Document 4pw0LZ9YKg5xn6k9bMqrvZnp

Report .API--EA7102-1 LEAD ACETATE, 22-MONTH CHRONIC TOXICITY STUDY - RATS D. Clifford Jessup, Ph.o.; Leonard D. Hazleton Laboratories, Inc, P.0. Box 30 Palls Church, Virginia 22046 Shott, D.V.M., ph.D; February 28, 1969 Final Report Prepared for American Petroleum Institute 1801 K Street, N.W. Washington, D.C- 20006 Reproduced bV NATIONAL TECHNICAL INFORMATION SERVICE 5pr>n.s(eld, V*. N 29321 BIBLIOGRAPH/C DATA SHEET 4. Title andSubtitle 1. Report No. API-EA7102-1 LEAD ACETATE, 22-MONTH CHRONIC TOXICITY STUDY - RATS zZ> o / A?d~ 3. Recipient's Accession No* 5- Report Date (issued) Vebrua rv 23, 1969 6, 7* Authorfe) D. Clifford Jessup, Ph.D. .T.eonard n. ') Performing OrganizationName and Address Hazleton Laboratories* inc, P.0. Box 30 Falls Church* Virginia 22046 Shofct. 8. Performing Organization Kept. D. V. M.. Fh ,D. No' Z&MQ10. Projeer/Task/Vorlr Un:t No. 11. Contfact/Gr am No. P-150-14 LR 12. Sponsoring Organization Name and Address 13' Type of Report & Period Covered / American Petroleum Institute 1801 Street, N.W, .Washington. D.C. 20006 ... ~ 15. Supplementary Notes Attached to final report is supplemental Summary of Renal Tissues ________ Final u. Pathology Report:: compendium '........................................................................... A ^"acetate was incorporated into basal laboratory diet at concentration of 0, 10* 50, 100 and 1000 ppm (calculated^basis of lead) and offered to groups of male and female albino rats for 22 months. No compound effect was demonstrated at any test level with regard to appearance, behavior, food consumption, growth* survival, or hematologic and clinical chemistry results. Increased kidney weights, histopathological alterations in the liver (nodular hyperplasia and vacuolated hepatocytes), and unique and distinctive pathologic changes in the kidneys (intranuclear inclusion bodies and cytomegaly) were observed in the 1000-ppm group. Atypical renal epithelial hyperplasia was seen in decreasing numbers of animals from the 1000, 100 and 50-ppm groups. Murine nephropathy was found in all treatment groups but the frequency and severity was similar to that ob- 17, Key Words and Document Analysis. 17c. '0escriptots\_sefVed ih the COntrol group j_/ Lead poisoning Lead organic compounds Ingestion (biology) Rats Toxicity Pathology 17b, ideotifiers/Open-Ended Terms 17c. CQSATJ Field/Group 18. Availability Statement Release unlimited FORM NTiS->* 00-70) 19.- Security Class (.This Report) UNCLASSIFIED 20* Security C lass (This Page _________UXCl.ASSlFfED 2l No. oi Pages 580 22. Price USCOMM-OC 4C52S*F.7 1 DUP040013886 HAZLETON LABORATORIES. INC. r t r w ure sciences c c n t c r l Sponsor: American Petroleum Institute Date: February .28, 1969 Material: Lead Acetate Subject: FINAL REPORT 22-Month Chronic Toxicity Study - Rats Project No. 229-100 ' SUMMARY This study was conducted to evaluate .and characterize the effects of lpng-tern dietary adr.inistration of Lead Acetate in male and female albino rats. Lead Acetate was administered to the rats for 22 months at dietary levels of 10, 50, 100, and 1000 ppm (calculated on the basis of 54.6% lead content). Criteria evaluated for a toxic effect were physical appearance, behavior, growth, food \ consumption, survival, clinical laboratory results, organ weights, and gross and microscopic pathology. No compound effect was demonstrated at any test level with regard to physical appearance, behavior, growth, food consumption. Survival, and clinical laboratory results. During the early part of the study, body weight gains and food consump tion in the 100 ppm and 1000 ppm male groups were somewhat lower than the control; however, after this initial lag, growth and food consumption for these groups were comparable with the control. The clinical values for the test groups showed no significant differences from those for the controls. Hemoglobin determinations for the 1000 ppm male group were somewhat lower than the controls but within normal range for laboratory rats. r pn A SUBSIDIARY OF TRW INC. P.O. BOX 30 FALLS CHURCH. VIRGINIA 22046 * TELEPHONE (703) 893-S400 DUP040013887 / HAZLETON LABORATORIES. INC. -2- TRW, LIFE SCIENCES CENTER At 12 months, the glucos e-6-phosphatas e determinations for the 100 and 1000 ppm groups were lower than the controls; however, the terminal glucose-6-phos ph a tas e values for all test groups Were comparable with those for the controls. The blood lead content determined at 12 and 22 months for the high level rats was somewhat elevated compared with the control values. There was i also an increase' of delta-aminolevulinic acid in the urihe of the high level i animals at each1 determination and at 22 months, an increase of coproporphyria in the urine. I Statistical evaluation of organ weight data revealed significantly I increased kidney/body weight ratios for the 1000 ppm male groups sacrificed at / ! six and 12 months and significantly Increased kidney weights and ratios for the males and females in the 1000 ppm group sacrificed after 22 months, / Grossly, the kidneys of the .1000 ppm rats which died late in the study or were sacrificed at termination presented more alterations than those from rats in the control and other test groups, Histopathological evaluation of tissue sections revealed a definite compound effect in the kidneys of the rats at each test level and in the livers of the rats in the 1000 ppm test group. Pathologic, changes in the kidneys were characterized mainly by alterations of individual renal epithelial cells including regenerative forms, hyperplasia, and neoplasia of the tubular epithelium with development of renal adenoma or adenocarcinoma. Both the incidence and the degree of regenerative epithelium in the cnyMc.il i-yhniag mrp p-i-ai-pr jp thfi_Ipc:t~ rats With a definite dosage relationship. Neoplastic renal alterations were observed in male rats only. Compound-related, histopathologic alterations in the liver consisted of nodular hyperplasia with vacuolated hcpatocytes observed primarily .in the 1000 ppm females. DUP040013888 HAZLETON LABORATORIES. INC. -3- tttvj. u f e sciences cent.es MATERIAL Identification teed Acetate. /- Description A white, granular powder- Receipt Op August 16, 1966, from J. T, Baker Chemical Company. purity Dosage levels calculated on the basis of the lead content (54.62 bv weight) of the Lead Acetate. . METHODS Experimental Animals three hundred male and 3Q0 female weanling albino rats of the Charles River Caesarean-derived strain. Weight Range at Initiation: Males - 96 to 148 grams; females - 93 to 142 grams. Housing: Individually in elevated wire mesh cages. Diet: Appropriate diet and water available ad libitum. Animal Groups and Dietary Levels Method of Grouping: Stratified randomization. rVpW 4 DUP040013889 HAZLETON LABORATORIES. INC, -4 m, LITE SCIENCES CENTER Croup No? Up. of Animals at Initiation* male female Dietary Level ppm - calculated 1 (control) 100 100 0 2 50 50 10 . 3 50 50 50 4 50 50 100 5 50 50 1000 * After four weeks on the study (on October 7, 1966) , six male and six female rats from the control and each test group were transferred to Project No. 229-107 (Pharmacology Division); during Keek 6 (on October 18, 1966) three control rats, one male and two females, were transferred to ProjectiNo, 229-111 (Electron Microscopy Laboratory). A separate group of five rats of each sex (Group No* 5B - not included in the initial number of rats on the study) received 1000 ppm of the. test material for four weeks and was then transferred to . Project 229-110 (Radiobiology Division). Piet Preparation The control rats received a basal diet of ground Purina Laboratory Chow. The test material was incorporated into the basal diet on a weight-uer-weight basis and mixed in a Patterson-Kelley, tvln-shvi.. blender to provide the desired dietary levels (based on lead content) for the test groups. Fresh diets were prepared weekly. Samples of the test material, the basal diet, and the mixed diets were analyzed for lead content at initiatici. (first mixes) and at one, three, six, nine, and 12 months. n V- V'V DUP040013890 HAZLETON LABORATORIES. INC. -5- t r w . Life sciences ceweR Observations and Records Records of individual body weights and food consumption and the general appearance and behavior of each rat were maintained weekly for the first six months., twice monthly for the seventh through 12th months, and monthly for the remainder of the study. Observations for mortality were made daily. Records were maintained on the incidence, location, and sice of palpable tissue masses noted during the study. Clinical laboratory Studies * The following clinical studies were performed on five rats of each sex from each group. Hematology: * Intervals - One, three, six, 12, 18, and 22 months. Determinations - Erythrocyte counts; total and differential leukocyte counts; reticulocyte counts; platelet counts; and hematocrit, hemo globin, and coagulation time determinations. Biochemis try: Intervals - Three, six, 12, and 22 months. Determinations - Blood urea nitrogen, serum glutamic-oxaloacetic tran saminase, alkaline phosphatase, fasting bipod sugar, glucose-6- phosphatase, cholinesterase in red blood cells and plasms (cholinesterase not determined at 22 months); in addition, lactic dehydrogenase (at six, 12, 18, and 22 .months), methemoglobin (at 12 months only), and lead concentration. Urine Analyses: Intervals - Three, six, 12, and 22 months. s ^ v>A DUP040013891 HAZLETON LABORATORIES. INC: -6 ~ t r w . nee sciences c s n t c r Determinations - Appearance, pH, specific gravity, sugar, protein, bili rubin, occult blood, and microscopic examination of the sediment; in addition, determination of coproporphyrin and d-aminolevulinic . acid, . .No terminal clinical studies performed on Group No, 4. Blood samples were obtained from the tail vein or intestinal vein or aorta (biochemical determinations at six., 12, and 22 months). Urine samples were collected from rats housed ojvernight in Individual metabolism cages and pooled by sex for each group. Terminal Studies Deaths: Necropsies were performed on all animals which died during the study or were sacrificed due to moribund condition; gross observations were recorded and representative tissues preserved. Sacrifices (By Exsanguination Under Diabutal Anesthesia) Took Place at the Following Intervals: At Six, 12, and 18 Months - Ten rats of each sex from the control group and five rats of each sex from each test group. At 22 ijonths - All survivors. Tissue Preservation; Hie following tissues from each sacrificed rat were preserved in 10% neutral buffered formalin: brain, pituitary, spinal cord, eye, thyroid, thymus, lung, heart, liver, spleen, kidney, adrenal, stomach, pancreas, small intestine, large intestine, mesenteric lymph node, urinary bladder, testis, ovary, uterus, skin, hone, bone marrow, skeletal muscle with nerve, and all unusual lesions encountered. CC7 DUP040013892 HAZLEION LABORATORIES. INC. t. -7- rmv, uf sciences cemen Organ Weights: The weights of the heart, liver, spleen, kidneys, and gonads were recorded prior to fixation; thyroid and adrenals were weighed after, ' fixation. Organ/body weight ratios were determined* Histopathological Examinations After the six- and 12-month sacrifices on, the following tissues from the control, 100, and ,1000 ppm level groups.: brain (five sections!, spinal cord, pituitary, thyroid, lung, heart, liver, spleen, kidney, adrenal, stomach, pancreas, small intestine, large intestine, testis, ovary, bone, bone maferow, and unusual lesions. After the terminal sacrifice on the following tissues from five male and five female rats from the control and each test group: brain, \ thyroid, liver, kidney-, and bone with bone marrow; in addition, on samples of other grossly altered organs from rats sacrificed at termina tion and on selected samples of grossly altered organs from rats that died during the study. All remaining tissues are held at Hazleton Laboratories, Inc., for possible future reference. Statistical Evaluation Criteria: Survival at 26, 52, 76, and 92 weeks; growth rate and food consump tion at six and 12 months; and terminal body weights, organ weights, and organ/body weight ratios. Methods: Life-table technique for analysis of survival; analysis of variance, or F-test, at the 5% probability level for the remaining criteria; pre liminary tests (where applicable) by. the methods of Rao, Bartlett,'Scheffe, Sachs, and Fisher-Behr.ens (modified t-test). CC8 DUP040013893 HAZLETON LABORATORIES. INC. 8- - TRW, UFE SCIENCES CENTER References: Ostle, B., Statistics in Research; low-t State College Press, Ames, Iowa, 1956; Snedecor, G. W., Statistical Methods, Iowa State College Press., Ames, Iowa, 1956; Sachs, R., Toxicol. Appl. Pharmacol. 1, 203, 1959; Sachs, R., J. Assoc. Offic. Agr. Chemists 42, 741, 1959. RESULTS Appearance and Behavior " $> No signs of a compound effect with regard to physical appearance and behavior were observed among the test rats at any dietary level. Signs of res piratory involvement (wheezing, labored respiration, and a discharge from the nose and/or eyes) were noted with comparable frequency in all groups including the control. The incidence of these signs was slight to moderate during the first year and increased gradually as the study progressed. Late in the first year and throughout the second year, an increasing number of control and test rats exhibited the usual signs of aging: a rough, discolored fur coat; sores on the body, tail, or forepaws; alopecia on the abdomen, back, ..or hips; reddened eyelids; a hunched position; stains on the facial fur; and/or staining of the abdominal fur by urine. Incidental observations in one or a few rats included opacity of the right eye (also described as a white film over the eye) noted in a male control rat beginning at Week 18; spastic bead movements exhibited by .another male control beginning in Week 42; and persistent circling to one side or "spinning" V while being handled - observed during the second year in one fennle control, three 10 ppm rats, two 50 ppm, and one 100 ppm level rat. This response was not DUP040013894 HAZinQN LABORATORIES, INC, -9- t r w . un sciences cenren r.o'.ed among the high level (1000 ppjn) animals and was considered unrelated to Coai; owvd administration.. The following number of rats in each group exhibited one or several^ palpable tissue masses, nodules, or wart-like skin lesions. Group No. Males Females No. of Rats in Group* male female 1 (control) 4 21 83 82 2 4 9 39 38 3 29 38 39 3 4 2 10 39 37 5 3 10 36 39 * Number remaining after si5c~mo.nth sacrifice. \ The great majority of the tissue masses appeared during the second year of the study. Externally palpable tissue masses. for the most part associated with the mammary glands, are a common occurrence in aging laboratory rats and unrelated to administration of the test compound. Growth, Food Consumption, and Survival Mean body weights, weight ranges, food consumption values, and survival data are presented in Table No, 1. Pertinent data are presented graphically in Figures No, 1 (growth and food consumption) and No, 2 (compound consumption). Statistical analysis performed at six and 12 months did not reveal any significant differences between growth rate and food consumption for the various test groups and those for the corresponding controls. Inspection of the data revealed somewhat lower mean body weights for the high level (1000 ppm) male SrouP and, to a lesser degree, for the 10.0 ppm 010 DUP040013895 HAZLETON LABORATORIES. INC. - 10 - t r w . ace sciences cenres males compared with the male control, this Was probably attributable to the slightly reduced food consumption in these groups during the early part of the study (through approximately the 18th week). After this initial lag, weight gains and food con sumption for the two higher male test groups war6 comparable with those for the male controls (mean weight gains from Weeks 19 through 52 - 86 grams for the 100 ppm group And 111 grams for the 100,0 ppm group'compared with 100 grams for the control). Growth and food consumption for the males at the 10 and 50 ppm levels and for all female test groups were comparable with the respective controls. Fluctuations in mean body weights for all groups including the controls during the latter months of the study reflected the increasedmortality rate and increased incidence of spon taneous disease during this period- Growth and food consumption data foT the second year were net evaluated statistically. Survival in the test groups was apt adversely affected by dietary agministration of Lead Acetate. At the end of the first year* survival at the high test level (1000 ppm) was 90.6% in the raalfe group and 100% in the female group. Survival data remained comparable among the high level and the control groups until termina tion of the s tudy. The mortality rate for the various test groups was low to moderate through the 18th month (highest in the L00 ppm male and female groups). During the last three months of the study, the incidence of deaths due to spontaneous disease increased in all groups including the control group. Survival data at 92 weeks are .presented below. > *^5 V ni DUP040013896 1 'A HAZLETON LABORATORIES. INC. - 11 - t r w . lift sae/vces c Mt er Dietary Level ppm Mean Survival Time - Days main female Percent Survival f s.e. male female Control 10 612 631 76.1 5.3 87.9 * 4.0 601 625 79.4 + 7.0 95.2 * 3.4 50 581 620 66.6 i 8.5 77,7 ,r 7.0 100 594 582 64.6 8.0 66.2S? 8,6 1000 587 627 80.9 + 6,7 87.1 t 6.0 s.e, " standard error S- = Significantly lower than control M Clinical Laboratory Studies The results of clinical studies are presented in Tables No. 2, No. 2A, No. 2B (hematological values); So. 3, So. 3A, No. 3B, No. 3C, No. 3D (biochemical * values); No. 4,.and So. 4A (results of urine analyses). The clinical values for the test rats showed no significant differences from control values. ' Hemoglobin determinations for the high level (100,0 ppm) male group Were, at most intervals. Somewhat lower than the control values but still within normal range for laboratory tats. At termination, the hemoglobin values for the three female test groups (10, 50, and 1000 ppm) were lower than the female controls, but no dose-related, downward trend was evident. At the 12-month interval, the glucose-6-phosphatase determinations for both sexes at the 100 and 1000 ppm levels were markedly decreased compared with control values. At the remaining intervals, prior to 12 months ana at termination, glucose-6-phosphatase values for the various male and female test groups were within normal limits and comparable with the res pective control values. The group mean lactic dehydrogenase values determined at 12 DUP040013897 ,HAZLETON LABORATORIES, INC - 12 TRW. UF SCtmCeS c e n t e r 1.8 months (male and female groups) and at termination (female groups) ranged rather widely but showed no consistent pattern that Could be associated with administration of the test material.. The terminal lactic dehydrogenase values,, for the male control and test groups were comparable. The blood lead Content determined at 12 and 22 months for the high level (1000 ppm) animals Was Some what elevated; however, the lead content in the blood of control rats was also high.. Apart from occasional elevated or decreased individual control or test values (low hematocrit or hemoglobin, low platelet, high reticulocyte counts, or high blood urea nitrogen) , the remaining hematological .or biochemical values were within normal limits and comparable among the groups. The urine samples from high level males and females revealed an increase in coproporphyrin (at 22 months) and in delta-aminolevulinic acid- (at each ..determination). Otherwise, the results of urine analyses were within normal limits and comparable between the test and respective control groups. Proteinuria, ranging in degree from slight to severe, was present in all samples collected at 12 and 22 months from the male groups and, t.o a lesser degree, also in the sampi s from the female groups. This was a common finding in the urine of aging labora tory rats. Gross Observations at Necropsy The detailed gross findings at necropsy in the rats which were sacri ficed at six-month intervals or at termination, or which died during the study, are on file at Hazleton laboratories, Inc. A summary of tho-e findings follows. H The organs and viscera of the test rats which were sacrificed at six and .12 months showed no consistent gross changes other than also seen in,control DUP040013898 HAZLETON LABORATORIES. INC. <- i --------1 ' ' ------------------------------------~ - 13 raw. uee sctmces c en t er At six months, the organs of the great majority of the sacrificed control and test rats bad a normal appearance. Isolated gross findings were randomly dis- s tributed in the various groups and were hot remarkable. At the 12-month sacrifice, gross signs of lung involvement (distention,' consolidation, or abscess formation) were noted in a few control rats and test rats at each dietary level. Infrequent gross alterations in other organs included discolored livers and/or 'kidneys; dila tion of the renal pelvis; enlarged adrenals; an enlarged pituitary (1000 ppm rat); and two bear-shaped tissue masses in the right uteriqe horn (control rat). A 1000 ppm female showed enlargement of the liver and adrenals, an ovarian cyst, and a subcutaneous tissue mass. Lung involvement was the most common finding in control and test rats which died during the first year* Gross alterations in the livers and kidneys were similar to those seen at the 12-month sacrifice; and in a few animals, enlargement of the pituitary, thyroid, adrenals, or the spleen was noted. Unusual lesions were found as follows: a tissue mass in the lung (50 ppm female); a greenish nodule in the left kidney, greatly enlarged greenish tinged liver, and cervical and mesenteric lymph nodes (50 ppm male Rat No, 58-692; histopathological diagnosis - infiltrating myelogenous leukemia); a renal nodule (diagnosis neoplasm of undetermined origin), nodules in the abdominal fat (diagnosis hemangioSarcoma), and a subcutaneous nodule histologically identified as undif ferentiated sarcoma were found in female Rat No, 58-875 in the 100 ppm group; a 1000 ppm male'(Rat No. 58-901) presented a tissue mass in the chest cavity identified histologically as a liposarcoma. Necropsies performed on the rats sacrificed after 18 months revealed kidneys with a pitted, greenish tinged cortex in three of five males and in one 014 \ DUP040013899 HAZLETON LABORATORIES, INC, - 14 - rftw. itee sciences cenren female in the high level (1000 ppm) test group, and the livers of three high level females contained numerous firm, yellow areas. Additional gross alterations In various organs of high level rats were similar to those observed at the 12-month sacrifice in both control and test rats. The incidence .of lung finding and enlarged pituitaries and adrenals was greater than at 12 months but was comparable among the grO jps. At the terminal sacrifice, an increased number of rats in the high level test group, particularly among the males, presented grossly altered kidneys com pared with the control and other test groups. There was'Also an increased incidence of kidney findings in high level rats which died late in the study. These findings included enlargement of the kidneys, a rough or greenish tinged cortex, and cortical cysts occasionally extending into the medulla or discoloration of the medulla. t Nodules or firm, yellow areas in the kidneys were noted grossly in one rat each at the 50 and TOO ppm level and in eight high level rats (five males and three females). The right kidney of a high level male (Rat No. 58-909 - terminal sacrifice) was involved in a large tissue mass; and one kidney of another high level male (Rat No. 58-890 - died in keek 85) was distorted bv a large, firm, pale yellow-pink nodule. These two lesions were identified Illstotogicolly as renal tubular adeno carcinomas. Gross findings in other organs including the liver and the Incidence of these findings at termination or in rats that died late in the study were generally comparable among the various groups including the controls except for a relatively larger number of yellow-tinged livers noted in the high level female group. Other gross changes in the liver included discolored or thickened, rounded lobes of granular .ox friable consistency; a rough, uneven surface; at dark red indentations vr>'^'K.V DUP040013900 HAZLETON LABORATORIES. INC. * 15 TRW, Life SCIENCES CENTER on the surface of the lobes. Kodules in the liver were noted in five control rets* in six high level rats, and in one or two rats at the lower test levels. The most common findings in both control and test rats were gross signs of lung disease* '' enlarged pituitary glands, and enlarged and/or discolored ("speckled") adrenals. Incidental, less frequent, gross changes in other organs included abscesses (pus) in the ear; nodular or cystic thymic tissue; enlarged thyroids or parathyroids; dilatation of the t.ioracic aorta;.thickening of the heart muscle; thickened stomach walls or sore-like areas in the stomach lining; enlarged or small spleens; enlarged cervical or mesenteric lymph nodes; firm nodules in the pancreas or mesentery; thickened bladder walls or bladder stones (two instances); small, soft, bluish testes; ovarian cysts; and firm bodies or fluid in the uterine horns. Unusual lesions or tissue masses in the body cavities involving various organs were noted grossly as follows: a mass of soft, fat-like tissue in the chest cavity attached to the backbone (each in a -female control and two male test rats - 50 and 100 ppm levels, respectively); a tissue mass in the chest cavity attached to the rib cage (1000 ppm male); a tissue mass involving the thymus (SO ppm female); a mass involving the lung and thymus (1000 ppm female); a tissue mass in the liver (100 ppm male); a tissue mass in the abdominal cavity (each in a 10 ppm male and a 50 ppm female); another tissue mass in the abdominal cavity involving various organs (1000 ppm female); and a soft mass protruding from the vagina (1000 ppm female). Externally palpable tissue masses or nodules noted during the study in control and test rats were confirmed at necropsy to be subcutaneously located and, for the most part, associated with the mammary gland. W is DUP040013901 HAZLETON LABORATORIES. INC. - 16 - Tftw.. utc sciences ceuren Organ Heights Mean terminal body weights, organ weights, organ/body weight ratios, and their respective standard deviations for the control and test groups are ^ presented in Tables No. 5 (six-month sacrifice). No, .6 (12-rmonth sacrifice). No. 7 (18-month sacrifice), and No. 8 (termination). Statistical analysis revealed the following significantly increased values for the test groups in comparison with control values. At Six Months: Kidney/body weight ratio for the males at the 1000 ppm level. At 12 Months: Kidney/body weight ratio for the lOOCWppm males and terminal body weight and liver, spleen, kidney, and adrenal weights for the 1000 ppm females. At 18 Months; Thyroid weight and thyroid/body weight ratios for the 1000 ppm males and heart and spleen weights and heart and spleen/body weight ratios for the 50 ppm females. At Termination; Liver/bpdy weight ratios for the 10 ppm and 1000 ppm males; heart weights for the 100 ppm and 10.00 ppm males; thyroid weights and thyroid/body weight ratios and kidney weights and kidney/body weight ratios for the 1000 pp.rn males and females; adrenai/body Weight ratio , for the 1000 ppm females; and testes./body weight ratio for the 1000 ppm males. The kidney weights determined at six, 12, and 18 months and the kidney/body weight ratio at 18 months for the 1000 ppm male group Were higher than the corres ponding control values but not to a statistically significant degree. The consistently increased kidney values for the high level males at each interval DUP040013902 HAZLETON LABORATORIES. INC: - 17 - TRW. UFE SCIENCES CENTER and for the high level females at the terminal sacrifice were, possibly, a Reflec tion of compound-induced, his topathological alterations observed in the kidneys of high level rats. The significantly increased liver ratios and increased liver weights determined at the terminal sacrifice for the male test groups showed no doserelated trends (weights highest at the two lowest levels) and were, probably, not meaningful, although some his topathological alterations were seen in the livers of the high level rats. The terminal liver values for the high level female . group were comparable with the controls, although his tologically, alterations in the liver were more pronounced in the high level females than in the males. The increased thyroid weights and ratios determined at 18 months (males only) and at termination (males and females) for the high level group, as well as the increased values obtained at the various intervals for other organs in the test groups, were also not considered to be meaningful since these findings showed no consistent pattern and were not supported by any histopathological alterations in the organs. Microscopic Pathology Microscopic evaluation of tissue sections at three and 12 months and at termination of the study was performed by Leonard D. Shott, D.V.M., Ph.D., Pathologist. C1B DUP040013903 HAZLETON LABORATORIES. INC. - 18 - raw. u f j sciBNces cfi/Tea Suitunaries of microscopic findings, incidence tables of histologic alter ations, and detailed findings at each interval are appended to this report. Report ..Preparation.: M. Kundzin Supervision: Fink mtg J IS DUP040013904 ; ; f o r f o o t n o t e s Values in parenthesis are not included in the iaean. Key to urine analysis table is as follows: T P TEL - turbid pale yellow V T TEL = very turbid yellow C YEL * clear yellow 0 * negative T * trace () 1 * slight (+) 2 = moderate (++) 3 ~ marked .(+++) 4 severe (++++) ___/ *= denotes change in sample size S+ *= Significantly higher than control S- * Significantly lower than control C20 DUP040013905 fem ale) albino rats. 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O' --1 lf\ 4- 0 -< <M P DC O SC LL Q U. co UJ UJ HP -J < < Hp > UJ u J <t < 0Q -* -< 0 UJ 0 -J -J 0V--. < HXi X 1 Ai 9 O Z UJ < h- * I< 1 H- *? 1 UJ X l to .1 1z i-> < CO cO 3 -11 2X t *- t VO 1z 0a tc *-* dC -J 1 ~j 1 -- 1X CO fcf x X a Cl O * H> OW X _! .< VO UJ > X Ztf'K - ui Z 1-- v- C ZX O OO X CL CL IA ; 4- AJ *0 !. h- co .4pm 4* ; - 4* CA t < fn C\| m* AJ in ,m in* *-< ro: 43 fO A- A- fVl -* M *H f<1 H Cvl CNJ 4 >C H .O' 0 O AJ 45 AJ 43 AJ 4> * 4> 4) >0 43 1"*" *0 4* 4* O' CO O' m . ' : * 4* 4- Ai 4- 4* 4* H H.fH H H tA ; ; in in P . . .4" fs in pp^.n* 4- 4* 4- sf in *4* 9--t H *r< p--< 4* f)r4r in *- 4* tn tn 4* * * :* * NO 0 >c >P 4" is* <4* --i I** . ,* 9 9 . 4- ^ 4* 4- 4 un 0 o m . 4 in so 4- in in .*4- .in in CO UJ x X zX Xxz t t -J cc < UJ x *-* X. zi <z CD O' ^ 04 > tA lA lA in lA . Z in in in in in < ai X CO O' O H N 35 00 O* O' O' sO 4) 4) *0 43 : Z lA IA lA lA lA < UJ S' S DUP040013911 o> rv \ - pt T A B L E N O . 2 H E M A T O L O G IC A L V A LU E S FOR M A LE AND F E M A LE A L B IN O R A T SLEAD ACETATE FOR 22 MONTHS- uo as cc I CC X I *o I OP I Z3 --I I ,2N I I Io I vo*r t 1o I UJ _J <3 O H--- .2G39* 2X Ul ac . UJ.X U. Q. H U. CC >- C _i !o I UJ as I VI c.ccfio ooooo O O it O ift in h cp ep cc O' *p f^ti ow nh m nO' poo O D O o o cn c m ooop o >0 c m r- O' o CC CO O' coco CD CO <0 O' I I IQ I 3f I< IP op o op o O X X - a* .-a. O o oo O a CL o o o o o UJ ft. Xo o op I V) Ie i z 4- O' >0 O f- 00 cn O' o m in:m o< Jfi V) Jt Pa o csx O' f-- cn c m PJ(\IW IM <M CM lA N M i >J- <#--h m ro <n j (Sj (x I 9- I VO z 0o cfc --j i .1 ix rf.iCO rtw si- 4- fd .o fM.N f<3 +Q vQ v() LA >0 <> >0 O' CO in* pf ro, csj -a * ip <0 <o >6 IA >o cc o at x <:0 C-O O' .--< r** f\J <M &\ st ^ tn P- CO tA >0 oO OJ m ra m ; ; c m m ,H H M pH rH o X O m * ' . O' r- h n m o -if- *4- in -I" in t o tn p o** o ; tA *t VO UJ > X X o:*** UJ Z I-- C3 zx vo UJ x XXX XXX x x sXxs -<JUOJC X cc - X 2 <Z CC O' o i-i AJ CO CO O' O' O' rCO rCO r** CO rCO- ;po* .2 LA IA iA IA IA < UJ X co ff' O -h nj CO CO O' O' O' CO GO GO CC CO oo CO CO -CO CO 2 iA uvm tn uv< ui x DUP040013912 <v CV' oo 11 X X XP3 11I OPz P s TABLE NO. 2 HEMATOLOGICAL VALUES FOR MALE AND FEMALE ALBINO RATSLEAD ACETATE FOR 22 MONTHS o1/1 V c pp p p iX I t2 I t t/i 1O I tii -j C - X H H- O U2J X lXit X uti. ax. Q >_-l i II 1 toil 3<e V> 1 I i i ~< ii re i (v p <*> o op p p p O' v c m MOOt.lO DIMS lOtfl pPo o o l ui 4S Coc P O P O p X t-- oX I l/l o O 0 X tX</1 -O..P.P. H. tf.lO. F O' si til .O' N .3 3 1 o-.X I </> 0 cX ce ~ Ot --1 1I ---J X X XXV. ONX r- wN c m m -o P r-t <M Nf-)0 p c- c- r~ 4- in p -o . .. . . in cr> SP ?4- -4- sj- ......pptnp'4- r'-ip mom tAtntn uitnifl < i/i UJ > x X OC H- *. ui 2 *- c XX wtnc<i Mitin t/l til X X XX X X -J Cx! <t UJ X-Cp <z dz CO O' o CO GO O' O' O' m ro to rn m oo co co CO CO 2 lA.in m tf\ tn <i UJ x p- 23 DUP040013913 TABLE NO. 2 HEMATOLOGICAL VALUES FOR MALE AND FEMALE ALBINO RATS.LEAO ACETATE FOR 2 2 MONTHS TIME INTERVAL MONTHS 2 1 8 i O' cm cy 4f uo rc cc f lt .a o3: Oo t :0~< l 2n at opoe c co in -ri p h O P 0 CO -3OONrl ppOpO POOP I iI awt It <1 CO I i II </> _1Il w ill < o- >- z at *.z- U4 IoaL:-' K cc iii it uti-. O I II I I I OacV--tt1l:I -av>t a Z <t VoC3lID1O>: XLOoOf I L- I i II I tI I <0CqaHCI1O:tOV..Wz0*j-)?1 Io 1-- 1X CC OM 'X h.X m cn ff1 m tn p co as p co -P CM O J" *J- P O P P r c pO p O CL CL <n j >o cp0>0 41 . * * O' 4- in n0 jfv Np M t--4 ""I ^-5 *C IfWVJ w r* sQit er\ & o .9 . 9 9 .9 r-- r*co S >o Is" in o si* cn co o . '.# . .* <r m *4* in m in .*-4 rH r-4 r--l rrC 0 0 0.000 .9 *.*' ,* O f\l tD r-4 --i m m sj- in xi m p P P CO p P P CO CM o P :p O p SE P Pp C CL P in fO o Is- >o *-4 --J CM .+*4 rv -< o in o ; : n- p> o* *>-4 sf 99 9 9 .9 r-- ch io co,fs- co n. . mm .* 4 rH -* rt tr. m * < r sf "*H *-! p o in opf . ,m o co o' cv o in sf m in mmo in w k i k i ro m m en m x%S) UJ --or <t UJ XlB *~3E Z=> <1 Z xtt ? tt CC O' o rt N CO CO O' O' O' SO CQ zin in in tn in * 00 CO 00 tn in in in in ui X Z Z X X XX 0CC <> *-< TV Cp CO O' O' O' f<Q>0 %0 *0CQ co CO CO Z m m tn in in < UJ X C29 DUP040013914 TABLE NO. 2 HEMATOLOGICAL VALUES FOR MALE AND FEMALE ALBINO RATSLEAD ACETATE FOR 22 MONTHS 3 3 3 37 38 37 O' t*> sCc O cc tv t as I G l GO I P -H 1 Z s I I Io I 1/5 X J< t as I I I2 t -- >* 1 vo Po p o g N0"*0- 0OO QO H (ft H O t ULJ -1 <O ZM - P 22 UJ a: X IL. .CL $0 U. 2 > Q _l I I S> I vu a# I iSl I I CMN0 O' O' O' O' X so m tv 0* p p . f\J -4 Vf\ O' CO O' O' O' r- p -t- -4- I > I a* I< oPoP PP Ia II I J CL O O O I UJ CL 0- O x o . IM IQ I2 c\j ob --J to m tv h tv st- in O' 0U . * * ** CC s. IS} O' t^ r- in so 0s rH H H (\ H fM os> in O' ^ O' 1e ix i t- I VO 1z oo cc -* o -J 1 -J 1 --tX 00 in tx X O' &S - f fCMTi I*- lf\ l- co oo in ... *o O ^ 4 c m tn XT PA ** * ro in >4 in sf .r-4 i-- r- f-- oomn *-l *q cn r* co O' -4- co . :t . t"** i'- ; - r- op r*- M O p CO !AH ft **> *$ ?t <t if --1 H H rM **< -- O LA OO k Or* 0 o in in in in * X IT NH r--< >0 H O' CD sO c m in .<* IA IA ; in in *4* *4- >t cn *4 < y* UJ > x X CC HHI2 H- t- C 22 '< 4 </i UJ X X 31 X m m m tn ro tn XXXXXX -J CC <r uj X do X 2P <2 CC O' o r- fSJ do O' O' O' r-- f? CO co co cc co ^ IA yvih in in < iXj X CO O T* <V to OS O' O' it co 00 co 00 co . 00 so so p cc.2 initiinitiifl< UJ 2- 0 DUP040013915 TABLE NO. 2 HEMATOLOGICAL VALDES FOR MALE AND FEMALE ALBINO RATSLEAD ACETATE FOR 22 MONTHS oo CO CD f1 sc ao i oo 3.