Document jBRMwoLBpby482DdOxGM7Qvd2

HASKELL LABORATORY FOR DU PONT USE ONLY Common Name: Lead Oxide Chemical Name: Lead Oxide [PbO] Synonyms: C.I. 77577 C.I. Pigment Yellow 46 Lead Monoxide Lead Oxide Yellow Lead Protoxide Litharge Plumbous Oxide Massicot Yellow Lead Ocher CAS Registry No.: 1317-36-8 Chemical Structure: (9CI) Pb-0 Chemical and Physical Properties (1) Appearance: Molecular Weight: Melting Point: Density: Solubility: Yellow crystals 223.21 888 C 9.53 Insoluble in water and alcohol Soluble in acids and alkalies Threshold Limit Value (2) TWA = 0.15 mg/m-13 * (as Lead) t o x ic it y A.. Acute iV 27659 1. oral Lead oxide as a suspension in peanut oil was administered by intragastric intubation to two groups of ten male rats at dose levels of; 17,000 and 25,000 mg/kg. One rat of ten died at each level. Clinical signs were soft feces an^/or diarrhea containing lead oxide for two dajys, ? weight losses for as long as 12 days affcejt dosing, emaciation and anorexia (17). ;i 110866  Lead oxide dust, as a suspension in distilled water, was administered by intragastric intubation to male rats at dose levels from 670 mg/kg to 17,000 mg/'kg. Rapid breathing occurred after dosing at 2,250 mg/kg dose level. Weights losses were noted for 1-3 days after dosing at 3,400 mg/kg and above. The lethal dose must be greater than 17,000 mg/kg (20) . The lethal dose of lead oxide when fed to bees in honey was 0.32-0.50 mg per bee. Toxic symptoms included increased inertia, slow wing movements and inability to climb followed by paralysis, inability to feed and death (3). 2. Skin Lead oxide, when tested on the intact skin of male albino rabbits, produced no irritation in 24 of 4,8 hours (19). Lead oxide has been evaluated as safe for contact with intact or abraded skin, irritancy was less than one on a scale of 1-4 (4). Lead oxide (29.5% by weight) is a component of a preparation useful in treating eczemas, allergies, inflammations, itching, infections, prurigo and of healing Wounds (5), 3. Eye 0.1 ml of undiluted lead exile dust was placed into the right conjunctival sac Of 2 albino rabbits> After 20 seconds one treated eye was washed with water for 1 minute. The other rabbit's eye was not rinsed. Observations are as follows; Conditions_______^ Pose Treatment 0,1 ml (129.4 mg) Hot Washed 0.1 ml (129.4 mg) Washed __________Ocular Effects Corner iris Conjunctiva Hone None Redness.; mild 1 hr-2 days Discharge: slight 1-4 hrs Swelling; moderate at 1 hr, mild at 4 hr None None Redness: minimal 1-4 hrs Discharge; slight 1-4 hrs Swelling: mild 1-4 hrs -2 - DUP040010867 Lead oxide dust produced transient mild conjunctivitis with no iritic or corneal involvement in the rabbit eye (18). 4. Inhalation "Ten rabbits were exposed to a time-weighted average concentration of 3.72 mg/1 lead oxide dust (98.3% respirable particle size) for a single one^-hour exposure. No mortality occurred during exposure during the 14-day recovery period- Under these experimental conditions, lead oxide dust is not a Class E Poison* by the inhalation route" (21). "Ten rats were exposed to a time-weighted average atmospheric concentration of 4.38 mg/1 lead oxide dust for a single one-hour head only exposure. One rat was sacrificed five days post-exposure be cause of a non-compound related injury. Under these experimental conditions, this sample of lead oxide dust (200 ppm organolead content) is not a Class B Poison" (22). 6. Injection LD50 (rat, intraperitoneal) = 630 mg/kg (7). LD50 (rat, intraperitoneal) - 430 mg/kg (8). Following intravenous injection of lead oxide into rats, lead was found in femoral bone tissue (6.). B. Extended Studies 1. Oral Lead oxide as a 10% suspension in peanut oil was administered to six male rats 5x/week/2 weeks. Three test rats and three control rats were killed four hours and 14 days following the last dose. The results are: ^Hazardous Material Regulations of the -Department of Transportation, Agent R. H. Graziano's Tariff No. 31, March 31, 1977 -3 - DUP040010868 Dose mg/kg No* of Poses Mortality 1000 10 0/6 Toxic Signs______ Pathologic Changes_______ First. Week: severe weight loss, weakness, chewing and pawing motions after dosing, salivation Second Week: severe weight loss, weakness, emaciation, incoordination, chewing and pawing motions after ^jqsiipg;'. Recovery Period: although rate of weight gain s^igf?ttji.y /grdjaifcef .fljian that of $Ihs'Jj; average weigiaf; 110 slightly