythrocyte}, delta*asmoievulir.ie........ acid and cepropoiphyrin. These observations are consistent with reports that blood lead levels greeter than 40 ug/100 al ABC are needed before seeteus changes in porphyrin metabolism occur.!!/ The body lead burden of rats fed paint containing lead octoate or lead chroaate Seam no different from control until 13 weeks. At this time lead was found in the kidneys of one to three Tats on each of the lead octoate and lead chroaate diets, and the blood lead levels in the 12.45% lead ehronate group were significantly elevated. Since rats fed lead nitrate show elevated w lead levels in blood, kidneys, bone and liver within 2 weafre.ii/ it appears Jf] that the lead octoate and lead chromate were m eitherTfeadily absorbed ex' available for absorption. .......................... * Complete gross and microscopic pathology was performed on the rats that were fed the control, 2.05% lead octoate, 12.45% lead ehrosate, and 11.92% SIS lead paint diets for 13 weeks. All of these rats were relatively free of lesions, and these lesions which were observed, occur naturally m rat eolonies. . . ' . .. ..""~T7.............. * ' ",............ / . . r~ **^ .a w* `Wk 64C u i . - 0007--SWP-03703 6 0007-SWP-000115604 PREFACE This resort was prepared at Midwest Research Institute, 425 Volksr Boulevard, Kama City, Missouri 64110 under Contract No, 62-W-42GC & NFC, MRI Project No, 3729-B, "Lead Paint Ingestion Study.* The Research was sponsored by the National Point and Coatings Association, 1500 Rhode Island Avenue, N. W., Washington, 0. C. 20005. Royal A, Brown, Technical Director, National Paint and Coatings Association was the project monitor. ' The research was conducted in the Biological Sciences Division, under the direction of Dr. W. B. House from I December 1972 through 31 July 1973. Dr. Thomas R. Castles, Principal Pharmacologist, was the principal investigator, assisted by Dr. Jaime Sanyer, Associate Pathologist, and Mrs. Jane Hoch, BToIbgy Research Assistant. Dr. James L. Spigarelli, Senior Chemist supervised the lead "analysis with the assistance of Mrs. Hope M. Miller, Assistant Chemist. >' Members of the National Paint and Coatings Association Industrial Metals Task Force prepared the paint chips aid consulted with Dri>Castle, 5anyer, Spigarelli and House during the course of the study. The personnel of the NPCA Industrial Metals Task Force is as follows; Richard A. Moore Royal A. Brown Dr. John P.Frowley Charles M. Joekson Joseph G. Kingston S*. S idney Lauren Wiiliom W. Ringle Edwin . Swain Jeon P. Teos Domenic J. Tessari The Sherwin Williams Company Chairman The National Point 6 Coatings Association Hercules, Inc. Celanese Coatings Co. Glidden-Durkpe Division of SCM Corporation Coatings Research Group, Ine. Pratt and Lambert, Inc. E. I. duPontde Nemours & Co., Inc. The Flood Company De Sato, Inc. AoDroved for: MIDWEST RESEARCH INSTITUTE W. B. House, Director Biological Sciences Division 14 September, 1973 ft:-' i-. W .* 0007-SWP-037037 0007-SWP-000115605 SLIGHT MODIFICATION OF CASTES' COXCU'SIQSS This study shows that Tats fad 0.1% diet (peint/feedl of old paint containing 11.92% lead and new paint containing 66.05% lead as lead carbonate exhibited early signs of lead poisoning. These signs consisted of erythrocyte ALAS depression (S0%) and significant increases in blood, kidney, bone, liver and/or brain lead. Rats fed a diet eon* sisting of 0.1% new paint fila containing 12.45% lead as lead chromate exhibited only elevated blood lead after 15 weeks of feeding. A similar diet of new paint containing 2.05% lead as lead octoatc produced no signs of lead poisoning. The lack of any narked change in the body lead burden in these lead chromate and lead oetoate rats fad paint containing chromate and octoate suggests that very little lead was absorbad frost tht gastro intestinal traet. Since there it considerable evidence that ths rat can absorb lead in several forms, one must conclude that the lead in the forts of lead chromate and lead ectoste and incorporated Into paint was not readily available for absorption. In conclusion, the results retorted herein sunaort the contention that lead is not readily snsoroed rrc- newer ;a:r.:s. ........ ..................... \m\'-\+ SStt fS if %*S-5 n.r