-H 2> I io I iA Pf 1o I ui ._ M< Q 2 . HO 22 ui coc oo OHO o <-* opPop . i u. 6. K U. X h > P -J O <NJ M r*- p O' o p !p isw -4* t*- O' O' Cvi w ,h H i i i Io I z I< o O C O I CD I I ( <1 HSSO O <\l ?!* CO !/J a3 NP fOsINiHS' NO' fN\J ID IX I t- I to pI oz |SO ^ oc: i -i i *IZ lO h H O fr~ o o ^ .p.h- ....* CD t~ p P p <3 ... ...C O (K- iMcoto ppm X p pn p -4- st ... ...o o o o o o ox P m p O O '***4 p p -4- p p p <X </j at > x X SC. f~ wlU z H- fr- O zx sQ *0 sO *iQ VO Ul x XXX X'X X -4 P <t Ui Xm H.X Zp <z p O' p -- oo 03 QO O' .O' in rh m (<i m P PP P p2 p p p p p <t Ui X i r 31 DUP040013916 TARl.E NO. 2 HEMATOLOGICAL VALUES FOR MALE AND FEMALE ALBINO RATSLEAD ACETATE FOR 22 MONTHS 6 6 6 P oo rvj <S; - SaCc C3C: * I o oc ` D^ Z\ I- p K I J S<Ct c- o o p poop I *- >iF I VJ 1O -IJ UJ <1 c >Z-- O2 1 K Ui it* x uu.. a ZL k -- >- p I io l iu H I i/> 0^0 p o QOo oo fO ^ cr in p p eg so p n- in *- >0 m oo o -< o O' m co p CO Is- p f- *-- CO .* >0 O' _4 CM \-A I I .1 Q I I <CZC <>* C O Q 0-0 I I I i I iu .aax CO O O op p XQ. o 0 0 O o CL II Vc> pCXIO uz<o p III >Xo- I i/) Iz Po CaO: il *---"j*i iZ so Xo oin c\j*H tn in h n.* n o h in.rnr~< CM *-* (Si Oi CVI f\| ^ sC >0 *-H ' i\ O O r-* >0 & <si css <\j <SJ c m nj r- O' c m re <\j m OJ -* CO f*- in ia >0 O co* co * ^* O.' cn tn m >* co *4* Is- m in m sOro toO(^ Hf>-cs) * , . tn c in *o r*"0 rt sP -* st* -h o . : 4* >fr ro ^ 4*-sh O& X O O* O' <\ in 4* o Hf-<M in m \n m m in tn HOh Oc oOo*PCO tn >4* 4* n ^t < l/5 U5J O>J HX UJZ h- *z c X VJ UJ x >o *o >0 *n o ?222SJ *0 >0 jr X X 5: z* .<-J oUcJ X CC Z-xX z CC O' HN . .OCinCO mC3O0 iCPnO iCPnO CPinO ;2: in in in in in c Ui z tCtOOco'Op Hp<P\] Cm->O0 i'COnO tCnO oCinO iC<nOo z <t UJ Z } I i r *3* 2 DUP040013917 TABLE NO. 2 HEMATOLOGICAL VALUES FOR MALE AND FEMALE ALBINO RATSLEAD ACETATE FOR 22 MONTHS 5 6 6 c <V x .* > oo texts 1 1 1 1 t <o o%c * '2 N fI 1o 1 1 i<C t 1 2 1 t 1 t LOU <o h- DZ Z ' UJ CC ill X u. o- U. X p* > Q -I I l my> w I uo I C oo oo to o n m o o Q >6 >0 O' O O' qo cp o' .< co cy co oo t t Ct IZ J| C<Q I I I< iI it--ii o O o 0.0 X a. o o o o a 1 Up O o .**4 1O 1 o z< m com <> 4^ . CO up '5e :=> cn 6 4 m fo c m cv j ro c m eg to 1 5C 1K 1 UP 12 uoo o .C --1 i --i i >-* IX to s* :x <v in >o fv --4 co NfCNr^Ovl- Is- y '.r> 03 ?!* N O O .CO 4* CO O CM <1- vtn trv >o tr\ *4 rH fH pH pH :pH hO 9C X o oo ooo * ' - . in >4* in *n m in -J < V> UJ > X X vi UJ Z - 1- *- -c ZM 2 4> *0 M> O O yO %/% u j x XXXXXX to CO O o o P QO O SO CO CO S- rrf op po o> . O' co -n o> h c iw h opo p5 A Q O Oi o> N fT. iM ** cn in o 00 :in fv in cn o <M N -< m CM CM SO CM r-t %o -.4 cc c m m in <4- cn rv . . * tv r- r- H C0H pH fs- CO 4" st 4* m c m ro M ,r- v* #H .>4 f-H o oo CP^ -<m O' tc O O* m m 4 4 4 4* 4> SO >6 *0 0 MS z?i: zzz -J oc < UJ 2: cxo Z3 <Z co O' O r-< CM 30 CO O' O' O' h* |> tv tv fv CO op CO CO CO z tntfun m m <t UJ CO O' o ,p*h cv CO CO O' O' O' CO 00 CO CO cc CO CO 00 Op Cb X m mm jun< ui X 3r o V 'C/ DUP040013918.. TABU: NO, 2 HEMATOLOGICAL VALUES FOR MALE AND FEMALE ALBINO RATSLEAD ACETATE FOR 22 MONTHS 8 7 6 O oo Cm cc .as 1 a: Dt i 1 .* o 1 oo 1 3 - 111 .2 N* 1 1o 1 1 V) >C ' O -4 i 1 .CD 1 UJ 1# 1 l/> i 1 1 1O 1 2* 1 < 1 33 1 i Xp 1o 1X 1 .Hr o ' co St vn co ty .# COO'iA >p n in H H .**4 f--4 r~* 1 CO t2 ao cD a: -J i -J i1X CD CD 3* X O O <v -* m f>" sf in p * * * n- 'A h- O 0 o o *-* . , .* m st rf- 4* 4" StH rt *H ~4 H >~ CD * X ooo o o * st r** *b O' t" SO tn *r it St- -4- D < to 1X1 > X X a: h - ID 2 H" H* C ?2 t-4 fu cu tv rs nj <\j * -- 4 :r^4 *4 *^4 -"*l V) UJ x t.?s d af < iii .X 02 , Z rs i 2 CO O' O *" (\l CO o O' o\o* mmm mm co co so CO sc z tn tn in in tn < at :i 4r ^ V- v DUP040013919 TABLE NO, 2 HEMATOLOGICAL VALUES FOR MALE AND FEMALE ALBINO RATSLEAD AGETATE FOR 22 MONTHS cr Ces*'t II o0oc=oo25 loo I Z3r-t I Z*l .'ll I o V I t/) 3-P O h O 4* ^ *- O im 0 .0 ' I *f I CO I I2 I **>&> II vo') _Ii u>' < O <- Z 3* Iz- *O i\i :<y ru o o *-< O P **'*& QW O 0 O O -> of uj x U. Q. K y, z .oio- CM <4>i 4 0o ra 4 evt -> (Si - >* 0 _J I I <3 1I -OwI 9< c m to r-i o r~ 4 . O' ?i" l l I iII a2 *.f Oo6oO 0 O c? P O II CO I I4 1 . I UJ XO. OOO Oo X ooo oo O- 2 Cl i CL O I .to O in I o< aav) so o I2 I -- o t0- 0>o0*0---0* tf\ 0 ^ w *-<jn H H -f%J H CM.* fSl ->*sf O O ro o rev cn *--4 co M h n rsi . - IX xn -4- in cvj co rn ? >o m >q r*- <? in cc c mpm c? O' CO O HP- N ^ #* *o in in *0 * 35 0 31 X sO : O-0' -h ' >o * m m CM A! PCI CA TO c m <y tn rsi y r- # # . 0 0* *? St* CC\ <M .fCi pit I O, O Oi O 4 -O !* . 444444 m* o, o o.* o, *n N 4 .f, O 4 4 44 4 04 4 00 IXD > ec tX- - Ul 2 H- b- O XM CO f\l <M fSI v <4(V (V OJ (4 nt LO UJ X XXX X XX as: tzs -J CSC < fcU Jfc co *-* X X3 <'X CO o> o t\! m CO CO O' 0> 0> in in in UN in oo co co co2 in in m in in < 111 X co 0 0 jp-4 m cp cp <y* O' O' %0 <sQ >0 ">0 co 00 .co co co z in m .tn in in <c . uj X CDS DUP040013920 Jp * . s.V %" * *\ \"V. - \"a * - oo tv r\) XX t a: 2 { 1 o IOC .3 % K vo> H1 CQO Op -* * p p ,o p < -CD V) .. H* -<t OC itl </*>- x> _11j OUJ .*-4 O *-$ <3> *-l4 *4' C < :C a .--X1 ~ t- 2 G 3 UJ'.3E *- *** O Q o o ^ H < aU;I X JJJJ u--. Pz>:. 90 nO .Is* O' co co CO m in co p x j^-JOO ao UJ Uf VO z< ix- -J I|1 OUJ ^ .11 v> 1 cp rg *o co in in xn n .CV *"* H ui zO 1 G -<J .X' t i <Z ** Oo o OQ 0O X ecgv X tX ti X uO. XO CO u. UJ UJ ,-><D4 H hU<J- -J o < Sf* 3: H ^ CV a. a. p p P o o O * t- >6 ob c<> .# * * 0(V'fMwmir*H ifn"4OW''f64 o*- o< 1 1X O uj 1 H* O -J J -foc- 1 to o1 Zo t m co o co <4* 0 sr o >o in .ift.O sj' h mr?o mm to c n j n~ <J XUJ ' X X X ---J {1 .-M4 . * .< . p*** r>* r*,>* h-ajcph r-n- '1 1 x CV OX 3* X' a 5 UJ _j rU 3V X X < --1 < to UJ > ;x XX - >H--4 X- Q3 XX ^ eo -b.o*'o* -3- in .4- in in 4- H f*4 ">4 4 O Dft pp .0ppmo h- CO n- CO O GO CV CM C\i CV <V iM r-4 H *"4 <*4 .^4 ~i . co in * c'o h-- in' co X x -g- x x x .*--4 H --4>-H OOP osf . . . X e- 0 *4* qo g> *t in >4* sr rsi cv csi eg cv cv VO UJ x ZS 52X 5552 .J a: i u j X ~x 2 <1 2 f\J CQ CO e- f>* f>* Is- f* sc co cc 2: in in m in in < UJ x O CM *4" CO so CO 00 GO Cp x in in u> icvm < UJ X' .j n V- DUP040013921 CV o tv \ V\ TABLE NO. 2 HEMATOLOGICAL VALUES FOR MALE ANO FEMALE ALBINO RATSLEAD ACETATE FOR 22 MONTHS UU ic a: II e*tao: I uo i o--t I 2N I I I :om if l P -J I to I UJ if Im I l ococ c n rt -J in (\j p,NNort >0 >0 .H (V >o '0j ^ >o *o*o r-M <H O CO O' m *\j ro rsi eg i if 1 UJ X 1 *n lP 1z u> '3t P 1O 1X ih 1 < > tz p00 'Kp> 0 _J i -J -* 1X <0 ow .X X oo o^ -J o o oooo O' fr iz o o 00 >r ATI * * . * O 00 00 Oi *4 80 fil *-4 (\J rSj r-H OJo^NCO>t oo >o o m J^- op LH xO LA sO in .* .*'# *4* t v in m sMn H H H ^-4 '.rH -4 o O. P. OO. P* P' JftO "4- *- O' -* lA tO ,j- jj- it <C c/> Ui > X >-4 UJ X i--- ,c- ZX co oo co CO 00 00 r4 H H r-4 f-4 H 10 UJ X X xx x& X _J oc < UJ X CC ~x. ZP <z O' O H N CO O' 0s O' O' .00 cp 00 CO 00 ^ in vn in uvm < UJ X rO v*37t DUP040013922 \ O' o o CM sa ct <V l cc 9 3cE O =p zx < > H .<t c* O pO Q O . to 1< C a .z CO ~J c tu -J < X UJ u. o to ZX < I- z UJ o -J X .< CM CM OC a oc tL O Ur V) UJ UJ p-H-J <1 < > UJ u _ < wt o v < UJ o -j c L-< X UJ 'X 1 tv o z UJ -J SC < H* iz i -- 1 ui 1O 1 1U _i <G -- Z **' *- C ' ZX XU oC j X u. ct * u- x ~> O _i 1 1 IU* 1 V> 1 1 1 1 1 zw I 1 .<53 1 1 1 < J t-- W I UJ x i /> 1z o< /) 3: lO 1X 1h I to tz oo CO v a t --4 i iX .. so O tK X V* o ac X to UJ > X X CC ** ui.Z >-- V-- o ZX 4 to UJ X -- <Si Q .rtf c m .-j 4- <\j O O (V H o 7* 9 D .0 1 fn p CM CO !>0 fv f- C^ M) IV m> *'-<* co c m CM CNJ CM CM CM . 0 hh ^ o <V f 4- M h0 4\ l*\ PJ i-< (4 45 <KN(Oro4 OP O X odd do Cl CL X O 9O 0 a a. o e-l *d \ in sCO :f- SO O U% f* 9 .9 .9 so tci <> o o r*H ,H H C\J H *H h O' >0 >0 O' *}* ' : 9 ICO |V sjh O' co H rl CM *--* iH H *J- 4-N H OH fV r-i ~4 CO CM eSi .* .9 0 c- co r- MD r- <0 CM CM CO Mf* -r-l . * 4 * in tr\ 4- trv in :*~l w-l ^-1 ." f< 1 0q 0 d 00 * fs. ~4 Qs fw _! gv -it- if\ *t *jt w% st CO CO 00 0 CO' CO f-4.-4H H H H XXX xXX 0 |V'H o> c m rn 0 4 ; 0 cn .9 9 .9 9 .9 < *0 vA 'O r- tA 0 |v CM CM CO O <M 9 99 m co cn sf* co H V H ,**4 H H 0 d0 00 9 9# 9 9 * IA O *A C0 C JA ^ xe\ it st & <t co co ao CO CO CO H 94<iH tH H H * ,X X X X -J at < UJ XP *- X ZX cz CO O' CM fA tA co co O' O O' lA lA UVlA P cO co oo co co 2 IA UVtA IA JA < UJ X 9(0 4- so co o MO O xO O :0 00 00 CO 00 CO z in ih ur\ in <t UJ X 8r ^ vv DUP040013923 /- O' f\2 *V /* TABLE NO. 2 HEMATOLOGICAL VALUES FOR MALE AND FEMALE ALBINO RATSLEAD ACETATE FOR 22 MONTHS uu {C CO OCX 1 o i oe i x* \ z>. 1 1 It toft* t CO 1 1 1 1 2 r oo 1o 1 Uj a o ** z t- o ZX UJ cc ill X U. CL ' u. X ' > Q --1 jo 1 114 9$ 1 V) 1 t 1. 1Q Z$ 1 <t I1 a? 1 1< t H* *f | UJ 'St 1 V5 1c 12 U< CO \A 3: d i1 .Oor 1 H- ZCL CL e-< POOCO co 4- 4- 4- 4C --4 O P --i <0 in INI CO r-l h- us o >p o o a- oe -4fH f<l (M c\l OPo oc OPo oo O' 0 <t oo 4- t . * ... HrJmnNM 6 3 2 0 0 0 00 0 00 0 00 o * eg r-* O qo 04 .co <-*in CO Ol $A *0 4) *o o <0 m coco .gCO in CO 2 a a. o o oO o CNJs*- * ry no . in* co h in O' eg h ^fv wcc eog <-> C cc .- 6: -j -j I * St .CO k T 1-- OM X ~t <x co uj > x SE K 1* wlU2 J- :H- C 2X ,*-- CO `UJ X to us o -a- co <UI iM O Cp O ... ... O to O to -0 do 49- rH 0- f" c*> Hs* iHn *h | ,mr4 .mH 4 : O dOO'O* h* O 05 CC O CD >4- in ^ in 4- co co CO CO GO oo rM --1 fH i-^ 4 X X X X x.x 03 0 o e- m m*p O in r . o o e' o gb >p er* snco * OO -4 rn ^ *4- ro ro co r** *--4 H H p OP o p os ^ CM* C0 co.* in9 in US 4" 4- 4- -4 st* cp COP CO CO 00 rH rl --l *-4 -4 X xX --1 cc < UJ XP X ZX <z flCOHlOO co p* a* o a* h fv Is* h- r*- CO CO 00 CO CO Z in in ; in < Ui O' CO O' O' co ff> 4O' ao CO coco 00 CO 00 00 oo ep x in m in us uva UJ X M M M DUP040013924 a cm V v> a: 3 2 *-* cC < ILi <t UJ u. Q t/J .2 X < .H- Z U1 o _J < X-.tM CM ac o or u. o a. V) UJ LD J < <t Hr > UJ O -J < < VJ P * O UJ O -J o H<t X UJ X 1 CM ! c 2T ui -j C2 H- ou CP go I QC X I O I OO I 3h iz i 1o I v) X I< 19 1 1 I2 J -* *f 1 vo 1D 1 uj aJ <O "* 2 :X 1- o 2S iu cc tu x U, v w u. x *- >aj i 1o I UJ M 1 VO 1 1 1 1O I 2 &e I< J =o 1 i< 1 l-K 1 UJ * 1 VO 1o i2 1_) < CO VO 33 ia l .2 1 JTM 1 vo t2 uo CD *-* CC --J 1 -J 1 -* J :X tc o X' -J a pc '.H* Z o o HO fcf X -J < uo UJ > X X CC H* mu j 2 .I-4, H* O 5*-5* S vi .u j >> OOP P 0 h -4- o N fO O ^ O o r-4 P tA CM 4* 4* LA 4* tA >0 fA O sp--t >0 CM LA 4 in 4 CA oOo o o OO O 0 o <M --4 h N fO fO .* r- AJ-- r* <V <M H (M CM ",4 H >f\ CM 4 >OCMA in ; A- CO CO f!- CO Is* f* f** f!- --MA CM lA A* ft : ' 4- CA co fO CM CA i-l fj HW 0-00000 . .* Is- o O P N f>* 4* 4* -4 4* 4* 4* CM CM CM CM AJ CM TM CM AI AI AJ AJ X ? -J Of . 00 O' O *-< CM < UJ CO CO ^ O' O' CO TO cA fA fA fA CO CO to CC CO 2 Z3 <Z LA lA A IA A < UJ sfi r. 0 DUP040013925 O' CO tV *y \ V .uCQ Iuw CC 3 uo Z3 <-* I .1 o .00 3^ i - 0 C .Q 0 . to H<t OC o z .-I* SO -J <t UU ~> < 2: UJ UL O to XX z< hr Ui C JX < X CM CM oc O cC UL UL to Ut OJ t- -j<t <> J- uoj -J < < o ** <4 O UJ O -J ,_J o ** <x uj X 1 CM o. z UJ -J CC < 1- 12 1 *- W 1 </> 1O 1 UJ <O 2 ** >- O 22 Ul CC UJ x U. PK ti. 2 > a *j i 1o 1 UJ . I VO i Ii 1c 1 2 JE 1< 1 CO 1 1 1< A- SC t UJ 2 I V) Ii oz a to 3C 1 1X I H- t to 12 oc CO aC ~J 1 -J .1 fIZ CO w X K O 3* X -J <r to ui > X t OCh *-iu z *>- Z5 *--i I/) tu x -4 Q CM CM C\J tn CO o -<.-*4 0 o H 5fl f!- H OMAtO^O to ^ Q h co c m M* <* cn . o >-4 O --* .H .0 n- OO P' *n 0 OC\j C^O oCOmCO ofO O O x o o Cl CL X CL 0. o ^0 >0 fO N C* o in m h > .*" 4 -^-4 Ail *o *--< rM >t in cc . -4- ; - cn so O' co f~4 .^4 r~4 r*4 coO'h Csl O' >0 qo CM CM <t CO : h- CQ CO h- CCCO CQ - CD *-l <Ci CO 4 ^ ^ H H H HH . o o o o O >0 (A ip (MA VO >T <J- US J- sjr CM f\l f\t CM t\l <M (VI Al AJ Ai At (\l 222222 CO ~<f0 in o Cp HfV K* *CO CO tfl.flpN r- c- A- 2 5 1 CM CM . . * .*-4 in c m CO CO co ^-4 r4 v-4 O O 0 .0 0 #. * * < O' <- *4* in 4- ,4* *4- < >4 M- CM CM CM CM CM CM CM CM CM CM CM CM XXX XXX -j cc < UJ 2g -- 2 2O <z ce CO rtN CO C O' O' to cc ic;o io;o in ao ii\ po z to ; ; ift m < UJ X oo <0- 0 -- ro CO CO O' O' >o 'O O GO CO CO CO OC Z in in in in in < uj v- -VX DUP040013926 TABLE NO. 2 HEMATOLOGICAL VALUES FOR MALE AND FEMALE ALBINO RATSLEAD ACETATE FOR 22 MONTHS JOts'j ou CC' CV*r I * 3 i I o II 03.^0 I 2 S. . I 3 I II O V> at I< DO o III at I2 l 1 at 10 O eg '.<M " I p 1 uj _1 <O 2 .at V- o 2 SC Poo o o ouci I 0UL. Xa. st *-* o>- I fII o (l/it) 3, I: II II I o 2 St <C t CO <M .Q >fr CO *o *o *6 >p ..f!O* O *r4c*j faoo Osi* CoO oO 1 I P3 ro~4 ^ inh<\l i(-\4J*i*~4 1 XH* I 0I WZo CC ** a: -J t ,-J !1 --X h- -tCOr-4 ;mO o-*i oO' .* . rv aot- r-.00 CC co in *4- o H>Oo O Csl o ** X -<4 LO LU > X 5t tCuC *- zr fc- V- O 2X 0 0*0,00*^ r- -v o.o oo to at.a aaa CM CM CM CM <NJ (M CM CM <M CM CM CM tssi?? _ a: UJ X do -- :x 2O <Z .-i oo O' CO CO ao co iTi !A <*\-4O*O' O' CO CO CO cocp oo X tAtf> m ct XLU ?2 DUP040013927 CoC uCC I1 0.:02 i. 0 0 1 9-s 1 2S 1 11 vC>*c 11 <CC 1 c 00 0 0 (/> jz 1 .- s *<- cc VI 11 UOJ ~1 p 0 -* p 0 2 *H<-->:O0z.ac p 9p 90 -3J5 UZJ < Ui cCOuLtt CX.L K -J a<s: wU, Z>- ' O _J co st si Qf .tO .(C >c0* <c\*i oi u. > t/> 11 O 1 UJ 1 VJ NiO:r"*t4<tl <2 hX- 1 1 OI cZ I1 a < X rAvli 1z 11 C<O 1 9 <3 p P 0 cc ua. oali.: in-t us 1 <x --1 Il hU-J z O0f H 2 999 O OJH* a >< *<- UJ o -> < < 1 C/1 0 Oc11b 0 tZ<o 35 * * P *m< rO-<' 4rH> OrH' (0\J 00< CO -u*r 0 o -iU< t1 9X t~ O_J -1 t CO o 1 Z CVJ O' O -< ,f>- O X<r UJ X WCO O* a: --1 1l -J m >0 co .) m m <0 <v >0 i<n10 !Z 1 M OCO 3C *4" - -j4* 0* r-4 >$ .* * * X' sHt Hst St4 H-t St W>t O 2 u-Ju cc Ho X tn. in# O m o*-* 00 a* r^- co r*- 0 <4- st 4- -t <t st <r _J I-- <. CO UJ >OC >X-- ^*4 *H ^4 0*4 .0*4 ft-U*J- ZO zs U)UJX a. u~ u_ u- u_ u. ---<1 ca:. X CG X -2 2 <Z cc ,> 0 r-4 fsj C CO O' O'O' 4* 4* 4* 4* 4* iCnO iCnO iCnO mCO m00 <2 Ui X DUP040013928 TABLE NO. 2 HEMATOLOGICAL VALUES FOR MALE AND FEMALE ALBINO RATSLEAD ACETATE FOR 22 MONTHS 6 0 4 o> P O (V 1 cc cc k 3t 4 I> I 2U ~C z-s I I I -c v> 1 <t Ooo pP po o 4 .03 I 1 II Z it t ts> IO 2 ~*'.Q O p *- o . -* t UJ -O <O --2K I-*- 3 Ooo oO O 2 uj UJ X U- Q. H M--L >X O' O' O' tp tp . in in o *o o CO O' O' CO O' Io I Ui w I VO p >p o> m 4- m o *4* f- o <2 o p O P o o o SO x ooO o x OOP UJ CL s cl CL a oo I VO ^ m Io 1z O 0 op IM CO 4" * . 9 * 4" 4- *0 9 * p .. - CO 1/) mmps m *h m ro m .*-* io * H CM H r4 H (TI i( NCSlfNI 1o 1 i *- IV) 1z oc cc OC -j 1 -J in m m Ift hit .H co jh- * >0 -O *0 f*~ >C <3 MfOO r--* c--4 in <n m so p.^m * >0 p N in o >o 1 2? CO jfioa * ^ * o*o o j O' ~o co . 9 X r4-H* >*mo4 r-4 in4 ,4*H-mtm-i 4- 4- in * *4 .*--4 y*4 4kH- mrH 4^-*4 >-- 0:3* X O O O OOP * . . . O' O k p O' r in -* + in o * O 9 O O' 9 O' S3 H 0 f>N 4* m 4* 4- 4* -J id co UJ >x X a: *- to r KHo 2r 4 H rH ~4 *-4 iH fH H r--< rH .*^4 MU X U-U.IL u> u. u. U. U. UL X U.U. --I <k < uj X as 2 22 <2 CO O' o *-* t\i m m 4- 4-4sO *0 vO >0 p co cc cq cocos in in m in m <x UJ X cc O' o M c\| rn cn f- c- 4 4* r- 4- - C0 CO CO 30 2 m in in m m < UI X / vr* -lv. 4I*y DUP040013929 T A B L E N O . Z H E M A T O L O G IC A L V A L U E S F O R M A L E A N D F E M A L E A L B I N O R A T SLEAD AC ETATE FOR 22 MONTHS *j u scff be* I I o c I -* I I I I I a* I I cO I I Iz I <- I to J I uj < H* .Og* zz Hi cc UJ ll. X O- M . V _J I e> i iu,ae l to i t 1 |k OcO C o M p *-< O OOo Oo *--< --* ni O' fU O' O' SO CO O' i- O' ** so i< ,o o o p o I co I t l l -M a ooo o UJ CL o i to <o l z rno-b t .O'f C3 V) X Io IX I t- O' SO CHOC' H r4 r--I f\J f\J H Ii tz'1 yo CD ee-i t -i I * x CD X Wr-.H4..N1iLo --' --0.>* ^N ih*0 j C 4" in in *-t op si- si- in in 4-4 gc X u**\ in.* ot o * o* 0 4> O' CP.lv 00 4* 4* 4* 4* 4" 4^ Q O C OOO o '^0 N h* W 0s SO <0 .0 O' CD m fNj ?n rv 0 O Po Po s Q. Ql o c o o o . fO CM CM *-4 C * N ^ (M^ ^ H H f~4 W .N H mO rfvoo00<0*c%O' >0 SO O O h* >0 H >0* - 0* -tp* 4* -4* -4* try >0 4* iftCino ,o 4* 9 v*- ' in %o tn h> co o si* -4* -4* 4* st- 4* < vO Ui > X X MlUZ i-*-o zz -4 v> u j x H H ""* H H U- IL XC ILli-lL 4 oH W *S ,vH| #-4 U. U. U. -U. U. U. --i ce < UJ Xco si z <x .00 O' O M N fflfO 4 4 4 CO 00 cO CO CO co co co .co cb z IfUMfun < tu X CO O' O --l t\l fn m 4 o sf O- O' O' O' O' <o co p d o co z in m in in in <. UJ X C~ 5 DUP040013930 c- sJ O Xr at j z c 1 U0 1 23 * * r*. A. 12 ( 1C 1 i/> M c- o o o o I< X 1 1 12 V 1 >C *c fi *3Si .- .*H.O <M ~ 1 I 1 1a 1 Z** ? .< 1 aj 1 1 1< t *-- K 1 Vi i* <\J O O' ^-i O' O' CO O' .00 O' t>- . --* ^^*i .p C oO o O --i 1 O O OO 0 o ar - UJ %XJ 22 l-- < <> U"J -J < < 1m ie I2 u< X to 3C o Z o o 4 1 00 * O <.M -* fO 4 x 4* co 4 n* r*-) p-4 O3 0 UJ .2 -J 22 H< iXTX-I 1o 1X tw CO !2 uc j C -J t ---J r-- x 4> -nf\ m cu --* 4* 0 x *0 4 '*. a: t*- >o o n tX r- r- n o o <m <m fV ?K 2 .. : * * * 4- ^4* in -4- .'C >H O z :U K UJ X X v-- -J < VO u2j :a>:Hx in in o oom 'O O CO Is 0* CO >t co 4* 4* 4" 4* m cr oo m ro ,m uj z t-- '22 2X vo u j x U. UL U. U- CL UL -J Qt <? UJ a. x *r- x XD <1 2 cc 0> O AJ to CO O' O' o> 4CC 4" .CC 4" 4 CO 4 tQ 2! i\ 0 lf> V% U% UJ # / rv> *.C -y O DUP040013931 c H O' OP rv CD CC fV 1 CC X 1 .0 I 00 i P-* 1 z^ 1 !0 1 />** 1 <' 1 CO 1 oOO OO 1 1Z CO 1 *-.9 Hop ^p 1 00 .<* 1 O qC J UJ --1 C <1 0 2 ZM 'M 1-0 CO zx *pl UI pO Q M O <C Ul -i < Ui 4. pm S qt cc uj X u. 0. UL X >. O -J i0 l iua 1 00 1 o -<o m o o O' N in f* o <>- x ui 0 jr < X *4 CM 1 1 lO 1 Z*f 1< 1 CD 1 | o op O o O cc u. O CL. V) UJ Ui 3> *-J < ;i < 1 h X o o o o o 1 UJ ,0. X a. 1 00 P ^4 > Ui O -4 < < UP *- O UJ 10 1Z O< CD 00 Z'X 10 lX 1 - 4. * 4" ,0> p .-4- HHsf -- .INI fM 0 J u 0 -- 1 Op 1z op cot- *n O' oa O' *0 >o.<nr^pfnf- t X d --1 f- n- f* .r- oo n- UI I p X 1 " z 1 oa P* 4* o o a* >o m a sc . .. * X >0 V> 0 ** if f 0 z bPftf O 0 O ;* >0 to X O' O' tO O' 03 00 4- 4" >* si' * sf CQ < _l *- < 00 W> X x o:*-> UJ z >-1-- 0 tn co m en m m ZX 6 co o o v 0 .0 0 C o to r* i" o o O' CO CC CD O' in C0 fO 4- op o oo oo O Oo p p Ol Q. o A N.OlO c m (V.4H H 4f*4 jHn rO- -cNjoD nCp- in cn 00 cOo' * > .* f- h-PN^ - \J>- M 45 4" .* * ,* OVVl 4* "O 'A in if.* O O. in. O 00 IV fr~ O O' O CO 4* 4 U> 4* tf\ 4- co co to co to CO i/> UJ x U_li-tl.U-U.U_ U. IL IL u. IL U. J o zo 20.z CD P cn m o >o s' .00 i tn --I DO 4-4- 4<o>co CDCD 00 2T inm in < ID 21 OO .O' O r-l CM fC*O fc**o4A- A4-- 4fV* 00 in co co in in CO in A00n z < UJ X / r* f. -r v Or' / DUP040013932 PO tnv' sc a: I o:s i o. ec a -* TABLE NO. 2 HEMATOLOGICAL VALUES FOR MALE AND, FEMALE ALBINO RATS*LEAD ACETATE FOR 22 MONTHS o IS> M t *S I S3 II I I Jf I VI II uOu --J <O Z if Hz- Cx uj 0f UJ X u. a. if a. X >0 _J 1 o I uj K I V3 I I I IO II Z if I sO C Cp Oo -t -J .lA <\l O OO poo O >6 CM r*. iA O' f- so S> <0 O' <fNAJ fA ,iw-*4 IA p p HK 0J X I oo (P z uCO V XlOCK -- UJ z 1- f- C zz oo o fVNfV N HO .4 * isrOH (O O j*p-t*ji fO ^4 LT\ O raO o N M O,(<\ !>* (V,H co coco cor^co CO o MNO r- 4 9 .4 * 4 m H >o H tn H cm W <0 'H *$ P m o4 o 4 p4 <> p o in p r*- 4* >r m 4* sf 4* r0 cO (O rn ((i,r0 to UJ X U. U. u. u. u. IL oooco PS) O H < rt o oo w rt w(M O' p .CO O' O' >0 I*- *"4 sp jhf O p =0 Q O X Cl a o o o >t O' "sO p H Q' * * , 9 COsl *4* H4* r4-H* H in * lf> p P m *H m St* co >0 c\3 44 9 -9 . CO CO Q0 CO N 0 so m CM p P CM 9 .9 9 m*H *4--*4 miH f4H r>H6 ii-n4 A...U.\ O. . O eo CO f~ O' CM.OSf 4 Sf Sf iA 4- fA CA CA c a rAfA tLltUltU-U. -J QC < UJ .X x X 2: is z .. O' O 1-4 (V (O 44 CO CO <30 CO CO co co co cb oo 2 in in.in m in < LU X <0 P o -H CM co ro 4- 4 -4 pp Pp p co so cb co co z A IA lA iA *A< UJ S c !-v-qU DUP040013933 O' U O n-N- to to I at I O I 00 t 0 <rt !2 ^ 9 i a I V0? i <COt OO.rtOO to I- a: o z a) tti < i%uu. Osr ta/>: <r>* II *tof9* _IIJ UJ <*-< sZ ,99 i- a Ztu MbueJ. UL Xa. X m O-- >- 0 tu w on 0 --I -l 0 CM 0 0.00 .0 O' 0* ffl J> >a<a 0 to O' co foO rin< Hso ^ tu o c> aas: -*<m efiC a: VuUZ<>>Jti-.auV1<U--o--J.i -J < *aOOJa * o<U-Ji SUaCIt i tvj O UCJDi *- ZM Jiliii <0c tt<Xu~ w oC31tii11OCtztgQ<Xt.oo~0t o0a11111t tzoo X-0j 00e X hOX frE 0E1 -l<>z1_0tJH-s0z0X Ho-CoQZJ p O o O .0 00poo 0 0 SO 0 0 9Sf* JHC*l <(\\Jj .*O--'<* *r-Q< f>* h- fM Q\ ro O' M>o Ins*. o*'o ro*." ; j>h.o* SrHoF >c*"n* <<4* GHcOn*Hm4Qc*"Oo< m< I*so4.-- p0<40* iCn<OP *C4*3c*>4o* >0 *C -O tO.'OO V) tu X u_ u- u. u. u. u. *x<<2*-j. C02aUsOJ:: <i*oon40oo* .000 Qmo ^0oi0n>o ^*Qci4rno*" OOJ' pin 2U<J: C49 DUP040013934 COM' <\J * o *1 uu tC E J 9C X C 1 UD J p1 Z N. 1 1 11 QWK. O 0O 0 O 0^00 !t1 c*e* l/> i !i 2*-. 1 VI < 1O c* --11 UJ O <O -- ;Z W H- p .CO 0UJ t < uIXj x UJ u- a. K -J U. Sc .< `1 > x tu O 1 u. ,i o O CO I UJ M 1 in 2X 1 < h- t 1 uj O -<j X 41 He f I< X CV 04 1| CD a: 1 uO. Cq c 1< 1 i- sc X . 4- 1/5 UJ UJ 1 UJ X a a V- o -J c 1 to <> uh.-` 10 1X -J <o o <t 0 CO < is z> 0* o<3 .0 UJ 1o 1X 1 O _l _} 1 VO o b~ t2 0O < .0 *- XUj OC -J t X 1 --* 1 : X CO N O d< X O z u^t s-Jo X tt -< -J < V) UJ > X X o: UJ 2 , 1- O MX x moo wo OCP Qo r- ^ p r-* 45 r- r-~ o cow <Ov ^ru-o"i- rv 4 H.H OoP 0O POP o o Sf t- in 4 4> m c m <X> 0V. -O Sf \\mi 4> r> f*- >>0 ,N, q o co u' ** 30 . >9 T* mrH 4 4 4 m4 rN .^4 ,f~< Oon in in O' * * OOP m 4 4 in in 4* 4> >0 <? 43 vO <l -M* * ro cv .0 p 0 O o rvj r-4 tn cp >o t* cb r* tv op >o iv 4 0 c m OJ W (NJ r-i H O 0-0 O.Q x o Cl Cl *. in cpM4 cn m * <CnsCMM 4V3 H4)HHHO' O 4) CM r*. sf co oo O' o 4m . . . . 4 >0 Is* f'* h- n* 4> >0 4 st* U3 4 4- 4^ i4* m 4" 4" .^4 ,r4 r<f rH o P in p P p O CO 43 4> O'h* in 4 4* 4" 4" 4* 45 'O >o P *0 >0 1/5 UJ X U_ U. U- UL UL q. U-U-U.U-U-U- _IcC < UJ X CD x z r> < 3: P o .-* -*0 C CO CO cc in in in 58642 58643 MEAN 0 O' (ft fO n CO CO id in O*- CM 44 4 r-*t*- f*1 COSO 0.2 inn :ina C-- 1c 1 v>f : <* .1 a? p *h ru p *-< 1 Z tO 1 i v> < 1o u 1 UJ -I CM M J- O m IA .H t o .m wf o <o !- Z Of H- O OO Op O p <D Z X -J u. 4 tie. UJ X Ui u. a. a* -J u. X C oO crst*p> CO BO f>- CP O' f" -4* f< m o *o CO O' CO < X Ui u_ p oo M* V os t 1 1 UJ 1m co h*--* i*n* o(Spi t*f*>4 SQ f* fi\ *0 t*\ fsl <SI .H H 2: x <H- Z Ui O -J 2 < S Ai CM DC i 1 1 )a 1 -z w 1 s 1 00 l l coo o o ppp op b QC iL O u. in Ui u j hb< .< i-1* > ui U -i < D CMf SO* >0# iA ,h4 st- tn .in O -i o K> < X ui x 1 cU 1 B0 tz aa CO CC -J |l -MJ 1X CD ^ X rn -* >o cn O' 0 (\J in CM CQ CM >0 h- p* N .!* n* >4* AiCVJ CO 4- >0 * ^c4n irn*4 .(fMt ^-4 4H .'#t*4 m *0 < *-* ; j <v O 9 in ** -*< * fn* P'- Is* f>* I'hh. 0>c0<fc0sj- m <n^ sj-m^ -f^4 -l r*4 I r*H r**4 O .z tOK oo.min op (A lA. o. o, o * Ui X ,_J Q Q ,Q 0 Sp 4* in in in O BO O O' 4- lA >4 lA in do x X a: - >o o o -o p .M3 M) .MO MO 'O >0 9* UI Z ..hhO ZX i/ ui x U. U. U- U. tL U. u. u- u. u. a. li *J cc <t Ui X CD ** X X ex O' o .*-#; <n mco c^o c4o*co 4c4o* CinD iCnO iCnOiCnO mCO 2<tT LU X ce O' o --< AJ mO' O' O' j*j4*- sOf' CO .GO cp co 2 in in in in in < or. 4 ] 3 I I '-ri. DUP040013936 t X. T ; \\ .. \ A .\ _ i / i j. ? 1 T . > -^^ \^ O' . fv .Pa . i t4} *t * oo XX 1 3d b 1 o 1 oc ib 1 z*s. t i tX 1 to K 1< x O O O - :0 . i 1z to 1 *- K 1 tO <SX i c QC 1 UJ O H "H Aj CVJ o <C z *- 5T df o o ***< p l- c cd z X -j UJ < cd UU x . uu .tL a k ro ms i-4 rv * .*1 <. tL X --V O' .to p - us c- x O -J lU i u. 1 o 1 UJ H 'O fOiCO 4* <Ni O to 1 to *-h C\J 4* CM ;z x ,< H* 1 I 1 Ui O 1C -J X < 1Z 1< oOo pQ X pm PM ec o a: JUL D U to UJ UJ b-J H<< > .4* O _J < < oa *" < 1 33 1 1< 1 h- : 4 UJ X 1 to 1o \z u< X to xo 1o II <r p o o o o ja--: 2a o M h N --* US *--< * CV !\1 --< --i O UJ 1 V- o -j .O-4 f< X 1 tO 1 z- ugo c m X -J CC PM US US PM * o :c- -4* c m t*vu\ r- P- MD us *o *o UJ 1 -J X t-- rx I tc CNj O H X <ts CO >0 CM US US ,* <ipO"4 sr-i4* ^ s>i4 *r<"<s .4#**4 o z Ho &< O us* O us Q/. o: UJ X f** *4* Vfs (M US 4* ^ ^ ^ ^ cc < -J < to tu > X aC a: >UJ2 H> *-- C Csl CM PM CM CM PM H H H H H rJ ZX to UJ X M- a. u. u. u- u.- ' -j a: CO O' <? ^ CM <C UJ 30 CO .0* 0* O' X aD *- X z4" -4* 4* >4* 4* CP CO CO 00 CO Z X5 IA UV.US US tA < <z UJ DUP040013937 ;\ i oo PS cC ii ec os l uo 1 >1 1 1o I v> k 1 *t 1 CD 1 O :p o o c COON'' Ol i1 z k ; (fl O ^ H p (fl VI -< >- 1 vs < 1o oc _.1J UJ o * O z 1~- zO k 0*^0 'O o O O OG CO U JZ,X < o uj r UJ u. a. m _j < u*1".* S X O f> pNh P 0- iO I** Cp rr* CO it cn r-> t- t*- r~ k co UJ u. O V) 2X < fc- 1 1o 1 UJK 1 VI 1 J (JNJ*0M^WOH' H^ P CSJ O Pf* fsj PJ <NJ <\l --< UJ zo 1 1a ,<j .x 2 <tsVi a: O .oc u- oILL to ui at l z'a* o Oo P < 1 CD l I l< 1 H--M f UJ Xa. CL o Qo 6 o o X oo o Cl CL p *~j < <C *> at v IA 1Q 1Z o< CO V) ,3: O.J* O' *0 >0 -tfn* to O' >0 .N >0 >0 .N SJ- CM M3 O St - -*. MON c m > o H ,?~4 r~4 i-r* o* a^ O Ui IP 1X 1 H- OV -J Ho* < X 1 V) 1Z oCO^ CC -J aNOHMp^tOf\ ^JO ' * . . i>- r- k >o uS *o .ro <V PJ tv S OP *t Ppr~M3 f- O >0 M3 >0 Ui 1 -J X i-- 1x I 04 cO W X p r- .co st ito *0 tf\lA #~4 ,H *-<l H H H c m- c m >-* * MtM r--1<" t--P< *---<1 .-tM4- *(C-ll c X OK o o o o # tn Op m -* .* * Ui X -J 00 o <v iA 04 *n st ^ si* ^ st P coin co irv<v j Ki J J M M- 4- cc ,< _J h- < VI uj > x Xcct*-> UJ Z 04 04 f\J A! fy AJ H -H H r4 H H CM CM IN! M CM INI *-H r--t H H *H h- - O zz *~4 to Ui >c U. U- U. UL O- U- U. U.U. -J PC < at .X- *XP :z x <x O' O 04 CO rO ^ -4* '4',4' OcO'O'O'fl co co CO cc CO X urs (A tA crvtn < Ui X COO'Oh M CO St "4 t- r^- r- o* CO CD QO CO co x uS (A tA 1A lA < at X rro K' vv DU P040013938 / / . "* \ Ji /* 7 J / -- - \ -* \& ^ -*** * r ,X\ * it , * *! *> c\: cm i* u j , tA h~ < Of O z p -j < its J < UJ u. j VJ :z x < *- 2 UJ 0 -j X < X CM CM O CC UL O U. vo Ol LU O f-J < < H > UJ O -<1s < 00 ^< O ui O >-> O H <t X UJ 1 CM . 0 2 UJ -J C < H OO CC OC 11 OC 3t O 11 UO 3 -H 1 1O 1 V) * 11 < CD 1 11 Z -* H I to 1Q I UJ -j O _J 1 1P 1 UJ d* * to i l 1 l0 11 2K < 1 CC 1 1 1 11 < H* H *4J X t l/l 10 1X 0 1O 1X * *- 1 VO 1Z CJ 0 CC ?-* a: -J lj 1~ 1X CC OK X VO ** X -J C VO UI > x X .CC H- ~ UJ z f-- h- C 2X Li V) U_` X h Oh OC CM * eg *0 CO in 0 *N Q AA P CO IA Is- C- C- CO CO ; - co ~4 p tvj H C\i CM '*Li Q0O O O X Dl a O OO O O 0 p .1* mfON(VP p' h- 00 f>* Cp 4 IA 0 *-1 CMft CQ CO 0 O' *> <N .# ; .* ; - >o co >0 'O ^ 0 O <M AV>0 4 .**.* . . lA in 4 ; A AJ 4 *"i r--( il r H 0 0 O O ui O' . * 00-1-10 to 0- ro -1- -1- -1- -I <0 4- 0,1 OJ fSJ <M IM <M M .*--4 ir-4 >H UL U_ U. U_ U. U. O 0 O O IM fUO# p (M 0 ,--i r-i p Q m -a- 0 <v iO sO ff* if) :00 fV ro Aj iO co 0 CM CM *-* <SJ P OO Q P Cl Q. O O P O P Cc 0 t>4 fO 4 ; O u* 4 # .f . P' 4 CO <M<> CM *- NrncOfvcbc CO oP 4 fA 4 0 vO A" 'O A- >0 O CA P 4 CM O co 4 4 4 co 4 , H *--I H 0 cOooo . .# h- 't fH h O --* <0 4 4 4 4 4 CM CM CM CM CM (M H ** ! d .frl rH U-U.U-U.U.U- _1 a: < UJ X CC X Z < 2P O- m O.$ hj- iC4O- -1 to co co ob so CO 00 CO co co z in in in ifi in *? UJ ar 0 O 1 IM -I1 m -4- -4- -4 14- O O' O* (jv CO P P CO CQ 2 tn A IA 4A U2PJ DUP040013939 . t/J f-- .< cc o 2 CO :'a>J < Ltl < .2 UJ UL Q VI 2X < V~ u j 2o -J 2 < 2M Al o: a. Q u. </) UJ UJ r> h * -J < < y- > UJ u -J < < oo *-- < O uj O _J <-1 o 1** < 2til X I CM .< O X UJ --1 .cc < 1- ,o o SC CC 11 ar^c ^o I oQ G -* 1 Z> 1 1G 1 V) K i < 1X 1 1 1 1 Z fl; 1i vi c1 su r c .2 ' H- G xx UJ a: uj X u. a li. X --> G -4 1 !1 U^i.K 1^ 1 1 1 1O 1 2 9* r -x t3 i * i ** 1 UJ X 1 so 1G 2 G *4 CD tO 1G 1X 1 t- 1 to 12 OG <E.~ SC --1 1 -J 1 -- 1X CQ G at X O aim mJ C </5 IU > x 2 OC P i-UJ2 1-- h* P XX 1/5 UJ X .p c C p t\I fO cy --< fsi cp cp ir ro sb > p h* p o rt in co cO CU t<D in (M Opp 0p -J O Op GP a: hX O P 0 ro O >w *4 mH <?**4vro p^ 4- O' f'*' CM <4* oT" 06 o 00 O O' -- . * . O >o 4* tn 'O 'O H4* vO ,4H- to sHf <* irn--4 tO# mH t4HA0* O P O o O OJ ) .-i- 0 N 40U\ 4* 4" 4" 4* 4"-4* 00 CC Q' 'O 00 00 H " H H H H IL U. u. u. U.4t -J cc < UJ 2 C2O X3 <Z 4 m ^ to O' O' O' O' O' 4 4 4 4 -t CO 00 00 00 CO z m m m in in < UJ DUP040013940 jPfv O* K \ ;* v TABtE n o , 2 HEMATOLOGICAL VALUES FOR MALE AND FEMALE ALBINO RATS.LEAD ACETATE FOR 22 MONTHS x. x X% Ii Ur> C f 2 V. j * Io I CO 54 i 0 -J I Io I 1 UtoJ w I II II I o z .** <--i ft* I UJ X 1 i/> 1 .o 1 z o <t CO to 2o o 1r 1 t1 </> 12 oP CO a: i i so O ft* x O ftf :x <t oO U- > x 3: x t- *-* ID z . t2- :cX pop co *-4 <\J <V ,j- o G MOH !* IT N* |>* <o <4* *0 >o JO (N <t A ry c\* P C* P C o '5*1 O O O P ,x a. *4 in o o nD 4- m p * .* so in c sj -< to *o r-H --4 (V H H O .cO ^ CD m CM p m in iv.inp * in m o VT 00 CMA rJ N CO 0 * m it tn f>j 4* o o o <> 0 9 0 9 .. ^ h t- CO Q p tn 4" >4* *4" 4" -f cc co cc op co co n u. it a. u. a. pOO OO o O o -* o iOn At** mP om s!>oo f*O4* N> f0A3 f* ToO O PO ^O x o o o p a xa in nj o *c >-OJ <o m go p* ro co .9*4 (\i S| *"4 ^4 NO r-4 00 *--1 cv 00 *t so *t p m cr> sO in in in >o in !*-i in *-< <si m -4* * St Ap *t cO 4*-4* p O o O OP 00 h- o CO ,n~ <o 4* St 4- t * *4" dh coco coco cb co IL II It tt U. II -j cc < OJ X CD .*-! X ZO <1 2 O' o - <\j ,m ,.m o *4* i? nO st *0 4* o CmD 0in0 .i0n0 CinO CinO 5<:t UXJ 0 O' o HAT <t*n tco rs-t sf>t n'tf*' i0n0 iCnO tonp tcno CinO z < UJ X LO ; DUP040013941 o -- > j v * * ' > -/ / /. TV / -7* T A B L E N O . 2 H E M A T O L O G IC A L V A L U E S FOR M A LE AND F E M A LE A L B IN O R A TSLEAD ACETATE FOR 22 MONTHS uo tc a: oc 3: u oo - z >. o to frf -at OC OPQO O p p VO ID I u< <Q - Z W z1-*0 UJ car ULLJ.Qx. M UL I .-- >Q _i ! ti> I UJ hi I VO I i t i I l z-a .*? 1 x .X-< tii z *- *- O ZX V5 ID X fo- -tf- *4* *P` . O' eg >> *-< m in<> ^ oO 4- CO --< <*> c m <n op o o o OL O O O O o CL oo ~f r< (fj O* fO CvJ H H tn o P cc eg eg O' eg . eo ;* . f* v'C sb "O ,Q <4** co to m *** sf e% . o. oo.* o a* gs e* *4* gp *4" ^4* <4* <t CO 00 CO <x 00 U- LL u. a. U. U- eg in q > eg h Q O !*4 Q tn -- eg ^ co p->o e- vo .*o M ^>0 eg c*y*-4 e" rp PO P z CL CL O o o o o oo o ... -O* o <C Kl CO CO CO CO P- J" O' l>- CO tv tn O oo co rsj in # . * o r- o <0. -o -0 in r- co a- to . * oo men <v rft 4 o o * * *v. m in Is- ro oc em <4- ^ >4* st *4* CO CO TO CD IL U- LC U- UL UL _J cc <t 111 X CD z <2 O' o *-4 cn 4 -t s#* oo cc CO to co 2 tn tn tn m tn < . uu X O' O -4 eg rn >4- g.-J ,C* O' O' CO CO (O CO CO z in in in m uo < ' #: S' %*/ DUP040013942 TABLE NO. 2 HEMATOLOGICAL VALUES FOR MALE AND FEMALE ALBINO RATSLEAD ACETATE FOR 22 MONTHS 00 02 00 c0c Ucc oc X 1 0 o0 11 ? s. 1i ** E 1 i i i zF"* |W V) O Ui < *4 " O o2 a* zx LU cc wX u. Cl W u. X > o 0 i 1 LU W 1 1 o i <* i i t <v- *f i LU X 111 0Q Z u< CO tA zt I1 P=> .x H Pj CC >- X .o O I1 X oo ACI*1CO *X-JJ* CD OK X tL--> K X 0 o I I 0 0.0 0 H r-4 HO I'OA *'p-'OQ CM <3 *4* 'D trAo Ort ,r0ns mO tmA o ooo o 't * CC . O * O . O>*0 CO *i4 <M <N pM H'X AW- p<44* CcOr * osQ.*> .*0 r- Qv CA tA CM M*"4A.* CO CO CO CC 03 00 00 tHA A* H b Hp .0* #* # o* *--1 tHnv O ; o 0 O OOP CinM s0sf XinO ihn ^sr ion tu r-* H <c > AC UhJ- LO x *2o XX +* l/l \jj x CM CM CM C\J CM A] CM CM CM CM CM (M U tt IL a LL LL CC <J Cu X cQ za z co a o rH (M co cr> o> O' p >4- ^ M- COCO CC W 00 2 mm in IA IA < UJ X / ;S8 DUP040013943 TABLE NO. 2 HEMATOLOGICAL VALUES FOR MALE AND FEMALE ALBINO RATS. LEAD ACETATE FOR 22 MONTHS pH O' (!Ns>i UO <6 P I oc? Q III UPZ O **-s< II Il O <s> h ii c<c O O o OOO oO I it X *f. I U) _IJ oUJ co H- X0s* XX UJ uouc X uu*4.. xa w> 0 _J IO II JvJ>J 4P II 1l a X< w CO ooo-to -* O r-4 O *~4 i>np >0 ^>0 00 oo 4 h- N0 0 ,m c<) cn cn rt o O -* r-t --' i-n144404.CO f0~ co in o t'i o *0 CO WV 0 co P OP xa O O p a XOu O P P a It LCAJ i 0 <2:t co to a: 3 1o II fXr-- O tA f*.. c k ofo r>- >p 35 OH HNMM Hxt IHs- ; >* st> eo co c m * . .* 4* >* H 4cim-i *~i f\J rsj jA h H i *0 iz 0CO 0* tc -j' 1| M "J IX CA --* xO CM <J* ip co O' h 4 ; r>- ro ..co co .^O^co^pOMVf* O hc o co co r*** r- co fw CO O fce .at IT' *H lA CO NO vn ,h co <n c m f* *h u\ cnco>t .s$* *j* c%j xt --< <A V> ** X , O o O* o lA xfr CC CM CM fA Sfr CM lA tA !4" O O P O P CM * * p .* . o* o* >o *h -* r- iA sC < to u j > qc X ec >** HH* UI--J Xp :zx CM CM CM CM CM <M CM CM CM AJ CM CM CM CM CM CM CM CM CM CM CM CM CM CM to UJ X U-U-U.LLU.U_ U_ U- U. U. LLU. -J oc < UJ X CD -* X 2O <X CP Oh CM Cfl CxpA sX0f xO VXf0* OO CO CO 05 CO Z m uvin m in < UJ CO ^ H CM cn tn xt- x* fx* f-- fx-. t>- fxCO CO <00 X in m ,in ; m <c UJ X s" **' V Qv DUP040013944 O' cm 0CS O. in f oc X .! t c t 1 o 3 -i 1 zs V It t f*S t in sc 1 <' ooo c0 1 1/5 1< O' O !2 ' P -J < UJ <x Uu_J 0p <2 X UJ .O2 < XN CM C a cc u- UoV) UJ UJ 0 *- < < K> > uj u ~J < < Oa *- < O LU t 1 11 .2 1/5 1 1 oUJ -J <c *-* 2 W O UeJ X uar.x u. CL. u. X > o *4 11 o t 1 Ui/>J K 1 1 1 1o 11 < 10 ) 1 1 2D 11 xO .1 H- -* O O O -* P OO O i4n* no .oin sor icno JftfiPO O' 4" 4 4vin in >o -P O o p x a o- o oo p o oo O' CO 03 N t n c o o p in co O -1 o H< X UJ X 1 cO 12 UO CD al: -J I O' :*-* Cfi O' p CvJ r*- *h. <n, . p. o. o *n f>*. f*- h" 43 1 1X <M Po ** CM 4* O X in --< &\ nj rg c m o z H- OX ooPo *b . > . UJ X h c mo m in 4- p in cn 4- 4* 4- 4* < -J H uj *>t to x X ** iv.z i-- >-- o 2X A| tsj <\j (N CN CN CM CM CM CM <M CM CO UJ x u. U- 4- u. U. U- -i pc < in .2 03 ~'X .2 => <t 2 , P O' o co rn 4* cm 4 44 O' go pO' P0 0* a coz in in in tci io <c LU 2 r*. SO DUP040013945 Table .Ijo, 27 Hematoloflcal values for male and female albino raps. LEVEL ppm' leau/ju;,' SEX Control V M K K K PAT HO. PLATELETS per cr?n . 0UE-M0!!T:i ih t k h ; 58-381" 58-389 5.8-390 58-391 58-332 858,000 1,330.coo 1,214,000 1,224,000 986,000 Mean 1,122,000 PETIOULOO /> 1.6 1,6 OQ 1,2 1,6 10 ppm M 58-588 1,442.000 '1 U 58-589 1,372.000 M 58-590 1,026,000 M 38-591 1,232,000 fi 58-592 1,194,000 Mean 1,253,000 2.2 2.6 1,4 0,4 0.2 1.4 50 ppm M 52-688 M 58-689 K 58-690 M 58-691 K 58-692 Mean 1,142,000 926,000 784,000 1,540,000 1,100,0C>0 1,100,000 100 ppm M 58-738 1,342.000 M 58-780 1,110,000 M 56-790 1 ,086.000 M 58-791 1,100,000 M 58-792 1,490,000 Mean 1,200,000 0.6 0.2 0.2 2.0 1,6 O.9 2.0 2.0 0,2 0.8 0.1 1.0 r.si DUP040013946 &Z pto la-uJiilay 10.00 ppm M H M M M Table No. 2A - Continued > RAT NO. PLATCLETS per cairn* ONE-MONTH INTERVAL 58-388 58-889 58-890 58-891 58-892 Mean 880,000 8.10,000 1,180,000 850,000 814,000 906,900 Control F F F F F 53-488 58-I489 58-490 58-491 58-492 Mean 1,120,000 1,250,000 1,300,000 1,140,000 1,280,000 1,200.000 10 ppm F .F F :F F 58-638 58-639 58-64o 58-641 58-642 Mean 920,000 750,000 720,000 ' 520,000 1,000,000 800,000 50 ppra F F F F F 53-738 53-739 58-740 58-741 58-742 Mean 840,000 790,000 1,112.000 830,000 770,000 900,000 100 pi^m F F F F F 53-838 58-839 58-840 58-841 56-842 Mean 778,000 1,290,000 1,220,000 1,030,000 1,254,000 1,100,000 RETICUlOCyTE "7 0,4 3.8 3-8/ 8.2 9.6 5.1 0.1 1.2 0.1 0.8 1,0 0.6 0,8 1,4 1.2 2.0 1.6 1,4 0.2 1.2 O.S 0,6 1.8 0.9 0,6 .1,0 1,4 2,8 0,6 1,3 2v- O DUP040013947 LEVEL SFX ppm lead/day 1000 ppm F F F F F Table No. 2A Continued R; n o , ; k l k t s ' per.cm, ONE-MONTH I NTERVAL 58-938 56-93'1 58-9^0 ,55-9^1 58-312 1,33V**-' 1,588,00-.' 1,312,000 708,000 V-,oo; Mean 1,100,000 RETTCatcrrt'p l,fe 0.6 l.C 0.3 1,0 1,0 Control 10 ppm 14 14 M M 14 14 14 14 14 M THREE-140i<TH INTERVAL 'V 53-358 58-309 58-390 58-391 53-352 39O.OOO 696',000 306,000 l,oL,ooo 1,106,000 Mean 936,000 58-583 58-589 53-590 58-591 58-592 1,021,000 1,116,000 1,071.000 972,000 1,250,000 Mean 1,087,000 1,1, O.B 1,2 1.0 1,2 1.1 0.6 1.2 2.6 0,6 0,6 1,2 50 ppm M 53-88 M ' 58-687 M 58-600 M 58-673 14 58-672 Mean 1,031,000 ,1.186.000 1,322,0.00 1,lie,000 i,082.,in/> 1,113,000 0.1 0.2 0,2 1.0 0.6 0.5 100 ppm M 58-788 776,000 K 58-789 1,110,000 H 58-790 1,176.00' 14 58-791 1,258,000 M 58-752 1,512,000 Mean 1,166,000 1,1 0.4 0.6 1.2 0,1 0,7 :s3 DUP040013948 i .pyp-i Vi" iVa-i/in-- PKX 1000 ppja i-: V, u u .M Control F F F .F F 10 ppm F P F F F 50 ppm F F F F F 100 ppm F F F F F Table No. 2A - Continued RAT NO. . PLATELETS per own. THREE-f-iONTlI INTERVAL 58-883 58-889 58-890 58-891 58-892 - 916,000 1,030,000 1,564,000 980,000 1,106,000 Mean 1,119,000 ' 58-488 53-489 58-490 58-491 58-492 Mean t 58-638 58-639 58-640 58-641 58-642 Mean 960,000 920,000 1,032,000 864,000 1,052,000 966,000 866,000 1,128,000 1,520,000 1,438,000 1,420,000 1,274,000 58-738 58-739 58-740 58-741 58-742 Mosul 1,612,000 1,610,000 1,306,000 1,536,000 1,000,000 1,409,000 58-839 58-840 58-841 58-342 58-843 Mean 1,634,000 1,266,000 1,268,000 1, OCX), 000 1,082,000 1,250,000 RETICULOCYTE %- 1.0 1.4 2.8 ' 1.6 1.0 P,6 0.2 1,0 1.2 1.4 0.4 0.8 0.6 2,2 1-2 1.8 0.8 1-3 0,4 1.4 1.2 0.6 0.2 0,8 0.1 0.4 0,8 0.2 1,0 0.5 Wr- *3o, 4 DUP040013949 AT Table No. 2A - Continued l evel ppm lead/day SEX RAT NO* PLATELETS pei' cram. THREE -MONTH INTERVAL 1000 ppm Control F 58-933 1,184,000 F 58-939 1,120,000 F 58-9AO 1,110,000 F 58-9141 898,000 F 58-942 1,250,000 Mean 1,112,000 SIX-MONTH INTERVAL M 58-388 M 58-339 M ' 53-390 M 58-391 M 58-392 785,000 940,000 880,000 1,015,000 1,360,000 Mean 996,000 RETICULOC --------- T~ 0,8 0.6 1.0 0.2 0.2 0.6 0,8 0.4 0.1 0,6 1.4 0,7 10 ppm M M M M M 50 ppm M M M 14 M 100 ppm M ,M r V M 58-588 58-589 58-590 58-591 58-592 Me all 58-688 53-689 58-690 58-691 58-692 Mean 58-788 58-789 58-790 53-791 58-792 Mean 1,040,000 1,110,000 975,000 1,380,000 775,000 1,056,000 1,525,000 l,4it6,OO0 1,380,000 1,626,000 1,680,000 1,531,000 1,316,000 938,000 1,278,000 1,066,000 1,104,000 1,150,000 1.8 0,4 1.2 3.0 2.6 1,8 1.2 0,6 2,2 0,4 0,5 1.0 1.2 1*9 2.3 0.4 1.7 1.5 DUP040013950 -A > `s "able Ho. 2A - Continued C.FX rip.:! ,i eta/ lay 1000 pp:~ U 'M M M M Control F F F F F RAT NO PIj ATELETS per cnm. S1X-M >NTfI INTERVAL 55-888 58-889 58-890 58-891 58-892 1,174,000 804,000 994,000 1,240,000 1,226,000 Meta 1,088,000 EETlCtHOCYTE % 2.5 0.9 2,0 1.6 1.7 58-488 58-489 58-490 58-491 58-492 Mean 988,000 1,236,000 664,000 . 