Document 99yGv1dGzo6xg5j87rY082o4p
PRELIMINARY DRAFT LEAD PAINT INGESTION STUDY
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PINAL RETORT 14 Septenber 1973
Contract No. 62-U-62GC&NPC MRI Project No. 3729-J
For
National Paint and Coat Inga AsaoclacloB 1500 Rhode 1aland Aveoua, N.V. tfaehlngton, D.C. 20005
Acta: Mr. Royal A. Brown
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PRELIMINARY ORA FT LEAD FAINT INGESTION STUDY
FINAL REPORT 14 Saptaabar 1973 Contract No. 62-W-62GC&NPC MRI Projset No. 3 7 29-B
For National Paint and Coatings Association
1500 Rhoda Island Avtn.ua, N.W. Washington, O.C. 2000S
Attn: Mr. Royal A. Brown
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0007-SWP-000112898
PREFACE
Thl* report was prepared at Midwest Research Institute, 425 Volker Boulevard, Kansas City, Missouri 64110, under Contract Mo. 62*w*62CCANPC with the National Institutes of Health, Department of Health, Education and Welfare, MRI Project Mo. 3729-B, "Lead Paint Ingestion Study." The research was sponsored by the National Paint end Coatings Association, 1500 Rhode Island Avenue, N.W., Washington, D.C. 20005. Dr. John P, Fravley, Chief Toxicologist, Hercules, Ine., Wilmington, Delaware 19899, was the project monitor.
The research was conducted in the Biological Sciences Division, under the direction of Dr. W. B. House from 1 December 1972 through 31 July 1973. Dr. Thomas R. Castles, Principal Pharmacologist, was the principal investigator, assisted by Dr. Jaime L. Sanyer, Associate Pathologist, and Mrs, Jane Hoeh, Biology Research Assistant. Dr. Jaaea L. Spigsrelli, Senior Chemist supervised che lead analysis with the assistance of Mrs. Hope M. Miller, Assistant Chemist.
Approved for:
MIDWEST RESEARCH INSTITUTE
W. B. House, Director Biological Sciences Division
14 September 1973
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TABLE OF CONTESTS
Pa ee
Introduction.........................................................................................................
1
Method .....
e ^...............................................................
2
n.
A. Prepiration of jjtii^rilB* Containing Different Concentration! of Lead. . .......................................................
B. Preparation of Diet!......................................................................... C. Experleental Procedure.................................................................... D. Analyte!............................................................................................... E. Pathology ..................................................... F. Scecittlcel Analytes. ....................................................................
2 3 3 A 6 9
in.
Result! .............................................................................................................
9
A. Concentretlont of Lead In Paint Flint ........ 9
fi. Lead Analytes of Diets Containing Different
Paint Flint......................................................................................
9
C. Preliminary Feeding Studies ....................................................... 10
D. Gross Observations, Feed Consumptions and
Body Weights .................................................................................. 10
E. Weekly and Total Lead Consumption ......................................... 11
F. Hematology of Rats Fed Paint Films Containing
Different Concentrations of Lead......................
12
G. Tissue and Fluid Chemistry of Rats Fed Paint
Films Containing Different Concentrations of Lead . 12
H. Lead Content la Tissues of Rats Fed Paint Films
Containing Different Concentrations of Laad .... 13
I. Pathology of Rats Fed Paint Films Containing Dlfftrcnt
CoDcsnc rat ions of Lead........................................................... 15
IV. Discussion....................................................................................................... 17
V. Conclusions.....................................................................
Re ferences
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Figures................................................................................................................................... 22
Tsbles........................................................... .... ................................................................... 26
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t. INTRODUCTION
Fv persons will disagree that eld lead-based paint presents a dangerous and unnecessary health hazard to young children. As a result of reports by Kehoe,!^ Chisholm,^ and King^/fiedical researchers, paint manufacturers and legislators have recognized the seriousness of this problem and are acting to establish safe concentrations of lead in paint. To do this, they have voluminous reports on clinical observations and animal research from which to draw. Unfortunately, moat of chi* information is based upon the old Itad-baaed paints ot soluble lead salts, which do not reflect the aasmmv^paint formulations on today's market.
Before safe concentrations of lead in paint ean be Intelligently established, we must evaluate the toxicity of the lead as It exists cur rently in modern sasmal paints. These studies must be as complete as possibLe and oust ba performed upon several animal species, since a complete modal for man hat not yet been found.
It was the purpose of this study to evaluate the toxicity in rats produced by modern enamel paints containing lead oetoata, lead chromat or laad carbonate. The results are presented in the follow ing pages.
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II. METHODS
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A. Preparation of P&int Tllmi Containing Different Concentrations of T-ead Paint film* containing no lead or laid in the fora of liad ottoate p*V
*>* or lead chromite were supplied by the Sh*rww>Wllllams
"7 . , Company. --- ^
Enamels which contained either lead octoata or lead chromate (medium
yellow) were prepared using a flat alkyd mtmmtt formula baled upon a
TT-R-266D Typa 1 Claea B alkyd. Tha flat alkyd mm1 without astlnil laad
compound was used for control. The percent of laad In aach sample was
calculated on the la sis of the nonvolatile materiel. Dispersion was ac
complished with e Cowles Dissolver and the nmlentiaiiiarfMnvfr was held at -Vv"*t \y-'>i C*kC>
on* level. The paint* wara plaead in pens and allowed to air dry. This
was followed by force drying sc 120*F to voletlllte any remaining solvent.
Feint films vere ground, sieved and chips ranging from 0.5 to 1.0 an in
,, site used for this study.
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The concentrations of laad in tha different paint films wara
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determined independently by tha Dt^Soto jlilsr ftswpeny, SHenasm-Ullllau
Company and Midwest Research Institute, using Atomic Absorption
Spectrophotometry.
Samples of old lead -bistd paint vara obtained from tha I'.S.
Department of Comarca, National Bureau of Standards, Washington, D.C.
This paint had bean pulverized and sieved through 325 mash screen and con
tained 11.87X lead by weight. This staple will be called "NBS lead paint"
for this rport.
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B. Preparation of Diets Dlti were prepared by mixing paint filmj with Purina Rat Chov
math in the concentration of 0.1X (w/w) . Thia ua a accomplished by first
--
preparing a 101 concentrate (paint film/fee, v/v) in a high-speed tvin shell mixer. This concentrate vaa then added to the appropriate amount of Purina Rat Chou mash to give a final concentration of 0.1X (paint film/ feed, v/u) and mixed for 10 min in a bulk mixer.
Each diet was prtparad thraa time* during the experiment and samples of eech of these preparations were assayed for lead concent.
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C. Experiments! Procedure Two hundred veanling (40-60 gm) Charles Riverrats (100malea and
100 famele rats) vara uaed for thla study. Uponarrivalrats ware housed indlvidually in air conditioned quarters In polycarbonatt cages containing hardwood bedding and filtar taps. After 5-7 days of equilibration, all
rats were aaalgned one of the following dleta. 1. Rat chov plus paint film without laad
2. Rat chov plue paint film containing 0.08X laad aa lead occoate 3. Rat chov plua paint film containing 0.53X lead aa laad oetoaea
4. Rat chov plu* paint film concaicing 2.05X laad as lead octoace
5. Rat chov plua paint film containing 0.42X lead aa lead chromate
6. Rat chov plue paint film containing 1.93X laad as laad chromate
7. Rat chov plua paint film containing 12.43X lead aa lead chromats
8. Rat chov plua paint film containing 66.05X laad aa laad carbonate
9. Rat chov plua NBS laad paint containing 11.92X lead in an un-
known form
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Twenty male and 20 female ract ware assigned to the concrsl diet, and 10 sales and 10 female tats were assigned to each of the remaining diets. Each diet was fed in a 9 or vide-mouth glass jar which was secured to the cage. Tap water was available ad. libitum during the entire experi ment .
Feed consumption vas measured daily and body weights were mea sured weekly. All rats were observed twice or more eaeh week for toxic signs.
After 4, 8, and 13 veeks a fev sale and female rats were placed in metabolism cages for the collection of 24-hr urine samples. A portion of the collected urine was used for urinalysis sod the remainder froxsn for assay of dalta aminolevulinic acid and coproporphyrin. After urine collection each rat was aneseheslzed with ether, exanguinatcd via the abdominal aorta and bone marrow smears were prepared. Blood staples were heperinized, cooled end used ionedlately for hematology end enzyme assiys. Aliquots of the remaining blood were taken for protoporphyrin and lead assays. Aftar urlns and blood samples ware obtained, each rat " neeropsied and tissue taken for lead analysis or microscopic examina tion.
D. Analyses 1. Lead analysts of paint films and diets containing paint film: a. Faint films: Ten milligram staples of paint films con
taining no lead or 0.08X lead octoace were charred with 3 ml of concentrated
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nitric acid and dry-ashed at 500*C for 2 hr. Tha ash was dissolved In 1 xl of aqua regia, diluted to S ml with distilled water and this final dilution measured for lead content by atomic absorption.
All other paint films (10 e<g samples) were digested in 1J al of 2:1 concentrated nitric acid: 372 perchloric acid, evaporaced and the remaining perchloric acid solution diluted to 25 ml with distilled water. This final dilution was used for atomic absorption spectrophotometry.
b. Diets: One-gram samples of feed were digested in 2:1 concentrated nitric acid: 372 perchloric acid and their final dilutions adjusted to make their lead concentrations within tha detection limits of the atomic absorption technique.