emaciated for 1 week' After 10th Dose: bilateral dilatation of tubules of inner cortex of kidney; absence of perinuclear y vacuolation of liver cells 14 Days After 10th Dose: histologic changes in kidney still present; kidney very large; liver essentially normal "Lead monoxide induced signs of severe cumulative oral toxicity when administered to rats. The animals lost weight during the dosing period, became emaciated and exhibited signs of central nervous system stimulation.. Histologic exam ination of tissues revealed severe damage to the kidneys, which was not ameliorated in 14 days, and transient cellular changes in the liver" (23). The toxicity of three poisons , lead oxide, lead acetate and arsenic oxide, was investigated in white mice given the poison in feed every day for 30 days. The survival time of the animals fed lead oxide was significantly longer than the others (11) > Broilers fed lead oxide in the diet at concentra tions as high as 30 ppm for 7 weeks, showed the highest concentration of lead accumulation in the bones (12), 2, inhalation The lungs of rats which inhaled 200 ug/m3 for 14 days showed damage to the alveolar macrophages and type X pneumocytes, Ultrastructural changes included changes in the structures of the mito chondria and endoplasmic reticulum (24) . 4- DUP040010869  Workers dismantling an elevated train network were exposed to high levels of lead oxide fumes. The average concentration for 32 burner workers was 4.36 mg/rn^ while the mean was 0.23 mg/m3 for non burner workers. Some observations were: Blood Lead Average Hematocrit Mean Peroneal Motor-Nerve Conduction Velocity Burner Workers 44-110 pg/lOOg 41.4% 1134 pg/dl 43.2 m/s Non-Burner Workers 24-75 pg/lOOg 44.0% 714 pg/dl 49.0 m/s Burners also experienced nausea, abdominal dis comfort, mood change and irritability, sleep lessness, fatigue, headache and numbness and tingling of the extremities (25). Exposure of rats to lead oxide at 2.4 pg for 78 days decreased the activity of choline sterase and levels of Hb and protein sulfhydryl groups in the blood. Also observed were increases in reticulocyte count, decrease in the ascorbic acid content of lungs, liver, spleen and central nervous system. A high accumulation of lead was found in adrenal glands, bones, spleen, liver and lungs. Lead affected the activity of the central nervous system (16). "Nearly continuous exposure of monkeys and rats to airborne particulate lead oxide for 1 year increased Pb levels of the blood to 28 pg/lOG ml in rats and 17 pg/100 ml in monkeys. These maximum levels were reached after the first few months of exposure and did not increase after that. Pb levels rose to 2-3 pg/g in soft tissue and up to .006 pg/g in bone. Delta-aminolevulinic 5- DUP040010870 acid dehydrase of erythrocytes was decreased by approximately 70% in rats, however there was no alteration in the excretion of heme precursors. There did not appear to be any change in blood chem. cr hematoi. nor were there any gross, microscopic, or ultrastructural pathologic changes" (13,14). "Inhalation of 150 yg lead oxide/m^ for 4 days caused ultrastructural damage to the lung paranchyma of rats and significantly decreased the activity of lung benzopyrene hydroxylase. A similar treat ment for 14 days increased the labeling of pneumocyte I cells by 3H-labeled thymidine, but pneomocyte type II cells were unaffected. Exposure of rats to titanium dioxide dust followed by inhalation of 82-168 yg lead oxide/m^ signifi cantly increased the retention of dust in the lung. These results indicate that the primary site of toxic action of Pb in lung is the reticular membrane and that low concentration of Pb can cause localized damage in the lung" (15). C. Intratracheal Instillation After 10 weekly intratracheal instillations of 1 mg of lead oxide in combination with benzo[a]pyrene (1 mg) hamsters exhibited typical epithelial pro liferation, ademoma and adenocarcinoma of the lungs. "Similar administration of lead oxide or benzo[a]pyrene alone produced only alveolar hyperplasia and metaplasia. No tumorous changes were found in control groups. Thus lead oxide exhibited a cocarcinogenic effect with benzota] pyrene in the lungs. The induced tumors generally appeared in the peripheral areas of the lungs, indicating bronchioloalveolar origin" (9). In a forty day study the intratracheal administra tion of moderate doses of lead oxide to rats resulted in a significant increase