1,328,000 1,334,000 '1 1,110,000 1.0 1.2 0.8 0.8 0.2 0.8 10 pp.u F F F F F 50 pprs F F t F F 58-639 58-640 58-641 58-642 58-643 Meta 58-738 58-739 58-740 58-74.1 58-742 Mean 1,284,000 i,6ao,ooo 1,056,000 1,218,000 1,180,000 1,272,000 990,000 1,126,000 1,118,000 1,078,000 1,040,000 1,071,000 3*4 1.0 0.8 1,4 1,8 1,7 2.0 1.6 2,0 0,2 0.3 1,2 100 ppm F F F F F 58-839 58-840 58-841 58-842 58-843 Mean 1,244,000 1,258,000 .1,150,000 1,302,00c 1,154,000 1,222,000 1.2 1-5 0,6 0.4 2.0 1.1 r~ C f> v OO DUP040013951 Table Wo, 2A - Continued LEVEL ppm .W-ad/day SX 3.000 i>pm F F F F F BAT MO, PLATELETS per ciffiri, , SIX-MONTH INTERVAL 58-938 58-939 58-9LO 58-941 58-942 1,122,000 1,018,000 826,000 656,000 1,002,000 Mean 925,000 RETICULOC~'TE ~f 1.1 0.8 1.0 2-3 1.-4 1-3 v07i DUP040013952 LEVEL SEX PPm l&l/daj- Control M M M M M Table No. 2A - Continued RAT NO. PLATELETS per etnfl. 12-mq :j t h INTERVAL 50-388 53-389 58-396 58-391 58-392 990,000 1,066,000 1,302,000 1,092,000 932,000 MEAN 1,076,000 .10 ppta M 58-588 M 58-589 M 58-590 M 58-592 M 58-593 MEAN 792,000 1,592,000 1,110,000 870,000 1,424,000 1,158,000 JO pp:n M 58-688 M 58-689 M 58-690 M 58-691 M 53-693 MEAN' 1,09*'-, 000 1, 29*3,000 1,802,000 1,274,000 1,004,000 1,294,000 100 ppm M 58-788 M 58-789 M 58-790 M 58-791 M 50-792 MEAN 1,192,000 846,000 1,096,000 1,076,000 1,286,000 1,099,000 1000 ppm M 58-889 M 58-890 M 58-891 M 58-892 M 58-894 MEAN 1,186,000 1,038,000 1,006,000 852,000 1,092,000 1,035,000 RETICULOCYTE f. 0.8 0.6 2.1 1.9 1..3 , 1.3 1.4 1.6 ' 1.8 2.2 2.5 i-9 1.6 1.3 1.2 4.2 1.9 2.0 1.6 1.2 1.5 1.7 1-9 1.6 1.0 1.4 1,4 2.9 2.6 1.9 f' r*o v vQ DUP040013953 LEVEL SEX pjan lead/day Control F F F F F .10 ppm F F F F F 50 ppm F F F F F Table lip. 2A - Continued F; n o . ; l e t s pel* ejran* 12-MOOTH INTERVAL 58-11S8 58-18$ 58-490 58-491 58-492 996,000 806,000 1,228,00.0 1,422,000 1,116,000 MSAN 58-639 5.8-640 58-641 58-642 58-643 1,114,000 1,392,000 1,226,000; 874,000 990,000 978,000 KEAN l 58-738 58-739 58-740 58-741 58-74:2 1,092,000 1,156,000 1,020,000 1,168,000 1,246,000 1,044,000 MEAN 1,127,000 100 ppm F 58-839 F 58-840 F 58-841 F 58-843 F 58-844 MEAN 1,040,000 848,000 952,000 1,090,000 1,592,000 1,104,000 1000 ppm F 58-939 F 58-$40 F 58-941 F 58-942 F 58-944 1 MEAN' 1,324,000 784,000 1,222,000 1,194,000 1,320,000 1,169,000 PETICULOCYTE ---------- --^ 2.4 1.2 2.1 1.8 i-3 1.8 2.0 1.8 2.4 2.2 2.3 2,1 1.8 2.2 3-0 2.5 2.0 2-3 1.3 2,0 2.7 1,7 1.6 1..9 2,9 2.7 3.0 3.1 2.3 8 srJ,;Sr*S DUP040013954 LEVEL ppm lf>ad< day Control 10 ppm 50 ppm 100 ppm 1000 ppm Table No. 2A - Continued LEAD ACETATE DEX M M' M M M M M M M 'M M M M M M M M M M M M M M M M RAT HO. PLATELETS per cmm; 18 MONTHS 58-389 58-390 58-391 58-392 58-393 MEAN 58-588 58-589 58-592 58-593 58-595 MEAN 58-688 58-689 58-690 58-693 58-694 MEAN 910,000 738.000 550.000 858,000 606,000 732.000 656.000 400.000 600.000 104.000 1,078,000 568.000 50^,000 500.000 764.000 540.000 686.000 599.000 58-788 58-790 58-791 58-795 58-799 MEAN 58-889 58-890 58-891 58-89^ 58-894 MEAN 610.000 632.000 792.000 750.000 588.000 674.000 916.000 792.000 766.000 622.000 774.000 ny H a) h O RETICULOCYTE % 1.7 1.7 1.0 0.7 1.5 1.7 1.3 2.1 1.6 2.5 2.4 1.7 2.1 1.9 2.0 1.4 l.l 2.0 1.7 3*7 2-5 2.7 2.0 2-3 2.6 v iU DUP040013955 LEVEL ppm lead/day Control 10 ppm 50 ppm 100 ppm 1000 ppm Table Up. 2A - Continued LEAD ACETATE SEX HAT NO. PLATELETS per cmm. 18 MONTHS - Continued F 58-193 814,000 F 58-494 856,000 F 58-495 886,000 F 58-497 912,000 F 58-498 1,114,000 KEAN 916,000 F 58-639 884,000 58-640 854,000 F 58-641 798,000 F 58-642 710,000 F 58-643 1,198,000 KEAN 889,000 F 58-738 F 58-739 F 58-740 F 58-741 F 58-742 670,000 692,000 732=000 738,000 654,000 KEAN 697,000 F 58-839 F 58-840 F 58-841 F 58-843 F 58-844 MEAN F 58-938 F 58-939 F 58-940 F 58-941 F 58-942 198,000 936,000 672,000 876,000 928,000 722,000 746,000 910.oco 626,000 512,000 602,000 MEAN 679,000 HETICULOCYTS %........... 2-5 2.0 1.8 1.5 2.1 2.0 3.3 6.3 5-1 2.6 1-5 3.8 2-0 2.5 1.9 2.7 2-3 2-3 2.6 2-2 2-5 2.6 1.8 2.3 4.1 1.9 2.0 2.9 .2.0 2.6 DUP040013956 LEVEL ppsi lead/ iay Control 10 ppra 50 ppra 1000 ppra Table fib, 2A - Continued LEAD ACETATE s>:;< RAT *N0, PLATELETS per anew TERMINAL M 58-388 / 58-389 if 58-390 M 58-391 M 58-392 MEAN 970,000 690,000 600,000 800,000 800,000 812,000 M 58-588 M 58-589 M- 58-590 M 58-591 M 58-592 620,000 860,000 900,000 830,000 370,goo MEAN 816,000 U 58-603 a 58-689 M 58-690 M , 58-691 M , 58-6r'- 890,000 730,000 970,000 950,000 820,000 MEAN 872,000 M 58-889 M 58-891 M 58-893 M' 58-89L M 56-895 MEAN 660,000 960,000 830,000 870,000 830,000 830,000 RETICULC % 1.1 0.9 0.6 1,6 0,8 1.0 0,5 0.9 1.2 0.4 1.1 0.8 1.4 2.0 0.7 1.5 1.8 1.5 0.8 0,8 2.1 1.0 1.5 1.3 72 DUP040013957 y. Table Ho, 2A - Continued LEAD ACETATE LEVEL ' ppa lead/day Control 10 pjsn 50 ppra 1000 ppm SEX F F F F F .F F F F F F * F F F F F F F F EAT HO, TERMINAL 58-E88 58-489 58-1*90 58-491 58-1*92 HEAR 58-639 58-640 58-64,1 58-642 58-643 HEAR 58-738 58-739 58-740 58-71*1 58-742 MEAl-I 58-938 58-939 58-940 58-942 58-944 MEAN ELATflLETE per era. 940,000 1,030,COO 770,000 790,000 1,020,000 910,000 1,270.000 600,000 1,U0,00 900,000 960,000 968,000 990,000 550,000 960,000 1,120,000 820,000 968,000 180,000 860,000 540,000 720.000 900,coo 640,000 RETIC'il/jCTTE 7. 1,1 l.i 1.2 1-6 1.2 1.2 1.0 1-5 10.0 1,1 1-6 3.0 1.2 i-5 0.8 1.-.3 1.8 1-3 1,8 1.6 1.6 1.7 1.8 1-7 s' ; V-` i \> DUP040013958 Table No. 2B - Hematological values for male and female albino rats. LEAD ACETATE IEVEL ppm lead/day Control 10 50 100 1000 SEX M M M M M M ,M M M M M M M M M M M M M M M M M M M HAT NO. ONE MONTH 58-388 58-389 58-390 58-391 58-392 MEAN 58-588 58-589 58-590 58-591 58-592 MEAN -:J 58-688 58-689 58-690 58-691 58-692 , MEAN 58-788 58-789 ' 58-790 58-791 58-792 MEAN 58-888 58-889 58-890 58-891 58-892 MEAN COAGULATION TIME miri' sec. 0 h6 0 hS 0 59 '.1. 04 0 52 0 54 0 50 1 14 1 04 0' 52 0 54 0 58 1 08 1 00 0 4o 0 58 1 15 1 00 1 02 1 ol 0 43 0 58 1 06 0 58 1 03 ,1 09 1 04 1 09 0 58 1 04 DUP040013959 LEVEL ppm lead/Gay Control 10 50 100 1000 Table No* 2B - Continued LEAD ACETATE CSX EAT NO. ONE MONTH F 58-188 F 58-189 F 53-190 F 58-191 F 58-192 MEAN F F F F F \ 58-638 53-639 58-610 58-611 58-612 MEAN F 58-738 F 58-739 F 58-7I0 F 58-711 F 58-7I2 MEAN F 58-838 F 58-839 F 58-8IO F 58-611 F 58-812 MEAN F 58-938 F 58-939 F 5S-910 F 58-911 F 58-912 MEAN COAGULATION TIME min.. ' '-'sec 4 0 16 0 59 1 ll 1 10 1 12 1 01 1 06 0 15 1 02 1 16 1 12 1 01 0 12 1 01 0 57 1 05 1 13 1 00 1 18 0 59 I 06 1 01 0 .58 1- ol 1 07 1 17. 0 17 1 ll 1 15 1 08 r -jC ^ ' V* DUP040013960 LEVEL ppm lead day Control 10 ) 50 100 1000 Table No* 2B - Continued LEAD ACETATE . .SEX RAT NO. THREE MONTHS M 56-3*3 M 56-389 M 58-390 ft 58-391 M 58-392 mm * M 58-588 M 58-589 M 58-5.90 M 58-591 M 58-592 MEAN M 58-688 M 58-689 M 58-690 M 58-691 M 58-692 MEAN :M 58-788 M 58-789 M 58-790 M 58-791 M 58-792 MEAN M 58-888 M 58-889 M 58-890 M 58-891 M 58-892 MEAN COAGULATION TIME miri.. sec* i 1 11 .1 1 0 1 1 0 1 1 0 1 1 1 1 1 1 0 1 1 1 1 0 1 1 1 1 1 53 08 26 35 02 24 56 21 13 58 12 08 42 52 47 54 18 22 08 57 08 26 28 05 48 17 27 06 09 01 DUP040013961 LEVEL ppm lead/day Control 10 50 100 1000 Table No. SB - Continued IffiD ACETATE SEX RAT NO. THREE MONTHS E 58-1(88 F 58-48$ F 58-490 F 58-491 F 58-49? MEAN F 58-638 F .58-639 F 58-640 F 58-641 F 58-642 MEAN F .58-738 3? 58-739 F 58-740 F 58-741 F 58-742 MEAN F 58-839 F 58-840 F 58-841 F 58-842 F 58-843 MEAN F .58-938 P 58-939 F 58-940 F 58-941 F 58-942 MEAN COAGULATION TIME mlrj.. sec. 1 i '1 1 1 09 01 05 09 02 ,. : 1 05 1 08 0 - 50 1 19 1 30 1 24 1 06 0 48 1 09 1 00 1 14 1 18 1 05 X 19 1 06 1 11 1 13 .1 07 1 11 0 0 1 1 1 56 46 18 28 01 1 05 DUP040013962 .LEVEL ppm lead/duy Control 10 50 100 1000 Table Ho. SB - Continued LEAD ACETATE SEX BAT NO. SIX MONTHS M 58-388 M 58-389 M 58-390 M 58-391 ;m. 58-392 MEAN M 58-588 M 58-589 M 58-590 M 58-591 M, 58-592 MEAN M 58-688 M 5S-689 M 58-690 M 58-691 M 58-692 ; n M 58-783 M 58-789 M 58-790 M 58-791 M 58-792 MEAN M 58-888 M 58-889 M 58-890 M 58-8>l M 58-892 MEAN COAGULATION TIME mift.. sec. 1 05 1 15 1 23 1 28 1 35 1 21 1 h2 1 31 1 10 1 30 1 36 1 30 1 20 1 30 1 21 1 26 1 30 1 25 I 29 1 46 1 24 1 32 1 44 1 35 1 10 1 38 1 44 1 30 1 45 1 33 v-,, s DUP040013963 LEVEL ppm lead./day Control 10 50 loo 1000 Table No. SB - Continued LEAD ACETATE SEX FAT NO. COAGULATION TIME min. oec. SIX MONTHS F 56-1483 F 58-489 F 58-490 F 58-491 F 58-492 1 06 1 38 1 03 1 01 1 25 MEAN 'J 1 14 F 58-639 F 58-640 F 58-641 F 58-642 F 58-643 1 28 1 39 1 27 1 25 1 20 MEAN 1 28 F 58-738 F 58-739 F 58-740 F 58-741 F 58-742 1 36 1 35 1 38 1 29 1 24 MEAN 1 32 F 58-839 F 58-840 F 58-641 F 58-842 F 58-843 1 30 0 57 1 31 1 20 1 30 MEAN 1 14 F 58-938 F 58-939 F 58-940 F 58-941 F 58-942 .1 26 1 20 1 34 1 31 1 35 MEAN 1 29 DU P040013964 y IjXj .pp: i lead/day Control 10 50 100 1000 table No,. 2B - Continued LEAD ACETATE SEX RAT NO, 12 MONTHS M 53-388 H 58-389 M 53-390 M 58-391 M 58-392 MEM . ^ M 58-588 M 58-589 M .58-590 M 58-592 M 58-593 \ MEM M 58-68.8 M 58-689 M 58-69O M 58-691 M 58-693 KEAN M 53-788 H 53-789 M 53-790 M 58-791 M 53-792 MEM M 58-889 M 58-890 .M 58-891 M 58-892 M 58-894 MEM COAGULATION TIME bin,' sec. 1 17 ' 1 20 1 05 1 30 1 27 .1 20 1 26 0 57 1 09 1 32 i 29 1 19 1 07 1 12 1 12 1 10 1 15 1 11 1 2S 1 31 1 15 1 14 1 26 1 23 1 08 1 15 1 26 1 31 1 27 1 21 V-gVnw DUP040013965 "N NS Table No. 2B - Continued LEAD ACETATE LEVEL ppm lead/day Control 10 SEX BAT NO. 12 MONTHS F 58-1(68 f 58-A89 F 58-4so F 58-49! F 58-492 MEAN F 58-639 F 58-640 F 58-641 F 58-642 F 58-643 COAGULATION TIME min.. see, 0 52 1 05 1 21 .1 07 1 15 1 08 1 12 1 04 1 14 1 17 1 26 50 100 .MEAN F 58-B8 58-739 F 58-740 F 58-741 F 58-742 MEAN F 58-839 F 58-840 F 58-841 F 58-843 F 58-844 MEAN 1 15 1 22 1 19 1 13 i 01 1 36 1 18 1 20 1 12 0 57 1 12 1 21 1 12 1000 . F 58-939 F 58-940 F 58-941 F 58-942 F 58-944 MEAN 1 05 1 01 1 31 0 57 1 29 1 13 DUP040013966 .LEVEL ppm lead/da/ Control 10 ppm 50 ppm 100 ppm 1000 ppm Table No. 2B - Continued LEAD ACETATE SSX RAT H0> 18 MONTHS M 58-389 M 58^-390 M 58-391 M 58-392 M 58-393 MEAN M 58-588 M 58-589 M 58-592 H 58-593 M 58-595 ** MEAN M 58-688 M 56-6S9 M 58-690 58-693 .M 58-694 MEAN M 58-788 K 58-790 M 58-791 M 58-795 M 58-799 MEAN M 58-889 M 58-890 M 58-891 M 58-893 M 58-894 MEAN ` COAGULATION TIME mn. tec 1 42 1 15 1 25 1 07 1 26 1 23 1 03 0 52 0 56 1 15 0 44 . 0 58 1 16 1 50 1 35 1 56 1 31 1 38 1 32 1 .24 1 11 0 47 1 09 1 13 0 59 1 34 1 31 1 17 1 45 1 25 v04 DUP040013967 l evel ppm lead/day Control 10 ppm 50 ppm 100 ppm 1000 ppm Table Bp,. '2B - Continued LEAL ACETATE SEX RAT NO. lS MONTHS - Continued F 58-493 F 58-494 F 58-495 ,F 5.8-497 58-498 MEAN f ,58-839 F 58-640 F 58-641 F 58-642 F, 58-643 MEAN ^ F 58-738 F 58-739 F 58-740 ,F 58-741 F 1 58-742 t MEAN F 58-839 F 58-840 F 58-841 F 58-343 F 58-844 MEAN F 58-938 F 58-939 F 58-940 F 58-941 F 58-942 MEAN COAGULATION TIME min. sec 0 0 1 1 1 1 X X X 0 1 V .1 1 1 1 1 1 .1 1 1 1 1 1 1 1 1 1 1 1 57 59 08 03 13 04 00 15 32 59 08 11 46 39 49 43 58 47 31 39 16 13 20 24 44 1;: 26 30 40 31 r v vy DUP040013968 Table No, 2B - Continued. I LEAD ACETATE ' LEVEL 5ian load/day Control 10 ppm 50 ppm 1000 ppm SEX EAT NO. TERMINAL M 58-388. M 58-389 ,K 58-390 M 58-391 M 58-392 MEAN M 58-588 M 58-589 M 58-590 M 58-591 \j M 58-592 KEAN M 58-688 M 58-689 M 58-690 M ' 58-691 M 58-693 MEAN M 58-889 M 58-891 M 58-393 M 58-894 M .58-895 MEAN COAGULATION TIME min. sec 1 10 1 16 0 34 1 31 1 10 1 08 1 08 1 48 c 54 1 26 1 so 1 19 1 07 1 40 1 28 1 30 1 24 1 26 1 32 1 45 1 00 0 59 1 44 1 24 r n i VV DUP040013969 LEVEL . ppm lead/day Control ID ppm 50 ppm 1000 ppm Table Ho. 2B - Continued LEAD ACETATE SEX EAT HO. TEHtEiAL F 58-433 F 53-489 F 58-L90 F 58-Lo t . F 53-492 F F F F,, F F F F F F F. F F F F 52-839 53-640 53-641 . . 53-642 53-643 MEAL 53-733 53-739 58-74.0 53-741 53-742 FCEAH 53-953 58-959 5V;4o 53-942 58-944 iaiEi * COAnULATIc:.' TIME lain. see. 1 21 1 on 1 1 33 0 59 1- la 1 03 i 29 1 IO 1 *37 1 ' 42 1 26 1 27 1 2*S 1 '2$ 0 >c:j'Cw 1 2'' 1 20 1 43 1 X 1 48 D 45 1 5r n VV DUP040013970 TABLE NO* 3 BIOCHEMICAL VALUES FOR MALE AND FEMALE ALBIN O RATSLEAD ACETATE FOR 22 MONTHS 4O--4 O' CM csi t X9 I-- UJ </> O Xu cc *- uu .6. f*-V> <? t\ .H *-*i <\*J Qn CV m CM Sf CM CM CO o *Q--- 2? 3 * -i< < id <> r- Sf" ^ .r*- <\J '* f CM oj- CM C\l CO V) h<X 2 oUIOUX_ i od 2 .c2C IS* 2 .CD ct--c ,o e P. pt ooft z o H in c m co 4v-< CM pH f t CO CM CM o <t P 3O 00 X as iv ico co ** r-4 r^oof^f>-5occ < CO UJ > X 2; c *-- >- UJ x H- K-O Xx V3 UJ X ~J cc < LLf x ca --X Z3 <t 2 co co co co co co X X X X XX co ^xn mD CO' crO' O' O' co coco co co oo cbco co co z u*\ tnuS tn in < ui X / c r, ; DUP040013971 TABLE NO. 3 BIOCHEMICAL VALUES FOR MALE AND FEMALE ALBINO RATSLEAD ACETATE FOR 22 MONTHS 50 5 0 0 5 0 P a> N csi .# . . .:X * K I-- UJ l/l 6 XO C UJ a h.w tv fsJ qo eg st <<v .* tfi sJ- eg m| i--I r~4 rH Oven cc .-< f>- ru % ; ** riM-< N_4 --* iHn rg ro *4* V) 0:hQ.*2-? '3 *J < < M </> t o V) U(- cc ; W <> tNJ *-4 CM .-* f*> C\l 0<V^*-*<M^ <M tNJ Ai C<S fA fM .z X CD O X X CL O o o Oq N a. . in.NH cp in O O *-4 C\J .W r*7* *"* X a. P Cl . : . in ro in i>* O' cp r4 CnJ ^4 M sf: XO< ** 3O V> X CO lA LA f*i H f> O' o ^ CO flQ SO IA (flh 03 ^ o f> N CO N ,00 CO < V) UJ > I x ar *- - o j e H H* O 2X M UI X --I <x ? UJ z < 2: m nl <*> M <<1 XX X S2 rO 4- in O D* O' O' O* O' O' mm in in in CO CO CO CO CO tz m m m m m n<st s to rntfl co i 4o n0*s <5 O*C vO vO 00 CO3 CO Cp 2? in mm m m < iii r~ n-j DUP040013972 TABLE NO. 3 BIOCHEMICAL VALUES FOR MALE AND FEMALE A LB IN O RATS.LEAD ACETATE FOR 22 MONTHS O' cm CM Xw UJ tO oXo cc * + M- CL V) >p st 0' <x c ^ ' . . m v <m <M rf* cn WjQh o cp in 0 00 * CM CM CM CM t<\ CM >J- </> Oa '*--* z o *<4 *< M* *-.P0 ^ oc M N m rt CVj :(N1 co sf- c m 4- in cn CM CM cn m fO t/y a. z i ,P o 1/1 U. I x X Cl CL :CL z 3 cc o Q. o -0 *n o O , in co *0 oo in CO ao --J vO o r"4 l 1 CM --< ** * n4 O p wO ino'f' o ON * O' co o 00 O *~4 r-4 *-4 CM h aL <K O3l/) O* >t h IA vO ifi O cd co t- f-- f-- ob *- co in >J* co O' co cp K r- <V) ui > X MX UO'/HZ* H- H-.O zz in qj x <ttu X 2< 32 rn m m cn m xxx XXX m <j- in O fO' O' O' O' O' l>* :1s* 03 co co co oo z in *J?\ in n n L N/ 3 DUP040013973 TABLE NO. 3 BIOCHEMICAL VALUES FOR MALE AND FEMALE ALBINO RATSLEAD ACETATE FOR 22 MONTHS O 4 0Ws eg x vS Xh'iiv)* C X <-> CC *-- UJ . ' cv <\j is\ in eg m CL H* l/) H M H H WH gj- v) aOu - -J < < 56 IV--) I-- *-* CL'Z I => :l<> U. at . z x CO o X o a: .V*** o: o o o. o c Z o rM g- iH rH CC eg eg eg eg ^ eg a at < <j . 1=/>1 ;cS? in m in P m 4f- r- j>- so r~ n- <*/> tsuc > at ti- uj z *- b- O zz t/> UJ X -4 Q < uj X xCD 2p <.2 O *0 sD *o >0 re, m o r- 0c*o Om' Om' Oc'e 0res oo co cp co co 2 in in in tn uv< UJ X J rf'Q V Vv DUP040013974 TABLE NO. 3 BIOCHEMICAL VALUES FOR MALE AND FEMALE ALBINO RATSLEAD ACETATE FOR 22 MONTHS Vi M t fXr-- LU </> CQC XU CL h- ^ <v ^ c m <c k rr fv <V C Jfsi Cp .CA C lA ift <M so >* cSx rv* rA rH -4 rM Sf CO O H* fD U< < 54 J/J h- .*-> QI. 23 C0O 0. pIc 2 p* CO o ; q. tn p U o O ^ :G- cl .#' *. Cl C ^ O o in *V . * M p' O CO CO h .00 '<>** C5^w' o C\I (\J CO ^4 Cvj O tA pc <0 3 0 CO X (V Ntn r*. F- t"- ^ fs_ co f>- 0<M -sp f>* >>o0 cvp .-* r^ -J u j >< CxO M UJ z H h* O Z CO UJ X -j a: < UJ X-* x5G z3 <z s OO'O'O'O'O x X X -X X i O' O' O' CVCT* tTv lA VfV UVUTV i0n0 t5A0 m00 uCOrif<N0 X< UJ X <iO S5 'O "0^0 'O. Z Z ZZS cn tA xo f>- *0O' O' O' O' O' S3 o -s -o . 00 COOO 00 00 Z trv ifiiA tfS th <t UJ y y on V v/.U DUP040013975 TABLE NO. 3 BIOCHEMICAL VALUES FOR MALE AND FEMALE ALBINO RATSLEAD ACETATE FOR 22 MONTHS .V f\i fSJ - UJ 1/) XU M UJ J-- oo O (A O ?>0 in in i(<n1jiOn*>4#- <.#~4 <0 m m co .< rn 4- .... s- in H H --4 H H H sA a h -* ,-J < <X Hr QI . oOo oIr x r> <o o X 2 CL a. O o* O* m e* n.* :O0 co ifr-\1f ap fH cn --4 O' o> n4 x a. d. o o* o o m* c w co co co 'p in r*~ H H H ,H ,H H a: o< . 3O WDS 'O >p ro O' P O -O "O >o <o Osp' AHOp ^sO O<)' r(S-i o05 <1 LO UJ > X .>SWw1o :-z0h - .z z iA lil X -4 GC < UJ X CC 3E 2< O Z o o O o >o o z zz z zz (<> it id yQ O' O' O' O' O' inCO os CO co 2 y\ ; .n < ai sO 'O 'O 'C nO >o . z z z s.? s <f m %o n .O' O' -O' O' O' CC CO 00 CO CO in iCnO CO w m iCnO <Z UJ f* v o v 1 DUP040013976 TABLE NO. 3 BIOCHEMICAL VALUES FOR MALE AND FEMALE ALBINO RATSLEAD ACETATE FOR 22 MONTHS O' CCNsj *s X-- u j cO* exu U> CL -J* CO O H* o. ^2: -j <1 <^ -U> 0 t-4 >}* ssjtsi c<4i 0 a2 oC1O li_ aIC 3* 2 53 cc .0 X :C OhC*T 2 C u a: o< ^ 2)0 co X < CO UJ > X :X X I*-* Oi 2 - I- O 2X CO UJ X --I X < UJ X CD ^X 2< 3Z "O nO ^ *0 >0 ^0 XXX X XX ^>0 fr>*-a|So fO**' .o3) 03 coac qo CO 2 U1 V rho yviL DUP040013977 *Q*i*4 (aM> OJ X !-* UJ to OxU a: f-- ui C. h- i/% to K> <St cC P2 *-* P < UJ -J < X Ui IL \A ax z *- <z o UJ < CM X O* a: x oo LL U. oo ui UJ H* p< -J H> < ui >o < <t tA O *CL .w 2 3 j< <z >-i O r-- s*' tn tf' . t~ -< *~4 oo <) m .-i cO --< CM r-4 --< -4 lA sf -O >0 CC 'O .!* HH K > s3 fn *.<* ,C\j CM CM ** * CM CM */> H* .i** *-+ a2 co o tnu. i a: ,Z 2> CP U se X CL li. o X Xa Cl a CL Oo in ,X a. Ou o o o < o< -* UJ .X -1 UJ X o c. <t O => o wi: CO i m -J <t l/l .* o IU > x X a: i~ -i ou h h* O UJ 2? J CO < H O0 UJ x sQ n0 >o ^ <5 >0 i e s 2: 2:2 sO %P v0 %o tSS Z sO >0 *0 vp >0 ; O sQ ^C \Q *0 >0 >0 z S ZZ X -j a: < UJ X <a -* X ZP <Z CO O'* O csi c nj <v m co *& ->C >6 <C >c CO CO CO CO CO X in in in in in < .r- co O' >-- cm cm cm m h- 00 cp rco- fc>o* z in in m n < til r- O' o h c m c m c m m ni <co cO co cc co co oo ab cc co 2: in tn tfun < Of n 0'Oh cM c m c m co r<i cr O' 0s O' O' C^CXf;fi CCCC in m z 3* ** fo ro *4- ,3- I-- V) r- -- -< #-t.p-4 4" O 3 CL z-* 3 -J < <X v> Q. 2! I3 tOf>UL a1: :C3zOO X 3a: Zoo O,#' >c ^* to to to.* r* tHn *O-4' .*H4 fC*OI f>H0 a: o<**4 30 WX *4" cb O -i Cr* <4* O' co it* f*\ *o O' Ul<> v.x> X*- U>X--J *zo- Z U} to X -j ac < UJ X ap --zr X3 <x CM .CM CM CM CM CM X XX X XX *- CM *4- U% sO 'O >O nO *o ao co cp co co Z to to to to lfV<t UJ X rtyoSi, DUP040013979 cm A* * i .. - w </3 O CC a--: vU>J a. t- vi O <M .p in O' t- * at at at KlWrt Is#- IT! at W O*W < oi <O VH) O. ** oz ' ? zb -J < < *: tu *yj u. iA aZ x t- :Z ttiol -1 < fM Znj a: cc Uc.UaL VU)M11*1 3< < ai >o _> <o <aQi ZUJ --J I o0-4 03 1 Cfl O X CO t- -f CL Z 1o oL0 CL 1 - CC Z' C3D O X <oc w O3 O v> x C to u j ;> X XM<W*>2rhl-O XaCL. P l>- |a*- .CM C*M4 >4* r>--6^ rOo.' o*-.< ot*n9* rW H at r-4< in 4ro4 oH c m 4* HCM (OH Hr< sOJ CM CM f\| CM CM X CaL, in O M(.f*i>P1.-' '\i o >b .0 r*, CH o (A M3 >0 tf> sf O' co Sf CO *-i (Si HCV c m csi <m c m c m <y CD < v>m x IZ Z:Z * XXX XXX --i q : < Ul z aa -*z Z3 <Z <NJ CO at IA aO Cv (M OJ Cal'.CNJ *0 CD *0 CO *0 *0 'O CO CO Z in in m in in < LU W(n .<t in >o <M OM <\l CM CM c- r-r- i-* r- cp co.co ro co z in in in ih m <t LU X 5 DUP040013980 TABLE NO. 3 ~ BIOCH6MICAL VALUES FOR HALE AND FEMALE ALBINO RATS, LEAD ACETATE FOR 2 2 MONTHS PPM G> e0g0 Si .X . y~ l u co h- ; 5 ^ c ^ *- e* co ro pvco Qcc X <u-r> .Q- H L/> m m cn <4* get cn rH H H H -4.1 W* N* *t c-o m fH H H H rM 4- </> C I- CL .*: ,2: X -J < <X CO a 2: I& OCO CIL cc z a z Q. ^ r-M O on Z5 * .# . * CO O o e- r* eg ,* r-* gp X ,o . .*4 >4 '*4 4 rH H .4--4 p- <\J 0 O' eg o Q fO 6 ^ o O' >o O --f *!-l r"4 4 p H r-4 $ <^ o3 O CO tA O"4 oHj O' eHg ,rM H P- O' -* f^ eg co O' o- o 00 -r-4O' < C/l 10 > X X o h *-W2 i-- -- a 2X CO Ul X --i oc C Ul X CO *-*X 2 Z3 --4 X XX X XX eg eg eg eg eg eg X COCCCCQO X 0CO cp co Z in m n in in U<l X* Z X .X -.X x x in eg cn o eg eg eg o j eg O' O' O' O' .O' CO bo CO GO X 2 in in in in in <i Ul f-rcO DUP040013981 TABLE NO. 3 BIOCHEMICAL VALUES FOR MALE AND FEMALE ALBINO RATSLEAD ACETATE FOR 22 MONTHS 8 8 5 O' Of\J x. ts 1-- U? 00 au cac. h - u j 00 O H* CL *-* 2 -i -<t CNJ st c\j CO H H H^CVJ 00 a1- ^^3 ot/) Ui or - 2 03 O 2 O yo-r oa2 <oor * g> to x x< CO UJ > si or h * bP~- UI-J zo z sc co in X -<j or UJ X - X z rj <2 H W W CS fNJ <V <M CM <M iH --< #-< --< --< rH XXX r* O * f\J fO *0 *0 st >fr <4* tsOt m S3 sr. CO CO 00 00 CO x m ur\iA UJ 3: DUP040013982 TABLE NO* 3 BIOCHEMICAL VALUES FOR MALE AND FEMALE ALBINO RATSLEAD ACETATE FOR 22 MONTHS COsJ' tv i x* h -u j i/> a xo ar *-- u j a. h- V> >* i/l a h- Ol *--* St 93 -J < <X vo h" az oi ^ u. I at CM 00 >$00 C0<t : * ' * . t-inj *0 iiO O ''O >C c m -cv q <n c m SI 2 -3 . c> 13 X X 0- CL P * 4 Xa a o in ' $ at 13 Z> 13 v>X < CO U| >x *X- uaj:*2~ HHO zx .*<--M< (\J C\J H<\| CM <s(i fH\l <--NJ* <#r\4J >C*V<J fr\4* O#-J4 i/>u j x xxxxiz x xx xxx -J cc <t.Uj N fO 't IA >0 <\j fO < in '& X CD CM CM CSJ <\l <\J cm cm cm cm { Z " X3 <2; 'cOoc>0poM3o* ,f*lo>a6oz if\iruA(Ain< h'- f"1- h- fuCS0 *CnO ACnO t0n0 i0n0 z< itt Ui XX 8r V v DUP040013983 O' <<N\i # * TABLE NO. 3 BIOCHEMICAL VALUES FOR MALE AND FEMALE A LB IN O RATSLEAD ACETATE FOR 22 MONTHS -PT UNITS x H- UJ </S O X-.U ece. t~ amt -t VJ O H- ,o. -1 .< < a cn sO co >o fn O g *N "* "* >o <M <v it X X C MlUZ f-- H- O 2X cotux -1 QC <t aj X CD *- r 2 => <2 <V CM CM CM CM 04 #- H H H *-< CM CM OI 04 04 M *~l HH H HH 2XX 2 XX c m co >4- in o CM CM CM CM CM co co oo X cd GO 3? GO CO QD 2 in u% to in in < UJ x XXX X 2 X ; ro in o CM (M Psl <M OJ CP O O' O' O' 00 CO CO 00 CO 2 in m in sn in < iu X rI i 9 DUP040013984 TABLE NO. 3 BIOCHEMICAL VALUES FOR MALE AND FEMALE ALBINO RATS.LEAD ACETATE FOR 22 MONTHS &feKsii iX-- UJLO P >0 O ^ *-4 Caor X h- ooj oo .<*> .-#-! -**<*M {\ .rH |H H -0 da. h** 2: d w< ; csj ,cr cb .r-i csi H H Q H H >H oo ai dz o to U_ i CC z a z o of P tA O , us m .* .< 2O >0 4* ~4 O CO i\M\j H HfO U <x a* o dto OX ro- m<veoo b* '*0h o at <> txo Ztau: iz-- o Z VOUlX --I CC < iu -- xco Z3 <Z CM c\J Ni (\l NN Rl WlM (M (M M a za zt m >1- o c- o' wo> m^mO' mcr o> m Z in in w <t UJ z X 0- 0 DU P040013985 -C O' <eNg -,-JL. h ui v9i d<X - u UJ fl. H* {/) i/i O I- CL *- *-:d -<j < co m r- rg as w ^ (V fvj ^ h h h .Hh h fOlrt *-4 .(A ,<M* *H H* H H4 H in <o u> .3- Np rg.* # hn ^c#vni t>* O>'co.* .o O. w #~i * CM <M (VJ T A B It NO. 3 BIOCHEMICAL VALUES FOR MALE AND FEMALE ALBINO RATSLEAD ACETATE FOR 22 MONTHS CL 2 s o CO u. I CC tZZo> M o. z :CQ:aLc. Oo ' ,|* rOl H H H O"4' .Sr*t4* MS Xa. A. IOA O O o O -4* .0 0 .0 0 0 Wst ,*<Mtt^\i H# x*YftHf\ oc <o v3> Oa; ro O' O' *-< >o 03 rt(MO> O m <toob oo> <v O.tf- cv < to tu > x XoK M 04Z K !K O Z2 to tu x -ic* < UJ z: c q * * Z Z -3 - z CMOdCMAJfMAi CM CM CM CM CM CsJ sc -i z , <0 m o 1*- O' CT O' O' O' 0s IA in to to IA co co cb oo co 2 m thin m in < UJ z CM CM M CM <M*M CM eg CM fsl CM 04 > CO O' O 4o O' o' p o >0 *0 Is* Is" co CO CO CO CO 2 in m in m in < LU X DUP040013986 TABLE NO. 3 BIOCHEMICAL VALUES FOR MALE AND FEMALE ALBINO RATSLEAD ACETATE FOR 22 MONTHS 0 5 0 0 3 O' rv tv V ( ^I m i/i DOC >- O111 a t-w ac o > ** c m .5-. ry rvj rvi 4* VI 3 Ha. *-? . '3 XL -<J ^3t <* o* <vr~ it * *H "* .04 <H 1H/5+-- a:2 I3 ci) l/5 U. I cc K 2; 3 50 O Q. Q O 0 c, r-4 >0 <M Sf CO 45 --* H (V OOat f 3 <jj </> x m'OmHrOsj rO-* COM C^M rM H H H H <c1/5 in :> X a; a: h :i-i Ul ,Z 1-- H O ZX LOUJX C-J LCU X CP - X Z< z3 o j in i c m c m c m nj CsJ Pvl C\| CVJ <\f CM X XX X XX cc O'Q- 04 m O' O'O O O 50 COO* 9* O' iCnO CinOcino mco <COn z< UJ X / 122 DUP040013987 o . ""I O' CM <Sl 3 X *- U P OXO GC -< UJ ak w O rsi >o .h oc 1--4 ro cM cO m *4 H H H rr* --4 CO >< ce 0 z *-- cc .j < Ui ;-4 < X Ui u. co ox as*<2 O Ui ,3E -i < <M s CM a: ac 0O u. a. V> Ui Ui H* O >SJ < <0 O-* U*J XUi 'X 0 a*--* CO i CO O X uj .i CQ < *4- cO O *Cl Z *0 < jZ ec <0 CS| /-< <0 O' HHH (V (Mh </> .*h* - e 13 O VO U. i a: H Z' 3 * as 0 as -J O CC H- C. in;in 0 O 'fr* Z ir\ 'O O' ifi t*O - .H H H *--4 Al H U a < 0. 3 V)X 0 h j ^p co 00 ro O' co co n- h* co ,_i < to UJ > X X Ua.:I t2I--- 0 ZX tm* MlU X m m ra tn cn in U. U. U. II U.U. l ,-j ac < Ui .2: CO <z c<; ? O' <J> O' O' O' S' <t" ^ t 4' CO <X> 00 CO CO Z in min in m -4 tu Tr / ' '# \s 1 j i 1 | :;i 1 if 1 "i .! i i 1 ; } | '! j l :j 3 DUP040013988 P04 IT S 2 1 1 5 1 2 ** L -3 ' 'N,. - *. * 1 / /" l i-^v" ** '***' '' * * '* '* -t* * * , */ 4 ***' \ .m '' .- * ... .O .. f0ss. re is X . hUi(/> O XO # CL? a >- v. M CO Csl Sf\ ry <Ss eg h m fg pH H p- pH p_( ,*H o. m. cM .< O ** 0 >* * eg .cv nj <n eg ni pH H pH pH *H H : */> 1-r < X p ^ cp H p N 0^ ; , *o. <,** .<) ^ . -it to cv m (M cn c m .P-4 rc ~j < -n < Jsc. < uj -p # < X U4 U- CO 3X *Z H< ZT o UJ X < f\l 2E eg VJ 1- a. x 13 P v> u 1 a: cc ac ,c o LL CL vU>i cy *-- 3< -H < HUJ- > v> < -J <Q o< *h Ui X -J UJ X oC*-* CD z *? 3* Xa. Ou O ip p O in w * CL a p in in * c. c >o. .CD 0 90 O' h <^i o M in *0 tn in to in X o H .H N <> H fvj 0 H pH pH pH pH pH pH in a: < 3* 0 30 VI X in ^ co in in eh* cji r- Is- t -- ff *- r*. oo oo in O CO CO pH r>- r*- .co I CO 3 < CO UJ > X o X CC *~ 2 mu j z 1-- H- O UJ j Xx CQ .H<* wiux * f co co m co m UU.U.U.LLU. 3 3 3 tn <n co U.ILU. IL IL U- -Jet: < Uj X3 CD >t JA O N ^ >* z? <t sf nO 'O'O -vO ro >t r- f>* r- *i4no". est-* \.X <Xt 3X 00 in Gp m CO m (O m CQ m Z< UI CO CO CO CO 03 2 m in m m m< UJ XX Zk DUP040013989 o CM h .fi-' TABLE NO. 3 BIOCHEMICAL VALUES FOR MALE ANO FEMALE ALBINO RATS,LEAD ACETATE FOR 22 MONTHS PPM 0 PPM HoqXcaH:IUVoJ.1 a. h- i/3 00 ~O --< (M LC\ ... ... v ro si- v <v ro o.c.>.J-O' o. tv frt sf- tv m V- VI O ba . 2: s_ cJ* 3 <r < s*: -.1 .*!. f" a>. >-< so to W <V <V f*\ XV in sj- --< o o o .l r-*'< l\.J* I1'1I C\J I"1, VI a1. 2 3 V) u. ' 2* 3 C0 Ci -x O^.iAOpcv Q in 0s fCj m co so O .H h M H *- tn Q O 0 M> sf . * 4 - O c m m in co so rO CM H <H *-* 4 r-* oc <N o .3 0. COST 4* ^ <4* f- >6 co op O' co 00 cq CO if CO co iv co <0 <t v uxi >a: 1x-- *-* ttl z. t-- H* .0 .Z X -J a: < UJ X CO *-x zp <z co cn cn c p ra fO IL IL U. UL ILIL sf m |v co O' sf Sf >f CC CD CO CO .CO 00 CO CO 00 CO X irvirvtn in in < ui X ro cn rP rP fO cp u. u. u_ u. u. a. I cn-ftnof 4* sf >f sf >f O* O' /O' O' O' CO co CO cp CO 2: ift uun uvm < ui X -i ICS DUP04001399G TABLE NO. 3 BIOCHEMICAL VALUES FOR MALE AND FEMALE ALBIN O RATSLEAD ACETATE FOR 22 MONTHS X* I-- MJ t/> OOf X*-* UQJ CL H OO c m u-\ M* co co , > CO <t >* </> O Ql . Zf M -J < <X az i ooo a. i a: -4 M Z Z5 * oac O O p* * SO COO in co oo co *-i co h" H H CM H O QC <.K O O 00 ar *4" -co <Ni O <3p co>- r- co d? < 00 tiu a> XVm- UH-IQZ ZX V0 LU X -i a: a a> s: z<t 2zJ z=> >o * 'O 'O -o o u. U. U. U. n il. co -*fr -O f'- O' O' O' O' O' st- sr st- 4" co 00 CO op 00 3Z tn wvm *nifid tit X o DUP040013991 ' -/ 0* CV rg IS X , I- ttJ V> OXo PC ,*Ju 0. t-- \n tfWMQIsjfflrt * . * IN/ CO >0 IA O conooin , . >o in n C sf <4* in VO < cc o 2 s -J < Ui J < X UJ u. VO O2: x *- <2 o wX < CM X nj ec.cc QO U. U. l/> UJ UI h- 3 -< ) K < UJ >o < -J <o o< UJ X -J UJ X u 0--i C 1 (O o 2 CD 4" 1/1 o - Pl .H* X 3 sc _J < 4 54 1/J .1M- OIl 2 3 O {/) u. * z .5 to o X 2 PL o tn m us p *-i Q. in >o *0 O' e pO rJ r*i *-4 ~4 fH *-4 r~& PC e> . oo t/) X --* t-tf-- f>* fM.fO 0 CO PO Bp 00 CO < on Mu2j >tcUc VX^K H- O . Z nO >0 "O 'O 4) a in OoO m im Ou O' -* eb co c* o o _tn in in o ** m > h- .N .O' cp i>-n- >0 O >0 xO >6 VO ULI X U.U.U.ILLLU. LL 1L U~ U- tL li. -i: < ui X-< 2E 2< 23 r* oo 0sf 4<*K4*K>)t40- co CD co co go z in m in in in < UJ 2 m4* *g1-* Is- f> CO CD in in ; *o c* sft' 'th*t> f>* CO dD co 2 inm in.< UJ 2 / i i-k WM* Mitt tttteai DUP040013992 Biiffriitf.iifiiini tiniPifflir aniiaiiVB TAB' E NO* 3 BIOCHEMICAL VALUES FOR MALE AND FEMALE ALBIN O RATS.LEAD ACETATE FOR 22 MONTHS TOV' Cs3 V X fXr- 0* to O X& Oat. H---.ul/.l O lA Osl <M <35 UN sf >t si* ^ <C *** si* "t r>4 * * < .*-4 .wM H <4- l O C^ -_J< < ^ /> tc/S1 LL oif 2 x> 2 0 X X 2: a a Ol a o o 00OOOS in oo co in co o f~4 *-< >*^ ,f^4 #-- oo p m* o* o .* . p O' -* 00 C0 >O CO .>C f>J H rH H H r*t t s<c *V IS .. VX>I VX? H.oom^o o to r- r* g) sp ro --`r- I'' --i -o <> to <t v> tti > X X of >~ .UJ Z H- -- O '2S V5 111 >0 -J0f < UJ X at r-x Z3 <2 >0 ^0*0 *0 *0 *Q U. U- U. U- U- U. >t lA 0 C1 4- *$ *4" *4' sfr CO CO 00 CO CO CO C0O0 CcoO z tA JMA lA lA < UJ X o >o o o -o 0 U. U. U. U. U. ti ro in ,> f'(*J > i(Oj>" -(JJ-\ Q-l>" O<j"\ co c d co co co 2: ; ; in tn in < UJ x j i * 1 ZB DUP040013993 o o r\! CS) X K*U)M <3 X O or j a co <t <f oO or O *- o Z CL -- ..z a *? . , . N (\j H,fvj CO -J < < 2 at u. QX 2 H<2.0 -UJIX < <v 3; c m PC pC QO u. U- i/3 Ui Ui H- 0< -J H< UJ >o <1 *<45 Q Ut-* U<j .-4 uri U 5 <0 1 V) cto>a. 1 or w z z> ee C x O Of X 0 u or s* M O* 3O CO X <t v> D UJ > X 111 2 +-1- a zx co < 00 OU X O O -O O >O ; O UMi. u. U. u. u. -<J Uori X CD *-*X ZZ I z cr\ o co p> N NN N 10 in m in in co co co co co H % ifi in m in <t ui X HU * "CS DUP040013994 O' fM N X h* UJ tA 00oc. XH--* 0(tu/) to H < sf* l/> c O .CL --. z t> in f>- sr -* sj* . * . . CM CMCM CM <M * .* 9*4 r-4CM CM .*-rf tA fS] INIHr< H .lA o CM iO CM 4A CM 9*4 9*4 *><. 9*4 ^ CM OvtA >4- f^, * csl f-- > -< CM *-* .as X ~J-<e -J < X < UJ J z co H* v> &z X <z Q UJ X o. z ID o 00 UL I a: < (V X <M X Cl oo . St? X X CL a. U. UL z Q_ a a. p a a O0 UJ as o o . UJ >-- Xo o p -> < in H h <t UJ >o < x a ?: X-ua:j -H* z H- H- O UJ 2 X -j as < CO UJ x >0 >0 ^0 v0 <) U. UL tL U. VL vO >0 M3 M3 sO o IL U. U.U. U. U. <o xQ o .4) .%o 11 IL U. U. U. UL iO xD >0 >D ; O >0 1iLL LL U. U. U. U. --i ec <JLU X CC X 2 Z5 <z CO O' O H n - p- co co >ooo >b ao co co co z m m m in < 11J X N O O' O H N P- P* tf) CO N P* N ,N t>O O CD CO CO 2 in m in in m < Xu X N CO O' O tC-O fco Pco do co CO co 00 CO CO CO CO z in tn in in in < to X p- CO 0VO r* N O' CO in CO lA CO .CD CO loin m Z < UJ 1.10 >*ii^fifriairwiiirtr imirtf Hi DUP040013995 TABLE NO. 3 BIOCHEMICAL VALUES FOR MALE AND FEMALE ALBINO RATSLEAD ACETATE FOR 22 MONTHS ojCM <v x H- UJ V> Q 3T U pC >- UJ A- I-- to o 0s c m m >o m ro -4* *fr in ro >* <o O6- fc*Z- < to az io too a. l C z 3 mo X o at :Cp . ^ c m cv in .h* ' .* . .* n-m m .f*- in e> r-4 r-f *4 * 1 o C<C W o i0D0 2ol o co m <> in O'O'OQfnp <t 00 Ui > X X cc H UJ z H- H* O .2 X oO l u X < UJ X CD *" ' X 2 tD <Z CM rsj fy (VNfV tL LULL UL tL U. O .** ^ >o c>mom'C vb m m in m in 00 CO 9 CO CO 2 m m mm in < x matrrilrrffiraTfiMifiiiiriwf rnifimnintfnm inmiii iatti - * i DUP040013996 3 >*< O' CM CM X* UJ oo Ooc .X UtJp 0L H O< W <Q UM U<J X -i UJ i u o SaO.f '0H*-0** e -,3 -<j <St (h/*) H v* a1 Z 3 <<4/>> aI. M Z aX. in m.i> m --t t\j a. Ifl O' N to I'' H 3 Cl .* .* .* a. CO o X OH 0 O' O tv tn o IA cv sr <M *? otn <x. <t 8* 3 . 033 OX O' *H o "* V- O' r--i r--4 ^4 t 3 0 Q O' O <J0 sO <A 00 03 r-l O --< 4-< O i oo uj > x Z JXl--0IVU- KO2 lu z t CO < wvux --1 oc <t UJ zse - X z< oz tv (V tv cv tv tv >1 ILU. U.IL 4. CM CO <4* ur\ *0 A- r>- n- n n * *C *0 *6 *0 >0 cp co :p cc cp z IA UMA U\ lA < UJ X. t\i tv tv tv *v tv U. LL u. U-tLU- :<M CO ^ JA >0 A* is. fhw~ Af--"- P A- ; t- Cin0 tCnO CinO CinO Ctn0 X< UJ X tnrtwwwririrnt- '"jlimirrr"`*,,u"lllil^^ 1 I DUP040013997 TABLE NO. 3 BIOCHEMICAL VALUES FOR MALE AND FEMALE ALBINO RATSLEAD ACETATE FOR 22 MONTHS PPM 6 <OM' CM fX-- Hi V) 0tr X*^ ,0u j a. >-- uo cc co o^ so .# <v in M" <4* m| .|-*4 r-i W ,--4 r-4 O' co 4* is- <r> d .* ro cn 4* 4* 4* 4" H -r< W4W4 4CD* Ics*o Q* xs> X-J < <* </> a2 1o o i/5 XL T cc 2w 3c> O* c m c mro '0~fr-- oo 4H ^0fH iWH) C^M^H0 X a a. O N^ .* O N mu% oo ,cp op *-* .*<* O **>< OH' fn ,< '0 cc < ** <Dp O 09 X m *m o o <v vp p OH HP CO 00 -* f*. *- \ oMor*(4v,Wcp.Pd*-M < to W > 0 1- -- iu 2 - (- O Z . V) UJ X -ioc < iu as -- z < sz fy CM (M CM CM CM ,H r4 rt H H u. U. iu XL UL %U ** CMfO 4* 4> NCO NCO hCO- CO hCOco co CO CO CO 2 in uvm trt uv<t LU CM Al CM CM CM Os! **4 H H rH.H U, UL U. U. U. U_ c m w $ us -0 h* r- n r^- O' O' O' O' O' oo co co co cp 2 in in in m uv< LU X " DUP040013998 rrvui IX- UJi/*l 0Ct X*-* 0w flu ^ t/> c/) H- < ?4* .1/3 air o>* .a *-* C2 ..2v **3 c: -J < < ixi <. vf sd rj >o -ut ,aa pCHOHp UJ o < X UJ tiu cO Q2 X <2 tou XO < CM X CM tho- Jfr- *-* a, x tooi 3 u. I CL or or IoV uo. UCOJ UhJ- 3 x CO I n 3 < to 2Q UXJ > or xh- *l-- HUj-OX U_Jj Z-- CO .-b<* tO U- X c m c\j <v ry c m c m u. U. u. u. U.UL \ A N IM A L NUMBER o ^(Vf^ .* ?o >0.>0 >0 ir\ ur\ u 'n '.r\ *r co cp cpco co-'2 ur\ iA vhi/\ u% tuc X * 'Iillili uinwittiii tHWitri 2.14 DUP040013999 TABLE NO. 3 BIOCHEMICAL VALUES FOR MALE AND FEMALE ALBINO RATSLEAD ACETATE FOR 22 MONTHS, A t K P 04 P r\j IN! x* t- UJ CO o at u aCC *- oUoJ to *- .'mz0 _ X 1/5 K 5CL I 0 00 LL I CC >D Osf <> 6 r- * * .# 9Oh D -TO St- O CCH * A1 **.0 ^ Q H 2 3# CO O X CL O. o r+ X CL a. ion oC 025 O oo at to LU > IX2- OJ t\J ,<\l <\J M CsJ CM <V tv 04 fvj INI 00 u j X -J o: C UJ at co z < -2: IL U. IL U. IL IL rsi m *4- in o r^ iv r- r>- >o >6 *0 co co co co cb z jn in m m uv< UJ U. U. U. U, jLL U- fv K cf>o rs--<- tf*n* N>c r- r> ^ n co oo oo co co 2r ; in 'jvtn m <1 UJ . is DUP040014000 1> <\! fM X U V*" :C X O aa. - u_ 4* ^ :>a5 >-*- .Xj *a *6 CD sC *C >0 c m . Q O ^ C O r-4 CC -CO K -4* 4* 4* * fn O O -H *"* LEAD ACETATE FOR 22 MONTHS BIOCHEMICAL VALUES FOP. MALE AND FEMALE ALBINO PATS .a :x i x> o I/O U. I CC & za cc O t CL a oo cc < -V? O 3uo OX ax a o ,oo -J < v" UJ > -X ZX < jj X *-J oc <X UJ X CC -- X z < z2>: f\l <V CM <\< CUfSJ U-U.U-U.tJLU. h t v; go 4 >C f> h** N X CC CO CC CO mso cmo iCnO iCnO m <2t uj 2 CM CM CM CM l\J C\J U- U. U U- U- U- .0^4* in sfi> f- h* !> F** CO 0s O' O' O* CO 00 CO CO <0 Z in in m in m < JJ TABLE NO. i - --o DUP040014001 I 1K * o- 1 j k ,c X h uj v ) o2o CC ** Ui G. >- l/) AJ Q -Q 0 lO fO ' . m4 c m fo cv c m c m Mwl.H CO 1<t o z CO ~4 < Ui -4 < X Ui u. CO OX 2 < .2 O UI X -J < rg 2 CM a: cc oo 4- U. CO Ui ui i-^ .3 < -4 < Ui >O < -j <o o< ai -J tu X u o *--* CO .i* m o .2 UI j 03 < H- T IM E Ter v ONYH 4* VO P Ha. *-- 2 3 -J < <^ VO K az 13 O CO u_ I cc a* 2 3* COO ;2t a: < a* o* 3O VO X < vo 22 >< UO UJ X O >C O' fO CHC- O.*o'.O io O h 2 O' CO tn f>* >0 P r*4 H H H H >~l <-> i; h- O o -si* O' IA vO lA O <NJ fO rsj f\j <M n NM cm cm cm cm cv ; a. u. u. u. u. u. -J cc < Ui .2 CO 20 <2 fA CP O' IA Ch O' O' O' o 4- ^ ^ lA <0 ; iCnO GO ; tCnD CiAO Z< in i l & } DUP040014002 O' AA.. 'H- u j Vi O x .o or *-- u j <6. J-V> cc o in .o c ..*** # * ro ro fn osj r- sJ~!< *--4 .^4 ,r--t -y--4 --4 co ; o ^o p * <V ro ro cc c\ m i-H wM.+-* V? hr <c cc o ? cn < UJ < y UJ u. V5 OX .2: *<2 O lb .X -J < CM X dl 4* 10 O H d 2 vX>3 ,_J < < it to h~ H- *-4 az 13 o to u. $ cc flO O' 4* ^ O'* *"4 o o --i *-< o ** sO Is- c n j *>4* cn * * * "9 O rH t-H . --* --4 cc cc \ OD U_ LL to UJ IK Z 3 CO O X 0. oOoPOft cc tA h im^- mb I O- o oO*oo 4* <A .4- 4* S> CO !> UJ H* 2 o r-4 c--l .--4 H o AJ rH .1--4 H jH >H .3 < * 4 in 3 *r- < UJ >o < <Q o <t UJ X .-4 UJ :X o 0V- CD 1 rO UJ -j cc < oc <t o 3O to X < l/> UJ > I X cc h ,H" I-- CD ZX to UJ X O <A IA 4- O' r^- A- r-* Cp 0 4" fc-- H N *H H r-IH c\j ; ; ; * .; ; c n j eg c\i ; o j ; U. LL. ,U_ U_ UL U- <? OM O OlA AJ tf\ -H 4* O' 4 .Aj ; ; Aj esi tv Ai AI CM ; j ; i AI U. U.U. u_ u. u. 3 (X <J UJ 4* *0 CO O' 4 lA CO r- 9-9 CA * X CO --X 4 4* ^ 4* in nO >0 'JD 'O <* 4* 4 in *0 *0 r-- f** p- Is- f>- Z3 00 CO 00 CO co Z CO CP 00 co co 2 <X tA in id in <t IA IA lA lA lA <C UJ UJ X x *0 -i ntMemi.t tasmatioMi M^^ti*iwiaiwaagMa^ DUP040014003 - . t -- o> N <S1 <S X U! 10 o sc o Sf o.o o * O' f tat iM-iU/i.' cn ro ro m --4 H iH cH C--sJi fW- *0* i/) q: o O H* a j2nj . CO O * :** O>' '|v. C,O *c-2c g p --r <t *- <n o .