2. Analyses performed uoon each rat: a. Hematology: (1) Hematocrit: Hematocrit was determined in capillary
tubes using a microcapillary cantrifuge (International Equipment Company, Model MB).
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(2) Hemoglobin: Hemoglobin wet meaeured at eyano-
(3) Erythrocyte and Ituhocvta counts: Total erythrocyta and leukeeyta wera counted using a Coultir Electronic Particle Counter with 100 u aperatura.-^
(4) Reticulocytes: Reticulocyte* wera counted by the methylene blue method using the Millar difc.^
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^ (51 Differential leukocvte counts: Wright's scsin vas used co scsin the leukocytes for exesilnecion.
(6) Ervthroevce osmotic fragility; Osmotic frsgilicy of erythrocytes vas quantitatively determined by subjecting heparinized
7/ .whole blood to sodium chloride solutions of different osmolarities.- The concentration of sodium chloride which hemalyted 5OX of the erythrocytes vs* obtained from a plot of ptreent hemolysis vsrsus sodium chloride concentration.
b. Body fluid end tissue chemistry; (1) Pleswe nroteln electrophoretic patterns: Total
plasms protein were determined using the Hyeel Biuret Reagent (Ryeel, Inc., Houston, Texas). The quantity of each plasma protein was determined electrophoreticelly on cellulose acetate end expressed at a percentage of the total plasma protein.
(2) Erychrocvte-i-tmlnolevullnic acid dehydrate (A1AD): 6-Aainolevulinic acid dehydrate activity was detarmined by the method of Liehtman and Feldman.-^ This procedure was performed immediately after
each blood sa^le was taken.
(3) Srythrocvte protoporphyrin: Protoporphyria in
erythrocytes was aaasurad by tha method of Hellar, at
This analysis
was performed the day aftar blood vas withdrawn.
(4) Urlntrv ^-aminolevulinic acid (ALA): Urinary 6-aeinolevulinie acid was measured according to tha Davis and Andtlosn*^
modification of Mauierall's and Craniek'i Mathod.Ii^ These analyses wart
performed in subdued light. 6 .r
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(5) Urlnarv cooroporohvrin: Urinary coptoporphyrins were determined by the method of Sehltnker and KiccheU.il'' These analyses were performed in subdued light.
e. Urinalvsis: (1) Urinerv protein (albumin); Urinary protein was
measured with "Uristix" reagents strips (Ames Coogiany, Elkhart, Indians). (2) Microscopic examination of urine: Urine samples
were centrifuged, the residues resuspended, and examined microscopically for the presence of erythrocytes end leukocytes under high pover field tnd far easts under low pover field,
d. Tissue lead: (1) Blood: One milliliter of blood vat mixed vlth
1 ml of 3:1 v/v 52 trichloroacetic ecid:37X perchloric acid. The sanple was cenerifuged and the supemate filtered through an AAV? 0.8 is Mlllipose filter. The superrate vet analyzed for lead vlth an atomic absorption spectrophotometer using standards prepsrad in control rst blood.
(2) Other tissues: Bone, liver, kidney, end brsin vere digested in concentrated nitric acid, evaporated to dryness and re constituted to the lowest possible volume vlth 201 nitric acid. These solutions vere analyzed for lead by atomic absorption spectrophotometry.
(3) Atomic absorption analysis; lead concentrations were measured using a Varlan-Tcchtron AA-5 atomic absorption spectrophotometer. Sample solutions vers as pirated into an air-acetylene flame and the tbeorbance was measured at 2,833 nm. Background interference tree determined with tbe
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use 01 a hydrogen continuum lamp at 2,833 no and subtracted from the absorbance obtained ac 2,833 no with the Fb hollow cathode lamp.
E, Pathology 1. Gross pathology; At necropsy, cats were examined for gross
abnormalities and their livers, kidneys, spleens, hearts, gonads, thyroids, brains, and adrenals weighed and the relative organ weights calculated. After weighing, a portion of the liver, kidney, and brain were taken for microscopic examination and the rest of each organ was measured for lead concent. A feswr was removed to be used for the measurement of lead in bone.
2. Microscopic pathology: Bone marrow smears were prepared for a myeloid/erychroid call count. Tha following tissues were fixed in buffered neutral 101 formalin: brain, liver, spleen, stomach, small in* ttstine (duodeum, jejunum, ileum), colon, pancreas, kidneys, urinary bladder, adrenals, thymus, gonad, thyroid (with parathyroid attached), mesenteric sallvery gland, lymph nodes, heart, lungs, diaphragm, skalttal made, end proetete or uterus.
tissues from ell 13 week rats fed the control, 2.051 lead^ octoace, 12.431 lead chromate, 66.051 lead carbonate, and tha 11.921 MBS lead paint diets were embedded in perafln, sectioned to 6 u thick, stained with hema toxylin and eosin and examined for hiscopathology.
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r. Statistical Analyses Control and treatment values vera coopsred statistically using
Dunnett's multiple-comparison test with P < 0.05 as the criteria of significance.
III. RESULTS
A. Concentrations of Lead in Paint films
The concentrations of lead in the paint films supplied by the VI* Sheramm-tflillams M*e Company were analyzed for lead content by the
!* De Soto Pws.ui Guaaeu/, Sheream-Willlam* Paint Company, and Hldvest Re
search Institute (MRI). The reeulte of these analyses sre shwra in
Table i. The control enamel which did not contain lead oetoate or chromate
was found to contain approximately 0.017. lead. The agreement between the
different analyses was good, so an svaragt ppm of lead vas computed and
used for the actual laid concentration of each paint film. Lead concen
trations of the lead paint obtained from tht National Suraau of Standards
were averaged in a similar manner.
B. Lead Analyses of Diets Containing Different Paine Pllas Table 2 shows the lead content of tech diet. Purina Ret Chow
cash was found to contain approximately A ug/gm of lead (assuming 0.1 ug/gm of lead vee contributed by the control enamel). Tht ug of lead/gm of feed which vas attributable to each added paint file wet reasonably close to its respective theoretical value. The average total pg of lead/gm
of fead for each diet was used for the calculation of veekly and total lead
consumption for ,ch rst.
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c. ?reIlalMrv Feeding Studies Before beginning this study, a pilot experiment was performed
to see if the rats were consuming the lead paint film along with their feed. Briefly, three rats were placed on Che control diet and three rats on the 66.052 lead carbonate diet. After 48 hr, feces were collected and their lead content measured. Feces from rats on the control diet contained 11.5 ug of lead/ga feces while feces fros rata fed the 65.052 lead car* bonace diet contained 3,683 pg of lead/gs of feces. Thus, rata did con sume the paint file along with their feed.
D. Cross Observations. Feed Consumptions and Body Weithts During the entire study only two raea had remarkable changes.
One female ret on 2.052 lead octoata developed an abeeae on her left shoulder during the ninth traetoent week end one female on 66.052 lead
J
carbonate developed ebcessed hind feet in the 10th week end chew her toes off.
The feed consus^tlen of male and femalt rati ara shown in Figures 1 and 2, respectively. Except for the rats fad tha ditt containing 11.922 lead as NBS lead paint, all groups ata at tha aama rata aa tha control group throughout tha entlra experiment. The reason che 11.922 MBS lead paint group ate significantly lesa initially, was that they were sterced a month after che ocher rats sod were initially smaller. Since this group wes consuming fd at tha same race as the control group by 4 wseks, we con sider their initial food conawqitlon normal also (for chair size).
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The body weight gains for etch group of racs arc shown in Figures 3 and 4. As racneioned above, the rats on the 11.927. KBS lead paint diet were small initially but became similar to concrols by either the fourth or eighth week. Throughout the entire period the male rats in the other treatment groips gained weight at a normal rate. The female racs did show a change in body weights during the first eight weeks of feeding which appears related to the concentration of lead oceoate. After 4 weeks of feeding, rati in the 2.03Z lead octoate group weighed significantly less chan control. Tha pattern was tha saaa at eight weeks. After 12 weeks ---------------------------^ their average body weights still exhibited the same pattarn, but the 2.05X lead octoate group wet nee slgniflestly different from control. This was due to fewer animals and a alight incraase in variability.
E. Weekly and Total Lead Consumption The weekly and total lead conjunction during the experiment
were calculated on the basis of tha total lead/diat and amount of each diet eaten by each rat. Theae calculations ara shown in Tables 3 and 4. Dur ing che I3ch week period, tha control grot? consumed approximately 103 ug c iead/day, while rets es/clng 2.05X Ised octoste, 12,437. lesd chromate^ 66.051 lead carbonate, and 11.921 NBS lead paint conauaad sn average of 786.9, 3,391.1, 13,435.8, end 3,184.3 ug of lead/dey, respectively. Using the average body weights of rets surviving 13 days, tha rats in the con trol, 2.051 lead oceoate, 12.431 lead chroute, 66.05- and 11.921 NBS lead paint groups consumed 245.2, 1,957.5, 8,469.6, 34,450.8, and 7,804.7 ug of iesd/dey/kg of body weight, respectively.