in the number of recoverable pulmonary alveolar macrophages. Thus lead oxide shows low order of toxicity to alveolar macrophages (10). -6 - DUP040010871 D. Mutagenic Potential To investigate the correlation between chromosomal damage and occupational exposure to lead, chromo somal analyses and. biochemical tests were performed on workers in a lead-oxide factory, where all sub jects were found to have a significantly elevated blood lead level (74.7 microg/100 ml vs normal value of 14.9 microg/100 ml). Blood lymphocyte cultures showed an increased proportion of mitoses with secondary chromosomal aberrations in the workers exposed to lead-oxide, compared with a control group of healthy blood donors. The percent age of abnormal mitoses rose with an increasing delta-aminolevulinic-acid excretion in the urine. In addition to chrcimosomal breaks there ^ere also nonspecific changes such as spiralizing defects, chromosomal adhesions and pulverization. The pro portion of tetrapl'oid mitoses an'd the mitoses index were slightly increased over thdse in the control group (26). The lead concentration in blood and aberrations of chromosomes were detected in workers exposed to lead in the manufacture of lead oxide. The lead concentration was 30-75 yg/100 ml in exposed workers as compared to 15-35 ug/100 ml in controls. A significant increase of chromatid and chromosome aberrations occurred in exposed workers (28). E. Carcinogenic Potential A study performed by State University of New York began in June 1974 was completed ih December 1977. The pro ject summary follows: Male Syrian Golden hamsters were exposed to lead monoxide and platinum dioxide by intratracheal instillation once a week for 16 weeks. Each metal compound was administered alone and in combination with benzo[a]pyrene in saline suspension. Benzota] pyrene, alone and in combination with Fe203, a potent inducer of pulmonary neoplasia, was also given to obtain positive controls. Animals were maintained for their lifetimes. At death, gross and histopathologic examinations Were performed. These metals are being evaluated for their potential carcinogenicity in the induction of neoplasia, particularly of the respiratory tract, in conjunc tion with benzo[a]pyrene. More than 80% of the animals have been autopsied and data are presently being accumulated on pathologic alterations. A final report is expected in March 1978 (27). RELATED INFORMATION CA 79 : 88057p Cylotoxocity of lead. Beck, E. G.; Manojlovic, N.; Fischer, A. B. (Med. Inst. Lufthyg. Silikoseforsch,, Driiv, Duesseldorf, Duesseldorf, Ger.l, Proc., lot, Symp., Environ. . Health Aspects Lead 1972 (Pub. 1973), 451-62 (Ger), Comm. Eur. 'Communities. Cent. Inform. Doc.: liuxembours. Luxemw bonrg. Lead [7439-92-1] and airborne dusts were toxic to line L ceils, as shown by inhibitions of division and disturbance of cell permeability and intermediary metab.; the repro'dn. of human fetal connective tissue cells was also impaired, Guinea pig alveolar macrophages showed both rapid lysis of the cell and slower bullate vacuolation in response tit Pb. The vacuolation was produced by both Pb .and airborne dust and was comparable .in alvediar macrophages, line L cells, and human fetal connective tissue .cells. Treatment of lead oxide [1317-36-8] and airborne Pb with cdlciitm ethylenediaminetetTaUceiate [64-03-9] chelator decreased their, toxicity.. Pb.O, lead bromide [1,0031-22-8], and lead abgtaPp [30.1-04-2] .after diq. extn., or their aq, exts., had a toxic effect which varied according to the type of compd, Thus, atm, Pn may a pathogenic factor in a muiti-caus,al etioi. of various illnesses. 4-V- r-ejmpienmg CA 81: -g(129036z Effect of low lead concentration on human body. Saito, Kazuo; Sato, Toshlo; Sato, Y.uji; Niizuma. Kozp (Sch. Med,, Hokkaido Univ,, Sapporo, Japan), hid. Health 1973, 11(3), 85-93 (Eng). Miffrohema.to.cot, sp.gr, of blood, Pb concn. in whole blood, and 6-amino-. lev.ulinie acid de'nydrase activity (ALAD) in erythrocytes were measured in ,203" policemen on patrol by car and 19 workers exposed to PbO dust in a-ceramic factory, and the blood Pb levels and ALAD activity correlated with the Pb concn. in the working atm- The Pb level in blood the. workers and the policemen were 14.3-31,2 juid 2.0-31.1 /w/lOOffl, rasp., and the mean ALAD activities were .0.96 and 1.23, resp. In policemen with < 15 ug Pb/100 ml there was no - sigmticant decrease of ALAD activity and no correlation. . K, Aparajithna__-.' -8 - DUP040010873 CA 76" XOSiiy Comparative biological activity of metal oxides at the level of their threshold doses introduced singly. Rabotnikova, L. V. {Med. Inst.,, Perm, USSR). Gig. Tr. Prof. Zahol. 