*-< J < < UJ -J <r Ui u. i/> OX 2 < 2O UJ X f-- <,t--MA a. Z tC1o P a. ci. < CM St CO a: .eg QLL OU. VLU) UHJ-<PJ tHu> O oA * o o CO yvm HHH b H nCOr j--o< * ! a: <w o P<0 oX n O' 00" Ho cH* O; <o in( o <SC 1 rn ;* O 2 -<C<o uj > X M aUI iZ- 1- t- o U-UJ MZ X CO < <CmO co c m CO <\J ro CO vCCnOj ro CO 10 UJ X LL UL U. IL LL LL .paU:I XM Xto ZP <z tv in o r- o in uvirv in in O* O' O' O' O' OC CO CO 00 00 2 m in tn in in < UJ X L X' ** o DUP040014004 t * o '6 0 Tabic* No. 3A - Biochemical values for male and female albino rats. LEVEL ppm lv'.-td/day Control 10 ppm 50 ppm 100 pp>n ,1000 ppm SEX RAT NO, THREE-MONTH INTERVAL M 58-393 n 53-394 M 53-395 M 58-396 M 58-397 Mean M .M M .M M 58-593* 58-594 58-595 58-596 1 58-597 Mean M 58-693 M 58-694 'M 58-695 M 58-696 M 58-697 Mean- 13 58-793 M 58-794 M 58-795 M 58-796 M 58-797 Mean M 58-894 M 58-895 jM 58-896 M 58-897 M 58-898 Mean SG-CT R-F units 28 37 32 28 31 31 26 37 31 31 37 32 46 37 34 37 .32 37 34 32 41 37 32 35 46 46 37 37 41 41 3 si LEVEL . ppm lead/day Control 10 ppm 50 ppm 100 ppm 1000 ppm Table No. 3A - Continued SEX .SAT MO.. niREE-MQNTi! INTERVAL F 58-403 F 53-4S-4 F 58-495 F 53-406 F 58-497 Fie an F 58-643 F 58-644 F 58-645 P 58-646 -t .F 58-647 '* Kean F P F F P 58-743 58-744 58-745 58-746 58-747 Mean. . F 58-844 F 53-845 F 58-847 P 53-848 F 58-649 Ifcan P 58-943 P 58-944 F 58-04'5 F 53-94u F 58-947 Kean SO-OT E-F units- 26 32 .31 31 32 30 41 31 39 34 4.1- 37 28 28 28 60 31 35 3? 31 31 28 37 33 32 32 31 .31 28 31 r\ -t f DUP040014006 ppm lv.ad/day Control 10 ppm 50 ppm 100 ppm 1000 ppm Table Ho. 3A - Continued SEX BAT NO. SIX-MONTH INTERVAL M 58-4?6 a 58-477 M 58-478 M 58-479 M 58-480 Mean M 58-627 M 58-628 M 58-629 . M 58-630 ' M 58-631 Mean M 58-727 M 58-728 M 58-729 11 58-731 Mean . K 58-827 M 58-828 K 58-829 M 58-830 K 58-821 Mean .!! 58-927 M 58-928 M 58-929 5&-930 M 58-931 Mean SG-0T R-F Unit 80 80 76 88 70 78.8 80 95 101 76 95 89,4 91 70 88 73 80.5 70 67 80 76 76 73.8 88 84 76 73 88 81.8 ^99 mmm DUP040014007 Table Ho. 3A - Continued . I&EL ppm lead/day SEX BAT HO. Srx-).50HTH I'HTERVAli Control F 58-575 p 58-576 F 53-577 P 58-578 F 53-579 Mean 10 ppm P 58-678 F 58-679 F 58-680 'T 58-681 ' $' Kean 50 ppm F 58-777 r 53-778 F ' 58-779 F 58-780 F 58-781 Kean 100 ppm F 53-877 F 58-878 F 58-679 F 58-880 F 58-882 Mean 1000 ppm F 58-977 F 58-978 F 58-979 F .58-980 F 58-981 Mean SC-OT B-F unite 135 108 88 120 10$ 111.8 165 73 86 84 102.5 73 84 95 ,68 60 84 73 95 102. 120 95 98.6 150 80 . 88 80 80 95.6 X O . f LEVEL ppm lead/day Control 10 ppm 50 ppm 100 ppm 1000 ppm Table No- 3A - Continued SF.X RAT NO. 12-MONTH INTERVAL M 58-560 M 58-561 M 58-562 M 58-563 M 58-564 MEM M 58-672 M 58-673 M 58-674 M 58-675 M 58-676 1 MEAN M 58-772 M 58-773 M 58-774 M 58-775 1 M 58-776 MEAN M 58-871 M 58-872 a 58-868 a 58-874 M 58-876 MEAN M 58-870 M 58-973 M 58-974 M 58-975 M 58-976 MEAN SG-OT R-F units 105-0 127.5 . 87.5 72.5 127.5 104.0 82.5 95.5 82,5 110.0 87.0 91.5 145-0 126,0 55.0 72-0 45.O 88.6 112.5 57.5 105.0 112.5 80.0 93.5 80.0 127.0 102.5 . 65.0 HO.O 96.9 /' < r* 1 aairirtWiirWirafflrfflwii^^ DUP040014009 Xo/ LEVEL ppm lead/day Control 10 ppm 50 ppm 100 ppm 1000 ppm Table No. 3A - Continued SEX RAT WO. 12-MONTH INTERVAL F 58-U61 F 50-462 F 58-463 F 50-1*64 F 58-1*65 MEAN F 58-622 F 50-623 F 58-624 F 58-625 F 58-626 MEAN F 58.-722 F 58-723 F 58-724 F 58-725 F 58-726 MEAN F 58-022 F 58-823 F 58-824 F 58-825 F 58-826 MEAN F 58-922 F 58-923 F 58-924 F 58-925 F 58-926 MEAN ' gC-OT R-F unite 07-5 130.0 100.0 . 160.0 127.5 121.0 122.5 95.0 62.5 110.0 67.5 91.5 90-V 146.5 70.0 112.5 90.0 101.0 70.0 127- 5 100.0 125.0 126.0 109. ? 130.0 150.0 130.0 110.0 122.5 128.5 /' ' Mi DUP040014010 fflwiiwintwiMiMjl Table Ho. 3A. * Continued 'LEVEL Ijpra. J o-td/ day Control 10 ppm 50 ppm 1000 ppm SEX RAT 110. TEBMin/VL M 58-593 M 58-394 M 58-396 M 58-397 M 58-399 MEAN M 58-593 M 58-595 M 58-596 M 53-597 M 58-599 MEAN M 58-697 ' M 53-698 M 58-699 M 58-700 M 58-704 MEAN M 58-898, M 58-899 M 58-9OO FI 58-902 K 58-903 MEAN SG-OT R-F .units 140.0 113.0 82.0 113.0 106.0 110.8 86-0 113.0 132.0 115.0 97.0 108.6 125.0 109.0 115.0 215.0 130.0 138.8 121.0 110,0 (>250.0) (>250.0) 127.0 119.3 ii* :? r. DUP040014011 Table Ifo. 3A - Continued LEVEL ppm lead/day Control 10 ppm .50 ppm i000 ppm SEX BAT BO. TERMEIAl F 58 -493 F 58-494 F 58-498 F 58-499 F 58-505 KEAM F 58-644 F 5.8-646 F 53-648 T* 58-649 F 58-654 MEAN F 58-745 F 58-748 4 F 58-757 F 58-761 F 58-763 MEAB F 58-952 F 58-955 F 58-956 F 58-957 F 58-959 1IEAB SG-OT ' R-F unite 91.0 80.0 108,0 iG9.o 93.0 96.2 79.0 45.0 104,0 81.0 108,0 . 83,4 149.0 84.0 104.0 81.0 100.0 103.6 127.0 104.0 77-0 74.0 173-0 111.0 . DUP040014012 sm Table No. 3B - Biochemical determinations for male and female albino rats, I=EVEL ppm lead/day Control 10 ppm 50 ppm 100 pm 1000 pm GLUCOSE-6- SEX RAT NO, PHOSPHATE THREE-MONTH INTERVAL M 58-398 K 58-399 M 58-400 ] ! 58-401 M 58-402 1.5 2,0 4.5 2.5 1,0 Mean M 58-598 M 58-599 .M 58-600 M 58-601 M 58-602 2.3 0.5 1.5 0 2.0 3 *5 Mea. - M 58-698 M 58-099 M 58-700 M 58-701 K 38-702 1.5 1.0 1.0 2.5 3-5 3-0 Mean 2.2 :M 58-798 M 58-799 a 58-800 M 58-801 M 58-802 2.0 0.5 1,0 1.5 2.0 Mean 1.4 M 58-899 M 58-9OO M 58-901 M 58-902 M 58-903 0 2.5 3.0 3.0 3.0 Mean 2.3 CHOLINESTERASE RBC PLASMA 0,238 0.230 0.172 0,206 0,206 0,210 0.188 0.188 0.165 0.206 0.180 ' 0.185 0.180 0.172 O.165 0.160 0,172 0.174 0.180 0,180 O.188 0.214 0.172 0,187 0.206 O.180 O.180 0.206 0.206 0,196 0,425 O.303 0.328 O.345 0.311 O.342 0.303 0.354 0.362 0.311 O.31I 0,328 0.320 0.320 0.320 0.3U 0.267 0,308 O.328 0,328 0,311 0.267 0.286 0.304 0,320 O.303 0.320 0.320 0.328 O.318 DUP040014013 LEVEL ppm lead/day Control 10 ppm 50 ppm 100 ppm 1000 l Ta"ble Ho . 3B -- Continued GLUCOSE-6- LEX ; no. PHOSPHATE c h o u : ; "s RFC j-vr ; r!* * 1* THRES-KOLl'H IHTSSVAL F 5.S-4.9.3 F 58-495 F 5S-5CO F 50-5-M F 58-502 Mean F 58-043 F 58-o !*9 F 58-650 F 58-651 F 58-652 Mean F 58-748 F 58-749 F 53-750 F 58-751 F 56-752 Kean F 58-650 F 58-851 F 58-852 F 58-853 F 58-054 Mean F 58-988 F 58-949 F 58-950 F 58-951 F 58-952 Kean 1.5 4.5 4.0 3.0 3-0 3-8 0.5 1.0 0.5 2,0 1.3 1.1 5*5 3*0 4.0 1.0 2.0 3-1 0.5 5.0 *- * ,v 3.5 1.0 2.5 2.0 0.5 2.5 1.5 0 1.3 0.1S8 0 0.145 0.18c 0.214 z'r\ ;-~ 0. :17 0.?5C 1.058 0,132 0.927 O.180 '!* 0.l30 0.172 0,172 0.172 0.900 1.178 ,1.448 1.672 1.220 0.175 2.284 O.160 O.lSo 0., l!?S 0.157 0.157 . 1.117 0.85: 1,033 1,100 0.84 0.172 0.990 0.172 0.172 O.1I9 O.lSO 0.180 1.403 0.8-2 0.75?' 1.092 1,633 0.171 1.156 O.18O 0.172 O.188 O.18O O.165 I.O67 O.833 1.108 0,858 0.8:08 0.177 O.035 DUP040014014 142VEL ppm. lead/day Control 10 50 100 1000 Table Ko. 3B - Continued LEAD ACETATE 3EX RAT HO. GLUCOSE-6PHOSPHATE CHOLINESTERASE BBC PLASMA SIX-MONTH INTERVAL M 58-476 M 58-477 M 56-478 M 58-479 M 58-480 0 1.5 0.5 2.0 2.0 MEAN 1.2 M . 58-627 M 58-623 :M 58-629 M 58-630 M 58-631 1.0 0 1.0 0.5 2.5 MEAN M 58-727 1 M 58-728 M 58-729 M 58-731 1.0 2.5 0 1.5 1.0 MEAN .1.3 M 58-827 M 58-828 M 58-829 M 58-630 M 58-831 0.5 1,0 1.5 0.5 1.0 MEAN 0.9 M 58-927 :m 58-926 M 58-929 M 58-930 M 58-931 1.0 2.5 2.5 2.0 1.0 MEAN 1.8 O.667 0,708 O.650 0.733 0.642 0.680 0.767 0.650 0.608 0.617 0.633 0,665 0.567 0,542 0.525 0.642 0.569 0.683 0.667 - O.683 0.517 O.5I7 0.613 0,667 O.716 0.708 0,675 O.667 0,687 O.552 0.536 0.337 0-379 0.320 0,425 0.370 0.387 O.3S7 0,412 0,442 0,400 P.345 0.345 O.328 O.320 0.335 0.362 0.379 0.345 0,412 0.320 0.364 0.370 O.396 0.417 0,283 0.303 0.354 DUP040014015 LEVEL ppn lead/day Control 10 50 100 1000 Table No. - Continued LEAD ACETATE SEX BAT HO. SIX-MONTH XliTERVAl M 58-476 M 58*4*77 M 58-478 M 58-479 M 58-480 MEAN M 58-627 M 58-628 M 58-629 M 58-630 fo 58-631 MEAN il 58-727 M 58-728 fo 58-729 M 58-731 MEAN M 58-827 M 58-628 14 58-829 M 58-830 M 58-831 MEAN M 58-927 H 58-928 M 53-929 M 58-930 M 58-931 < MEAN LACTIC pEHYpKOPEHAAS 1,430 1,390 1,420 1,360 1,400 1,404 1,360 1,420 1,400' 1,3.50 1,400 1,386 1,430 1,320 1,390 1,400 1,385 1,260 1,320 1,390 1,430 1,400 1,360 1,270 1,330 1,270 1,420 1,450 1,348 DUP040014016 IEVEL ppm lead/day Control 10 50 100 1000 SEX F F F F F F F F F F F F F F F F F F F F F F F F Table No, 3B - Continued LEAD ACETATE RAT NO. GLUCOSE-6PHOSPHATE SIX-MONTH INTERVAL 58-575 58-578 58-577 58-578 58-579 MEAN 56-678 58-679 58-680 58-681 0.5 3.0 2,0 1-5 0.5 1.5 2.0 1.0 0 0 MEAN , 0,8 58-777 58-778 58-779 53-780 58-781 2-5 0,5 0.5 0.5 1.0 MEAN .1,0 58-877 58-878 58-879 58-380 58-881 MEAN 0.5 2.5 1,0 1.5 0.5 1.2 58-977 58-978 58-979 58-980 58-981 2,5 2.0 0.5 0.5 2,0 MEAN 1.5 CHOLINESTERASE RBC KASl-LA O.898 0.882 0.849 O.817 0.849 0.859 0.-809 0.930 0.825 0,825 O.867 0,784 0.809 0.783 0.717 0.700 0.759 0.809 0,882 o ,8q o 0.745 0.874 0.822 0.850 0.849 0.905 O.898 0.883 0.877 0.917 0.925 0,858 0,800 O.858 0.872 O.95O 0.900 0,883 1.042 O.944 1.067 O.808 O.992 0.933 0.741 0.908 1.017 1.075 0.875 0.883 1.083 O.987 O.608 0.825 1.050 1,083 1.075 O.968 DUP040014017 j LEVEL . Pl,m leed/day Control 10 50 100 1000 ^Table No. 35 - Continued LEAD ACETATE SEX RAT NO. SIX-MONTH INTERVAL F 58-575 r? 58-576 F 58-577 F 53-578 F 58-579 MEAN F 58-678 F 58-679 F 58-68O F 58-661 mm F 58-777 F 58-778 F 58-779 F 58-7S0 F 58-781 KEAN F 58-877 F 58-878 F 58-879 F 58-88O F 58.-881 mm F 58-977 F 58-973 F 53-979 F 58-980 F 58-981 MEAN LACTIC: DEHYDROGENASE 1,100 1,110 1,200 1,220 1,160 1,158 # 1,210 1,240 9S0 1,200 1,158 960 1,010 810 1,210 . 1,1 AO 1,026 920 700 1,160 920 9A0 928 810 1,000 l,.OLO 1,130 1,200 1,046 DUP040014018 ppm ie.ad/day Control 10 50 100 1000 Table Wo. 3B - Continued DEAD ACETATE SEX BAT NO. GUJCOSE-6PHOSPHATE CMr>LIWBSTER/.SE PRC PLAPi'A M M M 14 M M M M M 14 M M M' M M M M M M H M M M M M 12-MONTH INTERVAL 58-160 58-166 58-168 50-169 58-170 5.1 1.1 3.8 5.1 5.1 MEAN 1,8 58-622 58-623 58-621 58-625 58-626 l.o 1.1 5-0 1.6 1.7 MEAN 3.9 58-722 58-723 58-721 58-725 58-726 2.5 5.7 1.1 1.1 5-9 MEAN 3-9 53-815 58-818 58-819 58-820 58-821 0 0.1 1.1 0.9 0 MEAN 0.5 58-916 58-917 58-918 58-919 58-920 0 0 0 0 0 MEAN 0 O.683 0.691 0.683 0.683 0.708 0,690 0,766 0.658 0.171 0.633 0.683 0.613 0.611 0.666 0.666 0.586 0.6II 0.6I1 . 1.089 1,050 0.783 0,808 0.958 0.938 0.991 0.883 0,853 0.8I2 0.833 0.880 0.712 0.581 O.525 0.623 0.733 0.611 0.775 0.700 0.561 O.589 0.656 0.657 0.615 0.539 0,510 O.69O O.5IO 0,573 I.300 0.716 0,933 O.816 0.716 0.896 0.665 0.800 O.8I1 O.75O O.7I2 0.760 DUP040014019 l evel ppta le&d/dsy Control 10 50 .100 1000 Table.No. 33 - Continued . LEAD ACETATE SEX BAT. NO. 12-MONTH INTiBVAL M M M M M M. M M M M 58-461 58-462 58-463 53-464 58-465 6; n 58-622 58-623 58-624 58-625 58-626 \ MEAN M ' 58-722 ,M 58-723 M 58-724 M 58-725 M 58-726 MEAN ii 58-822 n 58-823 M 58-824 M 58-825 M 53-826 MEAN M 58-922 M 58-923 M 5S-92L M 58-925 M 53-926 MEAN LACTIC dehydbo c et : 630 >2,000 720. 1,290 1,510 1,230 1,060 ., 1,620 -*' 740 1,300 1,490 1,242 1,440 1,620 1,620 1,740 570 1,398 1,100 840 380 570 1,720 922 980 1,350 1,350 1,490 1,360 1>306 DUP040014020 Table No. 3B - Continued LEVEL , ppm lejtd/d.ay SEX LEAD ACETATE BAT NO. g l u c o s e -6PHOSPHATE c h o l b is 3; :'S BBC PLASMA 12-MONTH INTERVAL Control F 58-566 F 58-567 F 58-56$ F .58-569 F 58-559 5.1 , 0.766 1.358 5-1 0,816 1,445 6.4 0.791 1.321 6.6 0.700 1.309 0,7 0.891 1,300 MEAN 4.9 0.793 1.347 10 F 58-672 2.7 0.594 0.725 F 58-673 3-3 04611 1.066 F 58-671 4.2 0.611 1.150 F 58-675 4.2 0, 666 1.016 F 58-676 5.0 0.652 1.000 N5EAN 3-9 0,627 0.991 50 F 58-772 4.4 0.594 1.083 F 58-773 4.6 0.683 1.220 F 58-771 4,6 0,666 0.833 F 58-775 4.1 0.641 0.991 F 58-776 5.0 0.683 1.128 MEAN 4.5 0.653 1.051 100 F 5S-866 0 F 58-867 0 F 58-868 0 F 58-869 0 F 58-870 0 0.975 1.163 1.064 1.016 0.766 0.725 1.487 1.436 1.538 1,470 MEAN 0 0.997 I.331 1000 F , 58-967 0 0.900 1.368 F 58-966 0 0.950 I.368 F 58-969 0 0.916 1.462 F 58-970 0.5 0.875 1.368 .* F 58-971 0 0.833 1.245 fc. MEAN 0.1 0.895 I.362 ^ .; . r> DUP040014021 Table No. 4A - Urine analyses performed on pooled samples from groups of male and female albino rats. LEAD ACETATE FOR 22 MONTHS LEVEL ppm P-LEVULINlC ACID INTERVALS NO. OF RATS SEX THREE-MONTH SIX-MONTH 22-MONTH mg/100 ml. mg/100 ml. mg/100 ml. Control 10 5 5 5 5 M 0.158 F 0.191 M 0.222 F 0.268 0.120 0.051 0.111 0.091 0.30 0.30 i-- 0-33 0.25 50 5 M 0.160 0.057 0.41 5 F 0.210 0.019 0.44 100 5 M 0.139 ` 0.057 NOT 5 F 0.153 1 0.040 PERFORMED, 1000 5 M 0.383 0.398 1.30 5 F 0.556 0.130 0.68 * No coproporphyria detected at the three- and six-month intervals. COPROPORPHYRIA INTERVALS* 12-MONTH 22-MONTH mg/vol mg/vol 1.42 1.09 0.2797 0.0603 1.27 1.04 0.5088 0.1556 0.97 0.43 0.5104 0.1525 0.61 0.53 NOT PERFORMED 1.53 1.15 2.3R40 1.0448 ; DUP040014022 Table No. 5 Mean te rm in a l body w eights* organ w e ig h ts, o rg a n /to d y w eight- r a tio s , and standard d e v ia tio n s f o r male and female a lb in o r a ts . n 8s o H & < a r ca (J H rc o * n to p o P nO fO >t Is- H *0 O o oo o 0 . P0 ao p eg >6 O to ,ro eg * o c> St o O O' co V oV St o "1 k> CO o ;o p sO C-sJ o Q ' o 0 O0 C^ 0 o o Q 0' CO r- p -o > v0 c>J A C.mO <o 0 TO , .t 0 Q Oo 0 x> h* 00 o 04 H m o C' o Q .*o p o r-- *t o jp* >o t p A * .cr*l . *** H O' st ti\ A> r> M H oo 3 0 :i 0 -^1 fs o 0 .M H O *rl -* HHH HI ~-- ---- ' ; -'"7 Cl o o >s o M E-i ss. u> -v o >x* x Cl to w t o< TT. O to 3s Cl CO r xJ H re >- 3 .Dr> w S e x CO q (4 s > W aQ. >3 <Q o H r* rO t~4 0> o -* o o0 3 ? 0 o o O o .* o P 0 c> o fri m H cO M sO P sO K O CD 0 'J> O O 0 o -.3 o 0 QPO 0 CO n H' CO CO N sl oOo 3 D o O o 3 5 - .* .* .4 0o oPo a? P X) o 0-H p o P O '5 r~l o ooPo 0 . - st > O Oo p 0 o P '.3 o oo <N A o tv t"- 0 .O ,w o o p c> o o o . .f o KJ o p 0 p CO p O' o r\ CO 04 CM A o CJ c Kji O . 0 0 ,o o o * o o . m O' o m N A r- .0 st P --1 J n -a r~4 0J A -rl > Si O' O' St "VI '-0 00 A M A A A n .A st H H *j CO CNl <N fn CO D' co CO CO CO Si O A; fH AA i. i. s X CJ J P O r-* in p P QC H O 1- Z o o o AAAA *--1 tu U, lx. U. U. Pn o ' r--< oc 1-- o O A q *4 D Hi . r ro ----O .i ; .j ;i j^ .* i> 1 ,i i -i f l i 1' js jI J; j i 1 .! DUP040014023 la b ia No. 5 -Mean te rm in a l body w eights* organ w eights* organ/body weight r a tio s , and standard d e v ia tio n s fo r male and fem ale a lb in o ra ts . 0 V*. A `si A M 4 H *ri rrl rH .# ;H .P** ^--4 :at> H a . > . r*.Ha - :p .0 o o 0 o J o 3o *> 4-4 o0 -> p>- f\J A 0H * .a o 3 .O o o A f*- *s3* 0 t> A o * .3 3 p 0 O 'G <r? n . o o o 4 o . .* o :> Ji o * P4 o r\ AA a " * A f* .4 0 3 tn `rJ o X v-t 6< tit o& . tn CO Mi U.l m CD 4 >-H CO w & tn taO X 6a-:i w c X CO q u: a > W o Q. * . s 4 0 cn . A * :- H 0O O CM A **# a- 0 0 3 >. A 'i A A 'rH *M . .* : - . 0o o0 0> 4 Ai ;A * <M *\1 M 4o .30 * CM G o -M r*- A n 3 iZ A- ' . fM Ai A x> -H .A * AA A CM A 4- N. <\J ,r. rd O vO A p AA 0 4 4 H H H r-< rH c 0o .1-4 A A ,.'v < . AJ :> Q o .r--e A o -Vj A . A* .; A cm . # . ft A- fC c* a A > .3 C\J AJ A *>- 3 4 A rH 3 j C Ai rH a-* A ''*4 A VI CM CM > Os 4 fvi .00 3 3 A c m AA A AA H 4-4 3 <r. CM AJ fA G A *A A -A OM oA A A A oA h A -A it s 51 5T x a. U- u. u_ U- -J .0 O jC OH A j 3 & e--t j z o u .-J 3 0 *3 o A 3 w a; rH tz o .0 <!. vV DUP04001402- fa b le No. 5-M t-an te rm in a l body w eights, organ-w eights, organ/fcocy w eight r a tio s , and standard d e v ia tio n s fo r male and fem ale a lb in o ra ts . i * owH*: V*- < ZL O' a < . tt; J1 * s rWowc 3? s> fti *. wr-- o5 | X Mfr..- (A, rv* o >UV<<af--jj OSj .>v2UOJ? a!* i .ori eo } <Ua-JJ J. rOMWe;i' .410 w| M ai W! .3J. S-l 0- W) gw. 0 3: a WXC4 >ww4 aaa Ooo0 03' OOOM 4 OocQim hr oo ' oHo O o. . 0Oa30>o % *--O~4< o .o06OO' 04o>? o ,o o P'1 oo Oof1. 00o4* Ooo40* *oo00 0 4M*3 o I>o0'M-frt .C4M* O *JMO rN3~ Q. 6 r- <0 ao ro o ,rri M O 0 00 o 0 o 0 s <0 0 Q 0 0 A(A 0 7M 4 0> CM m Q tcno o. <mn o O o -0 0 o PM <0 Q Q' CN O 3 O .4* -4* 0M 00 . * Oo O' 43 Or*' H a* a o - o o 0 0 O <0 0 *n O 0 O' fN>* O ' O' iNn0 o 0<o*o . CM - o* .Oo4> cO O MQ4**) Coion#O 4" 0 .o'rOH0 O+0T.r4 m ooM . fiMn V0l . mHoM* cCOooM 43 o0 544o,0**} C.44O3 .-ro4n-* C4M0 4430* Oi4n" ',o0 oN0 04 -0 O' c4.o AnI <n O<bn' rCc4<n*| C(0Ah <4r*v .o1*0" m 0 ..0M^0 HM0- f4MM3 fv * <JOM aO4*y*l PCH,M- n o o o fNJ 4 f4N3 O -<A CO t\l tA O' ?V CM O' O' 4 CM co 0 0 j A CM m in <n m in 4 CM fO H CM <0 4 fO (O 0 to o to OCM' M tO in in iA ?x .X X M0 lA n in U. U- 4* u- u_ J o 0i-4 eI--c o 0 O Mo 0 O o .r-C 3E b aot o ri 0 in Hoo o o h* .M ' bu ' : . <: 10 ^ SC DUP040014025 Table N o . 5 -Mean te rm in a l body w eights, organ w eights, organ/body- weight r a tio s , and standard d e v ia tio n s f o r male and female a lb in o r a ts . SEX 1 mj:t& w ; .t f'i s) i A . < ' p --* ;> oo *> ppo o r j cj> c* 4- M 4i po o c *> ,6 o P Ci \ % ,)> o o si 4* -r Aj o o P o o * .# .4 * o Ooo o o ts -* 11 An vJ -V c\ iH fH r-< . o Po .` > tnj **. vO X H* o >" X JH O PS ai o a- Ui h* u lO H UJ VI t0 fr-- #-* ;u u < a t n: aj o Sr. tn h- i o *!-- l/ul aH: >* o c o S: to * u r ma, a. -t > Xw O P M oo 0 A O' Q p , Oo > fA f- 4- Aj ; cA <A A O' %. vO : 4) P sO ' P OoOo . .=4is oO ' Cy Ai *-v A -e f~4 aPooo A ;0 f*- o A* O oA* 0 9f A f m fO f* A* <f A > p *M AJ A K o ar >o H o o Al 4--i *> n H A >t Af O' srs <r Osl o P 20 A A| A A A A n >f --4 n4 (A AJ r0 CA O' A A A rA A4 O A *n A A ri '2l 5" s: is. OAA AA U- tu U- U- .VU D O at oVJ 0o *O- o P zOc >-* o P c* 1 DUP040014026 Mean- te rm in a l tc d y w e ig h ts -, o rg a n w e ig h t::, a n d s ta n d a rd d e v ia tio n s f o r m a le a ria fe m a le o r g a n / t c d y w e ig h t- a lb in o ra ts . tr*' V- uCi. oj <ta .rt.He9'` M a0 td ' :?c. .0 o 'NJ X 111 rc< o *i . a ' JC ?aC VS,; C d* h* a X P X .4 -J P51' * .M tj w sc, ti| ti '*I tans*! >! ^ *J7.; u-<\ O rz D O rO 4* AJ A4 AOl O O 3 o d> A P vO H aa h V 4 .n M # *> o0 o O 3p o a H |S 4* 4" O j\ O 3 PO # OQ .** 4 4- 4* -H A! JM >o > vn *o M O3 J5 ;M c*- A A Al **v <n oo .o io f> -P cn O <N 'M O 0\ P A 4 A sf A c<> A4 a o A4J* o P p pp o 3 p ,p p O A A P Nl A 4> A 4* P P PP PP POo P * PP P \ 4* P P P PP a 30 A A PP fN o o> pp p- 4* A A si PP Q p p 0 41 P 3 04 P PP P O P PP P P <JS P o> TO P A . In . P PP P 0 D PP o p * po z> 0 4* .0 iA 0 PPO P P PPP P 0 oP -H ap N 4A ..A M Ni n A P P3 6 3 * -'f O' o A 4- n a p> 4 O 30 4) A4P O r- o S0 '0 >< A p n O A >> O + O A P ~4 STO0 41 00P 'Is- 'j o <T S tA 4* T a b le N o . c ra tio s , DUP040014027 Table No. 6 -Mean te rm in a l body w e ig h ts, organ W eights, organ/body w e ig h t r a tio s , and standard d e v ia tio n s f o r male and female a lb in o ra ts . 0 .3 1 0 .1 7 Wj -tfc. tu UJ -J CL J) Vi -3 OH3' &Wi 4 <9 T\J C4O" O f O P 9 > P .# o O o 0 o. to p 9 <p o CJ 4P . O rvj O n 4 O0 o 9 H4 ;0 .*-4 --< A -- . . ooo 3O 44 h i --i m OO A .n . rj sO t- A 04 c?4 P *4 .9 O P O P A O* CO CO o% .9 op 9 o P p o -4 OAA p J H * 9 . P oOo + vO ; 0- ; CO '; .9 A A in ?o .* .9 o O O i J} r Ho *M 2 H 2< * X cc z>. U. a: Ul u > H-- ~4 < -J to 1-- Jj v < 3 < jU -J tc o ,* --< w .3: cn +-- r- o W ojJp. 6-t 33 >- O o t*q oo 3: bO c X W X/l v3 W a 3 0o. 0> to vO A *9 04 h # o o P *5 3 A H p sO H OJ 94 VI P fD o P o p 4 CO vO A 4 * , -M <N MN C9 O r> o 4 4A4 A 9 .9 Al 'J .'1 A4 >4 4- "3 4 >0 >M O 9* -H H HI N AA M H A .-A 4 P . 4 A f>* 4 O h r--4 H -H P 4f X> N -H 3 H >4 VI 4 . * .H r--4 H ^Hl w ..A o P A A >0 0 ON *-H P . l CO p o> > P --* --t A O' A ,r- 4 4 A 0 SO t> O o VI o\ o 3 A A; -o *o A On H >0 O A 4 n A 4 0 - . + CO O' p P 4 p A --i A h- x> C9 4 A rO 4 p; H o fi A 2 3: 2 OA rH oA A u. IL, U- U-. iu -J 0 O PO o0c H A O H O P H 2 O u _j p p O P O *- A P O 0: T* P .1- --4 z 0 0 s DUP040014028 Table No. S-M ean te rm in a l body w eights, organ w eights, oxgan/bocy weight r a tio s , and standard d e v ia tio n s f o r male and female a lb in o ra ts . R A T IO -J tu * a tn to < n: o* w to U] #cOH 00 0 Hoo4 0 <Ooh P6 oP7> tOooo o d 0 3 33 . 4 D -0 P A O H 3 .0 *: P JO 3 3 ..4 P Ss. -=rl H 0 f* r- P H O aoo 4> a p3 3 44 3 o oOo H O o o o >0 0 P .o o ? o o .4 b 333 o4O- oOs)f Qo OAQo roH Qp* o.nO O *1 iA O' r-4 r>- 4* N H AJ AJ M P3 oP > - * 4 4 4 PP o O .0 wH jo r-4 H oP ` # 00 A j 00 X> oo 44 *> Q oH Hi cn o S> 4 '# o 0' Sf O 4 o *o rH XO 0 o> Qo '4 4 H ---4 4 o3 > tn o 1. o z o M H H Eh X XU o >tii z 3 .. < *-- tn! co -- U j X. b i u -J 'CasJ! H to 3: ml M H* 1 J ill jC >Oo Oi *W--I;t CO o xi W: w{ W3 w ,,oQ.. >H 30 ; .o * 3 O !* >6 ; in * oo H0 O ,*H fA o H O .4 . 33P ?5;2 oP AP b P 4 . DOO A 00 Oo -O r--4 3o #1 Q o 0 4 o O 4* <A O vO A .4 4 3 3 oo -H P 4 o 4- Q Pn PH P <V <A A' 4 s? .A vO t> 4 3 K 30 i> >0 4* ro A ; JO . .4 3 b> 3p 3 O -H H 3 P JO 3 :b A r 4 * . A A 4* 4* !> r>HM 44 p t> A >1 -M A 44 Po <t A 4 .3 + O A 3NO M "SJ >r A -H 44 44 4 <\| M A A P> 4- 3> A 4- A P P f*~ Aj AA ch A A A 3A AA O > r-4 4A a> 0 n .4 3 *H CQ o3 A A <H A N m -t M rn 3 d 3A r-f A A A '2 s 2: 3E s 3A A A A H U. JL ti. a. u. -J o o o o o q: *-4 ; o *h o3 Oo _j o o a 0 aO: -* A o h O d uo s' 9 DUP040014029 Table No. 6 Mean te rm in a l body w eights, organ w e ig h ts, organ/body h e ig h t- r a tio s , and standard d e v ia tio n s f o r male and female a lb in o r a ts , L tW > * (.t. Tm I t i- UR 12 t'lOisT h j tfisI W*. Si S3 *JLl * < > O i* tn; to CJi WSK"S<): tO .Mj OM; ~ -- >0 *r ; 0 0 sr N H 43 m o 3 3 O f .4 ' d> o o O A 0 9 U o > > P\ A p 0 Jv A A AA; A p oD 3 .3 - - 0 o O' Q o *s-t ' ....... -^l -StI St A <> sT O A st A tr * .3 P 4 o 0o 4 : 4 O oo0 0 O PA0 St 0 sr *--< .*-4 H .9 9 .9 .0 s> 0 -.3 0 -st o A is. is* >t 0 r-4 st- D 9 O 9 P -9 * * O A :p p0 A M 0 *tt 0 t co A 0 A 0 'NJ hA .9 .# .* 9 oO 0oo . * y aEd- op WMii tO 0 >t X> >4 0 AA N AH 9 99 0 P :> 0 .0 0 *t P A A JO X> C7> 3% js* 99 999 AAAA A W 4> e-4 .X o ti w 5? G X w to *4 w a 1 cu A> IN* 4- A st- A r-~ 0 0 0O A A t 0 P 0 0* 0 0 M 0 >4t 0 0 P 0 A 0 + 03 O' P 0 A0 A AA p x> it O A H A AA X 2 Xx O AA A A U_ U_ IX. ,L lu -J 0 3 0 P 0 rH A O O X H P W r-< 2T 0 u rt-J P P 3 0 AO X H* a: 0 <0 O 3 -9 JiL"^'Ot: DUP040014030 Table No* 7 -M ean te rm in a l body w eights, organ w e ig h ts, organ/body w eight r a tio s , and standard d e v ia tio n s fo r male and female a lb in o ra ts . A E .p 5 --< X o w* J X U -4 DUP040014031 Table Nbi 7 -Mean te rm in a l body w eights, organ w eights, orgon/body weight r a tio s , and standard d e v ia tio n s f o r male and female a lb in o ra ts . O M JH * to to 2 E o -< to & A A A JA --4 0 4 oO 4* p P* o oop o o -a OV in A s* =4* & r4 H H --1 o 0 o p 0 .* ' O >oN . Al O 4 0 o o ooOp 0 + to ; N *; o* 33 -4 .i . * o O O p 0 0 -0 >o o p A M 'Si -4 P :P o P 0 Al A 0 '* Oo 4 o` ** 0 'V <7> AJ -ri o N # # o o P' P 0- . VJ 4* ao CA A ; A- 0 A- h- > . . 9 o 00 0 0 (ft A C 0' ro H H< (X V `i. U>J -1 * 4. Al * .3 v? . P O Q w& C X w to wa > A wA r- j H A f>- r>* W-4 t . 0p . A 4 O t) 4* .0 4 n N o fS n . * A A N A ; A> 0v *3 . J* O00 >& Si 00 ' "u& ;> "A - -H 4- A A >1 4: ,# .* ;A A iO A A 7* jv A* 0 0 ?0 A > :; .A H A-- A> A A* >o .A .* - ~> A > -M H --i 0 A 4* . : UA 13 0 'VJ T<| **SI A 04 0 A r*!* f 0 .*!4 -H 0 - i r~ H r** 43 A A 4 AA V .--4 -4 fri -4 4 >0 O0 4 4 A 4 > 4H r~ 4 A O r. A 05 f- s4{A >0 2AP A A 4O 0 0 *3n0 0 T) > 13 'O 4 4 4 A A7- 4 0 A A ,r*r{ AA - 2t s -J 0 P 0 ,, 6D; H A P H O0 z 0 0 0 A AA A .4 a. U^. 4. u- u _J O 0 r-4 or '2* 3 u 0 .0 A0 .**4 .0 .i3 ... 1 1 ] j 1 * .lo / DUP040014032 4 Table Bo. 7 -M ean te rm in a l body w eights, organ w eights, organ/tody w eight r a tio s , and standard d e v ia tio n s fo r male and female a lb in o ra ts . v? o 0 o iM O o <\l o o 4 O' 0 Oo 9 . oao oo 0 CO CM cO CM oQ H o *- O o :*-4 O * . o0ooo 1 1 t Hp iJt HH 0 *--4 CO A N 3 CO r>fM Q-o - *> 0P . 0 D 0 O Q O 0 * . * :* * ''pi, 0oP 0P 0. 0 O 0 p *> ON >w< HI o 0 o O P oo0 . 9 O' 6 0 o o r** r--4 H 4- 0 o r- o0 o oQ 0 o 0 o 0 O cO CN ,0* p' <M co 4O o ooo 9 ' 9 , oooo o CO : A 0 tn o> O H o <M o rH H H H4 * .9 * o o O o 0 > A D JO o * U* -J DUP040014033 Table No. 7 -M ean te rm in a l body w eights, organ w eights, organ/body w eight r a tio s , and standard d e v ia tio n s fo r male and fem ale a lb in o ra ts . Mo frt </> oJ *n X < > o 60 Hnci .wM: r** - O .0 O 00 .4 00 A 7> *M 4* n O 4 OO fx- <0 4* A 0o Q0 .4 : O *> PA Nl N OO , 4 OO A 0 0 t> 0 ; *M P 4 *sl N <-4 O' M > 4 P S> - 0 -4. P 0 O O 0 <M A r\i 'A tn A - H Q rsi rl H H .* 4 * 4 OO POP I ..m! k**. Ai ht* 37 1 0! A t-r iR r*4 cd < A ..i. Jj h-- -U A t . *<-- HoJ- <nj to i -a < 1 < Jj j XCH-5J*`. t.O* Wl *1 i to h* r" O til "S fH sra > 0 0 to 1) c! X w IQ P w > s0. wA 4* O A rH O A O' A OPO O .4 4 .4 4 4 P p *> P P A AO Os 25 .3 H O' p AA .4 .4 .4 O P O 0 > A =rNI !A* V > A J- 0 4 4 4 4 P O O i> O Jx O Oa' .Si > 4 > A > 444 <n r> <* ?A '0 4 D sr A J' A 0 4* 4 O' A* P 4 0AA St n A ?** 4" to A 4 A A AA A AA A to O' P A sr p O' sr 4* m *n 4 ---55 A A A A r4* 2 '2 _f O :> V J 0 -4 A O O PI i~4 3 .-4 s: O -> A A A A H U_ u. a. . -1 V 0 .w-4 A O O a: H > <r 0 < <^ .Q DUP040014034 Table No. 8 -Mean te rm in a l body w eights, organ w eights, organ/body weight r a tio s , and standard d e v ia tio n s fo r male and female a lb in o ra ts . </> xb* oZ X cv to QL uO. T uu u<t o U<l DUP040014035 Table No. (5 -Mean te rm in a l body w eights, organ w e ig h ts , organ/body w eight r a tio s , and standard d e v ia tio n s fo r male and female a lb in o ra ts . DUP040014Q36 Table No. Q -Mean te rm in a l body Weights,, organ w eights, orgiin/fcody w eight r a tio s , and standard d e v ia tio n s fo r male and female a lb in o ra ts . ftti b* c<d{ < z- LcLci o < to t-i *s 0 - oo B in o 0 in o in o Aol 0 .* 0 oo ot . o 4 o 0, 0CO T0 o m Ho 0f O 0 P -0 -0 90-4 o 04 >> co #--* O o .# P H f--4 0 SI CM f-4 oo . 0 0- . 31 csl sT >r rsi 0 COM . 0 |*V-4 !4 CM 0 J>in ............ COM C0M* co 0 0 0' <rOn p o o C0M* CM comt o Wo o so * O' w-4 o * C0M .C0M o --3e0t- . ->vO*. . mo 0 0 <cMo Q . 0 0 0 O 0 n-t *0 CO >0 P- 00 oo * p o * 6 P oop W *<4 oP f-H 9c*o4 .r-4 4**4 . * H *-4 H 00 o p 0 wiWS. V) a: 0 Xo M CM CM <A > CC ill uo. z 0M ui p* in CO <t H* iu u < 0 < a s* Ui c p -J H4 w co 00 h ro Hi (M O0 sn rT m co o * + <M <M 0 o #-4 fO _ op r* . o p o r- oio P* c m! * ^ 0 0 P CO o CO sb m r^ .9-4 4-4 o H 0 o CM CO 0_ 6 o Q ' sn in P- CM ^0 * P** . o0 *f................ 1 rH| .CO o to p CP 40 CM 0 . o .* O' .4 0o o p* co in *< m 0 o 4- m .c m P f-4 e-4 O *NJ o *> CM 4- Xto in O >s, <M cn loo C4| <r in m -4 >o 4 . PP in 0 40 P <M cM r- >4 o in op* CM O CO si- .0 oo ' ' C+O ................................... >0 & CM CO ' jf :hox*. Ui 5 aHc > Q :Q w? Q i Cl4- ~4 H H CM 'X X X X X to CO to 4- CO p- M" CspM CM 4- Mo>3 CO O' ^4^4- CM CO r-4 Cr*O4 CO u. it X u. u. DUP040014037 Table No. 8 -Mean te rm in a l body w eights, organ weights,, organ/body w eight r a tio s , and standard d e v ia tio n s f o r male and female a lb in o ra ts . </> XI-- zo ac CM fSl GC O Oi UJ o < Q .< UJ DUP040014038 BODY WEIGHT Grams the Indicated dietary levels of lead acetate. T>P3 O<D 41 O w 0 Oo (pA Yo3 .0v>vs. x: i '.a c P P g 0 0 o 5 o Q 3 '-fOP,VC TO07 I T&O p sa "5 1 .>* o ,o c pa S $ o Z d3 74 DUP040014039 rots which received the indicated dietary levels of lead acetate. DUP040014040 HlStOPATJlOLCWICAL E/ALUATIGN d? KALE AKD FEMALE ALBINO RAIS SACRIFICED AFTER SIX MONTHS LEAS ACETATE CONTROL Male Rat No. 53-471 Gross; No gross alterations were observed at necropsy. x' Microscopic: . . Pituitary: Two small nodules of hypertrophic chromophobes were present within the pars distalis. The remainder of the glafe was histologically normal. Thyroid: Appeared to be in a state of low activity. Lung: Slightly congested. Alveolar mils were slightly thickened in some areas by hypertrophy of the septal cells. i , Spleen: A moderate number of active lymphoid follicles were present, " Macropliages within the red pulp had phagocytized a moderate amount of yellow to amber pigment;. A -small number of megakaryocytes were present within the red pulp. Adrenal: A solitary nodule of hypertrophic cells of the zona fasciculata was present. This nodule was adjacent to the zona glomerulosa. Some of the individual cells within this nodule contained large vacuoles within the cytoplasm. The remainder of the gland was histologically normal. Small Intestine: There were small numbers of neutrophils present throughout the lamina propria. Testis: Spermatogenic activity normal and moderate. s DUP040014041 fe- \ J 'I I ( -2 Bone: The bone section examined was histologically normal. The tone marrow accompanying the section of bone contained a predominant amount pf fat. Myeloid and eiythrogenesis were present and both series were producir-j nature cells. . / Bone Marrow: The bone narrow originating from the sternum contained a eeas.i-1 srable amount of fat. Moderate numbers of both eryt.hroid end ftyaloiS Series were producing nature cells. Moderate numbers of megakaryocytes were present throughout the sternal and femoral bone marrow. ' The following organs were within the limits of expedfeed histologic appearance: brain, spinal cord, heart, liver, kidney, stomach, pancreas, and large intestine. CONTROL Male Rat Ko. 55-^72 Gross: Ko gross alterations were observed at necropsy. Microscopic: Thyroid: Appeared to he in a state of low activity. Lung: Contained free blood which probably gained, the alveoli at death. A mineralized lesion was present within the int.ima of one of the larger arteries in the lungs of the section examined. Small numbers of alveoli contained an eosinophilic fibrillar material, which was- probably deposited after death and, therefore, artifactual. Spleen: Moderate numbers of active lymphoid follicles were present throughout the spleeh. Small numbers of megakaryocytes Were present within the red pulp. A small amount of yellow to golden brown pigment was captained within macrophages of the red pulp. , __ DUP040014042 -3- Kidney: The pelvic epithelium was foeally hyperplastic. .<V>17 variably sized foci of nonsuppurative inflammation were scattered throughout the cortex > of the kidney. An occasional glomerulus '-/as hypereellular and completely ' filled the urinary space,. An occasional tubule contained proteinaceous material. Adrenal: Several small nodules of hyperplastic cells within the zona fasciculat were present. m | | Testis: Moderate and normal spenaatogenic activity. Bone Marrow: large numbers of megakaryocytes werej.in both sections of bone marrow. The marrow was also very cellular and contained elements c.f both the myeloid and erythroid series with maturation of both series. The following organs were within the limits of expected histologic appearance: Ink pituitary, spinal cord, heart, liver, stomach, pancreas, small intestine, large intestine, and bone. CONTROL Male Rat tip. .53-^73 Gross: Ho gross alterations were observed at necropsy. Microscopic: Brain: Occasional neuron within the brain stem contained a muddy red, very finely granular material within the cytoplasm. The remainder of the brain sections examined were histologically normal. j DUP040014043 i I ,U Thyroid.: The follicles vgre of various sizes from Very small to large. The lining epithelium of the various follicles also varied with the smaller follicles exhibiting a more plump epithelial cell.. H:istc-i6,tically the thyroids appeared to be moderately active. Lung: The lung was moderately congested. Some of the alveoli appeared smchysematous. Small Ijssphoreticular aggregates were present around some cf the arterioles and bronchi. Alveolar walls were slightly thickened from the congestion and also from small numbers of lymphocytes and occasional neutrophils. Chi occasion, the Septal cells within the alveolar wall were ':y hypertrophic. Liver: Small nonsuppurative inflammatory foci were scattered throughout the liver mainly at the portal triads. On occasion,the hepatocytes adjacent to the central veins were slightly hypertrophic. .Spleen: large numbers of mature and productive lymphoid follicles .. ere soot Sr-si throughout the spleen. A small amount of yellow to golden brown pigment was contained wlthih macrophages of the red pulp. An occasional -raSgakar;. ocyte was present within the red pulp. A slight amount of extramedullary hematopoiesis was present. Kidney: Small foci of nonsuppurative inflammation were scattered throughout the cortex of the kidney. Some collecting tubules and an occasional proximal convoluted tubules contained hemoglobin easts. Testis: Spermatogenic activity normal and moderate. Bone Marrow: Moderate numbers of megakaryocytes were present within the femoral bone marrow. The myeloid and erythroid components were well populated. Maturation was completed in both series. The .megakaryocytes in the bon1: marrow of the sternum were more numerous than in the femoral bone marrow. . ' G DUP040014044 * i i The folXovinG organs webe within the limits of expected histologic appearance: pituitary. Spin: 1 cord, heart, adrenal, Stomach, pancreas, small intestine, large intestine, and bone. ," Gross: CONTROL Male Eat Bo. 58-471 Bo gross alterations were observed at necropsy. .Microscopic: Fituitary: Small groups of chromophobes were hypertrophic. Thyroid: Variably sized follicles were scattered throughout this organ. The character of the epithelium and colloid suggested a low level of activity. lung: A small number of alveoli contained eosinophilic fibrillar to granular material. The alveolar walls were in some areas slightly thickened from small numbers of lymphocytes. Liver: Variably sized, usually small focal nodules of lymphocytes, throughout. Most of these aggregates were present around the portal triads. On occasion, lymphoid aggregates were within the midzonal areas of the liver lobules unessociated with changes in the hepatocytes. Spleen: . Moderate numbers of mature and active lymphoid follicles were scattered at random throughout the spleen. Kidney: A moderate number of the epithelial cells of the proximal convolutedtubules contained within their cytoplasm, a very fine granular yellow to golden brown pigment. Testis: SpermatogeniC activity normal and moderately high, 130 DUP040014045 -6 - Femoral Eona Marrow: Fetnomsa bone marrow contaiyiea large nviflibere of megakaiyoeytes. Maturing eiements of both the myeloid and eryihroid series were present. Sternal y Bong Marrow; Moderately high numbers of megakaryocytes were present, JS-rtyrinj elements pf both the myeloid and erythroid series were present. The following organs were within the limits of expected histologic appearance; brain3 spinal cord, heart, adrenal, stomach, pancreas, small intestine, large In testine, and hone. Gross: CONTROL Male Rat No. 58-t75 * . Mo gross alterations were observed at necropsy. Microscopic: 1 Brain; The meninges were slightly infiltrated with mononuclear cells. Small foci, some of which were linear, vf fresh blood were scattered throughput the cerebral cortex* There Were no inflammatory reactions or components about these focal hemorrhages. Spinal Cord; Small foci of fresh blood were present throughout the grey matter, which was unassociated with any other histologic change. Thyroid: Variably sized follicles comprised the gland. The epithelium lining the follicles varied from a very low squamous to a low cuboidal. The size of the follicles, nature of the colloid, and of the epithelium suggested a low to moderate activity. > ; * X DUP040014046 . Lung; Small numters of small foci of hyperplastic lymphoid elements were scattered at random throughout the lung. Some free fresh blood was observed within the alveoli. Moderate numbers of alveoli were emphysematous, liver: Small foci of lymphocytes were scattered throughout the liver, especially, around the poroal areas. The remainder of the liver was histologically unaltered. ' spleen: Moderate numbers of active lymphoid follicles were scattered throughout the substance of the spleen. Small numbers of megakaryocytes were observed within the red pulp. Kidney: Scattered throughout both the cortex and the medulla were variably sited foci of lymphocytes. Some of the inflammatory foci were associated with the glomeruli and extended from the glomeruli into the surrounding parenchyma. The epithelial cells of the proximal convoluted tubules, in ' . a?. some areas, contained variably sized vacuoles. Some of these tubules, also, contained an eosinophilic fibrillar to granular material. The epithelium of the pelvic mucosa was slightly hyperplastic. The submucosa was slightly infiltrated with lymphocytes. Testis: Spermatogenic activity was normal and moderately high. Femoral Bone Marrow: Femoral bone marrow contained numerous megakaryocytes. This marrow was also highly populated by both erythroid and myeloid elements. Critical evaluation was precluded by artifastual 'smudging of these cells. Sternal Bone Marrow: A large number of megakaryocytes were present. Maturing elements of both the erythroid and myeloid series were present, 132 DUP040014047 -8- the following organs were within the limits of expected histologic .appearance:: pituitary, heart, stomach, adrenal, pancreas. Small intestine, large intestine, and hone. - S CONTROL Male Bat Ho. 58-476 Gross;: No gross alterations were observed at necropsy. Microscopic: Thyroid: A great range of the size of the follicles was present.. The epithelium of the follicles was most commonly squamous with some tending toward low cUboidal. The histologic appearance of this gland reflected low activity. lung: This organ was slightly congested. Some alveolar walls were thickened by a moderate influx of lymphocytes and occasional hypertrophy of the residing septal cells. The remainder of the lung was-not remarkable. .Spleen: A moderate number of active germinal follicles were present within the spleen. Moderate numbers of megakaryocytes were scattered throughout .. the red pulp. Testis: The number of secondary spermatocytes in some of the tubules was low. Most tubules exhibited normal spermatogenesis with moderate numbers of sperms being produced. Bone Marrow: large numbers of megakaryocytes were present both within the sternal and femoral bone marrow. Both sections of bone marrow were moderately populated , and maturing elements of both erythroid and myeloid series were present* I.C3 DUP04001404J -9- The following Organs were within the limits of expected histologic appearance: brain, pituitary. Spinal cord, heart, liver, kidney, adrenal, stomach, pancreas, Small intestine, large intestine, and bone. . COKTROL Male Rat I.'o, 58-*77 Gross: Lung: At necropsy there were red areas on the surface of the lung. Microscopic; '1 Thyroid: Extreme variety in follicular site was present. Epitheliuni of the follicles varied from squamous to low cuboidal and the colloid stained variably eosinophilic. The histologic criteria of this gland revealed a state of low activity. Lung.: The lung was slightly congested, Iymphoreticular follicles were hyper plastic to a slight degree around some of the bronchioles.. The alveolar walls were slightly thickened from a light influx of mononuclear cells, mainly,lymphocytes and by some hypertrophy of the residing septal cells. Liver: Small foci of lymphocytes scattered throughout the liver with some associated with the portal areas and others within the midzonal region of the portal section of the lobule. Some of the foci were associated with eosinophilic debris, which tied displaced the hepatocytes., Frank, necrosis of the hepatocytes was not observed. The site of the hepatocytes varied within the different regions of the liver lobule. More commonly those associated near the central vein were larger cells than those near DUP040014049 - IP the portal area of the lobule. The size of the nuclei within the hepatocytes of the various zones varied, tremendously. Spleen# The spleen contained moderate numbers of various-sized lymphoid foiliclo: Kidney: The kidney was moderately congested. Small foci of lymphocytes were scattered throughout the kidney and, oh occasion, these foci surrounded tubules, whose epithelium nad undergone some, hyperplasia; The epithelium of the Convoluted tubules in some areas had undergone vecuolatloc. Adrenal: The cytoplasm of the cells of the Zona fasciculata was variably vacuolated. Testis: Spermatogenic activity was normal and moderate. Bone Marrow: The femoral bone marrow vas moderately cellular with considerable numbers of fat cells replacing the hematogenic elements. Moderate numbers I of megakaryocytes were present within this bone marrow. Maturing eler.2r.ts of the myeloid and erythroid series were present, Tlie sternal bone marrow contained large numbers of megakaryocytes, small to moderate numbers of fat cells, and considerable numbers of the hematogenic cells. Katuri::-r elements of the myeloid and erythroid series were present. The following organs were 'within the limits of expected histologic appearanc-.