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F. "tmtalow of Rats Fed Paint Films Containing Different Concentrations of Laid Th results of the hematology of rats fed paint films containing
different concentration of lead are shown in Tables 5-13. So differences were observed in the erythrocyte count, reticulocyte count, hematocrit, leukocyte count, differential leukocyte count, and the erythrocyte osmotic fragi lity.
G. Tissue and Tluid Chemistry of Rati Ted Paint Films Containing Different Concentrations of Lead Tables 14-22 show the tissue end fluid chemistry of rats fed
paint films containing different concentrations of lead. The serum electrophoresis, erythrocyte protoporphyrin, urinary coproporphyrin, and urinary delta-aminolevullnlc acid were not altered by any of the diets.
The activity of the erythrocyte Smyrna, delta-aminolevulinic' acid dehydrese (ALAS), in the control, lead octoate [0.087., 0.53%, and 2.051) and lead chromate (0.42% , 1.951 and 12.43%) groups did not differ throughout the experiment (Tables 14-22). AIM activity was depressed in ^^^fed^6^05T^ts^^rbona^s^nd^^^^^SBS^ssd^piiint^ At^4jaeeks there vet i depression of 567. and 59% in these two groups, respectively, /At 8 veeks the A1AD activity was depressed 44% in the 66.05% lead carbonate group, but the ALAS activity in the KBS lead paint group was not signifi cantly different from control. Ac this time s sax difference waa observed in both of these groups. The ALAD activity io the male rats remained depressed at the 4-week levels while the ALAD activities of the female rats returned to control levels. This sex difference may be linked to
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fiet that thest feaale rats had matured and were probably beginning chair menstrual cycles.
By 13 weeks the sex difference had disappeared and_chi ALAD activity in 66,051 lead carbonate group and the 11.921 NBS lead palnc group vere depressed 561 and 531, respectively.
H. Lead Content In Tissues of Rats Fed Paint Films Containint Different Concentrations of Lead
Tables 23*27 show the lead eoncanc of blood, brain, liver,
kidney, and bone froa rats fed paint films containing different concentra
tions of lead. The velues for the lead eoneantraelona In blood at 4 and
B vaeka vere omitted from Table 23 beeeuse It was discovered that these
sesples had been contaminated by tbeir storage containers. At 13 veeks the blood letd levels in the rets fed leed octoate and the rats fad 0.427. and 1.957. lead chromate vert not dlffertnc fro control. Jn the rats fad
seaeBP 12.431 lead chromate, 66.057, laid carbonate, and 11.921 KBS lead paint,
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blood levels vere found to ba elevated slgritflceocly.
At 4 weeks, tissue lead levels In brain, llvsr, and kidnty vara
belov the detection Units of our essay. The raaulta vara the same at
8 weeks with the exception of the KBS lead eaint group. All four rats in
this group shoved detectable leed in their kidneys.
At 13 vetka, dattctabla ltvelt of lsej^n_thj^braia/appeared
only in the rata fad 11.921 KBS lead pa lot. In th^UvirSdettctabla
..........
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levels of lead ware found In tvo rats fed 66.OS^es^arbonete inline
rats fed 11.921 NBS lead paint. No ltad was datsccsd in th W^tdn^L of the
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control iroup at 13 weak*. In concr*_*j_t_l_*fd_va* dec acted in the kidneys of 1-2 rat* in the lead oetoac* group* and the 0.427. and 1.957. lead ehromata group*, lead was dec acted in the kidney* of ehrat rati, tight rat*, and 12 r*ti_in_che 12.43Z lead chromate, 66.05% leadcarbonate^and | 11.95* KBS laid paint |roup*. raapactively.
The femur* of rat* fad the control diet, lead occoata or lead chromate exhibited very little lead at 4 week*. However, the femur* of rat* fad 66.0511 lead carbonate or 12.927. KBS lead paint contained 13.0 and 14.9 ug of lead/ga of bone.
At S vaeka, the femur* of rat* fad the control, lead octoata or lead chromate dieta contained aioilar quantitiea of lead, ranging from l.S-4.2 ug lead/gm bon*. Femur laid in th* 66.0511 laid carbonate and 11.92Z KBS group* were now 16.0 and 16.4 ug of lead/ga of bone. Both of these values were *ignificancly above control.
After 13 week*, the rat* lad lead octoata or lead chromate had no more lead in their fesuri then at B week* and that# level* were no higher chan those in the control group. The 66.0511 Iced octoata group exhibited even higher level* of lead in chair ftmur* (21.7 ug lead/gm bone) than at 8 week*. Th* 11,921 KBS lead paint group had let* lead in their feamra (10.9 ug lead/gm bone) chan at B weeks. The lead level* in both of these groups was still signifietncly grasttr than thosa observed in the control rat*.
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I. Pathology of Rats Fed Paint Films Containing Different Concentrations ai -ufl The pathology of ract fed the control, 2.05% lead octoate, 12.43%
lead chromate 66,05% lead carbonate or 11,9Z% KBS lead paint diets for 13 weeks is shown in Tablet 29*33. The control race had a few naturally occurring lesions. Pourteen of these rate had mild to moderate lynphoid hyperplasia in the lungs, characteristic of early sturine pneumonia. One of these rats had a moderate pneumonia and another one a mild emphyaena.
Other lesione included an unspecific myocerdltes in two rats; foci of subacute inflammation in the liver of tvo rets; a cross-section of a parasite (roundworm) in the colon of one rat; and foci of mononuclear cell infiltration in the kidneys of two rats. Tha bone marrow myeloid/ erythroid cell ratios (M/E) of til rets were vlchin normal limits.
Tha Itslons observed in ret* fed'the 2.05% lead octoate diet were similar to the lesions seen in the control rats. Seven out of the 12 rats had mild to moderate lymphoid hyperplasia in the lungs and one had mild pneumonia. Four rats had mild feci of subacute inflsmaciai is the liver characterized by a loss of sevaral hepatic cord calls which vare replaced by macrophages eod lymphocytes. Another rat had a foci of inflammation in the interstitial tiseue of the pancreas. The M/E ratios of these rats were normal.
Tha rats fed the 12.43% ltad chromate diet had lesions similsr ro the lesions seen in the control rats. Saven of 12 rats had mild to moderate lymphoid hyperplasia, and one had mild pneumonia. Only ona rat had a moderate unspecific myocarditis. The M/E ratios were normal.
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The lesions seen In Che rats fed Che 11.92% SBS lead paint diet were similar co chose lesions seen in Che concrol racs. Eight of 12 rats had differenc degrees of lymphoid hyperplasia in the lungs. In one rat pneumonia was evident. Unspecific myocarditis occurred in 2 rats while foci of inflantnacion in Che liver were observed in only one rac. The M/E ratios were normal.
In conclusion, the pathology seen in the concrol and treated rats were characteristic of thoe* in a normal population of rats. So evidence of lead induced lesions were found.
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IV. DISCUSSION
The levels of lesd fed to rats In tha atudy were sufficient to; r~t
produce significant elevation of body leed burden of rets end dogs if the ltid is In the fort# of leed nitrate^^ or leed acetate.--^ Although
it i queerioneble whether theee level* ere toxic to the rat,13/ they are
quite toxic to the dog.& If we equate the amount of lead contused by -
the average rat fed the 2.05% lead oeeoate, 12.43% 1eadftarbSnatej and
\ 11.92% N3S lead paint diet* to a 14.6 Vf 3-year old child, ve find that
the lead consumption would equal 28.6, 123.7, 503.0, and 113.9 mg of
lead/day, respectively. On the baeia of a 2% leed paint, the total
paint Intake would bt 1.5, 6.2, 25.0, and 3.7 ga/day. In huaans, thait y
daily intakes can produce lead poisoning.-^
'
There were no changes in hematology, urinalysis or serua
proteins throughout the tncire study. However, there was one effect
on porphyria metabolism. As early es 4 veeks, rats ftd either the
66.05% lesd carbonate diet or the 11.92% NBS leed paint diet exhibited
50% depression of erythrocyts ALAD activity. This effect appeared to be
inversely proportional to tha concentration of blood lead aa has bean
reported by others
However, there wee one exception, blood lead
in tha 12.43% lead chromate group become elevated by the 13tb week, but
there was no depression of ALAD activity.
17
0007-SWP-036930
0007-SWP-000112917
This discrepancy could b.a related Co the duration of situated blood lead or cht age of ch animal when blood lead beeosies elevated whatever the explanation, the fact remains although erythrocyte ALAD activity was Inhibited 307., no changes in erythrocyte protoporphyrin urinary delta-aminolevulinic acid or urinary coproporphyrin levels were observed. Thus the effects on peraphyrin metabolism oust hava been mild.
The body lead burden of racs fed paint containing lead octoate or lead chromate vere no different from control until 13 weeks. At this time lead was found in the kidneys of 1-3 rets on each diet and the blood lead levels In the 12.435 lead chromate group became signifi cantly elevated. Since rats fed lead nitrate (how elevated lead levels in blood, kidneys, bone and liver within 2 weeks.ll/ we conclude that the lead octoate and lead chromate were not either readily absorbed or available for absorption.