-: brain, pituitary, spinal cord, heart, stomach, pancreas, small intestine, large intestine, and bone, CONTROL Male Rat No. 58-1+78 Gross: No gross alterations were observed at necropsy. tz$ 1DUP040014050 11 - Microscopic: Brain: numbers of lymphocytes had infiltrated the .meninges, w Thyroid: The thyroid gland was comprised of variably sized follicles. The -`pi'.helium lining of the follicles varied from a squamous to low euVoidal, The histologic appearance of this gland indicated moderate activity, Tung: The lurg was moderately congested. Variably sized, usually small, foci of lymphocytes were scattered throughout the .lung.' Most of these foci were ir. association with blood vessels or bronchioles, The alveolar walls were thickened by small numbers of lymphocytes and neutrophils, accompanied by hypertrophy of the septal cells. Heart : One small focus of degeneration accompanied by a small number of lymph* ocytes. w Liver: Small foci of lymphocytes scattered throughout the liver, more commonly associated with the portal triads. Spleen: Moderate numbers of active lymphoid follicles were present. Small number of r-gakaryocytes were present within the red pulp. Moderate numbers of small foci of extramedullary hematopoiesis were .also present within the red pulp. Moderate to large numbers of macrophages contained a golden brown to yellow granular pigment. Kidney: On occasion, the cells lining the parietal layer of Bowman's* capsule had undergone metaplasia to a cuboidal type of epithelium. In other cases and with other glomeruli, the entire layer was thickened somewhat. The cytoplasm of some of the proximal convoluted tubules had a fibrillar appearance to :it with these strands arranged in a parallel fashion per* pendicular to the lumen. IDS DUP040014051 - 12. Small Intestine: Small numbers of eosinophils and lymphocytes v/ero present, within the submucosa, Testis: Spermatogenic activity was normal and moderate. Bone Marrqw: Large numbers of megakaryocytes were present within the femoral marrow. A moderate amount of fat cells were present within the narrow,. The myeloid and erythroid series were moderately cellular with both exhibiting maturing forms. Sternal bone marrow contained large numbers of megakaryocytes. The myeloid and erythroid series were plentifully rep^ resented and both, exhibited maturing form's. The numbers of maturing myeloid elements were moderately high. f l I I I The following organs were within the limits of expected histologic appearance: \ pituitary, spinal cord, stomach, adrenal, pancreas, large intestine, and 'ociyj* #? CONTROL Male Rat No. 58-^79 Gross; Kidney: A dark purple zone was noted at the Cortical medullary junction. Microscopic: Pituitary: Small numbers of the chromophobes contained vacuolated cytoplnTM. which, in turn, contained fibrillar or angular strands of material. Gome of the chromophobes contained a very finely granulated, slightly eosinophilic material within the cytoplasm. 3 Thyroid! The gland was composed of Variably sized follicles. The epithelium lining these follicles varied from a squamous to a definite eyboidal. The appearance of the colloid, follicles, and the epithelium suggested moderate activity. ,, - DUP040014052 3 V! " ' \ Lung: Lung was slightly -congested. The alveolar walls weie slightly thicke-nei ty small numbers of lymphopyt.es and hypertrophic septal cells. On occasions, small numbers of neutrophils were also present within the alveolar wail.' Liver:' Small numbers of hepatocytes, usually arranged in foci, contained vacuoles within the cytoplasm. These cells were present throughout the lobule out more commonly near the portal region. Spleen: Moderate numbers of active germina. follicles were scattered throughout the spleen.- Foci of extramedullary hematopoiesis were present within the red pulp. ' Kidney: The proximal and distal convoluted tubules contained eosinophilic material which was either granular throughout or in small variably sized globules. Some of the distal tubules exhibited hypertrophy of the epithelial cells and, on occasion, minimal hyperplasia. The cytoplams of ** some of the cells lining the proximal and distal convoluted tubules contained vacuoles. Considerable numbers of proximal and distal convoluted tubules were dilated. Adrenal: The cytoplasm of most of the cells of the zona fasciculata was finely vacuolated. Small nodules of hypertrophic cells within this zone were also present. Small Intestine: A small number of eosinophils and neutrophils were present in the mucosa of the small intestine. Large Intestine: Moderate numbers of neutrophils were associated around vessels, which were in turn associated with a rather diffuse lymphoid infiltration. The mucosa at this level was unaltered. DUP040014053 - 14 - Testis; Spermatogenie activity was moderately high and normal. Bone Marrow: The femoral bone marrow contained considerable numbers of fat .cells. Moderate numbers of megakai-yocytes were scattered tbicughoiitthemarrow*' Critical evaluation of the myeloid and erythroid series was impossible in f. the femoral bone marrpvj however, the cellnlarity yg moderate. The sternal bone marrow- contained large numbers of megakaryocytes. The myeloid and erythreid elements were present in high numbers with both elements exhibiting maturing forms. j 'in The following organs were within the limits of expected histologic appearance: brain, spinal cord, heart., pancreas, stomach, and bone. i COCTROL Male Rat No. 53-^80 Gross: to Lung: Dark red areas were noted on the surface of the lungs. Microscopic: Thyroid: Variably sized follicles vrere present. The ,epi+* . im of the larger follicles was predominantly squamous while than of the smaller follicles tended towards cuboidal. The histologic appearance- of this gland would place its activity low. Lung: Considerable amounts of free blood was present in the alveoli and the bronchi. * r r\ DUP040014054 * I .Hotirv,. **ome loci oi degeneration of* "the myocardial fibers.were present and v.'src accompanied by small numbers of lymphocytes nd histocytes, Livar; JfeaU foci of lymphocytes were aggregated around the portal, a aA or. occasion,the central areas of the liver lobule, "* Spleen: Moderate numbers of mature active germinal follicles were present. Considerable numbers of macrophages within the red pulp contained ,a yellow- brown granular pigment. Small numbers of megakaryocytes were present. Kidney; The cytoplasm of a small number of the epithelial cells of distal con voluted tubule contained vacuoles. Rarely a Collecting tubule contained a deeply basophilic aggregate of small granules that appeared to be mineral,. Adrenal; Artifaqtual tearing of the adrenal precluded critical evaluation; how ever, the cytoplasm of most of the cells of the zona fasciculata contained vacuoles. 1 \ Pancreas: A small focus of lymphocytes was present and in association with acini that were undergoing early degeneration. This focus was neither extensive nor exciting a more severe reaction. Testis; The organ was not histologically altered. The spermatogenic activity was moderate to high and normal. Rohe Marrow: Moderate numbers of fat cells were present within the femoral bone marrow. Moderate to high numbers of megakaryocytes were scattered through out the bone marrow. The myeloid and erythroid series was adequately represented both by numbers and maturing elements. The sternal bone marrow contained large numbers of megakaryocytes and large numbers of both myeloid and erythroid elements with maturing forms present in the latter,. 130 DUP040014055 i ; V* "IT The following organs were within the limits of expected histologic appearance; brain, pituitary, spinal cord, stomach, .small intestine, large intestine, and * bone. CONTROL Female Rat ITo. 58-570 Gross: Ho gross alterations were observed at necropsy* Microscopic: 0 Thyroid; Variably sited follicles_were scattered throughout this organ. The epithelium was of a squamous to low cuboidal type and the colloid was of a homogeneous and slightly eosinophilic in color. Activity low. Lung; The lung was moderately congested. Small numbers of lymphocytes and neutrophils were present within the septal wall causing a thickening of the structures. This was of a uniform character and constituted a low grade interstitial pneumonia. Liver; Considerable variation in the size of the nuclei was noted throughout the section examined. Some of the nuclei appeared to be hyperchroma tic. Considerable numbers of the hepatic cells were binucleated. Occasionally a hepatocyte contained vacuolated cytoplasm. Small foci of lymphocytes were occasionally observed near the portal triads. The staining character of the hepatocytes was variable with some talcing a distinct eosinophilic stain whereas others were more pale and somewhat granular. A Spleen: Moderate numbers of mature lymphoid follicles was present within the 4 spleen. Small numbers of megakaryocytes v.ere present within the red pulp. DUP040014056 The folio-,ring organ's -..ere within the limits of expected histologic appearance: brain, spinal cord, heart, stomach,..pancreas, small intestine, large intestine, and bone. ^ Cross: - CONTROL female Rat No. 50-572 Lung: The longs were dark pink in color at necropsy. 4 Microscopic: -jft Thyroid: This gland was composed of variably sized follicles. The epithelium of the follicles varied from squamous to low cuboidal. This histologic appearance accompanied with the staining quality of the colloid suggested that the gland was in a state of low to moderate activity. * Lung: The lung was moderately congested. Some of the alveolar walls were thick ened from the congestion coupled with small numbers of lymphocytes and occasionally hypertrophic septal cells. Some of the alveoli appeared slightly emphysematous. Spleen: Moderate numbers of lymphoid follicles were present. Small numbers of megakaryocytes within the red pulp. Macrophages within the red pulp contained within their cytoplasm a yellow to brownish yellow granular pigment. Kidney: The corticomedullary junction was.moderately congested and some of the collecting tubules at this level contained a homogeneous eosinophilic material. On oecasion,a collecting tubule contained a darkly basophilic granule, which appeared to be mineral. ic 4 DUP040014057 ; Pancreas: A small within the pancreas was surrounded;' and in*4aIea by. mononuclear cells, mainly lymphocytes, an! small numbers of plasm culls and neutrophils. This inflammatory reaction was limited to'the itaedtefce vi- y ' cinity of the vessel and did not involve the surrounding parenchyma. Ovary: Several Graafian follicles and atretic follicles were preser.u within the section of ovary examined. - Bone Marrow: The femoral hone marrow contained cpnsiderable amburts of fat. ' Moderate numbers of megakaryocytes were present. The myeloid and orythroid elements were fairly .numerous and maturing formsj wer r observed in both series. The sternal bone marrow* contained some fat. Megakaryocytes were present in considerable numbers. The myeloid and erythroid series exhibited numerous maturing elements. The following organs were within the limits of expected histologic appearance: brain, pituitary, spinal cord, heart, liver, adrenal, stomach, small intestine, large intestine, and bone. CONTROL - Female Rat Ho. 58-573 Gross: No gross alterations were observed at necropsy Microscopic: Thyroid: Variably sized follicles comprised this gland. The epithelium of the follicles varied from a squamous to cuboidal. The activity of this gland would be placed in low to moderate range. DUP040014058 'hr 21 - 48T' r<ur-' s Tire lung was slightly congested, 'The'alveolar walls were 'very slightly infillr'-ted by lymphocytes resulting in some thickening in some areas. >* Liver; ."sail foci of lymphocytes were scattered throughout the parenchyma of " These .focal infiltrations were Umssceiated with other pathologic change in'the liver. - - Spleens. Moderate numbers of active lymphoid follicles weird present.. Moderate., >2\ numbers of macrophages within the red pulp contained a yeHow to yellow- brown granular pigment. Small cunb.ers of megakaryocytes were present with?- ft in the red pulp. Small foci of extramedullary hematopoiesis 'were present just beneath the capsule. Ovary?: Variably sized Graafian follicles and corpora lutes were present, which indicated, histologically, normal activity. -* . Bone Marrow: Considerable amount of fat was present within the femoral bone marrow. Low numbers of megakaryocytes were present,. Maturing elements of a moderately populated myeloid and erythroid series were present. Sternal , bone marrpw similar to femoral. The following organs were within the limits of expected histologic appearance: brain, pituitary, spinal cord, heart, kidney, adrenal, stomach, pancreas, small intestine, large intestine, and bone. CONTROL Female Rat No. 58-57** 1* Crocs; [Jo gross alterations were observed at necropsy. ** } Vi* i: ,C6 DUP040014059 LEVEL ppm lead/day Control ID 50 100 1000 Table Np. 3B - Continued LEAD ACETATE SEX BAT HO. 12-MONTH INTERVAL F 58-560 F 58-561 F 58-562 F 58-563 F 58-5.64 MEAN F 58-672 F 58-673 F 58-674 F 58-675 F 58-676 MEAN F 58-772 F 58-773 F 58-774 F 58-775 F 58-776 MEAN F 58-871 F 58-872 F 58-863 F 58-874 F 58-876 MEAN F 58-670 F 58-573 F 58-974 F 58-975 F 58-976 KTAN LACTIC DEiriDBOQETJASE 790 720 840 660 750 : 756 790 1,050 1,060 1,380 1,190 1,094 980 930 870 870 1,480 1,026 900 1,740 1,300 1,350 jko 1,206 . (>.2,000 ) (>2,000) 640 1,380 1,180 1,067 ^ 'J ft a ? 1 DUP040014060 LE'r.L i ptit \.*-ad 'day Control 10 ppm 50 ppm Table Tip. 3B - Continued LEAD ACETATE 3EX TAT HO, 18 MOUTHS M 50-389 REPEAT a 53-390 REPEAT M 58-391 REPEAT a 58-392 REPEAT M 58-393 REPEAT MEAN > a 58-588 REPEAT a 58-589 REPEAT M 58-592 REPEAT M 58-593 REPEAT K 58-595 REPEAT ; : ,M 58-688 REPEAT M 58-689 REPEAT M 58.-69C REPEAT U 58-693 REPEAT a 58-69A REPEAT MEAH ' LACTIC DEtrYDROCgjArS (720) 1100 (>2000) (>2000) (740) 680 (520) 720 (600) 1290 948 (800) 46o (800) 340 (500) 280 (>2000) 360 (>2000) 430 374 (1690) 980 (1080) 540 (1020) 760 (390) 360 (680) 880 704 X Q DUP040014061 LEVEL ppm lead/day 100 ppm looo ppm Table Ho. 3B - Continued. LEAH ACETATE SEX EAT HO . 18 MOUTHS - Continued M 53-788 k EI-IAT M 58-799 . REPEAT M 58-791 REPEAT M 58-795 REPEAT M 58-799 REPEAT MEAH M 58-809 REPEAT M 58-890 REPEAT M 58-891 REPEAT M 58-893 REPEAT M 58-894 REPEAT WEAR LACTIC DEYDR<y.?jiASE (620) 380 (640) 280 (480) .280 (1800) 700 <94o) 540 432 (.920) 870 (720) 200 (760) ISO (9S0) 300 (520) 540 4lS 0O DUP040014062 LEVEL ppm lead..lay Control 10 ppn 50 ppa Table No. 3B - Continued ; A ; t e t 'EX RAT HO. 18 MOUTHS - Continued F 58-1*93 REPEAT T 58-1*9?* REPEAT :F 58-495 REPEAT F 53-497 REPEAT F 58-498 REPEAT MEAN ' -#i F' 58-639 REPEAT F 58-64o REPEAT F 58-641 REPEAT F '\ 58-642 REPEAT F 58-643 .REPEAT MEAN F .58-738 REPEAT F 58-739 REPEAT F 58-740 REPEAT F 58-741 REPEAT F 5-3-742 REPEAT MEAN LACTIC DEKYDROOEUASE (>2000) 15?0 (>2000) 850 {1080) 88.0 (l84o) 1260 (540) 1690 1240 (720) 580 (>2000) 410 (250) 320 (1100) 920 (>2000) 1200 686 (1580) 1490 (1390) 1400 (1840) 1040 (>2000) .1670 (1880) 4l0 1202 -- vu DUP040014063 asm ppm lead/day 100 ppm .1000 ppra Table Wo. 3R - Continued LEAD ACETATE SEX BAT, HO.. 18 MONTHS * Continued F 58-839 REPEAT F 58-840 REPEAT F 58-841 REPEAT F 58-843 REPEAT F 58-844 REPEAT MEAN . F 58-938 .REPEAT F 58-939 REPEAT F 58-940 .pimi F 58-941 REPEAT F 58-942 REPEAT MEAN '0 LACTIC DaryPP-OOHSASE (1730) (>POCO) 3X> (1070) 1180 (820) 520 686 (800) 1100 (500) 500 (460) 580 (1200) (>2000) (770) 500 .690 ' 1. * --. , DUP040014064 Table t!o> 38 - Continued LEAD ACETATE . LEVEL ye:a 1 eud/ d$y Control id 50 TQOO SEX EAT ;io. TERMIKAL M 55-393 M .58-394 M 58-396 58-397 58-399 t-ffiAir H 5.8-593 H 58-595 It 58-596 ' T 58-597 M 58-599 ..MEAil H 58-697 M 58-698 M 58-699 M 58-700 M 58-704 I-EAI1 fi 58-898 n 58-899 M 58-900 M 58-9OE 14 58-903 iiEAi; GIVJC05E-6- BioyniAT 10,0 15.1 15.0 14.1 15.3 13-9 M 12.1 1 16.0 14.1 20.0 10, r l4,5 17.5 15.0 l4,4 14.7 14.1 15.1 13.0 12.9 9.1 15-0 CLOT 12.5 142 DUP040014065 Table No. 3B - Continued LEAD ACETATE LEVEL ppa lead/day Control 10 50 1000 SEX PAT NO.. TERM3TAL F 58-493' F 53-494 F' 58-498 F 58-499 F 58-505 MEAN F . 58-644 F 58-646 F 58-648 F 58-649 F 58-654 MEAN F 5.8-745 F 1 58-748 F ` 58-757 y 58-761 F 58-763 KEAN F 58-952 F 58-955 F 58-956 F 58-957 F 58-959 MEAN 0LVC0SE-6HC03FKA.7 9-3 16.4 17.2 . 15.3 15.1 14.7 16.O 4$ 17-1 ' 16.2 7.1 13.1 13-9 14.0 10,2 CLOT I9.O 13-5. l4.2 17.2 CLOT 14-3 17.1 13.I 15-4 DUP040014066 Table No. 3B - Continued LEAD ACETATE LEVEL pprn. lead/day Control 10 50 1000 SEX NAT NO, TEBK32IAL F 58-493 F 58-494 F 58^498 F 58-499 F 58-505 MEAN F 58-644 F 58-64b F 58-648 F 58-649 F 58-654 MEAN F 58-745 F 58-748 F 58-757 F 58-761 F 58-763 MEAN F 58-952 F 58-955 F 58-956 F 58-957 F 58-959 MEAN GLUCOSE-6PHOSPHATE 9*3 16.4 17.2 . 15.3 15.I 14.7 16,0 17.1 * 16.2 7.1 13.1 13-9 14,0 10,2 CLOT 19.0 I3.5 14.2 17.2 CLOT 14.3 17.1 33.1 15.4 DUP040014067 LEVEL ppm lead/day Control 10 ppm 50 ppm 1000 ppm Table IIo. 3B - Continued LEAL ACETATE SEX RAT HO, TERMINAL F 58-493 T 58-4-94 F 58-498 F 58-499 F 58-505 MEAN F 58-644 F 58-646 F 58-648 F 58-649 F 58-654 MEAN F 58-745 F 58-748 F 58-757 F 58-761 F 58-763 MEAN F 58-952 F 58-955 F 58-956 F 58-957 F 58-959 MEAN LACTIC DEHYLr.O-lrLArE 7.00 80O 1200 9I1O 1340 .1012 360 250 3OO 4lO 1490 562 ' 280 920 (>2000) 920 (>2030) 707 I3OO ( >2000) 910 1740 (>2000) 1320 DUP040014068 Table No. 3C - Biochemical values for male and female albino rats. LEVEL ppm lead/day LEAD ACETATE SEX BAT NO. METHEMOGLOBin ----------- r~ 12-MONTH IN3EBVAL Control M 58-461 M 58-462 M 58-463 M 58-464 M 58-465 1,0 0.0 1.5 1-5 i.i MEAN ,, 1.0 ID M 58-622 2.8 M 58-623 3.3 M 58-624 3-7 M 58-625 3.8 M 58-626 2.9 . MEAN 3*3 .50 K' 58-722 4.1 M 58-723 3.2 M 58-724 3-8 M 58-725 3.5 ,,M 58-726 3'5 MEAN 3.6 10C 1000 M 58-871 M 58-872 M 58-873 M 58-874 M .58-876 MEAN M 58-972 M 58-973 M 58-974 M 58-975 M 58-976 1-3 3-2 QNS 1.9 3*0 2.4 QNS 3.6 2.5 2.0 2.0 MEAN 2.5 1 k-S DUP040014069 ** * urjM LEVEL ppm lead/day Control 10 50 100 1000 Table No, 30 - Continued LEAD ACETATE sax RAT HO. 12-MONTH INTERVAL F 58-560 F 58-561 F 58-562 F 58-563 F 58-564 MEAN F 58-672 F 58-673 F 58-674 F 58-675 F 58-676 MEAN F 58-772 F 58-773 F 58-774 F 58-775 F 58-776 MEAN F 58-822 F 58-823 F 58-824 F 58-825 F 58-826 MEAN F 58-922 F 58-923 F 58-924 F 58-925 F 58-926 MEAN . m-e t .h e mo J g l o b 'in 3.0 2.0 .1,6 2.9 2.0 2-3 4.0 * 4.2 3-9 2.9 2.2 3.4 6.2 5.4 3.8 4.6 5-0 5-0 3-3 3-3' 3-3 3-3 1.7 3.0 2.2 3.8 3-7 2.7 1.9 2.9 11 DUP040014070 Table No. 3D -- Lead content determinations performed on pooled whole blood samples from groups of male and female albino rats, LEAD ACETATE FOE 22 MONTHS / INTERVALS OF DETERMINATION LEV'EL ' NO. OF RATS SEX THREE-MONTH SIX-MONTH 12-MQNTH 22-MONTU ppm mg/lOO ml. mg/100 ml. mg/100 ml. mg/100 ml. Control 10 5 5 5 5 M ND F ND M ND 'F ND ND ND u ND ND 42.7 22,4 36.1 19.3 25 25 32 32 50 5 M ND 5 F ND ND 37,6 42 ND 32.9 46 100 5 M ND 5 F ND ND 27.7 NO ND 35.4 DETERMINATIONS DONE 1000 5 M ND 5 F ND ND 86.6 92 ND 69.4 78 ND * Nondetectable -! -D DUP040014071 tbor <ort o Z ,pmm4 C-JO < 1--112 <uXU.i -i< Ui xU<vtaU-aaU-CXoX<oJJLLJt>i AbbHZaNaaUt<xxo*J-:.*ijj CL cu. >ttt-oouJ UooCXL*- OX<at bXUaJ. uC&O oCcOc Q > Hua=O-J>.cooo-o.J *~C-1OJ** cX*Xcoc* aOCtC Uhz--i uo<1j Ubxa-i o3to atxeo>. CXL x UaaJ. < Ui * to X -X H VJ ui X to * tZOOu_o >- > > > . :Z 2 X' < -d < X 2 .2 X > z >> e2 > 2 :z . <r < < < X X* 2 X K I O oI -QJ o X bX- .CaL. za. o v> f--4 o X o 20. CL . ,cL a mo H op o a% a Ho o o p .* ! b* r-4 b- >- oOo O o o oo O Ha * H r~* O H (V of~4 *f-f4r o co *4 a ** 4 <0 O' CO --Ui1 > -J U>J mmj UJ > -J U>-i U~JJ > b- b- b- b- V" fO co m fO (A o o o Q 3 ,; 1ml , i ] *0 . "V ^ DUP040014072 i X ,rv TABLE NO. 4 - URINE ANALYSES OF POOLED SAMPLES FOR MALE -ANO FfM AI.F ALBINO PATS-. LEAD ACETATE FOR 22 MONTHS PRO TEI j j Cl kA O > < *x X > > zZ 2 < < <1 X X JE < ) > a: M > > >> -2: < 3: < Ui < :Z X X z u. X : aac, 4J j j --i -j Ox H-- *-- < UI j 1-- H :-4 -J ~j J x a I O oio ;x o 23 .cc c > t_3_J>oOa O -1 Q CO mi4 2 :.J CXC 30 Q 1z a ,1c-- O aX a. 2e o o o I in in z oO <*>- # o O/> ' coc <a/* aX. c<C Ui a. a < HI V) X I~- ZXXH- U0 ui X s/1 h* Cn< zo* -o IN -4 fv wi UI > m u. in oo o Xa. Xa a Pin ,op o H- o Po r* CM CSI O .H ;-* >0 r- -J ui Ui >> H H* m cn UL u. Xa Q 0- , -4 o H- o o CO o r~4 -J Ui > .1-- tn U-* o o o CO o<PH r-J Ui >* H- u. vCVO DUP040014073 TABLE NO. 4 - URINE ANALYSES OF POOLED SAMPLES FOR MALE AND FEMALE ALBINO RATS. LEAD ACETATE FOR 22 MONTHS X -c>o-4 a: u> a <r ty i/i z :3T Ui UJ UJ LL U- LL o < cc > >> >- > .< XXX < < > >> a: o X <r UJ H < X< X XX X :X a. a: O X < fXrua-i u CD X b > _l o 3yo0 O -J O OC W1* Xfr4 o O X o x jo tp a. <x * 1-- a. Xa CL l b o +?4 in o .<5 o X :X a. a. Q a. Q- o Ob oo rH r-< o o RUB ACE B IL n .m* dC UJ Ql fr1 UJ TON o lA ' Oeg a to QXu * or U<J aa < UJ t/> X fr- 2 HX- >-- .*-* X V3 UJ X >CMO . C u. < X C a: * < o o o o H O' U-JJ > a NO X *n o Q a -< op oo <v ra-4 o rH or-4 O' O' _J -J UJ UJ >> a. a t- fr>o o XX - *"< oo p f-H o CD -J UJ > a v- >0 X * o <c--o4 w O' -J uj > CL V>o DUP0400140T4 TABLE NO. 4 - URINE ANALYSES OF POOLED SAMPLES FOR MALE AND FEMALE ALBINO RATS LEAL) ACETATE FOR 22 MONTHS PH X UJ cv vi Ni of u :<0 K > <2 Z> -.< >z< 55 V <Z z > 2 < V> a>: p xX X > z . < >Z <x >z Z > z< z > 5; UJ UJ <4 H- X< X .a. uCC 3E o cc o > _i a pa <j a o -1 O co Kz- *-J- cC O 33 QC 1 .X0 X-- UJ CL H- 1 UJ UJ z OO <C H- O V) Of .# VQ). oZ ec a Ha Z O o OQ^ H O O Q Za. a. in P0 ,*ui >- 0 0 u> 0H. 0* z z0. O aCl CL O oo oo H *--*l 0 -<r P O .t*f-k4 ~4 CO O' Of _J J -J -J < 0UJ. a<L UJ V> H- X U>J CL H 'O U>J- UJ >- UJ > a CL ' CL *- H* H- OO --}-*Z-*- V5 UJ X u. u. U. u. VI H* tL O < .0: vn O O O O p t- p p pH *-< 0-UJJ > cl H n0 UL 'i 152 DU P040014075 o o UJ CL </> <M O .< CO v> .H - VO >ec M X a. oc o X < .i cL Oj o CO o CD cc 3t UJ UJ U. u. > > >- > x zz2 < X X -2< > > 2T z < <: <L X ..x x 04 > X X 2 .< X >Z <c j o vOuT.X cm CL CM 5* vi UG b U-JJ Vu--i OO0. H<UU o UL < o a vo <t VU uj 00 -4 >* < z <1 UI X cc 1 ** o 2 UJ -J CD < :.H- >o -J Q 30 OO o -4 o oo *-4 z *-- .**l CoO CD QC IX O~ CC UJ a h- 1 ui uj 2: oo < H* * b 3 vO oc o CL VO X CL . cc < UJ a. CL < UJ * VI f-I *- 2>H- -* X V) LU X * h O u. < x a cc -J 0 OX P X -O Of a a H> a a. Sr P o O r*4 *A m * 4 ro Q P o <\l co CM r*4 CM o oO * *--4 ,r4 o CO UI > -J -J Ui UJ H- .> > > Vr* 1CM CM CM -< .HI <^4 X X X vn o o p o 0 PPM X CL a o w4 PSJ P P #*4 CM : H 00 ! UI > jh^ CM X .. ro O O #~4 CM O * **4 CO -J UI > CM 4 x ,y 33 DUP040014076 NO. S TIME OF E 1N 7. RATS X MT'H'S AP 00005 F - 10-0r< O' O .2 c-Jc <c 4J < x UJ i-L Oa < 01 < 2 CO CC X O JU. 2 a .1/5 2; UJ -J <NJ CL C\J X < cc oO O tL e' tu til o -<O UooJ UJ -j > -j < 2 < tu 2 .CC .P 1 m* o 2 UJ CD < K- .se UJ Cl V5 H* u .< 5-- 0>0 CC u QX. CC .a < X .*- a. u- OCC 3: O CO ' cc . c> 5-- -j a PO Oo -oJ C CO V--1* 2t--t .*J cc co 2 at *2-* acc. t--u 1 UJ tu 2 UP .* O oPo cc o' oao. OX cc U<J a. > 2 .2< >z<a?s. > <z 5C >2 > 2 <C X s<: > 2 < >2<s > 3: tau. 2 2 2 uUJ. I Q 1 I I -1 CP 2 Q CaL. 0 W 0 2 a o 2Aa-. 4a. , CL o cz o o o o oo u r-4 in H .*>4 pop o p H- --4 <\J H ooP P o p oa o a 4- fnj #m4 *r-o* it r* iPH. P o r^l Or-4 O H r- >- Is- CO *o -J -J -j tu UJ ui Ul UJ > > .> > > h- *- J- c m <M CM -4 H r4 <M tL tL tL tL | | | sI S $ if DUP040014077 .cuacu o> \A (M u .s<o X *1 oo */} > < cc cc u X' a. a: m >4 XO '< LXJ > 21 >2 > 2 < C * 2X >2 < X 2 ill XOJ IL < 3: Ul UL < X UJ o 2 .<4 UJ < X s/i c*.X OH U. 2 i/> ajr UJ -0J. COSJJ 5* /j o u. o UJ UJ Ls H* aO h - CL UJ u g< a <iu/i < uj c/> > J < 2 <C Ul 2 IMI CC p 1 - o 2 Ul -1 CO H- a UJ <CO4 3C occ oc o-J > K- -4 Q UP PO O -4 P CQ 12 I CO co 2 IX o ** cc UJ CL 1 UJ jUzl va <w o o %n cc 3 a. i/i X a. . Cg < UJ CL CL < UJ * l/l IM w ZH h wse t/> u j >: -4 Oa: oxo CL X CX Q i* Q. a 2 Oo O H ion o o P o oo CM o o r?*< .#4 CM P o P *4 .*-4 CO r** CC . _! u _J iu Ul Ul >- >" > H* H* H(SJ CSJ CM fNJ CSJ CM X XX X CL Q. oO o r-l a Q .*-4 CM O ( #-4 UJ > H* CSJ CSJ X V) H O UL < ZOtf in o O o o y ' 5 DUP040014078 TABLE NO. 4 - URINE ANALYSES OF POOLED SAMPLES FOR MALE AND FEMALE ALBIN O RATS LEAD ACETATE FOR 22 MONTHS ACE TON O T* O' JV iu CL VO 4 >2: <r s >> .z<at ' <z > z< 00 .or u as X 3: UJ OJ UJ X LU X U- U_ tv u. a of O -<? x Cl Uj CUD X e Q occ o > _i a r? o OQ O O CO *--4 z-H -J CG ~3 CQ CC 12 a *- OC UJ A. -H1 Ul o J3to Oof CL VO aX. a<: Ua.i C<L UJ . t/) SHI *-* Z H- >- ~-.3l VO UJ X Jo* /H Ci< Z O a: QoX c* h- CL a ap p p #-* o ~4 O P to Q IA _J UJ > o CM CM IL IA O O Oa 4* o 04 r~4 H- -j UJ > H CM CM tv Xc CL a. oin o p ^H-O4 a * -4 o J UJ > 1-- CM CM U. X cl a o o o ,,r*4 o < Q O o OJ - r- J UJ > CM CM u. irs DUP040014079 I - 56 - 1000 PH-J Male Rat ifo. 53-930 . Grass: Ifo gross alterations "were noted at necropsy. Microscopic: Pituitary: A moderate number of basophils were slightly hypertropic. ' Thyroid: Variably sized follicles comprised section of gland examined,. Epithelium lining the follicles varied from squamous to euboidal* "1 The colloid was of a light eosinophilic color. Histologically this gland appeared to be in a moderate state of activity. Lung: lhe lung was moderately congested. Small foci of hyperplastic lymphoreticular elements were present next to the bronchioles. Alveolar walls were slightly thickened from an influx or lymphocytes and by hypertrophy of the alveolar septal cells. Liver: The nucleus of an occasional hepatocyte was hyperchroaatie and both it and the cell were enlarged approximately one and one-half to two times normal size. Some of the central veins were ectatic. Spleen: Moderate number pf active lymphoid follicles were present. Small numbers of megakaryocytes were present within the red pulp. A brown to golden yellow granular pigment was present within the cytoplasm of macrophages within the red pulp. Small foci of extramedullary hematopoiesis were present just beneath the capsule. Kidney: Small number of glomeruli were atrophic. The parietal layer of Bowman's capsule of these glomeruli and others was thickened by hyper trophy and some hyperplasia of the epithelial cell and from the increased r> *>* * DUP040014080 57 thickness of the basement membrane. Some of the epithelial cells of the proximal convoluted tubules exhibited degenerative and regenerative char.-res.. Many of these cells were eosinophilic cytoplasm, hyperchrcmct-ic nuclei, ana rarely th individual cells were greatly enlarged up to two times normal sine, The nuclei of these larger cells were also increased in dimensions and quite often hyperchromatic. In some of the proximal convoluted tubules, the epithelium was frankly necrotic. Some of the nuclei of the proximal convoluted tubules contained an inclusion which was composed of small granules or a single droplet. The inclusion stained from a faint yellow-orange to a light pink. Small numbers of proximal convoluted tubules and collecting tubules i* contained a homogeneous eosinophilic cast material* Adrenal: Most of the cells of the sona fasciculate exhibited vacuolation .of the cytoplasm. Testis: The sperroatogenic activity was normal and. moderate. Bone Marrow; The femoral bone marrow contained moderate amounts of fat. The hematogenic elements were represented by moderate numbers of megaka ryocytes and moderate numbers of maturing elements of the mye loid and erythroid series. The sternal bone marrow contained a slight amount of fat. Moderate numbers of megakaryocytes were present, as were moderate numbers of the myeloid and erythroid series. Most of the latter series exhibited maturing elements. I The following organs were within the limits of expected histologic appearance: brain, spinal cord, heart, stomach, pancreas, small intestine, large intestine, , and bone. DUP040014081 V - 58 - * 1000 EM f Male Hat No. 58-931 Gross: Up gross alterations were observed at necropsy. ' Microscopic: Pituitary: A moderate number of basophils were hypertrophic, thyroid: this gland was composed of follicles of various sizes. Larger and intermediately sized follicles were Iqss numerous than the smaller follicles. The smaller follicles were lined by cuboidal epithelium, the colloid contained within the follicles was uniformly eosinophilic, the histologic appearance of this gland would place it in the moder ately active category. Lung; Alveolar walls were slightly thickened from Small numbers of lymph ocytes and, on occasion, hypertrophy of the septal cells. , Liver: A Considerable number of the hepatocytes exhibited an increased granularity to the cytoplasm accompanied by distinct eosinophilic resulting in swelling of these cells and narrowing of the sinusoids. Small foci of necrosis of hepatocytes were present which were accompa nied by small numbers of lymphocytes. Spleen: Moderate numbers of active lymphoid follicles were present. Small foci of extramedullary hematopoiesis were present* Moderate numbers of macrophages contained a brown to yellow-brown granular pigment Ik- within the cytoplasm. Extramedullary hematopoiesis was noted to be scattered throughout the substance of the red pulp in small foci. Megakaryocytes were infrequently observed within the red pulp. DUP040014082 - 59 Kidney: On occasion, the parietal layer of Bowman's capsule was thickened from hypertrophy of the epithelial cells accompanied by thickening of the basement membrane. Some of the cells lining: the proximal convoluted tubules exhibited various stages of degeneration character ized fcy slight swelling of the Cells, increased granulation within the cytoplasm, and rarely hyaline droplet formation. The nuclei of a considerable number of the cells of the proximal convoluted tubules contained inclusions which were granular to droplet ir. formation and a light orange to light pink in tinctorial quality. On occasion, giant epithelial cells were observed lining the ^proximal convoluted tubules. These cells contained nuclei which were up to two times the normalsize. Small amounts of an eosinophilic' material were contained 'within the lumens of the proximal convoluted tubules, distal convoluted tubules, and collecting tubules. Adrenal: A moderate number of the cells within the zona fa'sciculata exhibited vacuolation within the cytoplasm. Pancreas: Small focus of inflammation was present within the pancreas which was characterized by small numbers of lymphocytes and early fibrosis. Testis* Small number of tubules contained exfoliated secondary spermato cytes and other cellular debris. Most of the tubules, however., exhib ited normal and moderate spermatogenic activity. Bone Marrow: Femoral bone marrow contained considerable amounts of fat. The hematogenic elements were represented by considerable numbers cf megakaryocytes and maturing elements of both myeloid and ex'ythroid <i. 0 k DUP040014083 - 60 - series. Sternal bone marrow contained very little fat. Large numbers ' of megakaryocytes were present, as were large numbers of myeloid and erythroid elements. Both of the latter series exhibited maturing forms. > The following organs were within the limits of expected histologic appearance.: brain, spinal cord, heart, stomach, small intestine, large intestine, and bone. . 1000 FB4 Female Rat Ko. 50-977 Gross: . . No gross -alterations were noted at necropsy, 1 Microscopic: Thyroid: This organ was composed of small, medium, and large follicles. The epithelium lining the follicles varied from a squamous to a low cuboidal in the large to Small follicles, respectively. Activity was low. lung: One small focus of hyperplastic lymphoid reticular cells was present near a bronchiole. / Liver: Occasionally, the sinusoids near the central veins were dilated. Small foci of lymphocytes were observed in the parenchyma, not neces sarily associated with any other pathologic alteration. Spleen: A moderate number of active lymphoid follicles were present. large amounts of a brown to yellow-brown granular pigment were contained within macrophages in the red pulp. Megakaryocytes were observed within both the red and white pulp in moderate numbers. Small foci of extramedullary hematopoiesis were present beneath the capsule. j %_/ DUPO40014084 6l Kidney: Some collecting tubules and distal convoluted tubules were dilated. On occasion, the parietal epithelium of Bowmen* s capsule exhibited hyperchromatic nuclei and, rarely, hyperplastic changes. Some of the proximal convoluted tubules exhibited early degenerative changes, ^ characterised by swelling of the cells, increased eosinophilic, and, in some cases, sloughing of the cell into the lumen. Some of the tubules exhibited a decrease in the number of cells within the epithelium. Small numbers of Very large epithelial cells were aligned along the proximal convoluted tubules. The latter cells exhibited '4 large nuclei that were regular in internal structure to hypercliromatic. Considerable numbers of the epithelial cells lining the proximal convoluted tubule contained intranuclear inclusions which were pir>k in tinctorial quality. Some of the cells which contained these inclu sions exhibited degenerative changes, whereas others were hot. Distal convoluted and collecting tubules contained, on occasion, similar inclusions. Degenerative changes observed within the proximal tubules were not observed in the lower parts of the nephron and collecting tubule. Small Intestine: Small numbers of neutrophils were present within the lamina propria. Ovary: Graafian follicles, corpora lutea, and atretic follicles were present. Bone Marrow: The femoral bone marrow contained some fat. The hematogenic elements were represented by large numbers of megakaryocytes and maturing elements of both the erythroid and myeloid series. The e~ -ZO DUP040014085 -a* cdtraj 62 sternal tone marrow contained less fat than the femoral tone marrow, large numbers of megakaryocytes vets present," as vets maturing elements of both the myeloid and erythrpid series. The following organs were within the limits of expected histologic appearance: brain, pitnitary, spinal cord, adrenal, heart, stomach, pancreas, large intestine, and bone. 1000 PM Female Bat IIo. 56-978 Gross-: No gross alterations w:ere observed at necropsy. Microscopic: Thyroid: The gland was composed of small, medium, and large follicles which were lined by cuboidal to squamous epithelium. The histologic appearance of this gland would place it in the moderately active category. Lung: Free fresh blood was observed within the bronchioles and alveoli, as were considerable amounts of a very fine fibrin meshwork. These reflected, most probably, the method of sacrifice. Heart: The myocardium was moderately congested. Liver: Considerable numbers of the sinusoids were dilated, especially' near the central veins. Spleen: The lymphoid follicles exhibited moderate activity. Low to mod erate amounts of a yellow to brown granular pigment were contained within the macrophages of the red pulp. Low numbers of megakaryocytes DUP040014086 j - 63 - < were present within the red pulp.. Foci of extramedullary hematopoiesis were present throughout the red pulp. Kidney; The glomeruli were slightly congested. The parietal 'layer of Bowman's capsule was thickened from slight hypertrophy of the epithe lial cells. The epithelium of the proximal convoluted tubule exh.ibited degenerative changes characterized by vacuolation and granulation of the cytoplasm. The cytoplasm often was of a deeper eosinophilic color than the more normal epithelial cells. The. nuclei contained inclusions which were granular to droplet, quite homogeneous, and from a light orange to eosinophilic in color. The inclusions were observed both within the nuclei of degenerating and more normal epithelial cells. The, proximal convoluted tubules exhibited these i changes much more frequently and with a greater Severity than did the distal convoluted tubules. Adrenal: Moderate numbers of cells in the zona fasciculata contained cytoplasmic vacuoles. Stomach: A slight amount of hyperkeratosis was present. Ovary: firaafian fclllicles and atretic follicles were observed within the substance of the ovary, indicating activity. Bone Marrow: The sternal bene marrow contained moderate amounts of fat. The hematogenic elements consisted of moderate numbers of megakaryo cytes and maturing elements of the nyeloid and epythroid series. . The femoral bone marrow contained considerable amounts of fat. Hematogenic elements consisted of moderate numbers of megakaryocytes and maturing elements of both the myeloid and erythroid series. DUP040014087 - 6k - the following organs were within the limits of expected histpiogie appearance: brain, pituitary, spinal cord, pancreas, small intestine, large intestine, and bone. loop .mi Female Bat Mo. 58-979 Gross: r Ko gross alterations were observed at necropsy. Microscopic: '0 Thyroid: This gland was composed of small, medium, and large follicles with homogeneous eosinophilic colloid. The epithelium lining the follicles was more commonly squamous in character; however, the smaller follicles were often lined by a low cubOidal epithelium. This gland was in a state of low activity. Lung: Large aggregates of hyperplastic lynphoreticular elements were present around bronchioles and vessels. The lung was moderately con gested, The alveolar walls were thickened from hypertrophy of the septal cells, congestion, and very few leukocytes which were mainly lymphocytes. Liver: An occasional small focus of extramedullary hematopoiesis was present, Small numbers of the sinusoids near the central veins were slightly dilated. Spleen: Active lymphoid follicles were scattered throughout the spleen. Small to moderate numbers of macrophages within the red pulp contained granular- yellow to yellow-brown to brown pigment within the cytoplasm. y -5 DUP040014088 - 65 Cmall numbers of megakaryocytes were present within the red pulp. Small foci of extramedullary hematopoiesis were present within the red pulp. .' Kidney: Some of the proximal convoluted tubules exhibited early degenerative changes, characterized by swelling of the Cells, increased eosinophilic, and vacuolation. The nuclei of these cells and others often contained inclusions Which were granular to homogeneous and a light orange to a light eosinophilic color. The distal' convoluted tubules and collect ing tubules exhibited, on occasion,, the inclusions; however, degener ative changes and the numbers of inclusions were much less than in the proximal convoluted tubules. Adrenal: Considerable numbers of the cells in the zona fasciculata exhib ited cytoplasmic vacuolation. Stomach: Slight amount of hyperkeratosis. Ovary: Graafian follicles, corpora lutea, and atretic follicles were present indicating activity. Bone Marrow: The femoral bone marrow contained some fat. Considerable numbers of megakaryocytes were present. The myeloid and erythroift elements were numerous and represented by maturing forms. The sternal bone marrow contained some fat. Large numbers of megakaryocytes were present. The hematogenic elements were numerous and well represented by maturing elements. The following organs were within the limits of expected histologic appearance: brain, pituitary, spinal cord, heart, pancreas, small intestine, large intestine, and bone. DUP040014089 - 66 1000 EPM' Female `Rat Ito, 58-980 Gross: No gross alterations were observed at necropsy. ' Microscopic: Spinal Cord: The spinal card was severely distorted, and precluded critical histologic examination. Thyroid: -Small, medium, and large follicles comprised this gland. The colloid was of a homogeneous eosinophilic tinctorial quality., and the follicles were lined by squamous to low cuboidal epithelium, The gland was in a low to moderate state of activity.. l Rung; Small foci of hyperplastic lymphoreticular elements were present around some of the bronchioles .and vasculature. The alveolar -walls Were thickened from slight congestion, hypertrophy of the septal cells, and small numbers of lymphocytes. Heart.: A Slight amount of fibrosis in the ventricular septum. Spleen: Moderately active lymphoid follicles were scattered throughout the spleen. A small amount of yellow to brown granular pigment was contained within the cytoplasm of macrophages within the red pulp. Small numbers of megakaryocytes were present within the red pulp. Kidney: An occasional glomerulus was atrophic. The parietal layer of Bowman's capsule of some of the glomeruli was thickened from hj'per trophy of the epithelial cells. Early hyperplastic changes were rarely observed. Considerable numbers of the proximal convoluted tubules | ] i DUP040014090 - 67 exhibited degenerative changes within the epithelium. These changes > were characterized by swelling of the cells, increased eosinophilia, granularity, and Va cuolation of the cytoplasm. . In soine cases, the epithelial cell was sloughed into the lumen of the tubules;. Con siderable numbers of giant cells were present within the epithelium of these tubules. These larger bells contained very large nuclei that were, in turn, hyperchromatic in many instances. Many of the proximal convoluted cells contained intranuclear inclusions which varied from a granule to a homogeneous droplet and from-^n orange to an eosinophilic color. The proximal tubules were much more -severely affected and more regularly affected than were the distal convoluted tubules or collect ing tubules. Intranuclear inclusions were observed within some of the epithelial cells of the latter tubules, however. Eosinophilic homogeneous material, probably proteinaceous, was contained within Some of the collecting tubules. Adrenal: The cells of the zona fasciculate were vacuolated. Ovary: Corpora lutuea, atretic follicles, and Graafian follicles were observed indicating activity. Bone Harrow: The femoral bone marrow contained considerable sunounts of ' fat. The hematogenic elements consisted of small to moderate numbers of megakaryocytes and maturing elements of both myeloid and erythroid series. The sternal hone marrow consisted of a moderate amount of fat. The hematogenic elements in this marrow consisted of moderate numbers of megakaryocytes and numerous maturing elements of both the myeloid and erythroid series. 2 DUP040014091 - 68 - The following organs were within the limits of expected histologic appearancef brain, pituitary, liver, stomach, pancreas, small intestine, large intestine, and hone. .1000 PPM. Female Pat Ho, 58-981 Gross: I;o gross alterations were observed at necropsy. ' Microscopic: ,' Thyroid: Small, medium, and large follicles comprised this gland. The epithelium lining the various follicles varied fr.pm squamous to plump cuboidal, and the colloid contained within the follicles was a faint eosinophilic color. The histologic appearance of this gland would place it in the moderate activity category, hung: Moderate congestion. large, irregularly shaped, mineralized plaques . were present within the intima of one of the larger arteries. Alveolar walls were slightly thickened due to a slight amount of congestion., hypertrophy of the septal cells, and sjnnll numbers of lymphocytes. Spleen: Active lymphoid follicles were scattered throughout the substance of the spleen. Small to moderate amounts of a yellow to brown granu lar pigment were contained within macrophages of the red pulp. Small numbers of megakaryocytes were present in the red pulp. Considerable numbers of foci of extramedullary hematopoiesis were present. Kidney: Considerable numbers pf proximal convoluted tubules exhibited de generative changes including increased eosinophilic of the epithelial ci n DUP040014092 \ --A. 1 \ \ * the lumen, and epithelial cells without nuclei. Rarely, loci of regenerative epithelium were observed, The nuclei of many of the / epithelial cells lining the proximal convoluted tubules Contained inclusions which were granular to droplet in formation-and orange to light pink in tinctorial quality. Moderate numbers of veSry large epithelial cells were present which contained very large nuclei that were, in turn, hyperchroraatic. Some of the distal convoluted tubules exhibited degenerative Changes but not nearly as severe nor as exten sive as the changes observed in the proximal tubules. The collecting tubules were, for the most part, spared of pathologic alteration. Adrenal: Moderate numbers of the cells in the zona fasciculata exhibited cytoplasmic vacuolation. Ovary: Graafian follicles, corpora lutea, and atretic follicles were present indicating cyclic activity of the ovary. Bone Marrow: The femoral bone marrow contained considerable amounts of fat. The hematogenic elements were represented by numerous megakary ocytes and maturing elements of both the myeloid and erythroid series... The sternal bone marrow contained considerable amounts of fat. The hematogenic elements consisted of numerous megakaryocytes and matur ing elements of both the myeloid and erythroid series. The following organs were within the limits of expected histologic appearance: brain, pitU-iaiy, spinal cord, heart, liver, stomach, pancreas, small intestine, large .intestine., and bone. 244 DUP040014093 gsam - 70 - SUMMARY Tissues derived from equal-sized groups of sale ar.u female rats, one-half of which were either treated with 100 ppm or 1000 ppm leal acetate, revealed, when compared to similar tissues from, untreated male and female rats, appreciable alterations in the kidneys. Other tissues including samples from brain, spinal cord, pituitary, thyroid, adrenal, lung, heart, liver, spleen, stomach, pancreas, intestine, ovary, testis., bone, and bone V marrow from the control and 'both treatment groups failed to exhibit appreciable between group differences, histologically, which could be assigned to treat ment effect. The proximal convoluted tubules from the group of animals that received 100 ppm lead acetate exhibited in seven of the 10 rats slight to moderate vacuolation and a minimal to slight incidence of degeneration of the epithelium. Characteristically, the degenerative lesions consisted of slight hypertrophy, increased eosinophilic of the cytoplasm, and loss of the brush border. On occasion, an eosinophilic to orange, angular to granular material was present within the nucleus of some epithelial cells lining the proximal tubules. Degenerative alterations were not constantly evident in those cells with the inclusion material. Tubular cast material was observed in eight of the 10 animals examined. The distal Convoluted tubules from this group of rats failed to exhibit appreciable changes histologically. 1 DUP040014094 n "he samples of kidney tissue examined from the -rats that received lu v ppm exhibited a slight to moderate incidence of degeneration of the epithelial cells in eight of the 10-animals* Intranuclear inclusion material was obsejr/od'in all animals from a slight to a moderately severe incidence in the epithelial cells of the proximal tubules. Seven of the 10 animals from this group exhibited a slight to moderate incidence of very large epithelial cells along the course of the proximal tubules. Both the cyto plasm ar.d nucleus of these cells were increased in volume up to. three times the normal. The significance of these cells was indeterminable. Minimal to slight degenerative changes were observed in th# cells lining, the distal convoluted tubules of three of the 10 animals examined. Intranuclear in clusion material was observed on occasion in these cells. In conclusion, the'( administration of lead acetate for six months to male and female rats, resulted in histologic alterations in the tubular structures of the kidneys when compared to the same tissues from control (untreated) rats. The tubular changes observed in the kidneys derived from the low level lead acetate treated animals consisted of vacuolation and mild degeneration, primarily of the proximal convoluted tubules, ac companied by an increase in cast material throughout the nephron and into the collecting tubules. Inclusion material was observed within some of the nuclei of the proximal convoluted tubules. The kidney tissues derived from the high level lead acetate treatment group exhibited slightJ y more degeneration of the epithelium lining the proximal convoluted tubules r- % C o MCMMMiUMtMttMpkB DUP040014095 M'rtifftti'fchriMi. 72 coupled with intranuclear inclusions and megalocytosis. Die distal convoluted tubules frpm this group exhibited a slight amount of degener ation and occasional intranuclear inclusions. Other tissues from the control and treated animals failed to reveal appreciable differences histologically, ' 4> DUP040014096 nil HISTOPATHOLOOICAL EVALUATION OF HALE AMD FEMALE ALBINO HATS SACRIFICED AFTER SIX MONTHS LEAD ACETATE KEY: P = Present MS = Ho Section X - Hot Remarkable +/0 = Minimal 1 - Slight 2 = Moderate 3 = Moderate to Severe h = Severe | i 1I Zk$ v v --t ii.k ;,v, ,, i mAoi~yuisitimartntTi`rffiTifta'< DUP040014097 fttfocnH&'t.-ysj&Sr' i ****! HISTOPATHOLOGICAL EVALUATION OF MALE AND FEMALE ALBINO RATS SACRIFICED AFTER SIX MONTHS LEAD ACETATE V* 58-471 58-472 58-473 58-474 58-475 58-476 58-477 58-478 58-479 58-480 X X .X X 1 X X I X X 58-570 58-571 58-572 58-573 58-574 58-575 58-576 58-577 58-578 58-579 X X X X X X X X X X 1 X X X X X X X +/0 X p +/0 p p1 p +/o p1 p1 B 1. p1 pi p p 1 2 X psA X X X X X X X P CONTROL - FB-tALE X P1 X X P1 X X P1 +/0 X X P1 X X P2 X XX PX X P2 X X P 1 PX X P1 X X P1 X X V I -- .-'0 1 X .1 1 X +.'0 *./o + '0 X t/o + -'.0 I1 X :i i x i iq T* v* * DUP040014098 spl een ; KIDNEY g l o me r u l i PROXIMAL CONVOLUTED TUBULES DISTAL CONVOLUTED TUBULES gS Animal No. a> r--l .cJ) U a> p; H H, -op pOu < Go O jg 58-471 58-472 58-473 58-474 58-475 58-476 58-477 58-478 58-479 58-48D 58-570 58-571 58-572 58-573 58-574 58-575 58-576 58-577 58-578 58-579 2 .2 1 X 2 +/0 1 3 1 +/O 1 2X 21 22 2 X 2 2 1 2X 21 221 CONTROL - MALE (continued)* 1 ii 1 .1 2 11 23 22 22 1 11 2 111 2 2 11 22 3 1 2 2 11 2 2 11 2 3 11 CONTROL - FEMALE (Continued) X +/o 1 1 2 1 3 3 0 1 c :& I 3o -P ctf ft 1 1 +/o 2 1 * St?O DUP040014099 V* 3 Animal No.. KIDNEY (Continued) W ,o r-i d I HcdP0) ADRENAL STOMACH CJ rrl 3 Cl -P PANCREAS HdGC5> ~dp 6jy5 1<3y SMALL INTEST. LARGE *H *> p=0: 4* ' 6P?: :o 58-471 58-472 58-473 58-474 58-475 58-476 58-477 58-478 58-479 58-480 58-570 58-571 58-572 58-573 58-574 50-575 58-576 58-577 58-578 58-579 1 ,1 21 11 2 T_ 1 1 1 2 1 ,1 1 CONTROL - MALE (.Continued) f/O X X ' {l- --/o 1 XX X X XX X X XX X X X X X. X XX X X XX X X XX +/C 2 YX 1 1X X +/0 X CONTROL - FS4ALE (continued) X X 1X X X X X X X X XX X XX X X .1 X XX X X 1X XX X XX X XX X XX X XX X X "X X X X V *% X X X X X X X V X X ns DUP040014100 V* 4 i TESTIS OVARY B(I3 MARROW FSMORAt, STMAL BORE Animal No. O*> < a<rf UIrl g O 58-471 58-472 58-473 53-474 53-475 58-476 58-477 53-473 58-479 58-430 2 '2 2 3 3 2 2 .2 3' 3 58-570 58-571 53-572 58-573 53-574 58-575 58-576 58-577 58-578 58-579 P P P P P P P P P ? >4 Q to +5 a Ma fl> % ,C aJ o Ig tT^-c* 4O*** S3 8p 3i r~i S3 >P> 53 S ) w a %c -0& .fcoD & D1 fl) to .se ss 3 3 . a> 4* S CONTROL - MALE (Continued) '' & 3 2 2222 X 33 22 23 33 23 22 X X X 3 '2 3 '2 22 3 23 3 23 22 2 3 32 X X X X 3 P2 222 3 33 X X CONTROL FifciALE (Continued) 3 2 2322 X 2 3 32 3 3 X 3 2 213 3 X 3 2 1321 X 3 2 2132 3 1 2322 X X 12 2 2 11 3X 2 2 9*x 2 2 2 .1 2 2 X 3 1 1222 X *w DUP040014101 5- - BRA331 riTUITAF'? TKXBOIP LUNS Animal No. J<-DI rf ;*<: Ko - oP ( Ml < * xOo* 4*r?i od .d 4O ^o C0 CdO -rf> 58-827 53-828 58-829 58-830 58-831 58-877 58-878 58-879 58-880 58-831 58-927 58-928 58-929 58-930 58-977 58-978 58-979 58-980 58-981 XX XX XX XX XX X X XX XX XX XX XX X X X XX XX XX XX XX 100 PB`I - MALE P P ITS P1 P1 NS 1 P 100 PEA EE4ALE P PX P 1 1 2 1 1000 Pm - MALE P2 P2 2 P1 P1 1000 PR4 - FB4ALE PX 1 P1 P1 HEART LIVER dH P 0 33 dt)8 3Ua ddU00*3 oot>> 3 C0O o0 JDri 4OP>< t0i rH a 3 s* 36Co 's d Sd03 o 4*A4 UA X X X X X XX XX X X PX pX X X X X X XX XX DUP040014102 -6- Animal No. 58-827 53-828 53-829 53-830 58-831 53-877 58-873 58-879 53-880 58-881 53-927 53-923 58-929 58-930 58-931 58-977 58-973 58-979 58-980 58-931 spl een KiprrsY GIOMEP'TLI PROXIMAL CONVOLUTED `TUBULES DISTAL CONVOLUTED TUBULE: <y CO 4rrf 1COr< 0 P v- I & O 2 * '55 H .:po >ti> g %A 0 >u - 4> J*! ^ dSjD --UP S3 & * Hd j/HH0auV> & < sH d >a4> f0fct3ai co 1.4bO) 3 .V3 Pd *daX> r2a-i w -S .* ?d S3 a p<Hy o & is * Vi a) r-f &a> ow 3oa o .*"i ^.03HP) C 5- <O3 . Mr* <u 5 oto3 MPC3 $da*t . (H3 raHjj 01 C XU 5 f-i Wf4 **TH3 -P .O 0 CP H 105 PH-f - MALE (Continued) j 2 111 2 ' +/0 13 2 .1 .1 .2 11 2 2 11 1 1 +/o +/o 1 11 +/0 1 +/0 +/0 2 2 111 .2 2 1 1 2233 2 312 2211 32 1 21 1 2 311 2 .1 1 1 22 11 100 PPM - FEMALE (Continued) 11 2 +/o 21 11 +/Q 1000 PEM - MALE (-Continued) 12 1 12 11 3 32 1 22 11 1 13 .1 1000 PPM - FEMALE (Continued) 321 111 211 11 11 .1 1 12 22 22 1 2 2 +/0 +/0 1 :,S4 DUP040014103 KIIXTEY (Continued) HeJ & vu* o u 0 u H o f->i 4 .oc55* toj o '*3 . 15 s 0 wooc<<rUy>li + > <u <!Uy 55 1a *rl & . CO 58-827 58-828 5S-829 58-830 58-831 100 PM - KALES (continued; 1 X XXX & X 1 X X X X 7, 2 X XXX X 1 X XXX X X XXX X 1 100 p - F2-IALE (Continue;) 2 2 2 2 2 58-877 58-878 58-879 58-880 58-881 1 22 2 11 1 X XX X 1X ,,x i X 1X X X xX X X X X X X X r X X 1000 PPM - HALE (ContJnuei) 58-927 5.8-92S 58-929 58-930 58-931 11 +/o +/o 2 1 1 X X X X X XXX XXX X XX XXX X 1X X X X X X 1000 PM - FS-IALE {Continuei) p? 1 2 p2 58-977 1 X XX lX 58-978 X 1X X X 58-979 X 1X X X 58-980 1 X XX X X 58-981 X XXX X 07AHY +>> p c cHi O:d> P P r r p |- '3 , t fi t -{ !l 4n *? i % 3* `i % 3 .3i I i I DUP04001410. ft>, / * -0- .' eo n s ; FrMOKAL 5TB3A.ti nittal Mo. i I? pco IPDGO w TGcJd t? ft* g -QW 5 I. Pa3 6 > ,bCl> tCol 1 pCl op O po d P ,C<*34 .$) Cl BOMB % aH* $ M (9 w i >rl u* 53-02? 58-828 53-829 5.3-630 58-831 loo pm * MALE (Continued) .1 3 31 32 3 1 3 3 1 2 2 -2 1 3 'f 2 22 NS 32 232 X X X X 100 PH-i - FEMALE (Continued) 1 58-877 58-878 58-879 58-880 58-881 1 3 2 1 33 X .3 3 .".2rO. 2 2 33 X 2 22X 1 3 2 1 3 3 X 3 p 2 2 32 X 1000 PPM - MALE (Continued) 58-927 58-928 58-929 58-930 58-931 53-977 58-978 5-0-979 50-980 53-981 33 33 X 2 3 3 2. 2 2 X 1 2 3 2 *<31 1 33X 1 22X 3 2 2 X 33X 1000 pm - FEMALE (Continued) 1 3 3 1 33 X 3 2 2 2 2 2 X. 1 0 3 1 23 X 3 2 2 2 22 X 3 2 2 3 22 X y r r-r DUP040014105 HISTOPATHOICGICAL EVALUATION FOR MALE AND F3SOLE ALBINO RATS SACRIFICED AFTER 12 MONTH? CROSS LEAD ACETATE CONTROL Male Rat No. 5S-*6q { _________ MICROSCOPIC Thyroid: ilo alterations described. Thyroid: Small- ani noliurn-sized follicles prcdomlnn* with iasgsc follicles at periphery. s' Colloid li's-rt eosinophilic and quite !*.*<:eo.~r Epitheii rt ~ ridominantiy lev with some j -Imr s . cuboidal. Lung: No alterations described. us liver: No alterations described. Activity fer rate.. Lung: Slight rczfgsestion, 't Minimal chyrmie murine pneumonia charact o-rine.i by .focal re-iilar iysphoreticular 'hypervlas; a in periVas-nuiar and peribronchial tissues.. Minimal ttirr-ening of alveolar trails by hypertrophy and hyperplasia of alveola;' septal cells along with infiltrations rf mononuclear inflammatory cells and small numbers ci neutrophils. One large v*rsel contained a mineral tic: osJr within the "nil. Liver: Minimal pericholangitis characterized by infiitm -.2. of the portal areas by mono nuclear inflammatory cells. Barely a fores of mononuclear cells within the parcEeu-ana unussoeiated with hepu-uuni: y. DUP040014106 V .V -2- CONTROL Male Rat No, 58-160 (Contirtaevili GRvSS -_________________ i______ MICROSCOPIC Kidney; No alterations inscribed. Kidney: Moderate northers of epithelial cells 1 Ssife.: the proxisat- convoluted tubules contain? i a yeilov to brown granular pigment. Slight-ecagestion. Slight 'increase in protein imbibition by cel 1: lining prcxtaal convoluted tubules chars..'i='r;: by snail droplets of an eosinophilic aster: si * y. within the cytoplasm. Occasional pccxisial convoluted tubule cental-n; a droplet to globular cast material Thar w eosinophil!r and quite homogeneous in -.niton'. Slight focal chronic nephritis characterincc by infiltrat-ior. of ihterstitium by re:;. r.Uri-:io inflsrnatcrr cells. Rarely a collecting tubule contained a h.'Scgeneous ecsimphilic cast material. One snail t'ocioS of proximal convoluted i h.' .c had changes characteristic ol` a nephr< 'h-Ls ' charaeterlca'i by a swelling of the imltH*':,;. cells, lar-Cfr numbers of protein droplets within the cytoplasm (eosinophilic dnrs*lr r" and ccT.tairs-d a homogeneous eosinop i;iic material >I thin the lumen. Occasional C- ileeting duct ililatcd and .* a. TTS an bocir. cSliic cast material. DUP040014107 A iwited*** -3- CONTROL Male Rat Ho. 58-460 (Continued) S50SS 1 _______________ MICROSCOPIC Spleen; No aiteraiicca described. Pancreas; Ho alterations described. Duodenum: IJo alteratirr-s described. Colon; No alteruXiaas described. Occasional tubule within cortex contained regenerative epithelial cells. Spleen: ' Moderately high lymphoid activity. / Moderate reticuloendothelial activity. Moderately large amount of a brown to yellov granular pigment within macrophages. Minimal amount of extramedullary hematopoiesis. Pancreas; Slight amount of a yellow to brown ^rar.ular. quite refractile pigment deposited ir. o he . , interstitial cells associated with the islets. Duodenum: Slight infiltration of the lamina propria by mononuclear inflammatory cells and by - eosinophils. Minimal congestion. Slight mitotic activity of epithelial coils in the mucosa. Colon.: Minimal congestion. Slight mitotic activity of the mucosa. DUP040014108 -4 GROSS CONTROL Male Rat No.. 58-460 (Continued) | ________. MICROSCOPIC Tertis: No alterations described. Rone Marrow: L'o alterations described. Testis: Spermatogenie activity normal and moderately o' high. . Occasional mononuclear spermaioioal prc-error $gl in lumen.. , Rone Marrow: Moderately large numbers of raegakaryocy. co. Numerous maturing elements of both myeloid and erythroid series.. Activity moderately high. The following organs were neither described grossly nor remarkable microscoyioally: "'rain, pituitary, spinal cord, adrenal, heart, stomach, and bone. ~O.U DUP040014109 CROSS CONTROL Male Bat Mo. 58-461 1' MICROSCOPIC Thyroid: Mo alterations described. Lang: Ho alterations described. Liver: Ho alterations described. Heart: Ho alterations described. Kidney: Bo alterations described. Thyroid: Medium and large follicles freicminatea. Colloid light eosinophilic and quite 'he*:-'c-r Epithelial predominantly squamous to lev cuboids!.. Activity low. Lung: Ho tissue available for sectioning or examination. Liver: Slight pericholangitis characterised by infiltration of portal areas 'by raononusi t-v? inflammatory .cells. Heg.rt: Slight congestion. Kidney: Slight congestion. Rarely a collecting tubule dilated ana contained an eosinophilic homogeneous cast material. Minimal amount of a yellow to brown, granolapigment vri.thin macrophages of i nterstit 3if~. or within epithelial cells lining yrcxfmrconvoluted tubules. DUP040014110 6- GROSS CONTROL Male Rat No. 58-461 (Continued) ___________| _________ MICROSCOPIC Opleetsi .4 lio alters. . described. Stomach: Ho alter*-. las described. Pane rear. : Ho alter-..Iran described. Duodenum: Ho alter: Ions described. Minimal focal chronic interstitial nephritis characterized by small .accumulations of mononuclear inflammatory cells. ^ Spleen: Moderately hi$i lymphoid activity. Moderate reticuloendothelial activity.. Moderate amount of a yellow to brown granular . pigment within macrophages. Slight extramedullary hematopoiesis. Stomach: Moderate focal vasculitis of blood vessels of muscular!s characterized by infiltrations of eosinophils into the vascular walls and peri* vasculaj* tissues. Pancreas: Slight amount of a yellow to brown granular pigment within interstitial cells. Duodenum: Slight enteritis characterized by infiltrations of lamina propria by mononuclear iiiflammatory cells along with moderate numbers of eosinophils. Slight mitotic activity of the epithelial rolls in the mucosa. 232 DUP040014111 GROSS CONTROL Male Rat No. 58-^61 (Continued) _j_________________________ .MICROSCOPIC Colon: No alterations described. Testis: Ho alterations described. Bone Marrow: Ho alterations described. Colon: Slight mitotic activity of the epithelial .ellin the mucosa. Slight congestion. Testis: . Spermatogeoic activity normal and mode im-triy high. Occasional mononuclear spermatosoal precursor "# within lumen of seminiferous tubules. Bone Marrow: Moderate numbers of megakaryocytes. 1 ' Moderate numbers of maturing elements c:' myeloid and erythroid series:. Activity appeared moderate. The following organs were neither described grossly nor remarkable microscopically: brain, pituitary, spinal cord, adrenal, and bone. / r^ DUP040014112 - 8- GROSS CONTROL Male Rat No. 58-462 MICROSCOPIC Thyroid: lio alterations described. Lung: White spot? observed after fixation.. Liver: Ifo alterations described. Thyroid: Small, medium, and large follicles with the former two predominating. Colloid light eosinophilic and quite homogeneous Epithelium predominantly cuboida.1 to tall cuboida! in the smaller follicles and squamous in the larger follicles. Minimal folding of the epithelium. Activity moderately high. Lung: Slight chronic murine pneumonia characterised by perivascular and peribronchial focal nodular lymphSid.hyperplasia. Slight congestion. One of the larger vessles had a mineralised plaque within the wall. Liver: Slight pericholangitis characterised by infiltrations of the portal areas by email, numbers of mononuclear inflammatory cells. Rarely a stmTl focus of mononuclear cells in parenchyma unassociated with hepatoj-athy. r - I DUP040014113 - 9- CONTROL Male Rat No. 5.8-R62 (Continued) gr oss }; _________mic r o s c o p ic Heart; ,IIo alterations described. Kidney: Ho alterations described. Spleen: Ho alterations described. Duodenum: 4 Ho alterations described. Colon: Ho alterations described. Testis: I.o alterations described. Heart: Slight congestion, x' Minimal focal myocardial areas characterized by infiltrations of mononuclear inflammatory cells accompanied by fibrosis. - Kidney: Minimal amount of a yellow to brown granular pigment within Epithelial cells. Spleen: Moderately high lymphoid activity. Moderate reticuioendothel-al activity. Moderate amount of a yellow to brown graminr pigment within macrophages. * Moderate extramedullary hematopoiesis. Duodenum: Slight infiltration of lamina propria by mononuclear inflammatory cells along -sri* h some eosinophils. Slight mitotic activity Jn the epithelial. Colon: Minimal infiltration of mucosa by eosinophils. Minimal mitotic activity. Testis: Sperreatogenie activity normal and modera*. o~;r high. r c . y- DUP040014114 - ID - CROSS CONTROL . Male Rat Ho. 58-ho2 (Continued) ' ,| MICROSCOPIC Sone Mazrow: Jio alterations described. Bone Marrow; Moderate numbers of megakaryocytes. / Moderate numbers of maturing elements of both myeloid and erythroid series. Activity appeared moderate The following organs were neither described grossly nor remarkable microseopically; brain, pituitary, spinal cord, adrenal, stomach, pancreas, and bone. ror DUP040014115 - 11 GROSS CONTROL Male Bat Kb, 58^462 _________| MICROSCOPIC Thyroid: Ho alterations described. Lung: Ho alterations described. Thyroid; . Small, medium, and large folli cles witfe the small and medium sited predominating. S Colloid light eosinophilic and quite homogenerur Epithelium predominantly cuboidal with seme folding. ' ISm Activity moderately high, bung; Moderately severe chronic murine pneumonia characterized by focal nodular perivascular and peribronchial lymphoreticular infiltracicc. and hyperplasia with extension .and ccnpressica of surrounding parenchyma, accompanied by ectasia of bronchioles which contain-: d polymorphonuclear leukocytes (bronchiecta-ic abscess). Lymphoid infiltrates involved mucosa of bronchioles. Slight congestion. Slight emphysema. Slight focal thickening of alveolar veils by hypertrophy and minimal hyperplasia of alveolar cells. One of the larger vessels contained a s^norr 1 plaque within the wall.1*. ',h?V .* " DUP040014116i \ - 22 -t. Microscopic: , Thyroid: This organ was composed of follicles, which were in turn basically of two sizes. The larger follicles were lined by a squamows to low eu- / boidal epithelium whereas the smaller follicles, which were quite uniform in =i?e, were lined by a more cuboidal epithelium, the colloi .i had a tinctorial quality of faint eosinophilic nature and was homogeneous. The histologic appearance of the gland -would place it in the rang* c? mod erate activity. :f Lung: The lung was slightly congested. The alveolar walls were thickened frcn a combination of the congestion accompanied by some lymphocytes and few neutrophils. The septal cells were somesvhat hypertrophic in some areas and several foci of hyperplasia of the septal calls had occurred near some bronchial aggregates of lymphoreficnlar cells which had undergone hyper plasia. Some of the alveoli contained a homogeneous eosinophilic material, which in turn contained a fibrillar eosinophilic material. The lesic.is in +his animal's lungs were compatible with those of mild or early chronic murine pneumonia. Liver: Small foci of lymphocytes were scattered throughout the parenchyma and were not associated with ether pathologic change in the liver. Spleen: Moderate numbers of active lymphoid follicles were present. Small foci of extramedullary hematopoiesis were present within the red pnlp,- Small numbers of megakaryocytes ware scattered throughout the red pulp, A small amount of yellow to brown pigment was contained within macrophages of the red pulp. Some of the proximal convoluted tubules -.contained within the cytoplasm of the epithelium variably sized, usually small vacuoiem. *1r. occasion, an atrophic glomerulus was -observed. DUP040014117? ,i - 2.3 - * Kidney: Small nonsuppurative inflammatory foci at cortieomedullary junction. Proximal convoluted tubules exhibited vacuolated cytoplasm. Occasional hemoglobin cast in collecting tubules. Slight dilation of some collecting tubules, Jnterstitium in pelvis contained slight nonsuppurative-focus of inflammation.. Adrenal: A small amount of a golden brown-yellow pigment was Contained within the cytoplasm of the cells of the zona fasc.iculata and zona reticularis. Pancreas-: Small numbers .of reticular cells edfitained within their cytoplasm golden brown to yellow granules of pigment. The pancreatic acini and islets of Langerhans were normal hisrolegicaily.. Ovary: Variably sized Graafian follicles and corpora lutea were present indi cating functional activity of this organ. Bone Marrow: The femoral marrow contained considerable numbers,of fat. Moderate manbers of megakaryocytes were present as were maturing elements of myeloid and erythroid series. The sternal bone marrow contained some fat, moderate numbers of megakaryocytes, and moderately high numbers of maturing elements of both the myeloid and erythroid series. The following organs were within the limits of expected histologic appearance:: brain, pituitary, spinal cprd-, heart, stomach, small intestine, large intestine, and bone. C CONTROL Female Rat No, 58-575 Gross: r Lung: Dark red areas were noted on the surface of the lungs. iCS DUP040014118 - 2l - "X 1* Microscopic: Lung: Macrophages within alveolar cells contains! snail amounts of a grfesaJLar golden brown pigment* The lung was slightly congested, Moderate amounts pf free blood were observed within. the alveoli of some l n nchicles a: ; probably*the result of the necropsy procedure. Liver: Small foci of lymphocytes were scattered throughout the liver. An occasional small focus of extramedullary hematopoiesis was present within, the parenchyma of the liver. Spleen: Moderate .numbers of active lymphoid follicles' were present, Small numbers of megakaryocytes were present. An occasional focus of arsrsl medullary hematopoiesl*5 was present. Macrophages within' the red pulp contained both the yellow to broynr, yellow-brown pigment within the cyto plasm; also, other macrophages had phagocytise.d erythrocytes. Kidney: The collecting tubules contained a homogeneous, eosinophilic material. The epithelium of some proximal convoluted tubules contained variably si.