Pathology was performed only on the rets that ware fed the control, 2.057. lead octoate, 12.43X lead chromate, and 11.927. NBS lead paint diets for 13 weeks. All of these rat* ware relatively free of lesions, and those lesions which wert observed, occur naturally in rat colonies.
IS
0007-SWP-036931
0007-SWP-000112918
v. cawausio n s
Thii study shows that rats can consume large quantities of seamed. paint containing as such as 2.02% lead as lead octoate or 12.437. lead as lead ehroute for 13 weeks without any toxic effects. The lack of any marked change in the body lead*burdan in these rats suggests chat very lieele lead vat absorbed froa the gastrointestinal trace. Since there it considerable tvidenet that the rat can absorb lead in several forms, one oust conclude that the lead in the enamel paints vas not readily available for absorption. In conclusions. the results reported herein support Che contention ehse lead la not as readily available in the newer enamel paints as in the older lead paints
U. \ .c a* f
, ^ ^ <>
; ' f
\'
19
5>
'5*
0007-SWP-036932
VV
0007-SWP-000112919
REFERENCES
1. Kehoe, R. A., The Metabolism of lead in Man In Health and Disease: Lecture II. J, Ro y . Inst. Public Health Hvg.. ,24:101 (1961).
2. Chisholm, J. J., Ped. Clin., North Amer., 47:591 (1970). 3. King, B. G. , Maximum Pallv Intake of Lead Without Excessive Body
Lead-Burden in Children. Amer. J. Pit, Child.. 122:337 (1971). 4. Selegson, 0., Standard Methods of Clinical Chemistry. Academic Press,
Inc., New York, Vol. 2, p. 52 (1958). 5. Brecher, 6., M. Schneiderman, end G. Z. William, Am. J. Clin. Path.
46:1439 (1956). 6. Brecher, 0., and M. Schneiderman, Am. J. Clin. Path.. 20:1079
(1950). 7. Faulkner, W. R., and J. W. King, Ed*., Manual o5 Clinical Laboratory
Procedures. 2nd Ed., p. 178 (1970). 8. Liehtman, H. C., and F. Feldman, J. Clin. Invest.. 4j>: B30 (1963). 9. Heller, S. R., Labbe, R. F., and Nutter, J,, Clin. Chea.. 17:525
(1971). 10. Davis, F. R., and S, L. And*loan, Arch. Envir. Health, 4J.:53 (1967). 11. haueenll, D., and S. Graniek, J. Biol. Chea.. 219:435 (1956). 12. Sehlenker, F. S., and C. I. Kitchell, An. J. Clin. Pathol..
i:593 (1958).
20
J'.-'-V S'SiTV' . *"V A' j- * ; n-r.-
r:f.
'-K'h 0007-SWP-036933
0007-SWP-000112920
13. Cage, J. C., and Litchfield, M. K., 3. Oil. Col. Chem, Assoc., 22.236 (1969).
K. Stove, H. D., Coyer, R. A., Krigsan, H. M., Wilson, M., and Cates, M., Arch. Pathol.. 92:106 (1973).
13. Haimwnd, P. 3., In: Essays in Toxicology, Vol. 1, F. R. Blood (Ed.), Academic Press, N.Y., 1969, p. 130.
16. Goldvater, L. J., Iadust. Med.. 41:13 (1972). 17. Millar, J. A., Sattlstlnl, V., Cuming, R. L. C., Carswell, T.,
and Goldberg, A., Lancet. Oct. 2:695 (1970).
8*?'
bv.-
21 0007--SWP-03693 4
0007-SWP-000112921
h5
F igure 1 fr* d (oAivmplion s f Mels lo ti fu t D tllu to t
( n < (A ii lio n t o l l o 4 in foin4 film *
Control
* <#t n
*
Ao <
<--s<
(x ./j j /w *) NomwnsNOS ojji
22
e
0007--SWP-036935
0007-SWP-000112922
-I aMBMIH-~v h *
S~
l-"> .-
HOIiiWft?N03 cm 23
0( 0007-SWP-036936
0007-SWP-000112923
F ig u re
0007-SWP-036937
0007-SWP-000112924
-E n
ian- ruitiii MM*--iiP^
'I'-:
\\\V.\* W.W.`. \\\* ' jWiff/f/Urwi'tr /' -
v * v < '*
1 r>. ir.eJ-
^4r.V'
("*) 1HOIJ(Y*001 j
25
0007-SWP-036938
0007-SWP-000112925
Paint Film
Control enamel Lead oetoace Lead oeeoat* Lead oeeoat* Lead chromate Lead chromate Lead chromate Lead carbonate MBS lead paint
TABLE l
CONCENTRATION 0T LEAD IN PAINT FILM
Theoretical Lead
Concentration
m
Pleasured Lead Concent ration
paint Congenial
r.i.
MRI fZ)
Average^.'
0 0.06 0.50
Z.00
0.50
2.00
15.00
0.01 0.08 0,50 1.90 0.42 1.80 12.57 63.2011.87*
< 0.02 0,07 0.56 2.20 0.61 2.10
12.30 68.90 11.98
0.01 0.08
0.53 2.05 0.62
1.95 12.43 66.05 11.9 2^
C 1} Measured by 0. S. Department of Commerce, National Bureau of Standards, Waahington, D.C.
V Average of paint eompaalet and MRI value*. e/ Average of Bureau of Standards end MRI values.
1 : ` '
rsfr'.
ei'' i
26 0007-SWP-036939
0007-SWP-000112926
TABU 2
UAD ANALYSES OF PIETS CONTAINING DITTBREMT PAIMT FILMS
Piet Control enamel plus rat chow
Theoretical2-/' (ue/gat)
0.1
Measured
Totel-' Paint Leads-1'
fug/em1*
fug/eiri>
4.1 - ' (5)
Lead octotce (0.08?) plus rat chow Lead octoata (0.537.) plus rat chow
o.s 5.2 1.1 (6) (6)
5.3
12.0
7.9
(6) (6)
Lead octoate (2.057.) plus rat chow
20.5
27.2 (6)
23.1 (6)
Lead chromate (0.42?) plus rat chow Lead chromatt (1.95?) plus rat chow
4.2 19.5
11.0 (6)
23.5 (6)
6.9 (6)
19.4 (6)
V
. mi
r. '* - . r m
Lead chromate (12.43?) plus rat chow
124.3
140.2 (6)
136.1 (6)
- '*. . '' * *4
Lead carbonate (66.05?) plus rat Chow MBS lead baaed paint (11.92?) plus rat chow
660.5 119.2
516.0 (5)
124.0 (3)
511.9 (5)
119.9 (3)
. :i *-5'-.-
itributed by indicated paint film. i shown in parenthesis. number of samples shown is parenthesis.
i'rSisV x/-s:%
-* i -
27
rry:
r'--" *rrTvr,T;j> v.1 :'?>> i"
c;
0007--SWP--036940
0007-SWP-000112927
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=1 j! V-1* 5s i': r i2 s
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f s *
3 is V- 5s i* 5s 5s
r rA* *;
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28
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0007-SWP-036941
0007-SWP-000112928
){ . 2 m2
a - : . i ,2 -2 \l
1" 2" S' 5 a a
=1 s' r rrst 2 a r: " s . a 2 a .2 -a 2ra r2 a s- S' *' SS 2
=3 J5 5s i2 rrs *a' "*.a- 2ra 2*a- 2r7 _ s::
=1
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"2 |! =5 55 55 55 ?5 i! 51 ii 2as
~3 i* S= S= i=i5 P 2a ~a 2a r a ?a 2 a ;= ss :: s' a s
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1.s 5 a
29
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t?i
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2.3.2.%
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f.'' .j,
0007-SWP-036942
0007-SWP-000112929
TABLE 5
HEMATOLOGY. OT RATS FED PAINT FILM CONTAINING SO LEAD
An* Ivses
Treatment Week 48
Erythrocytes (x 106/tns^)
Raticulocytea, 5 Hematocrit, vol., 5 Hemoglobin, gm, 5 Leukocyte* (x loVan^)
Neutrophils, X Lymphocytes, X Bands, X Eosinophils, X Basophils, X Monocytes, X Atypical, X Nucleated RSC, X Erythrocyte osmotic fragility [NaClJ&Z
6.17 O.uJi/ 1.5 * 0.7
46.1 0.8 14.0 0.3
5.0 0.3 ii.a 2.9 86.3 3.3
0.3 A 0.2 0.9 i 0.4
0 1.1 0.6
0
0 0.381 0.004
6.33 0.19 0.8 0.3
44.6 A 1.2 14.6 at 0.3
7.6 1,3 21.7 A 5.6 75.4 5.3
0 1.3 0.4
0 1.6 M 0.6
0
0 0.391 a 0.008
13 f N. 24
6.42 A 0.29 1.4 * 0.1
44.6 * 0.3 16.0 A 0.1
8.0 A 0.6 13.1 A 1.5 84.1 A 1.6
0.1 A 0.1 0.5 0.2
0 2.1 * 0.4
0 0.1 A 0.1 0.400 = 0.004
ya/ Number of no per period. Mean standard error. c/ Concentration of NeCl Chet hemolyted 505 of the erythrocytes.
.*- *.
, '\T
..