-id. usually quite large,vacuoles. Oyary: Graafian follicles and corpora lutea were present Indicating normal function of the ovary by histologic criteria. Bone Marrow.: The femoral marrow contained considerable amount of fat. Small to moderate numbers of megakaryocytes were present. The myeloid and ery- throid elements were not numerous; however, maturing forms were present in both series. The bone marrow of the sternum contained considerable- quantities of fat accompanied by moderate numbers of megakaryocytes. The hematogenic system was moderately populated with maturing forms of both .. the myeloid and erythroid series. DUP040014119 r- -! - 25 The following organs were within the limits of expected histologic appearance:: train, pituitary, spinal cord, heart, adrenal, stomach, pancreas, small intestine, large intestine, and hone. >1 COITCROL Female Bat No. 58-578 Gross: Ho gross alterations were observed at necropsy.. Microscopic: Thyroid: The follicles were various sizes. The epithelium lining the follicles was most commonly of cubpidal shape. The .colloid was faintly eosinophilic and fibrillar in nature. The histologic appearance of this gland would place it in a moderately active category. Lung: A small number of lymphoreticular foci were present associated with bronchioles and blood vessels. Some of the alveoli contained an eosino philic fibrillar to granular material. . The alveolar walls were slightly thickened by hypertrophy of the septal cell and influx of small numbers of lymphocytes and occasional neutrophil,-' The lung was slightly congesi.fd. Liver: One pf the central veins within the liver was surrounded by ,u focus of necrosis of the hepatic Cells. This focus contained moderate numbers of lymphocytes and a few neutrophils and scanning processes in the form of immature fibroblast and early collagen deposition. Spleen: A moderate number of lymphoid follicles were present. The reticuloendotheliura component of this spleen was moderately hyperplastic. Consider- 2CD DUP040014120 * - 26 able numbers of megakaryocytes were present throughout the re-3 pulp, Mod erate pumpers of macrophages within the red pulp contained a brown tj> golden brow granular pigment. Small foci of etrneaullarjr hematopoiesi-fi were also present. Kidney: The kidney was moderately congested, An eosinophilic heir.oreueous 4$^.' material was present within the urinary spaces of some of the glomeruli. There were small foci of lymphocytes scattered throughout the irtsrstitium of the cortex. Some of the collecting tubules and proximal and distal convoluted tubules contained eosinophilic cast'material. . Adrenal*' Small foci of cells of the zona fasciculata were hypertrophic end 'IS. * contained large follicles within their cytoplasm and associated cells. One group of cells of the coca arcuate 'were hypertrophic and unite vacu olated* Ovary: Graafian follicles and atretic follicles were present. Bone Harrow: The .femoral marrow Was moderately populated by hematopoietic elements. Moderate numbers of megakaryocytes were present. The myeloid and erythroid series were well represented both in numbers .ftp. 3 maturir^t forms. Small amount of fat was present within the femoral bor.e marrow. Sternal bone marrow contained moderate numbers of megakaryocytes. The myeloid and erythroid series were represented by large numbers of cell exhibiting maturing forms. The following organs were within the limits of expected histologic appearance: brain, pituitary, spinal cord, heart, stomach, pancreas, small intestine, large intestine, and bone. DUP040014121 - 27 - Gross: . CONTROL Female Rat No. .58-578 Lung: The lung exhibited dark red areas throughout its substance. Kidney: Cystic structur^gjsurrounded both kidneys at necropsy. ./ Microscopic: Thyroid': Follicles of varying sizes comprised the gland. The epithelium lining these follicles varied from a squamous to ld& cuboidal. The collagen was somewhat variable in staining intensity from a pale to a darker eosino philic and was homogeneous in appearance. Histologically this gland appeared to be in a state of moderate activity. Lung: Small numbers of alveoli were emphysematous. Fresh blood was contained within some alveoli and bronchioles. Liver: Small foci of lymphocytes were scattered throughout the heart, some associated with the portal structures; however, some were within the midzonal region of the lobules. Occasionally some small foci of hepatoeytes contained vacuoles within the cytoplasm. In the section examined, a ..mall focus of extramedullary hematopoiesis was present. Spleen: Moderate numbers of active lymphoid follicles were present. Low numbers of megakaryocytes wore present with the red pulp. An occasional focus of extramedullary hematopoiesis was present within the red pulp usually just beneath the capsule. Erythrophagia was common. Moderate numbers of macrophages within the red pulp contained a yellow to golden brow: granular pigment. 2Z2 t DUP040014122 i* j - 28 Kidney: The cytoplasm of the epithelial cells lining; the proximal convolute''; tubules had, on occasion, variably sized vacuoles, Stomach: The mucosa contained one focus of mature fibrous connective tissue ,, which was accompanied by considerable numbers of inflammatory cells, mainly neutrophils and occasional lymphocytes, large ' Intestine: Jfematodes were present. within the lumen of the large intestine.. Considerable amount of mucus was also present within the lumen. Ovary: Several Graafian follicles, corpora iutea, and atretic follicles nrescut indicating normal function, histologically. Bone Marrow: The femoral bone marrow contained a moderate amount of fat. Small numbers of megakaryocytes were present and the hematopoietic elements were represented by maturing forms. The latter cells were not especially numerous. The sternal bone marrow contained moderate numbers of megakary ocytes and was well populated with the hematopoietic elements. Maturing '** * forms of both the erythroid and myeloid series were present. The following organs were within the limits of expected histologic appearance: brain, pituitary, spinal cord, heart, adrenal, pancreas, small intestine, an*3 bone, CONTROL Female Rat No. 58-578 Gross: lio gross alterations were observed at necropsy. I j \ i i I ; i r ` 3r DUP040014123 I Thyroid; Variably sized follicles comprised the gland, The epithelium^lintf." the various follicles varied from squamous to a low cu*x>idal. The collpid- was of a faint eosinophilic color and homogeneous in nature, Histologically, the thyroid appeared to be in the state of moderate activity. Lung: Some of the alveolar walls were thickened from hypertrophy of the septal cells, in some areas by a homogeneous eosinophilic material, and on occasion, Small numbers of lymphocytes. Small foci of hyperplastic lympho- reticular elements were present around some Sf the vessels and bronchioles. Spleen: A moderate number of lymphoid follicles were present. Small foci of extramedullary hematopoiesis were present within the red pulp, especially near the capsule. Small numbers of megakaryocytes were present within the red pulp. Moderate number of macrophages within the fed pulp contained a yellow to golden brown pigment within the cytoplasm. Kidney: Considerable numbers of the proximal convoluted tubules contained cytoplasmic vacuoles. ' Ovary: Oraafian follicles, corpora latest, and atretic follicles were present indicating functional activity of this organ. Bohe Marrow: The femoral bone marrow contained a moderate amount of fat. Moderate numbers of megakaryocytes were present. The hematogenic'elements were moderately populated by developing forms of both the myeloid and erythroid series. Sternal bone marrow contained a small amount of fat. Moderate numbers of megakaryocytes were present. Cells of the myeloid ur.d the erythroid series were present in moderate numbers and both mature and immature forms were present. O I, I DUP040014124 A - 30 - The following organs were within the limits of expected histologic appearance: brain, pituitary, spinal cord, heart, liver, adrenal, stomach, pancreas. Small intestine, large intestine, and bone. CGnTROL Female Rat Upr; , 58-579 Gross: Ho gross alterations were noted at necropsy* Microscopic: $ Spinal Cord: Small amount of mineral in the leptomeninges. Thyroid: Variably sized follicles comprised the gland. Squamous to low cuboidal epithelium lined the follicles:. The colloid was of a fine granular to fibrinous character. Histologically the activities of this gland appear ed to he slight to moderate. Lung: Considerable portion of the section examined exhibited atelectasis. The alveolar -walls were slightly thickened by hypertrophy of the septal cells and accompanied by a small or slight influx of lymphocytes and occasional neutrophils. The lung was slightly congested. Small foci of l,\TKphorcticular elements were present about some of the bronchioles and some of the blood vessels. Liver: Small foe* of lymphocytes were scattered throughout the liver more commonly as, dated, however, with the portal areas. Spleen: Moderate numbers of lymphoid follicles were present throughout the spleen. Small foci of extramedullary hematopoiesis were present within 225 DUP040014125 * - 31 the red pulp. Small numbers of megakaryocytes were present within the red pulp. Macrophages contained considerable amounts of yellow to golden x 'irown pigment. hidr.ey: Some of the glomeruli were hypercellul&r and swollen. Considerable -+ numbers of the epithelial cells of the proximal convoluted tubules con tained vacuoles within the cytoplasm. Come of these same tubules contained eosinophilic cast material. large Intestine; No section was available for examination. Ovary: Graafian follicles, corpora lutea, and atretic follicles were present indicating activity of this organ. Bone Marrow: "die femoral bone marrow contained considerable amounts of fat. Spall numbers of megakaryocytes were present. The hematogenic elements were present in low numbers with both myeloid and erythroid series repre sented by mature and immature forms. The sternal bone contained less fat and considerably more hematogenic elements including megakaryocytes and myeloid and erythroid Cells, Elements that were maturing were present in both of the latter two series. The following organs were within the limits of expected histologic appearance brain, pituitary, heart, adrenal, stomach, pancreas, small intestine, large intestine, and bone. 100 PfM Male Rat No. 58-827 Gross: At necropsy the lungs exhibited dark red areas. DUP040014126 Microscopic: Pituitary: The section of tissue submitted for examinaticri was too small t< evaluate. Thyroid: This gland, was comprised of small, medium, a .1 large follicles the medium follicles /predominating. The colloid sat of an op-inophili color and quite homogeneous. The epithelium lining the follicle-s r predominantly CUboidal, varying from a lpw to plump cuboidal. 'l was moderately active. The gla: hung: A large amount pf blood present within alveoli and bronchioles. This was possibly artifactually produced at necropsy. Pocally, the alveolar septa were thickened by hypertrophy of the septal cells, si-;! influx of lymphocytes, and neutrorbils. Liver: Small collections of lymphocytes were present about the portal tri'- Spleen: Active lymphoid follicles were present.. Small amounts of a brexr. yellow granular pigment were contained within the cytoplasm pf macrCph within the red pulp. Small numbers of megakaryocytes were present wit the red pulp. Small fpci of extramedullary hematopoiesis were presepJ. Kidney: Some of the proximal convoluted tubules exhibited slight hypertro:> and lose of brush border of the epithelial cells. Hyperplasia was ra observed in the Same tubules. Some of the proxiiaal convoluted tubules contained eosinophilic fibrillar to granular material and sloughed epl lial cells. Testis: Spermatogenic activity was moderate. ] fat, The hematogenic elements were represented by large nurnibers of Sv > nkaryooytes and numerous .maturing elements of both the myeloid and erythroid series. The following organs were within the limits of expected histologic appearance* brain, spinal cord, adrenal, heart, stomach, pancreas., small intestine, large in f testine., and bone, '& 100 PiM Sale Pat Ko. 58-828 Cross: fio gross alterations observed at necropsy. Microscopic: Thyroid; This gland was composed of small, medium, and large follicles, and the colloid was of an eosinophilic color and granular in appearance. The epithelium lining the follicles was of a plump cuboidal nature. Activity moderate. Lung; The lung was omitted from this animal. Liver: Mont of the hepatocytes were slightly swollen, which resulted in the diminution of the size of the sinusoids. Spleen: Active lymphoid follicles were present, A very small amount of a brown to yellow granular pigment was present within :ra crophages pf the red pulp. A few small foci of extramedullary hematopoiesis were present just beneath the capsule. Very small numbers of megakaryocytes were present within the red pulp. DUP040014128 O / - -3*i " Kidbey: Considerable numbers of the glomeruli were swollen and somewhat hypercellular, in these, the urinary space was obliterated. The s' epithelium of the parietal layer of Bowman's capsule was also hyper trophic. Some of the proximal convoluted tubules exhibited quite ad vanced degenerative Changes characterised by swelling of the cells, increased eosinophilic of the cytoplasm, increased granularity of the cytoplasm, and, in some cases, vacuolafcian of the cytoplasm. Regen eration of the epithelium was often observed nearby, The interstitium "$ about the degenerating tubules often exhibited early fibroplasia. These lesions were, however, quite focal. foCally, the epithelium of the proximal Convoluted tubules was hyperplastic, Hematogeneous casts were Observed on occasion in the collecting tubules* tfcmll ''mounts of a brown-yellow pigment were seen within the cytoplasm of Some of the proximal convoluted tubules. Adrenal* Considerable numbers of the cells in the zona fasciculate exhibited vacuolated cytoplasm. Testis: Speimatogenic activity was moderate. Bone Marrow: The femoral bone marrow contained considerable amounts of fat. The hematogenic elements consisted of small numbers of megakaryo cytes and maturing elements of both the myeloid and erylhroid series. The sternal bone marrow ''ontained less fat than the femoral bone mar row. Moderate numbers of megakaryocytes were present, as were numerous elements of both the myeloid and erythroid series. The latter two hematogeneous elements exhibited maturing fonns. DUP040014129 r P .i-V: 35 - The following organs were within the limits of expected histologic appearance: brain, pituitary, spinal cord, heart, stomach, pancreas, small intestine, large intestine, and bone. 100 PPM Male Rat Ko. 58-829 Gross.: Liver: The liver was .iark purple-red in color- if~gf ' Microscopic: Thyroid: The gland was composed of small, medium, and large follicles fill ed with a light eosinophilic colloid and lined by cuboidal epithelium in the main. The activity of this gland would be placed in a moderate category. Lung.: A considerable amount of free fresh blood within the alveolar lumen and bronchioles,. Lymphoreticular hyperplasia was present around the semibronchioles and vessels. The latter alteration was neither exten sive hor large in amount. Some of the alveolar 'walls were slightly distended by hypertrophy of the alveolar septal sells. An occasional megakaryocyte was present within the lung. Liver; Small foci of mononuclear cells were scattered throughout the substance of the liver. Some of these foci appeared to be extra medullary hematopoiesis, while others were composed mainly Of lymph ocytes. Spleen.: Active lymphoid follicles were present. A small amount of brown tp yellow-brown granular pigment was contained within macrophages of DUP040014130 - 36 - the red pulp. Su2.ll foci of extramedullary hematopoiesis were present, especially, just beneath the capsule. Kidney: Some of the proximal convoluted tubules exhibited very early degenerative changes, characterized by slight swelling pf the epithet " lial cells, slight increased eosinophilia, granulation within the cytoplasm., and vacuolation. Some of these cells were sloughed into the lumen of the tubule.. Moderate numbers of feel of hyperplasia of of the epithelium of these tubules were observed. Proximal convoluted . tubules, distal convoluted tubules, and Collecting tubules contained eosinophilic homogeneous cast material. Hemoglobin casts were rsrt-ly observed. TestiS: Spermatogenic activity Was moderate. Bone: Small amounts of fibrous connective tissue were incorporates within the zone pf mineralized cartilage. The bone sporules being produced were normal. Bone Marrow: The immoral bone marrow contained considerable amount s cf fat. Moderate numbers of megalaryoeytes were present, "umerpus maturing elements Of both the erythroid and myeloid serif's were present. The following organs were within the limits of expected histologic appearance: brain, pituitary, spinal cord, heart, adrenal, stomach, pancreas, small in testine, and large intestine. 100 P3-S Male Rat I!o. 53-830 Gross: Ho gross alterations were observed at necropsy. DUP040014131 / Thyroid: The gland was comprised of small, medium, and large follicles, / with the smaller follicles predominating. The larger follicles, which tended to he at the periphery, contained an eosinophilic homogeneous to finely fibrillar colloid. The epithelium lining th<$3f|arger follicles tended to be more squamous, whereas, that which lined the smaller follicles was of a e aboidal nature. The activity of this gland would be categorized as low to moderate. 'i lung: The lung Wa$ slightly congested. The aveolar walls were thickened focally by hypertrophy of the septal cells; slight influx of mononu clear cells, mainly lymphocyt ;s; and a slight amount of Congestion. Small foci of lymphoreticular nodules were present, especially near bronchioles and arterioles. Liver: A slight amount of fibroplasia within the portal triads. In some areas, the hepatocytes were swollen resulting in diminution of the Size of the sinusoids. Some hepatocytes contained vacuoles within the cytoplasm. Spleen: Active lymphoid follicles were present.. Small numbers of s j ?- ocytes were present within the red pulp. On occasion, small foci of extramedullary hematopoiesis were present. Small numbers of macrophages within the red pulp contained a yellow to brown granular pigment within the cytoplasm. Kidney: Some of the proximal convoluted tubules contained globules of eosinophilic debris. The epithelial cells of the proximal convoluted 94 0 DUP040014132 tubules were somewhat swollen and granular in appearance. Rarely, intranuclear inclusions., which were granular to droplet formations and a light orange to a .light pink in color, were observed* Similar inclusions were observed rarely in the nuclei of distal convoluted Jn. tubules. The distal convoluted tubules contained .cast material which W ' tff was rather homogeneous and eosinophilic * Adrenal: The cells in the Iona fascieulata were finely vacuolated. Testis: Spermatogenic activity was moderate,. '$ Bone Marrow; The femoral bone marrow was populated by moderate numbers of megakaryocytes and numerous hematogenic elements of both the rayeloi 1 and erythroid series. `Both of the latter series ..exhibited mat\u'ing \ forms. The sternal bone marrow did not differ from the femoral marrow. The following organs were within the limits of expected histologic appearance.: brain, pituitary, spinal e.ord, heart, stomach, pancreas, small intestine, large intestine, and bone. 100 PPM Male Rat No. 58-831 Gross: Liver: The liver exhibited a mottled surface at necropsy. Microscopic: Thyroid: No section was available for examination. ::3 DUP040014133 - 39 - Lung: Seal! foci of lymphoreticular elements were present around some of " the larger bronchioles. One of the larger vessels contained a rather extensive mineralized plaque that occupied the intima and pari of the media. The lung was slightly congested. S Heart: One small focus pf myocarditis was observed within the wail of ft *sS> right ventricle. Inflammatory cells were predominantly lymphocygips. Liver: A considerable amount of blood was present within the sinusoids. Small foci of lymphocytes were present within the parenchyma of the liver and occasionally around the portal triadjs. Spleen: Active lymphoid follicles were present. Moderate numbers of macrophages within the red pulp contained a granular yellow to yellow- brown pigment. .Small numbers of megakaryocytes were present within the red pulp. Small numbers of foci of extramedullary hematopoiesis were present, usually just beneath the capsule. Kidney: Moderate. numbers of cells of the proximal convoluted tubules contained a yellow to yellow-brown granular pigment within the cyto plasm. Some of the proximal convoluted tubules exhibited alteration of the epithelium, .characterized by vacuolatior, increased eosinophilia, and sloughing of the cell into the lumen. Adrenal: A considerable number of the cells of the zona fasciculata con tained vacuoles. Testis: Spermatogenic activity was moderate. rL Bone Marrow: A small amount of fat within the femoral bone marrow. The hematogenic elements consisted of moderate numbers of megakaryocytes and numerous maturing elements of both the myeloid and erythroid series. 21k DUP040014134 - i*o The sternal bone marrow contained moderate amounts of fat. Hematogenic elements consisted of moderate numbers of megakaryocytes arid numerous maturing forms of the myeloid and erythroid cells. The following organs were within the limits of expected histologic appearance: brain., pituitary, spinal cord, stomach, pancreas, small intestine, large in- testineg^nd hone. .jp, . ioo mi female Hat Ho, 5.8-877 Gross: Ho gross alterations were observed. Microscopic: Thyroid: This gland ms composed of follicles varying from small to large which contained homogeneous eosinophilic colloid and Which were lin*d by squamous to cuboidal epithelium. This gland would be classified as moderately active, lung: The major bronchioles were Surrounded by lymphoreticulsr aggregates which had infiltrated the mucosa in many parts. The remainder of the lung was without significant alteration. liver: Several small foci of extramedullary hematopoiesis were contained within the substance of the liver. Spleen: Active lymphoid follicles were present. Small numbers of megakary ocytes were present. Small foci of extramedullary hematopoiesis wore present. A moderate number of macrophages in the red pulp contained a yellow to brown granular pigment within their cytoplasm. -r < n _w DUP040014135 Kidneys The epithelium of sons of the proximal convoluted tubule? was swollen and exhibited some vacuolation. Barely, .nuclei of these cells contained inclusions which were granular or droplet in formation and usually pint in color. Occasionally, the distal convoluted tubule -r . and iSllacting tubules contained eosinophilic homogeneous cast materiail Most of the glomeruli appeared to be somewhat atrophic with the urinary spaces dilated. Some of the collecting tubules contained hemoglobin Casts. ii Adrenal: Most of the cells of the zona fasciculata contained .cytoplasmic vacuples. * .1 Ovary: Graafian follicles ahd few atretic follicles were present. Bone Marrow: The femoral bone marrow contained some fat. Moderate numbers of megakaryocytes and numerous maturing elements of the myeloid and erythroid series were present. The sternal bone marrow contained small amounts of fat. Large numbers of megakaryocytes and maturing elements of bpth the myeloid and erythroid series were present. The following organs were within the limits of expected histologic appearance: brain, pituitary., .spinal cord, heart, stomach, pancreas, small intestine, large intestine., and bone. \ Gross 100 PEM Female Bat No. 58-878 \i No gross alterations were observed at necropsy. $ DUP040014136 i yt V Microscopic;: Pituitary: Several small nodules of hypertrophic chromophobes. Thyroid: This gland was composed of small, medium, and large follicles which contained a rather homogeneous eosinophilic colloid.. The W epithelium lining the follicles varied from squamous to a plump euboidal. The appearance of this gland would place it in the low to moderate active category. Spleen: Active lymphoid follicles were present, V lioderate amounts of brown to yellow-brown pigment were contained within macrophages within the red pulp. Small numbers of foci of extramedullary hematopoiesis were present within the red pulp. Small numbers of megakaryocytes were present. Kidney: Considerable estasia and filling of some of the collecting tubules with homogeneous eosinophilic proteinaceous material. The epithelial cells of considerable numbers cf the proximal convoluted tubules ex hibited swelling, loss of brush border, and cytoplasmic vacuolation. Rarely, intranuclear inclusions were observed that were bright pink in staining color and were granular to droplet in appearance. Adrenal: Considerable numbers of the cells of the zona fasciculata con tained cytoplasmic vacuoles. Stomacn : A 'slight amount of hyperkeratosis. Ovary: Several Graafian follicles were present. Bone Marrow: The femoral bone marrow contained considerable amounts of fat. The hematogenic elements consisted of moderate numbers of DUP040014137 megakaryocytes and maturing elements of both the myeloid and erythroid series. The sternal bone marrow contained less fat than the femoral bone marrow. Considerable numbers of megakaryocytes were present a.--were numerous developing forms of the myeloid and erythroid series. The following orgfes were within the limits of expected hisrpldgic appearance: brain, spinal cord, lung, heart, liver, pancreas, small intestine, large intestine:, and bone. Cross: 100 mi Female Rat No. 58-879 Ho gross alterations were noted at necropsy. y Microscopic: Brain: Small foci of fresh hemorrhage within the brain stem without surrounding reaction. Thyroid: Small, medium, and large follicles containing homogeneous eosino philic colloid and lined by low to plump cuboidal epithelium. This gland was in the state of low to moderate activity. Lung: Small nodules of lymphoreticular hyperplasia at the level of the larger bronchioles. The alveolar walls were slightly thickened from hypertrophy of the septal cells. Liver: A small focus of necrosis was present within the substance of the liver attended by infiltration of mononuclear cells. Occasional small focus pf vacuolated hepatocytes. s DUP040014138 -W- ' Spleens Active lymphoid follicles were present. Considerable numbers of megakaryocytes were scattered throughout the spleen. Moderate amounts of b.rovm to yellow-brown granular pigment were contained 'within, macron- phages of the red pulp. Considerable numbers of foci of extramedullary hematopoiesis wer^present. r I- Kidney: Most of the proximal convoluted tubules exhibited at least some . vacuolation in the cytoplasm. These cells also exhibited some loss of brush border and slight hypertrophy. Eosinophilic material was often contained within their lumen. The cortex was slightly congested as was the medulla. y Adrenal: Most of the cells of 'the zona fasciculata contained vacuolated cytoplasm. Stomach: A slight amount of hyperkeratosis. Ovary: Small numbers of Graafian follicles and several of corpora lutea were present. Bone Marrow: The femoral bone marrow contained considerable amounts of fat. Moderate numbers of megakaryocytes and hematogenic elements wefe present,. The erythroid and myeloid series were represented by maturing forms. The sternal bone marrow contained some fat. The hematogenic elements were represented by moderate numbers of megakary ocytes and considerable numbers of maturing elements of both the erythroid and myeloid series. The following organs were within the limits of expected histologic appearance: . pituitary, spinal cord, heart, pancreas, small intestine, large intestine, and bone. r . r> DUP040014139| - ls$ - > 100 PEN! Female Rat No. 58-880 No gross alterations were noted at necropsy. Microscopic: ^ Thyroid: The small specimen submitted for examination consisted pf small to large follicles that contained a homogeneous eosinophilic Colloid and lined by squamous to low cuboidal epithelium. The activity of this gland would be placed in the low category., lung: The alveolar walls were moderately thickened by hypertrophy of~the septal cells and a slight influx of mononuclear cells, predominantly lymphocytes. Some of the alveoli contained eosinophilic fibrillar material, most probably fibrin. Some free fresh blood was present within the alveoli and bronchial lumens, liver: Small infiltrations of lymphocytes around many of the portal triads. Small foci of extramedullary hematopoiesis were present. Spleen: Active lymphoid follicles were present. Large amounts of a brownish to yellow-brown pigment were contained within macrophages of the red pulp. A moderate number of Small foci of extramedullary hematopoiesis were present. Small numbers of megakaryocytes were present. Kidney: Moderate numbers of collecting tubules Contained an eosinophilic , "% homogeneous proteinaceous material. Some of these tubules were quite distended and filled with this material. The epithelium of consider able numbers of the proximal convoluted tubules was hypertrophic with * 220 DUP040014140 V 'li u$ loco of the brush border, slight vaeuolation, and slight increased eoninophilii of the Cytoplasm. Some of the epithelial cells . /ere distinctly eosinophilic and undergoing degenerative changes. Adrenals This gland was quite uniformly, severely congested throughout. One nodule of hyperplasia was present within the zona fasciculata. y There were a few small nodules of hypertrophy of the cells in the cpisa fasciculate also. Ovary; Maturing Graafian follicles and corpora xute.a were present. Bone Marrow: The femoral bone marrow contained some fat. The hematogenic elements consisted of moderate numbers of megakaryocytes and numerous \ developing myeloid and erythroid elements. The sternal bone narrow contained small amounts of fat. Large numbers of megakaryocytes were present as were numerous elements of the myeloid and erythroid series. The following organs were within the limits of.expected histologic appearance: brain, pituitary, spinal cord, heart, stomach, pancreas, small intestine. large intestine, and bone. 100 PH* Female Rat No. 58-&81 Gross: No gross alterations were observed at necropsy. Microscopic: Thyroid: Small, medium, and large follicles comprised this gland. The colloid was of an eosinophilic and. fibrillar to granular in appearance. DUP040014141 - *7 * The epithelium lining the follicles was squamous in the larger follicles and tcnciod toward a plump cuboidal in the smaller follicles. The activity of this gland wpuli place it in the slight to moderate range. Lung: Slightly congested. Most of the alveolar walls were slightly thick ened from hypertrophy of the septal cells, the congestion, and very small numbers of infiltrating lymphocytes, #' Liver: The sinusoids were quite dilated. A considerable amount of a homogeneous eosinophilic proteinaceous material was present at the central vein. "0 Spleen: Active lymphoid follicles were present, A moderate amount of brown to yellow-brown granular pigment was contained within macrophages of the red and white pulp. Small numbers of megakaryocytes were present as were small numbers of extramedullary hematopoiesis. Kidney: Moderate numbers of glomeruli were slightly atrophic. Some of the collecting tubules were dilated. The epithelium of a small number Of the proximal convoluted tubules was swollen and slightly more eosino philic than normal. Occasionally, individual epithelial cells within the tubules exhibited degenerative changes and rarely necrotic cpith-'linl cells wore observed. Adrenal: A moderate number of the cells of the xona fasciculate contained cytoplasmic vacuoles. Ovary: numbers of developing Graafian follicles, corpora lutea, and atretic follicles were present. 222 DUP040014142 - i(8 Bone Marrow: Considerable amount of fat was present within the femoral hone marrow. Hematogenic elements consisted cf moderate numbers of * megakaryocytes and developing forms of both the myeloid nnd orythroiu > series. The sternal bone marrpw consisted of moderate amounts of fat, moderate numbers of megakaryocytes, and numerous developing forms of both the myeloid and erythroid Series. The following organs were within tni limits of expected histologic appearance: brain, pituitary, spinal Cord, heart, stomach, pancreas, small intestine, large intestine, and bone. 1000 :?E-i Male Rat Mo, 58-927 1 gross: No gross alterations observed at necropsy* Microscopic:: Pituitary: SmaLL numbers of the chromophobes contained large'vacuoles -with* in their cytoplasm. Thyroid; The follicles comprising this gland were of various sixes; how ever, the epithelium lining the individual follicles was most commonly cuboidal in appearance. The colloid was eosinophilic and. quite homo geneous in character. The histologic appearance of this gland placed it in a moderate active category. Lung: The lung was moderately congested. Alveolar walls were thickened from hypertrophy of the septal cells, influx of lymphocytes, and the congestion. Nodules of lymphoreticular elements were eccentrically * > -.-iO DUP040014143 r * placed about some of the bronchioles and blood vasculature and, in > sene cases, these nodules invaded the wall of the bronchioles and in volved the epithelium# Liver: Small foci of lymphocytes scattered throughout the liver with larger numbers at the portal areas. . ' ` A . ' Spleen: Considerable amber pigment in macrophages of red pulp. .Slight amount of extramedullary hematopoiesis. Large number of active follicles. ' i Kidney: Small foci of lymphocytes were scattered throughout the section of kidney examined and constituted a focal nonsuppurative chronic m inflammation. Some of the glomeruli were hypercellular. The Bowman's \ capsules surrounding these glomeruli were, on occasion, thickened due to increased thickness of the basement membrane and, in other cases, due to hypertrophy of the lining epithelial cell. Most of the proximal convoluted tubules contained vacuoles within the cytoplasm of the epithelium. A small number of the nuclei of the epithelial cells lining the proximal convoluted tubules contained orange to red inclusion material. Some of these inclusion bodies appeared an a homo geneous droplet; whereas others were quite granular in appearance. In either case the chromatin was marginated around the edge of the nucleus with a fairly distinct halo immediately surrounding the inclusion. A considerable number of both proximal and distal con voluted tubules contained faintly eosinophilic homogeneous cast material. A small number of the epithelial cells of the convoluted r;.'U- , DUP040014144 ,, 50 - tubules contained cytoplasmic granules that were yellow to brown in color. Some cells of the proximal convoluted tubules were up to three times normal size and contained large veciculated nuclei. Or. occasion, . an epithelial cell contained eosinophilic rather homogeneous material that was probably proteinaceous. Stomach: Slight inflammation of muscularis by small numbers of neutrophils and lymphocytes. Testis: The spermatogenic activity was normal and moderate, Bone Harrow: The femoral and sternal bone marrow 'was very cellular and contained large numbers Of megakaryocytes and of cells of the erythroid and myeloid %eries. Maturing elements of both the myeloid and erythroid scries were present in large numbers. The following organs were within the limits of expected histologic appearance: brain, spinal cord, heart, adrenal, pancreas, small intestine, large intestine, and bone. 1000 P0>! Male Bat Ho, 58-928 Gross: Ho gross alterations were observed at necropsy. Microscopic: Thyroid: Variably sized follicles comprised this gland. The epithelium was mainly of the low cuboidal type, and the colloid war. of a faint eosinophilic staining quality. The histologic appearance of this gland would place it in a moderately active category DUP040014145 - 51 - Xiung: The Jung was moderately congested. The alveolar walls were thickened by the congestion, accompanied by hypertrophy of the septal cells, and a moderately heavy influx of lymphocytes. One of the larger vessels near the hilus of the lung contained a mineral plaque Within the intima.-' A focus of lympho.reticular hyperplasia was present wi-tbih the vail of the bronchus and some lymphoid cells had invaded the submucosa of that bronchus. Some alveoli were emphysematous and others contained a fibrillar eosinophilic material. Heart: An occasional smt t1 focus of myocardial degeneration was present within the papillary muscle with lymphocytes,- and occasional mast cells. liver.-: A slight amount of portal fibrosis and biliary hyperplasia within the substance of the lifer. These alterations were unassociated with inflammatory reactions. Several fairly large cysts were present within substance of the liver. The etiology and contents of these structures were not present within the section examined. Spleen: Moderate numbers of active lymphoid follicles were present. Small foci of extramedullary hematopoiesis were present. Moderate numbers of megakaryocytes were present. Small amount of a golden brown to yellow pigment was contained within the cytoplasm of macrophages within the red pulp. Kidney: An occasional glomerulus was hypercellular and had rarely under gone sclerotic changes. The epithelial lining of the parietal layer of Bowman's capsule was hypertrophic in some areas, and the associated -V basement membrane was thickened. Considerable numbers of proximal convoluted tubules contained faintly eosinophilic globular material. * :2S DUP040014146 A moderate number of these cells were enlarged three times the normal size and contained very large:, vesiculated nuclei. The cytoplasm of the epithelial cells lining these tubules was on occasion vacuolated, and the nuclei of ft considerable number of these cells contained in- ^ elusion bodies. These bodies varied in size and shape and tinctorial properties. The smaller ones were granular and faintly eosinophilic and possessed, an orange eastj whereas, the larger bees often assumes an angular shape and were faintly eosinophilic, A moderate number Of these epithelial cells also contained a granular pigment which was brown to yellow in color. Regeneration of the tubular epithelium was observed on occasion. A moderate .amount of connective tissue S9 hyperplasia was also present throughout the section observed,; however, s the incidence of inflammation was low. Adrenal: The cytoplasm of the cells of the zona arcaata was uniformly Vacuolated. The capsule of this organ was rather irregular and had a roughened appearance. Testis; On occasion, tubules contained precursors tp spermatozoa -which were mainly sloughed secondary spermatocytes. The other tubules ex hibited normal and moderate Spermatogenlc .activity. Bone Marrow; The femoral bone marrow contained a moderate amount of fat. The hematogenic elements were quite well populated, however, with considerable numbers of megakaryocytes and maturing forms of both the erythroid and myeloid elements. The sternal bone marrow also contained considerable numbers of fat. Moderate numbers of megakary ocytes were present as were maturing elements of both the myeloid ar.d :.2T DUP040014147 % * ' I - 53 - ., erythroid series.. The latter series were not as densely populated as observed in the .femoral bone marrow. The following organs were within the limits of expected histologic appearance: brain, pituitary, spinal Cord, stomach, pancreas, email intestine, large intestine, and bone, 1000 PPM Male Hat No. 58-929 Gross: . No gross alterations were observed at necropsy.j Microscopic: Pituitary: Some groups of basophils appeared to be slightly hypertrophic with small vacuoles and strands of basophilic material throughout the cytoplasm. Small numbers of these cells contained very large single vacuoles within the cytoplasm. Thyroid: The section of thyroid examined contained variably sized fol licles which were lined by very low cuhoidal epithelium. Activity was low. Lung: This tissue was moderately congested. One bronchus was quite sey.-r.-Ly involved with a fairly large nodule of hyperplastic lymphoreticular elements. The outer zones of this lymphoid tissue contained cells of hyperchromatic nuclei, evidence of mitotic activity, and some extension from the primary focus into the surrounding lung parenchyma. The epithelium lining of the bronchus was extensively infiltrated with the lymphoid cells and some neutrophils. In some areas, the epithelium 223 DUP040014148 was destroyed or removed by the underlying influx of lymphoid cells* Alveolar septae were thickened from hypertrophied septal ..cells, lymph ocytes, and small numbers of neutrophils. In some areas, an eosinophilic fibrillar material was also deposited within the alveolar walls. Heart: A small focus of myocarditis was present within the subepicardium. The AV valve of the left ventricle had undergone slight myxoid degen eration. These changes had resulted in the heart valve becoming thicker. Spleen: Moderate numbers of active lymphoid follicles were present. Con siderable numbers of macrophages within the rid pulp contained a brown to yellow granular pigment. Erythrophagia was common in the red pulp. Small foci of extramedullary hematopoiesis were present, especially under the capsule. Small numbers of megakaryocytes were present within the red pulp. Kidney: Seme of the glomeruli appeared to be hypercellular and somewhat swollen. The parietal layer of Bowman's capsule was often thickened due to hypertrophy and hyperplasia of the epithelial cells. Some of the epithelial cells lining the proximal convoluted tubules were under going degenerative changes exemplified by an irregularly affinitive for eosin, hypertrophy of the cell, and a definite granularity to the cytoplasmic content. The nuclei of many of these cells contained variably sized eosinophilic droplets. In some areas the epithelium exhibited regenerative changes. Some of the cells of the proximal convoluted tubules were enlarged and the nuclei were tremendously enlarged and contained three to four of the eosinophilic droplets. ! t 5 ! ' 22$ DUP040014149 ' 4 * - 55 nuclei of the distal convoluted tubules contained, on occasion, similar droplets as was observed in the nuclei of the proximal tubules; how ever, degeneration of the distal tubules was not as commonly observed as in the proximal, Many of the proximal, distal, and collecting tubules contained various amounts of an eosinophilic homogeneous to granular material. An occasional collecting.tubule was. dilated; and* in one instance, the epithelium was very hyperplastic. Adrenal': Small number of the cells in the zona fasciculata were vacuolated. Pancreas; In one focus a moderate amount of mature fibrous connective tissue was present dividing and surrounding some acini of the pancreas resulting in atrophy of these. A group of islet^ of Langerhans was also separ- 1 ated by considerable amounts of the fibrous connective tissue. Testis: Small numbers of tubules exhibited a general suppression of the spermatogenic activity characterized by fewer numbers of maturing spermatozoa and fewer numbers of primary spermatocytes. The germinal epithelium was unaffected in the section examined, 3one Karrow: The sternal and femoral bone marrow contained a small quantity of fat. The hematogenic elements were numerous with large numbers of megakaryocytes and maturing elements of both the myeloid and erythroid series. The following organs were within the limits of expected histologic appearance: brain, spinal cord, liver, stomach, small intestine, large intestine, and bone. ' - A* ' ' '.jfflfiti' T DUP040014150 ] 1 12 - GROSS CONTROL Male Rat No. 58-463 (Continued) 1 MICROSCOPIC Liver: No alterations described. Heart: No alterations described. Kidney: No alterations described. Liver: ^ Slight pericholangitis characterised by infiltration of mononuclear inflammatory cells into the portal areas. Heart: Slight congestion. "i- Slight myocarditis involving the tip of one of the atria characterized by infiltration of the musculature by inflammatory cells, pre dominantly lymphocytes accompanied by slight edema and minimal congestion. Moderate focal and linear myocarditis involving both walls and interventricular septum characterized by a slight degeneration of myocardial fibers accompanied by infiltrations of inflammatory cells, predominantly lymphocytes and some edema. Kidney: Rarely a deposit of mineral within the collecting tubules of the papilla. Occasional collecting tubule contained an eosinophilic fibrillar to homogeneous cast material. Minimal amount of a yellow to brown granular pigment within epithelial cells lining proximal convoluted tubules. f* r+ DUP040014151 - 13 - CONTROL Malq Rat No. -U58 63 (Continued) GROSS 1MICROSCOPIC_______________________ Spleen; No alterations described. Pancreas: Ho alterations described. Duodenum: Hp alterations described. Minimal hyperplasia of pelvic epithelium.. Slight congestion. Minimal interstitial nephritis characterised by focal infiltrations of mononuclear inflam matory cells'. Spleen: Moderately high lymphoid activity. Moderately large amount of a yellow to brown granular pigment within macrophage's. Moderate reticuloendothelial activity. Moderate extramedullary hematopoiesis. Pancreas: Slight amount of a yellow to brown granularpigment deposited within interstitial cells. Duodenum: Minimal focal nodular lymphoid hyperplasia within lamina propria. Slight infiltration of lamina propria by mononuclear inflammatory cells along with minimal numbers of eosinophils. Minimal congestion. Slight mitotic activity of epithelial cells in mucosa. DUP040014152 CONTROL ' Male Rat NO> 58-463 (Continued) .GROSS . I. MICROSCOPIC Colon: No alterations described. Testis; Ho alterations described. Bone Marrow: Ho alterations described. Colon: 'y No tissue available for sectioning or histologic examination. Testis; Spennatogenic activity- normal and moderatel.y high* Occasional ttfoule contained one to several mononuclear spernratozoal precursors. Bone Marrow; Moderate number of megakaryocytes,. Moderate .numbers of maturing .elements of both myeloid and erythroid series. Hematogenic activity appeared moderate. The following organs were neither described grossly nor remarkable microscopically: brain, pituitary, spinal cord, adrenal, stomach, and bone. 270 DUP040014153 - 15 * GROSS CONTROL Male Rat No. 58-464 1 MICROSCOPIC Thyroid: Ho alterations described. Lung: Ho alterations described at necropsy; however., after fixation cystic-appearing structures present on the surface. Thyroid: Small, medium, and large follicles. Colloid light eosinophilic and homogeneous to granular. Epithelium varied from squamous in the. larger to fairly tall cuboids! the smaller follicles. Activity moderate. Lung: Moderately severe chronic murine pneumonia characterized by infiltration and hyperpla-l* of lymphor.eticuiar elements in the peribronchial and perivascular tissues with .extension .into the parenchyma, accompanied by slight hyper plasia of the alveolar septal cells. Slight collapse of adjacent lung tissue. Alveolar walls focally thickened by the hyper plasia of the septal cells along with minimal congestion. Slight emphysema. * Minimal amount of a yellow to brown granular pigment within macrophages associated with the lymphoid infiltration and also occasionally Within septal cells in parenchyma. DUP040014154 - 16 - CONTROL Male Rat No. 58-464 (Continued) GROSS MICROSCOPIC Liver: No alterations described. Kidney: No alterations described. Spleen: No alterations described* Liver: Slight pericholangitis characterised by infiltration of portal areas by mononuclear inflammatory cells. Kidney: Slight congestion! Moderate amount of a yellow -to brown granular pigment within some epithelial cells lining proximal convoluted tubules. Slight focal interstitial nephritis characterized by infiltration of mononuclear inflammatory cells.. - Rarely a collecting tubule dilated and contained a homogeneous eosinophilic cast material. Rarely a tubule contained a concentrically laminated basophilic material, possibly mineral deposit. Minimal chronic pyelitis characterized by infiltration of the subpelvic epithelium by mononuclear inflammatory cells. Slight congestion. Spleen; Moderately high lymphoid activity. Moderate extramedullary hematopoiesis. DUP040014155 - 17 - CONTROL Male Rat No. 58-1)64 (Continued) GROSS __________ 1 __________ MICROSCOPIC Stomach: No alterations describ 2d. Duodenum: No alterations described. Colon; No alterations described. Testis: No alterations described Bone liarrow; No alterations described. Slight reticuloendothelial .activity-. Moderate amount of .a yellow to brown granular pigment within macrophages. Stomach: Slight amount of fibrous .connective tissue within deeper portions of mucosa accompanied by minimal dilatation of .glands and some atrophy of the deeper glands.. Duodenum: .Slight infiltration of lamina propria by mononuclear inflammatory cells, accompanied by a few eosinophils. Minimal congestion in mucosa. Slight .epithelial mitotic activity. Colon: Slight congestion. Minimal epithelial mitotic activity. Testis; Nominal spermatogenic activity and moderately high. Bone Marrow: Moderately large numbers of megakaryocytes. Numerous maturing elements of both myeloid and erythroid series. Activity moderately high Ai i 1j DUP040014156; - l8 - CCifTROL Male Rat Ho. 58-464 (Continued) GROSS MICROSCOPIC The following organs were neither described grossly nor remarkable microscopically: brain, pituitary, spinal cord, adrenal, heart, pancreas, and bone. r.74 DUP040014157 - 19 - !t I CROSS CONTROL Male Rat No. 58-^65 ! ___________ MICROSCOPIC Pituitary: No alterations described. Thyroid; Pituitary: No section available for examination. Thyroid; 's' No alterations described. Small, medium, .and large follicles throughout,. Colloid light eosinophilic and Quite homogeneous . Epithelium low cuboidal to cuboidal. Activity moderate.. j * Lung: Lung: Greatly distended ana postcaval Section examined severely altered by inflam lobe had small abscess. matory changes characteristic of advanced stages chronic murine pneumonia complex and included septal cell hyperplasia, brcn- chiectatic abscesses, peribronchiolar and perivascular lymphoreticular infiltrations and hyperplasia "with compression of adjacent parenchyma. Slight congestion. Slight emphysema. Liver: Liver: No alterations described. Moderate reticuloendothelial hyperplasia. Moderate extramedullary hematopoiesis. Slight pericholangitis. Slight bile duct hyperplasia. I f't; DUP040014158 - P.0 - CONTROL Male Rat No. 58-465 (Continued) GROSS \ MICROSCOPIC Heart*. ;,To alterations described. Kidney: Ijo alterations described. Spleen: Ho alterations .described. Stomach: Ho alterations described. Heart; * Slight congestion. Minimal focal myocarditis characterized by infiltrations of mononuclear inflammatory cells associated with small numbers of swollen eosinophilic homogeneous myocardial fibers. Kidney: m Slight congestion. Occasional collecting tubule slightly ectatic i , and contained a homogeneous bright eosinophilic cast material. Minimal focal interstitial nephritis charac terized by infiltrations of small numbers of mononuclear inflammatory cells -within the cortex. . Spleen: Moderately high lymphoid activity. Moderately high reticuloendothelial activity. Moderately large amount of extramedullary hematopoiesis * Moderately large amount of a yellow to brown granular pigment within macrophages. Stomach: Slight dilatation of deeper glands of mucosa. 76 DUP040014159 ui' ' III * 21 - CONTROL Male Fat Mo, 58-165 (Continued) CROSS MICROSCOPIC Pancreas: Mo alterations described. Duodenum: Mo alterations described. Colons No alterations described. Testis: Ilo alterations described. Bone Marrow: V.o alterations described. Pancreas: Moderate amount of a yellow to brown guana?ur pigment within interstitial cells. Duodenum: Moderate infiltration of lamina propria by mononuclear inflammatory cells accompanied '< by small numbers of eosinophils. Minimal focal nodular .lymphoid hyperplasia of lamina propria. Slight congestion. Minimal epithelial mitotic activity. Colon: Minimal focal nodular lymphoid hyperplasia. Minimal epithelial mitotic activity. Testis: Spermatogenic activity normal and moderately high. Rarely a seminiferous tubule contained more- nuclear spermatozoal precursors within the lumen. Bone Marrow: Moucrately large numbers of megakaryocjO.cn. Numerous maturing elements of both myeloid and erythroid series. Activity moderately high. 7 DUP0400141601 - 22 - CONTROL Male Eat No. 58-L65 (Continued) GROSS i MICROSCOPIC The following organs vere neither described grossly nor remarkable microscopically: y brain., sjdnal cord, adrenal, and bone. DUP040014161 - 23 - GROSS CONTROL Kale Rat No, 58-466 1 MICROSCOPIC Thyroid: Jfo alterations described. Lung: Ko alterations described. Liver: Wo alterations described. Thyroid: Small, medium, and large follicles with thd large- and medium-sized predominating. Colloid fairly bright eosinophilic and quite homogeneous. Epithelium varied from squamous in the large to cuboidal in the smaller follicles. 'W Activity moderate, lung: Slight congestion. Minimal chronic murine pneumonia characterized by minimal infiltration and hyperplasia of iyraphoreticular elements into the perivascular and peribronchial tissues. Minimal thickening of the alveolar septa by congestion and hypertrophy of septal cells along with minimal infiltration of mononuclear inflammatory cells (considered part of the murine pneumonia complex). Liver: Slight pericholangitis characterized by infiltration of the portal areas by mononuclear inflammatory cells. Minimal bile duct hyperplasia. DUP040014162 - 24 - CONTROI. Male Rat Ho. ^8-h$6 (Continued) CROSS ________ j MICROSCOPIC Heart; lip alterations described. Kidney: Uo alterations described. Heart; ^' Minimal focal myocarditis characterized by small numbers (as foci) of .eosinophilic, homogeneous, swollen myocardial fibers accompanied by an interstitial inflanrrr-tery reaction and minimal fibrosis. Minimal congestion. Kidney: Slight congestion. Moderately severe changes of rat nephritis characterized by dilatation and regenerative forms of the proximal convoluted tubules and of collecting tubules accompanied by an eosinophilic homogeneous cast material in the tubules. Slight interstitial inflammation characterized by infiltrations of moderate numbers (recall"'' of mononuclear inflammatory cells. Slight pyelitis characterized by inflammation of the pelvic epithelium by mononuclear inflammatory cells. Moderate numbers of collecting tubules dilated and contained the eosinophilic cast material,. :d g DUP040014163 caitsoi Male Sat Ho. 5S-h>6 (Continued) GROSS . .. . 1............. MICROSCOPIC \ Spleen: Ho alterations described. Stomach; No alterations described. Pancreas; Ho alterations described. Slight to moderate glomerulosclerosi s charaes terized by deposition of fibrous connective tissue within the glomerular tuft with or without thickening of the parietal layer' of Eowman`s capsule and with or without adhesions Of the parietal and visceral layers. Moderate amount of a yellow to brown granular pigment within epithelial cells, predominantly lining the proximal convoluted tubules. .Slight tubular nephrosis characterized by swelling and degenerative changes within the epithelial cells lining the proximal con voluted tubules. -Spleen; Moderately high lymphoid activity. Slight reticuloendothelial activity. Moderate extramedullary hematopoiesis.. Moderate amount of a yellow to brown granular pigment within macrophages. Stomach: Minimal focal gastritis characterized by infiltration of mononuclear inflanmancrv cells in the mucosa, focally. Pancreas: Minimal amount of a yellow to brown granular pigment within interstitial cells, 0*?! DUP040014164 - 26 *. CONTROL Male Rat No. 58-466 (Continued) CROSS I MICROSCOPIC Duodenum: Duodenum: * No alterations described. Moderate infiltration of lamina propria bf mononuclear inflammatory cells along with some neutrophils and eosinophils, . (Moderate enteritis.) Slight mitotic activity in the epithelium. Colon: No alterations described. Colon: Minimal epithelial mitotic activity. Testis: Testis: No alterations described. Spermatogenic activity normal and moderately high. Occasional 'mononuclear spermatozoal precursor free within the lumen. Rone Marrow: Bone Marrow: No alterations described. Smudging precluded very critical evaluation; however, moderate numbers of both myeloid and erythroid series present: however, degree of maturation undeterminable. Moderate numbers of megakaryocytes. Activity appeared moderate. The following organs were neither described grossly nor remarkable microscopically: brain, pituitary, spinal cord, adrenal, pancreas, and bone. -VnCo DUP040014165 - 2? - GROSS CONTROL Male Rat No. 58-468 i MICROSCOPIC Thyroid: No .alterations described. Lung: No alterations described. Liver: NO alterations described. Thyroid: Small, medium, and a lev/ large follicles ^ present* Colloid fairly bright eosihopliilic and quite homogeneous. Epithelium predominantly fairly tall cuboldul* Activity moderate* .sh illing;: Moderate lesions ..of chronic murine pneumonia characterized by infiltrations and hyperplasia of peribronchial and perivascular lymphoid elements. Moderate infiltration of mucosa c-f bronchioles. Moderate focal thickening cf alveolar septa by hypertrophy and hyperplasia of alveolar septal cells. Slight congestion. Liver: Minimal fecal accumulations of mononuclear cells within parenchyma ur.assoe.iated with hepatopathy. Slight pericholangitis characterized by infil trations of portal areas by mononuclear inflammatory cells. :.23 DUP040014166 GROSS CONTROL Maxe Rat Ho. 58-^68 (Continued) MICROSCOPIC Heart: Ho alterations .described. Kidney; "One kidney contained small, firm granules." Spleen: Ho alterations described. Heart: Slight congestion. Kidney: Slight congestion.. Small numbers of collecting tubules slightly dilated and contained a homogeneous eosino philic cast material. Occasional proximal convoluted tubule dilated and epithelium swollen and vacuolated and contained variably sized, usually small, eosinophilic droplets (possibly proteinaceous). Occasional tubule had regenerative epithelial cells. Slight nephritis characterized by infiltration of the interstitixua by mononuclear inflam matory cells, focally. Collacting tubules in medulla contained,on occasion, a homogeneous eosinophilic cast material. Slight hyperplasia of pelvic epithelium. Spleen: Moderately high lymphoid activity. Moderately large amount of a yellow to brown granular pigment with macrophages. 4 DUP040014167 - 29 ~ CONTROL Male Rat No. 58-468 (Continued) GROSS 1 ............................. MICROSCOPIC 'V i Moderate amount of extramedullary hematopoiesis. Duodenum: Moderate reticuloendothelial activity, Duodenum: / IIo alterations described. Slight infiltration of lamina propria by nv~uo- nuclear inflammatory cells and some eosinophils. Colon: Slight mitotic activity of epithelium* Colon; No alterations described. Moderate focal nodular lymphoid hyperplasia within lamina propria with extension into . the mucosa. Minimal epithelial mitotic activity* Minimal infiltration of eosinophils into lamina propria* Testis: Testis: Ho alterations described. Spermatogenic activity normal and moderate!-,- high,. Moderate numbers of tubules contained low t<- several mononuclear spernatosoal -precursors in the lumen. Bone Marrow: Bone Marrow: No alterations described. Moderate numbers of megakaryocytes. Smudging precluded critical evaliiation of other hematogenic elements; however, .appeared to be present in moderately large numbers. Activity appeared moderately high, '-nc DUP040014168 30 - . CONTROL Male Bat No, 58-b68 (Continued) GROSS _______ ( _______ . MICROSCOPIC The following organ? were neither described grossly' nor remarkable microscopically: brain, pituitary, spinal cord, adrenal, stomach, pancreas, and bone. 0 it' 23S DUP040014169 - 31 - It CONTROL Male Bat No. 58-469 GROSS 1 MICROSCOPIC ^ Thyroid: Thyroid: No alterations described. Small, medium, and large follicles. Smaller follicles predominated. Colloid light eosinophilic. Epithelium predominantly fairly tall ouboidal. Lung: Activity moderately high. Lung: *sH No .alterations described. Slight chronic murine pneumonia characterized by infiltration of the peribronchial and peri- s . vascular tissues by lymphoreticular elements.. Slight thickening of alveolar septa by hyper trophy and hyperplasia of alveolar septal cells along with slight infiltration of mononuclear inflammatory cells and slight congestion. Liver: Liver: Firm, yellow areas in median Moderate pericholangitis characterized by lobe. infiltrations of moderate numbers of mono nuclear inflammatory cells into the portal areas. Slight bile duct proliferation. Occasional focus of mononuclear cells viphin parenchyma associated with small numbers of hepatic cells that had undergone degenerative and necrotic alterations. Minimal fibrosis of the portal areas. 237 DUP040014170 V ( - 32 - COHTROJj Male Rat No. 58-469 (Continued) GROSS ________ I __________ MICROSCOPIC Heart: No alterations described. Kidney: No alterations described. Spleen: . Ho alterations described. Stomach: No alterations described. Heart: Slight focal myocarditis characterized by infiltration of the mononuclear ceils and reticular cell hyperplasia associated with degenerate or necrotic myocardial fibers.. Minimal congestion. Kidney: Slight amount of a yellow to brown granular pigment within some of the epithelial cells lining the proximal convoluted tubules. Slight congestion. Slight interstitial nephritis characterized by infiltrations of small numbers of lympho cytes into the cortex. Spleen: Moderately high lymphoid activity. Moderately large amount of reticuloendothelial activity. Moderately large amount of extramedullary hematopoiesis. Moderately large amount of a yellow to brown granular pigment with macrophages. Stomach: Minimal vasculitis characterized by infiltisitien of mononuclear cells into the perivascular connective tissue and into the vessel wall. DUP040014171 - 33 CONTROL Male Rat No. 58-469 (Continued.) GROSS MICROSCOPIC Pancreas: No alterations described. Duodenum: No alterations described. Colon; No alterations described* 'Testis: NO alterations described. Bone Marrow: No alterations described. Pancreas: / Sli^it amount of a yellow to brown granular pigment. Duodenum: Slight congestion:. Slight infiltration of lamina pr.opria by mononuclear inflammatory cells end some eosinophils. Slight epithelial -mitotic activity. Colon: Slight mitotic acxivity of the epithelium, Testis: Spermatogenic activity high and normal. Occasional seminiferous tubule contained e. few to some mononuclear spermatozcal precursors. Bone Marrow: Smudging precluded meaningful evaluation. V i; * Z 5 r ? ;; a I .1 S = I -8 j The following organs were neither described grossly nor remarKable microscopically: brain, pituitary, spinal cord, adrenal, and bone. I g r r>Q s. v*-V DUP040014172] - 34 * GROSS CONTROL Male Rat No. 58-470 1 MICROSCOPIC Brain: No alterations described,- Thyroid: Ho alterations described. Lung: Ho alterations described. Liver: Ho alterations described. Brain: ^' Slight thickening of .meninges over cerebellum. (Significance of this singular eliange unknown.) Thyroid: Small, medium, and large follicles. Colloid light eosinophilic an* -lite homogeneous., Epithelium varied from squamous in the larger to cuboidal in the smaller follicles. Activity moderate;. Lung: Slight chronic murine pneumonia characterized by infiltration of the perivascular and peribronchial tissues by lymphoretiqular elements with slight hyperplasia. Slight thickening of alveolar walls by infil trations of mononuclear inflammatory cells along with some hypertrophy and hyperplasia of alveolar septal cells and slight congestion. One of the larger vessels contained within -.he wall a mineralized plaque. Minimal emphysema. Liver: Slight pericholangitis characterized by infiltration of mononuclear inflammatory cells into the portal areas. r DUP040014173 - 35 - CONTROL Male Rat Ho. 58-^70 (Continued) GROSS I MICROSCOPIC Heart; Mo alterations described. Kidney; Ho alterations described. Spleen; Ho alterations described. Duodenum: Ho alterations described. Rarely a topus of mononuclear ceils vi-.hi:. parenchyma unassociated vith hcyatcy-atby- Heart: Slight congestion. Moderate vasculitis of one <?f the coronary vessels characterised by infiltration of mononuclear inflammatory cells into the wall > of the vessel. Kidney: Slight congestion. Mlniiaai amount of a brown to yellow pifmer.T within epithelial cells. Spleen: Moderately high lymphoid activity. Moderately large amount of a brown to ypHrw granular pigment within macrophages. Moderate amount of reticuloendothelial activity. Moderate extramedullary hematopoiesis. Duodenum: Moderate infiltration of lamina propria by mononuclear inflammatory cells and poly morphonuclear cells. Minimal congestion. Slight to moderate epithelial mitotic act5v:;y. DUP040014174 - 36 COMTRQL Male Bat Ko. 58"^-70 (Continued) CROSS _________________ |___ _______________ MICROSCOPIC Colon; No alterations described. Testis; No alterations described. Bone Marrow': \ Ko alterations described, ' Colon; y Slight nodular lymphoid hyperplasia. Minimal colitis characterized by infiltration of small numbers of eosinophils into the lamina propria. Slight epithelial mitotic activity. Testis; , , Spermatogenic activity normal and moderately high. Bone Marrow: Smudging precluded critical evaluation; however, moderate numbers of hematogenic elements appeared to be present. Activity appeared moderate, The following organs were neither described grossly nor remarkable microscopically: pituitary, spinal cord, adrenal, stomach, pancreas, and bone. nr>2 DUP040014175 ! t / - ; J i * 37 - ....... , 0B05S CONTROL Female Pat Ho. 58-560 . I ,, MICROSCOPIC Thyroid: Ho alterations described. Lung: Ho alterations described. Liver: Ho alterations described. Heart: Ho alterations described. Kidney: No alterations described. Thyroid; Large follicles predominated. s Epithelium predominantly squamous to a very low cuboidal. Activity low. Lung: Slight congestion. Slight Chronic murine pneumonia characterized by infiltrations of lyraphoreticalar elements w in the perivascular and peribronchial tissue Slight thicKening fpcally of alveolar septum by hyperplasia of the septal ceils. Minimal amount of.a yellow to orown oui'e highly refractile pigment associated with the lesions of the pneumonia. Liver: Minimal bile duct proliferation. ] Rarely a focus of mononuclear cells in parenchyma j unassociated with hepatopathy. Heart: I \ Slight congestion. j Kidney: Minimal congestion. 233 DUP040014176 ! ! - 38 CONTROL Femalie Rat No, 58-503 (Continued) GROSS .________ 1 MICROSCOPIC Spleen: No alterations described. Pancreas: Ho alterations described. Duodenum: No alterations described. Minimal amount of a yellow to brown granular s' pigment within cells lining the proximal convoluted tubules. Occasional fbcus of .cortical tubules contained regenerative epithelium. Minimal interstitial nephritis characterised by infiltrations of mononuclear inflammatory cells, Occasional collecting tubule contained a homogeneous eosinophilic cast. Spleen: Moderately high lymphoid activity. Moderately large amount of a yellow to brown granular pigment within macrophages. Slight amount of extramedullary hematopeies:5 s. Moderate reticuloendothelial activity. Pancreas: Minimal amount of a yellow to brown granular pigment within interstitium. Duodenum: Slight enteritis characterized by infiltration of mononuclear inflammatory cells and a few eosinophils into the lamina propria. Slight mitotic activity within mucosa. DUP040014177 - 39 * CONTROL Female Fat No. 58-560 (Continued) CROSS _______ 1 ....................................MICROSCOPIC Colon: No alterations described- Ovary: No alterations described. Bone Marrow: Ho alterations described. Colon: Slight mitotic activity within the mucosa-. Ovary: Ho section available for er-raminat'icn- Bone Marrow: Smudging precluded critical evaluation; 1 however, hematogenic elements appeared to be present i-ij moderately high numbers. The following organs were neither described grossly nor remarkable microscopically: brain, pituitary, spinal cord, adrenal, stomach, and bone- DUP040014178 - 4o - GROSS CONTROL Female Bat No. 58-561 1 MICROSCOPIC Pituitary: No alterations described. Thyroid: No alterations described. Lung: No alterations described Kidney: No alterations described. Pituitary: No section available for examination Thyroid: Large follicles predominated. Epithelium predominantly squamous to low cuboidal. Activity low. 1 Lung: Minimal chronic murine pneumonia characterized by infiltration of lymphoreticular elements in the perivascular and peribronchial areas. Slight congestion. Slight thickening of alveolar walls by infil tration of small number of mononuclear cells along with minimal hypertrophy of alveolar septal cells. Kidney: Minimal amount of a yellow to brown quite highly refractile granular pigment wi thin epithelial cells lining proximal convoluted tubules. Minimal, nephritis characterized by infiltrations of interstitium by small numbers of mononuclear inflammatory cells, foc&lly. DUP040014179