'
' :* :' 3.
v,..;
:r--
iE
30
St
*;Ci\ 0007-SWP-036943
0007-SWP-000112930
TABLE 6
HEMATOLOGY Of RATS TED PAINT HIM CONTAINING 0.087. LEAD AS LEAD OCTOATE
Am lvsts
______________ Treatment Week A8
13 (Nll^
Erythrocyte* (x 106/is ib5) Reticulocyte*, %
Hematocrit, vol., Z Hemoglobin, gn, 7. Leukocytes (x IG^/mn3)
Neutrophils, X Lymphocytes, X Bends, Z Eosinophils, X Bssophils, 1 Monocytes, % Atypical, 7. Nucleated Ric, X Erythrocyte oiaocie fragility [lisCl]^
6.14 0.32--/
0.9 * 0.3 41.3 0.9 14.1 * 0.4
5.1 0.8 24.3 1.6 74.3 * 1.8
0
00.8 0.3 00.5 0.5
0 0.381 0.005
6.33 0.09
1.0 0.3 46.0 0.7 15.4 0.2
5.5 0.7 20.3 * 4.7 76.3 4.7
0 1.5 0.6
0
2.0 0.8
0
0
0.410 * 0.007
3.92 0.39 1.4 0.2
43.0 0.5 14.7 0.8
7.7 0.9 16.3 1.7 80.9 1.8
0.3 0.2 0.7 0.3
0 01.9 0.5
0
0.395 0.005
a/ Number of rsts per period, b/ Mean = standard error. zt Concentretion of NaCl that hemolysed 50% of the erythrocyces.
fa.;
.*.*.1 -
*-
31
- , ; ; -
0007-SHF-036944
0007-SWP-000112931
TABLE 7
HEMATOLOGY Of KAT5 FES PAINT FILMS CONTAINING 0.337. LEAD AS LEAP OCTOATE
Analvs^s
Treatment Week
4 8 13
(S-A)
f N-12 >
Erythrocytes (x 10^/m?) Reticulocyte*, 7. Hematocrit, voi., X Hemoglobin, got, X Leukocytes (x 10^/ism^)
Neutrophils, X Lymphocyte*, X Bands, X Eosinophil*, 7. Basophils, X Monocytes, X Atypical, X Nucleated RBC, X Erythrocyte osmotic fragility [NeCl]/
6.27 O.i^
0.9 0.7 42.3 * 0.7 14.2 0.2
5.0 1.4 15.8 3.8 83.0 4.4
0 0.8 0.3
0 0.5 0.5
0 0 0.383 0.006
6.04 * 0.31 0.9 0.4
43.8 0.5 * 14,9 * 0.3
7.5 * 2.8 19.3 3.6 77.5 * 3.8
a 1.0 0.4
0 2.3 * 0.5
0 0 0.388 0.012
5.6 * 0.4 1.6 0.2 43 * 0.7 15.3 0.3 8.3 * 1.0 16.2 1.9 81.4 1.8 0.1 0.1 0.8 0.3
0 1.6 0.3
0 O 0.401 0.01
a / Number of race per period, b/ Mean standard error. c/ Concentric ion of NeCl that heaplysed SOX of che erythrocyte*.
'-'ii'-r
`-V
v.-'-r v
32
0007--SWP-036945
0007-SWP-000112932
TABLE 8
HEMATOLOGY OF RATS FED FAINT FILM CONTAINING 2.057. LEAD AS LEAD OCTOATE
-V'
Tree emetic Week 48
13
*-
Analvses
(N.Ai*y
i*1
item..
^f. Erythrocyte* (x 10 /an )
6.30 * 0.2-^
6.46 * 0.08
6.72 * 0.42
Reticulocytes, X
l.l * 0.6
0.7 4 0.1
2.0 * 0.6
1
Hematocrit, vol., %
41.8 0.5
45.0 * 0.4
43.4 * 0.8
)t
Hemoglobin, gm, X
14.4 4 0.2
15.5 * 0.2
15.6 * 0.3
L\'
r :
Leukocyte* (x 103/s*e3)
5.1 * 1.1
6.7 * 1.7
8.1 * 0.7
1
]
Neutrophil*, X
13.5 * 3.0
13.0 * 2.1
14.1 * 2.6
J,
}
Lymphocytes, X
B5.8 3.2
15.0 * 2.3
82.8 2.8
Bands, 1
0 00
- ' v>.
1
Eosinophils, 7.
o.a o.5
0.3 0.3
0.9 * 0.3
t Basophils, X Monocytes, X
0 00
0
1.8 * 0.9
2.2 * 0.7
r.\ *;-
Atypical, 7,
0 00
Nucleated RflC, X
0
00
Erythrocyte osmotic fragility [n *C1^
0.381 0.006
0.399 * 0.008 0.393 * 0.006
*/ Number of tts per period. bf Mean - standard error. c/ Concentration of NsCl that hemolyzed SOI of the erythrocyte*.
33 *i-'Z
0007-SWP--036946
0007-SWP-000112933
TABIX 9
HEMATOLOGY OF RATS TED PAINT FILM CONTA1KTNC 0.427. LEAD AS LEAD CHROMATE
Analyses
Trestmant Weeks 43
(N-41
Erythrocytes (x 106/*b ^)
Reticulocytes, X NesMtocrit, vol., X Henoglobin, gts, X Leukocytes (x loVmsP)
Neutrophils, X Lymphocytes, X Bands, X Eosinophils, X Basophils, X Monocytes, X Atypical, X Nucleated RBC, X Erythrocyte osmotic fragility, [HaCllX/
6.71 i 0.16^ 0.9 * 0.8
43.3 * 0.6 14.7 0.4
5.1 * 0.6 6.5 * 1.7 90.3 * 2.0
0 0 0 1.3 * 0.8 0 0 0.363 * 0.003
6.18 * 0.16 0.8 * 0.2
45.0 A 1.1 15.1 * 0.3
5.1 * 0.5 19.0 2.0 79.5 * 1.3
0 0.8 0.8
0 0.8 0.8
0 0.3 * 0.3 0.395 * 0.12
13
6.6 * 0.3 1.6 to.2 43.6 * 0.7 15.6 * 0.3 6.9 * 0.7 14.3 * 2.1 83.6 * 2.0
0 1.2 * 0.4
0 1.2 * 0.4
0 0 0.392 0.007
/ Number of race per period, except where Indicated otherwide, b/ Mean standard error. e/ Concentration of NaCl that hsnolyiad 50% of the erythrocytes.
V '.XV.-J
m
f.&z jv* "
34 mfressgstssp'**::'- - `-j-i-.y.;/ . . 0007-SWP--036947
0007-SWP-000112934
TABLE 10
HEMATOLOGY Of RATS TED PAINT FILM CONTAINING 1.95* LEAD AS LEAD CHROMATE
Anslvses
_____________Treatment Wesk
4 (N-A^V
8 J&&1
Erythrocyte* (x 10/bbs^)
Reticulocytes, % Heaatoerit, vol., X Hemoglobin, gm, X Leukocyte* (x 10Vas^)
Neutrophils, X Lymphocytes, X Bend*, X Eosinophils, X Basophils, X Monocytes, X Atypical, X Nucleated RBC, X Erythrocyte osmotic fragility, [NaCl]V
6.17 * 0.05V
0.8 0.4 40.8 0.6 13.9 0.2
4.9 0.8 10.0 2.4 92.0 1.8
0 0.5 0.3
0 0 0 0 0.383 * 0.007
6.21 0.13 0.8 * 0.3
44.3 0.3 15.3 0.3
6.1 1.2 18.5 6.6 80.5 6.6
0 0.3 0.3
0 0.8 0.3
0 0 0.385 0.007
13
6.37 0.52 1.2 0.2
44.1 0.7 16.2 0.4
8.2 1.0 11.4 * 2.3 85.9 2.2
0 1.5 0.5
0 1.2 0.3
0 0 0.404 0.005
*/ Number of rsts per period. V Mean standard error. cl Conceneretion of NeCl that henalyred 50Z of the erythrocytes.
*j.v-*ivcsx.*.y*;-' .tr m.
i.V*f
mr
:
rrr'-j:
:
TTT'T'-T ; --; -------,, yV&STrT 0007-SWP-036948
0007-SWP-000112935
TABU U
HEMATOLOGY OF RATS FTP PAINT FILM CONTAINING 11.43% LEAD A5 UAD CHROMATE
Analvses
4 (N-41S/
Treatment Week 8
(N-4)
Erythrocytes (x lO^/orn^)
Reticulocytes, 7. Hematocrit, vol., X Hemoglobin, ga, 7. Leukocyte* (x 103/mm3)
Neutrophil*, X Lymphocyte*, X Beads, X Eosinophils, 7. Basophils, X Monocytes, X Atypical, X Nucleated RBC, X Erythrocyte osmotic fragility [NaCl]-7
6.32 0.14*1/ 1.95 1.28 41.3 * 1.1 13.9 0.4
4.8 * 0.5
21.5 6.3 78.0 6.0
0 0.5 0.5
0 0 0
0 0.384 0.007
6.23 0.18 0.9 0.1
43.8 0.5 15.2 0.1
5.3 1.8 15.0 2.1 82.8 * 2.0
0 1.0 0
0 1.3 * 0.3
0 0.3 0.3 0.385 * 0.010
13 (N-121
6.61 0.38 1.6 * 0.2
44.1 * 0.7 15.8 * 0.2
7.6 * 0.6 12.8 1.6 84.8 * 1.7
0.1 0.1 1.0 * 0.4
0 1.3 0.3
0 0 0.396 0.006
a/ Number of rats per period. b/ Mean standard error. c/ Concentration of NaCl that heoolyzed 50X of Che erythrocytes.
. " '"
r-:1 :
a Vv .-.
si?
i'inr
WPT. ( i'f'r -
. ~
36 0007-SWP-036949
0007-SWP-000112936
TABLE 12
HEMATOLOGY OF RATS FED PAINT FILM CONTAINING 66.057. LEAD AS LEAS CARBONATE
Analvses
Erythrocyte* (x 10/ma^)
Reticulocytes, % Heaatoerit, vol., % Hemoglobin, gn, Z Leukocytes <x 10^/oo^)
Neutrophils, 7. Ly^hoeytes, Z Bands, Z Eosinophils, * Basophils, 7. Monocytes, Z Atypical, Z Nucleated BBC, X Erythrocyte oxmotic
4 (N.311^
Treatment Weeks 8
fN-Al
5.94 4 0.56^
0.4 4 0.2 41.3 4 0.9 13.9 0.5
4.3 * 1.2 14.3 * 4.1 82.0 * 5.6
0 0.7 4 0.7
0 3.0 * 2.0
0 0 0.388 0.009
6.13 4 0.06 1.1 4 0.3
44,0 4 1.5 15.0 4 0.2
5.0 4 0.9 15.0 4 4.1 S4.0 4 4.2
0 0.5 4 0.5
0 0.5 4 0.3
0 0 0.394 4 0.012
13 (N-12'i
6.60 4 0.37 2.9 * 1.3
44.7 4 1.2 15.6 4 0.6
7.7 * 0.5 15.2 4 2.6 82.7 4 2.7
0.2 4 0.1 0.9 4 0.3
0 1.0 4 0.3
0 0.1 4 0.1 0.397 4 0.005
*/ Number of rats per period, b/ Mean 4 standard error. cf Concentration of NaCl that hamolysed 50% of the erythrocytes.
37
1
J
- -- -
0007-SWP--036950
0007-SWP-000112937
t a b u : 13
orh e ma t o l o g y
ms f e d u a p b a s e s
PAINT CONTAINING 11.9 27. LEAD
Analvses
4 fN-4ii;
Treatment Week 8
fN41
Erythrocytes (x 10/no^)
Reticulocytes, Z Hematocrit, vol., Z Hemoglobin, gm, X Leukocytes (x 10-Vbse^)
Neutrophils, I Lymphocytes, Z Bands, Z Eosinophils, 7. Basophils, Z Monocytes, 7. Atypical, Z Nucleated RBC, Z Eryehrocyte osmotic fragility [NaCl^
5.72 0.15-/
2.3 0.3 39.7 0.8 13.6 *
9.7 1.4 9.5 * 2.1 90.2 * 2.3 0.3 0.3
0 0 0 0 0 0.389 0.006
4.49 0.83 1.0 0.4
42.8 1.1 14.7 * 0.3
6.7 * 1.2 7.0 * 1.7 92.0 2.1
0 0 0 1.0 * 0.7 0 0 0.412 0.006
13 fN12'
3.63 * 0.34 1.3 * 0.1
42.9 0.4 14.7 * 0.1
7.0 0.5 14.2 2.1 83.6 2.2
0 1.4 0.4
0 0.8 0.3
0 0.1 0.1 0,408 0.005
a/ Number of rat* per period, except where indicated otherwise, b/ Hean - standard error, c/ Two rata. d/ Concentration of NaCl that hemolyses 301 of the erythrocytes.
;;r.- .
36
'.-f.. T--- ' ~ y''-d
c~;
?-
;7* w- --f
. ' l: --"
0007-SWP-036951
0007-SWP-000112938
TABLE 14
TISSUE AND FLUID CHEMISTRY OF HATS EEC PAINT FILM COKTAIMIKG SO LEAD
Analyses
Treatment Week 4S
isai
13 (S243
Serum electrophoresis Albumin, X Alpha 1 globulin, X Alpha 2 globulin, X Bets globulin, 1 Genoa globulin, X Total proeein, tag X Albumin/globulin ratio
43 * 1-/
28 * l 5*1
20 * l 6*1
5.4 * 0.1 0.76 * 0.03
43 * 2 23 * 1
5*1
20 * 1
10 * 1 6.2 * 0.2
0.77 * 0.07
48 * l 21 * 1
5*1 21 * L
6*1 6.3 * 0.1 0.93 * 0.04
Erythrocyte ALAD, uool. PBS/ Males: 23.2* 2.3s-'
100 ml KBC/hr Females: 16.6 * 3.1^
Protoporphyrin, sig/100 ml RBC
Total: 19.9 2.2 19.6 * 1.6
15.1 * 2.3^
16.3 * 2. 2--' 15.8 * 1.5 23.5 * 1.9
14.5 * \.i&! 15.4 * 0.7^' 15.0 * 1.0 29.2 * 2.0
Urine Coprop orphyrin, Pg/24 hr ALA, u*/24 hr
2.5 * 1.2 78.0 * 7.4
3.3 * 7.4 83.3 * 11.0
6.0 * 1.9 43.4 * 5.0
tj Number of rats per period, except where indicated otherwise
b/ Mean standard error, c/ Four rata. i! Twelve rats.
a*-
r
: i'iJ-V
r -i >.
: `:
39 ; ~ 0007-SWP-036952
0007-SWP-000112939
TABLE IS
""MIST3Y OF RATS FTP PAIST ~ILM r. LEAD AS LEAD OCTOATS
Trcont Wetfc
13
> * lb/ -5 1 :1 .1 L
i 1 > O.l' ;6 0.02
..3 * 7. IS.1 . .5 4.4i/ -- 3 3.9 ... 2.4
44 3 20 2
4 1 20 1 12 1 6.3 0.2 0.79 0.08
48 l
20 1 5 1
22 1 71
6.2 A 0.1 0.93 * 0.04
14.9 i.a^ 18.7 0.3^
16.8 1.2 24.2 1.6
12.0 2.2^ 16.1 1.& 14.0 1.4
22.8 2.5
0.2 16.6
4.8 2.4 107.6 s 34.1
2.9 1.4 35.0 6.7
--- txeept hre indiecd othervi**.
5*_. . , * ; .. \ l \'
r", .4
* \ * * .* 1
40 0007-SWP-036953
0007-SWP-000112940
TABLE 16
TISSUE ASP BODY FLUID CHEMISTRY 0" PATS FTP PAIVT FILM CQSTAIS'IMC 0,13*: LEAD AS LEAD OCTOATE
Amlvses
4 fN4^
Treatment Week 8
fS41
13
Struts electrophoresis Albumin, T. Alpha 1 globulin, " Alpha 2 globulin, X Beta globulin, X Gamma globulin, 7, Total protein, mg 7. Albumin/globulin ratio
41 2^
26 = 1 5*1
21 * 1 8= 1
5.7 * 0.1 0.68 = 0.04
41 = 4 23 = 3
6* 2 20 * 1 11 * 2 6.3 * 0.1 0.70 0.13
50 1 20 * 1
4* 1 20 = 1
7* 1 6.0 = 0.1 1.00 = 0.07
Erythrocyte J .AUD, umol. PSG/ Males:
100 ml RBC/hr Females: Total:
Protoporphyrin, Ug/100 ml BBC
21.4 s 6.3^ 15.5 * 2.7--^ 18.4 * 3.3 23.1 * 1.0
10.3 * o.s^ 15.3 * 0.2-^ 12.8 1.5
21.7 * 1.1
12.5 = 0.7i; 17.0 s 1.& 14.7 = 0.9 27.7 * 3.3
Urine Coproporphyrin, Ug/24 hr ALA, g/24 hr
10.7 s 5.9 97.4 = 19.2
1.1 = 0.6 101,4 a 30.1
4.9 = 2.4 50.5 * 6.6
a / Number of rats period, except where indicated otherwise.
b / Mean = standard error.
e/ Two rats. / Six rats.
' /A , r'
: /'* A'-
j T.v-* r.
1 *
61 0007-SWP--036954
0007-SWP-000112941
TISSUE AND BODY FLUID CHEMISTRY OF HATS FED PAINT FILM CONTAINING 2.05% LEAD AS LEAD 0CT0ATE
Ana ivies
4
Serue electrophoreiii Albumin, 7. Alpha 1 globulin, X Alpha 2 globulin, " Seta globulin, X Gamma globulin, X Total protain, mg X Albumin/globulin ratio
41 * 32'
27 * 2 4*1
20 * 1 9*1
5.7 * 0.2 0.70 * 0.07
Treatment Week 8
SSs&
46 * 2 22 * 1 4* 1 19 l
9*1 6.0 * 0.1 0.85 * 0.07
13 ^-12)
48 * 2 20 * 1
6*l 21 * 1
6*1 6.2 * 0.1 0.96 * 0.07
Erythrocvtes ALAD, umol. PBG/ Mala*: 24.1 * U.C& 100 ml RBC/hr Faoalaa: 18.7 * l.0/
Total: 21.4 2.3
Protoporphyrin,
29.5 * 2.8
ug/100 ml RBC
12.1 * 1.7--^ 11.3 * O.Z^ 11.7 * 0.7 30.8 * 2.5
11.4 * 0.8^ 16.3 * i.9if 13.8 2.0
24.0 2.2
Urine
Coproporphyrin, g/24 hr ALA, Ug/24 hr
1.6 * 0.6 80.7 * 17.3
3.0 * 0.8 82.7 * 10.4
7.7 2.9 64.5 * 8.8
1 ' 'J : **
?:? : v-S<ss&
=,:p::'
m
*
:7-Av
... --
............. ------;
/ Number of rati par period, excapt whara lndicatad otherwise.
/ Main * standard arror.
c! Two rats.
- -,'.J
41 Six rats.
r;v>:J.
|U- |
0007-SWP-036955
0007-SWP-000112942
TABLE 18
TISSUE ASP BODY FLUID CHEMISTRY OF SATS TED PAIMT f il m c o n t ain in g 0.427. l e a d a s l e a p c h r o mat e
AnaIvses
4 (S4\i'
Treitment Week 8
(S-4^
13 (N-12)
Serum tleetrophoresi* Albumin, 7. Alpha 1 globulin, 7. Alpha 2 globulin, 7. Beta globulin, X Gamma globulin, X Total protein, mg X Albumin/globulin ratio
42 2--' 28 1
4* 1 19 * 1
8 3 5.B * 0.2 0.71 * 0.06
44 * 2 20 * 2 4= l 19 * l 12 * 2 6.0 * 0.2 0.80 = 0.08
47 X 1 22 * 1
5 1 21 1
6X l
6.1 - 0.1 0.90 0.03
Erythrocyte ALAD, u d o L. PBG/ Males: 100 ml RBC/hr Females: Total: Protoporphyrin, Pg/100 ol TBC
23.4 * 3.5^ 13.4 O.jC/ 18.4 s 3.3 27.3 * 2.8
14.1 = 0.6^{ 17.4 0.1--^
15.7 * 1.0
28.3 0.6
15.7 s i .s *' 16.5 i.t#
16.1 X 1.0
27.9 X 2.1
Urine
Coproporphyrin, ug/24 hr A1A, ug/24 hr
8.2 * 6.7 69.3 * 6.6
1.5 * 0.7 65.2 17.4
6.3 x 2.2 85.3 X 31.4
a/ Number of rat* per period, except where Indicated otherwiie. / Mean s standard error. cj Two rats. 6/ Six rats.
E-ar-fe-.
k : ..
t\ y
r * ...
..
43 0007-SWP-036956
0007-SWP-000112943
TABLE 19
TISSUE AND BODY FLUID CHEMISTRY OF RATS FEEP PAINT LH COSTAINING 1.957. LEAD AS LEAD CHROMATE
Ana tvses
4 -IH=1/
Treatment Week 8
fS4t
13 (M-121
Seruo eLeeerophoresis Albumin, X Alpha 1 globulin, X Alpha 2 globulin, X Beta globulin, X Ganna globulin, X Total protein, mg X Albumin/globulin ratio
41 2b/
25 * 1 4 1
20 1 9 1
5.7 0.1 0.73 0.06
45 1 19 1
4 1
20 * 1 11 1 6.20 * 0.04 0.81 0.04
47i 2 19 s 2
5*1 23 * 1
6* 1 6.4 * 0.1 0.94 * 0.08
trythroeyte ALAU, pool. PBG/ Males: 100 ml KBC/hr Females: Total: Protoporphyrin, ug/100 ml RBC
29.5 20.4 * 4.37 24.9 X 3.4 26.5 4.7
12.3 l.Cfi7 14.7 * 0.6=7
13.5 0.8 26.8 i 1.8
13.3 \.l&! 12.9 * 2.34/ 13.1 = 1.3 27.4 x 1.5
Crine Coproporphyrin, ug/24 hr ALA, ug/24 hr
0.9 S 0.1 80.8 7.2
7.0 6.4 67.7 * 6.8
4.4 = 1.9 66.5 17.5
a/ Number of rats per period, except where indicated otherwise. h/ Mean * standard error. c! Two rite. A! Six rat*.
\' '
Tz 'l ; :V'i; ycss ' %VO;v* jh*4.5V-*
-fir T*. . Wi'tZk
44
.. '
::c;
3tvay.,e>C:'7
0007-SWP-036957
0007-SWP-000112944
TABLE 20
Analyses
TISSUE ANP BODY FLUID CHEMISTRY OF RATS FED PAINT FILM CONTAIN'!NC 12.437. LEAD AS LEAD ChROMATE
. - '.r
Treatment Week-------------------------------------------------13
i2=m
v-.
Serum electrophoresis Albumin, * Alpha 1 globulin, * Alpha 2 globulin, 7. Beta globulin, X Gamma globulin, 7. Total protein, ag 7, Albumin/globulin ratio
40 - 2k/ 27 A 1 3* 1 2-2 A 1
8*1 5,6 A 0.1 0.68 A 0.05
Erythrocyte ALAD, uaol. PBG/ hales: 100 nl RBC/hr Females: Total: Protoporphyrin, ug/100 al RBC
26.4 * 7.4 14.3 A 3.2*'
20.3 A 4.9
25.5 A 1.6
47 * 21 A 4* 18 *
9* 6.1 A 0.1 0.90 a 0.12
46 * 2 21 A 1
5A 1
22 1 6A 1
6.4 s 0.1 0.88 a 0.06
16.5 A 1.4--' 13.4 A 3.8/
15.0 A 1.9 24.2 a 2.6
12.6 = I.67' 13.7 A 1.1~'
13.1 = 1.0 24.6 a 2.0
:
K'r.r:-.'. ii--
*>
Urine Coproporphyrin, Ug/24 hr ALA, Ug/24 hr
2.6 1.8 89.7 A 19.3
0.9 A 0.1 76.4 A 6.8
2.6 C.B 49.7 a 12.5
-r: *:"0T
a/ Number or rats per period,-except vhera indicated otherwise, b/ Mean - standard error, c/ Two rats, d/ Six rats.
45
,y^,.y,vrr.,-.,
-'y ,-v
-
0007-SWP-036958
0007-SWP-000112945
TABLE 21
TISSUE AND 80SV PLUTO CHIMTSTKY OF PATS F"D PAINT FILM CONTAINING 66.057, HAD AS LEAP CARBONATE
Analyses
4 fN-3^
Treatment Week
B (N4)
13 (SI2j
Serua electrophoresis Albumin, 7. Alpha 1 globulin, 7. Alpha 2 globulin, 7. Baca globulin, X Clone globulin, X Total protein, og 7. Albumin/globulin ratio
41 6 27 1
3 1 21 * 2
8 2 5.4 = 0.2 0.73 i 0.17
45 1 21 2 4 1 19 * 1 10 1 6.0 0.06 0.B2 * 0.04
47 = <9
22 l 5= 1 20 * 1 7= 1 6.3 = 0.1 0.86 0.06
Erythrocyte ALAD, pool. ?BG/ Males: 100 ml RBC/hr Females:
Protoporphyrin, pg/100 ml RBC
12. & 9.1 * 2.ll/
10.2 * 23.2 0.9
4.4 * 0,1^ 12.4 * 0.41/
8.4 * 2.3^
20.4 2.1
5.4 = l.oS7
7.4 = 0.8/ 6.4 = 0.71/ 27.2 = 6.8
Urine {X4) Coproporphyrin, Ug/24 hr ALA, ug/24 hr
2.0 0.7 90.3 27.7
0.8 0.3 72.3 * 13.4
6.7 = 3.2 42.2 =8.8
t Number of rats per period, except where indicated otherwise. If Mean - standard error. / One rat. if Two rats. If Six rats. if Significantly different from control (P < 0.05) as ehown by Dunnect's
multiple cocpamot test following an analysis of variance.
P**: iC'-":
r'-s "-~r'
46 .n?,. Vr-tV-
0007--SWP-036959
0007-SWP-000112946
k>
"ABLE 22
TISSUE AND BODY H.ITP CHEMISTRY 0? 3AT5 FTC LEAD BASEP PAINT CONTAINING 11.9 T. HAD
Analvsis
4 fN4)i'
Treatment Week
a
< ^.4^
13 fV-12'
: " -
Serum electrophoresis
Albumin, "
52 lS/
44 a 2
44 2
r~".
Alpha 1 globulin, ~
21 * i
21 * 2
24 1
r ,T
Alpha 2 globulin, *
4* l
8-5
7 1
Beta globulin, 7.
20 a l
21 * 3
21 = l
-) j
Gaana globulin,X Total protein, ag X
3* i 5.4 0.2
8* 1 6.0 0.2
5=1 6.1 0.1
f.2
Albumin/globulin ratio
1.1 *
o uo
0.78 0.06
0.82 = 0.06
]
Erythrocyte
AUD, uaol. PBC/ Hales: 8.5 5.o/
5.0 0.3^y
4.9 0.6-y
100 ml RBC/hr Females: 10.1 0.1^
15.0 5.1&
8.8 * 1.0iy
]
Total: 9.3 * 2.l-y
10.0 3.6
6.9 0.8*'
Protoporphyrin,
14.8 * 4.3
24.5 1.8
26.3 = 1.2
1 Bg/lOO ml SBC
Urine (N4)
Coproporphyrin,
2.0 * 0.8
6.8 4.9
4.6 2.1
J Ug/24 hr
AU,
110.1 21.5
72.0 13.6
51.3 3.6
ug/24 hr
a/ Number of rats per period, except where indicated otherwise, b/ been standard error, c/ Two rata, d/ Six rats. */ Significantly different from control (P < 0.05) as indicated by Dunnttt's
siltiple coa^arison test following an analysis of variance.
47 0007--SWP-03696O
0007-SWP-000112947
TABLE 23 LEAD CONTEST OF WHOLE BLOOD
Diet
Control 0.08X Lead OCtoate 0.531 Lead Octoate 2.Oil Lead Octoate 0.42X Lead Chromate 1.951 Lead Chromate 12.43X Lead Chromate 66.05X Lead Carbonate 11.922 Lead Faint
tli
Treatment Ueek e*
13
13.1 + 0.9 (16)^/ 12.8 : 0.8 (8) 16.4 2 2.4 C7)
14.5 2 1.5 (8) 13.2 2 1.0 (8)
12.0 2 1.4 (8) 19.4 2 2.2 C8)/
24.9 2 2.2 (&)-- 23.9 2 1.3 (12)^
a/ Values deleted due to contamination. b/ Averiie ug of lead/100 ml blood s Standard Error of number of rats In
parenthesis. z/ Significantly different from control (P<.05) as shown by Dunnett's multiple
comparison test following an analysis of variance.
'* . w.'i'/V
*
48 : 'v.'y- .ri*- tX.-r'h'Jl 0007-SWP-036961
0007-SWP-000112948
TABU 24 LEAP CONTSNT OF BRAIS
Piet
Control 0.08X Lead Oetoate 0.53" Lead Octoat* 2.05X Lead Oeeoate 0.42" Lead Chromate 1.951 Lead Chromate 12.43X Lead Chromate 66.05X Lead Carbonate 11.921 Lead Pain
4
n.d.^
n.de n.d. n.d. n.d. n.d. n.d. n.d. n.d.
Treatment Seek i
12
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. 0.2 0.1.
ai Not detectable. Below sensitivity of 0 .07 ug/gm of brain, b/ Average ug of lead/gm brain -- standard error number of raes shown
p*rtnthiU.
J-'Vt" :'r-
Itr |u
49 ** - - *. .
.r: 0007-SWP-036962
0007-SWP-000112949
TABLE 25 LEAD CONTENT OF LIVER
Diet
Control 0.037. Lead Oetoete 0.537. Lead Oeeoate 2.057. Lead Octoate 0.427 Lead Chromate 1.957 Lead Chroma ca 12.437 Lead Chromate 66.057 Lead Carbonate 11.927. Lead Paine
L
n.d.V
n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d.
Treatment Week e
13
Red. 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. l.l 2 0.6^ (2) 0.4 2 0.1 (9)
a/ Not detectable. Belov sensitivity of 0 .07 ug/go liver. b/ Values are average Ug iof lead/gs liver - atenderd error of number of rats
shown In parenthesis
m
~~'X
pr';-.
t -. *?_
881
ia.*a-<$/4r 1WSttfc fvp.z r-c-.Cr.-
50 0007-SWP-036963
0007-SWP-000112950
TABU 26 LEAD CONTEST OF KIDNTV
Diet
Control 0.08% Lead Occoace 0.53% Lead Octoace 2.05% Lead Occoaca 0.42" Lead Chromate I. 95% Lead Chromate 12.43% Lead Chromate 66.05% Lead Carbonate II. 92% Lead Taint
i
n.d.--^
n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d.
:nc Veek 1
12
n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. 1.4 = 0.
(4)
n.d. 0.2& Cl)
0.32 (1) 0.37 0.1 (2' 0.52 (1) 4.2 (1) 0.4 S 0.0 (3) 2.3 0.2 (3) 1.86 0.1 (12)
a/ Not detectable. Balov sensitivity of 0.07 ug/ga kidney, b/ Values ere wg of lead/ga kidney or average ug of lead/gm kidney - standard
error of number of rata in parenthesis.
-y .-- -
0007--SWP-036964
0007-SWP-000112951
TABLE 27 LEAD CONTENT OF BOSE (FEMURS
Diet
Control 0.081 Lead Octette 0.531 Lead Octoate 2.031 Lead Oetoate 0.421 Lead Chromate I.931 Lead Chromate 12.431 Lead Chromate 66.051 Lead Carbonate II.921 Lead Paint
l.bi/ (1)
n. d. 2.9 (1) 0.9 (1) 3.3 (1) 13.0 S 4.1 (4) 14.9 i 1.5 (4)
Treatment Week
8
3.9 t 0.4 (8) 4.2 t 0.6 (4) 3.9 i 0.2 (4) 3.0 0.7 (4) 2.6 0.9 (4) 1.8 t 0.2 (4) 3.1 t l.l (4) 16.0 i 2.1 (4)7 16.4 t 0.4 (4)--^
1
3.2 i 0.2 (24) 3.3 S 0.3 (12) 3.1 i 0.2 (12) 3.9 = 0.5 (12) 3.8 i 0.6 (12) 4.1 0.5 (12) 3,5 * 0.5 (10) 21.7 S 2.4 (12)10.9 i 0.9 (12)--
a/ Values are ug of lead/gm bone or average ng of lead/gm bone i standard error of number of rats in parenthesis,
b/ Not detectable. Below sensitivity of 0.4 ttg/ga of bone, c/ Significantly different from control (?<0.5) as shown by Dunnett's multiple
comparison test following an analysis of variance.
-6-;<X:
*4i-ri 52
: -.-7 0007-SWP-036965
0007-SWP-000112952
I
C - -
r:?V- *
V/ -:
.**
0007-SWP-036966
0007-SWP-000112953
0007--SWP--036967
0007-SWP-000112954
TABLE 30
PATHOLOGY OF RATS TED TOR 13 WEEKS PAINT FILM COWTAIKISC 7.057. LEAD AS LEAD OCTOATE
B3 g6 87 88 89 90 93 96 97 98
r
ui.'
99 ISO
*
~
>
Lymphoid hyperplasia Pntuaohi*
l-1 2
Uver
Foci of in fleam* t Ion
Ptnerees Foei of inflaaMCion
* -1>*'*
Bon* Mirraw M/E rttio
*1.*
0.
1.2 1.0 1.7 1.0 1.2 1.1 1.1 1.1 l.A 1-2 1-3 1-8
. '? ; ..
Tissues net listed were normel. a/ Severity of lesions: l*oininel; 2-oderte; 3*sv*re; 4-very severe; = questionable
.rZ-f."
0007-SWP-000112955
TABU 31
Rat No
PATHOLOGY OF RATS FED FOR 13 WEEKS WITH PA I ST FILM CONTAINING 12.437. LEAP AS LEAP CKRCNATE
.J>.
143 146 147 JL48 149 150 153 136 157 156 159 110 Vi^'S
Lung;
Lymphoid hyperplasia
Z& Z
l
1
Pneumonia
1
Heart
22 1
Vl i*. . 0* . '
Myocarditis
2
Bona Marrow
M/E ratio
1.2 1.0 1.0 1.2 1.1 1.4 1.1 1.4 l.S 1.4 1.2 l.S
Tnlues not listed verm normal. a/ Severity of lesions: 1-minimal; 2-ooderace; 3-ieve're; 4-vary severe; i questionable.
56 0007-SWP--036969
0007-SWP-000112956
TABU 32
PATHOLOGY OF RATS FED FOR. 13 WEEKS V1TH PAINT FILM CONTAINING 66.0ST. LEAD AS LEAP CARBONATE
Rat No.
163 166 167 166 169 170 173 176 177 178 1.79 1J0
lungs
Lymphoid hyperplasia Pneumonia
1*^ 11
1 1
2 1 '
Heart
Myocardiei*
12
1
Liver
Foci of inflammation
1
1
Skeletal wuicle
Miositis
1
Bone Mtrrov
M/E ratio
1.2 1.2 1.2 1.0 1.1 1.3 1.2 1.0 1.4 1.3 1.1 1.4
Tistuea not Hated vert normal. a/ Severity of lesion.*; l-mlniaal; 2-ooderate; 3-aevere; 4-very severe; * questionable
T-" --' /.Vi
;v-
iV ; .
57 rr~'
0007-SWP-036970
0007-SWP-000112957
TABU 33
PATHOLOGY OF HATS TED FOR 13 WEEKS WITH VBS LEAD PAINT CONTAINING 11.927, LEAD
Set No,
183 tat 1B5 188 189 190 193 194 195 198 199 200
-ungs
Lymphoid hyperplasia
2-^ 2
2
2
Pneumonia
2
1212
Heart
Myocarditis
21
Liver
Foci of inflammation
1
Bone Narrow
M/E ratio
L.2 l.A 1.3 1.2 1.5 1.2 1.2 1.4 1.5 1.3 1.2 1.3
Tissue* not listed were normal. a/ Severity of lesions: 1-minimal; 2-moderate; 3-aevere; 4-very severe; * questionable
e. ,7- .'._ *
58 0007-SWP-036971
0007-SWP-000112958