1971, 15(8), 33-6 (Russ). The exptl. found THRESHOLD DOSES for 24 different toxic METAL OXIDES, administered in a single injection to white mice, showed close correlation with the officially admissible max. concns. An equation for the calcn. of an approx, max. concn. for a given metal oxide on the basis of its threshold dose is recommended. The threshold doses were detd. by testing changes in blood, summation-threshold index of the nervous system, and total body, liver, kidney, and spleen wts. CA 6 6 " 7 84266q Toxicity of metal oxides and. its correlation with vari ous physico-chemical properties and the normal content of the element in the body. L. V. Rabotnikova. Vop. Ohshdi. Chasln. Prom. Toksikoi., Leningrad 1965, 52--5(Russ). LDw values were detd. fof 23 metal oxides on i.p. injection to mice. The correlation coeffs. between LDM and sp. gr. of the oxide, the m.p., the normal potential of the element, the primary ion ization potential, and the at. wt. were detd. A correlation was found between log LDTM of the oxides and. the log of the permissible concns. and normal content of the element in the body. For sev eral oxides, permissible concn. devia ted toward a higher toxicity not corresponding to LDa (e.g., PbO, PbO;, BeO, Cr03, CoiOj). For these compds., addnl. factors must be taken into account in calcn. of permissible concn. For quick detn. of LDgi of oxide compds. it can be calcd. from the correlation with the oxide m.p. From Ref. Zh., Biol. Khim. 1966, Abstr. No. 22F1786. _ '' _________ __ . " J.1VRL ' CA 84 : 84: 16021lg Growth inhibition by mercury, arsenic, and lead of crops. Shimagami, HIciec; Izawa, Kivomi (Tokyo Fen. Feed Insp. Off., Tokyo, Japan). Hiken Kaiho 1975, 28(4). 15-34 (Japan). The toxicity of Hg [as Hg(OAch [1600-27-7], HgO, HgCls, MeHgCl [115-03-3]], As [as NaAsOr, NaeHAsO^, Ca3(AsOa)2, CastAsCLh] and Pb [as Pb(OAc)j [301-04-2], PbO] to crops was studied under various environmental conditions, Pb: at concns. as high as 1500-2000 ppm was nontoxic to rice, Chinese cabbages, and small turnips. Hg was highly toxic to dry field crops, whereas As was highly toxic to paddy field crops. Hg was more toxic to rice grown in alluvial soil than in trass, and HgO was more toxic than HgtOAcJs. By contrast, soils and chem. forms did not significantly affect the toxicity of Hg to Chinese cabbages. NaJisOs was more toxic than CaafAsO-ib to paddy rice, whereas no such relation was obsd. in dry field rice. NaAs03 was also more toxic than CastAsO-iH to Chinese cabbages. The toxicity of As in various soils decreased in! the order: sandy sojl > alluvial soil > black soil > red day. PA 79 > 9 88C56n Pulmonary resorption of lead dusts. Schlipkoeter, H. 1V,; Pott, F. (Med, ' I^st./Lafify'g. ^ilikosefbrsch., Univ. Duesseldorf,; Dqesseldprf,, G.er.), Proc.,' Int. Syrnp.., Environ. Health Aspects Lead 1972 (Pub. 1973), 403-13 (Geri, Comm. Eur, Communities. Cent, Inform, Doc.: Luxembourg, Luxem bourg. The, percentage of .pulmonary and enteral resorption of lead oxide [1317-36-8] or lead bromide [10031-22-8] in rats was measured; by the ami., of Pb deposited in the bones and the decrease of \&-aminolemdinic acid dehydrase [9036-37-7] activity by Pb. Pb administered intratracheally gave the same results as i.v. administration of the same Pb dose. Orally administered Pb showed only 5-10% resorption. Pb compds. were apparently absorbed very rapidly and almost completely when m the lung, bpb Jn''th|!jij)t)sgti^e' fMfr^btpiibnjiwaS.'Qhly 5-UI% due to the poor soiv. conditions. -9 / DUP040010874 REFERENCES 1. Hawley, G. G., The Condensed Chemical Dictionary, 9th eh., (1977). Stecher, P. G, , Merck Index, 8th ed., (1968). 2. TLV Booklet, 1977, / 3. Jachimowicz, (P. , .2- Bienenforsch, , 3:29-31 (1955) (from CA 49 :9826) . 4. Campbell, K, I. efc al., Arch. Environ, Health, 30_(4) :168-70 (1975). 5. Verdie, P., Fr. Demands, 2,085,629 (February 4, 1972) (from C'A 77:10560;8x) , 6. Pott, F. and A. Brockhaus, Zentralbl. Baktenol. Parasltenk., Infektionskr, Hyg. Abt l:Orig. Reihe B, 155 (1) : 1-17 (1971), ("from CA' 76 :21686n) . 7. Burkhanov, A. I., Gig.. Tr, Prof. Zabol., 3:30-2 (1975) (from CA 8 3:54130 z). 8 ._____________ , Industrial Medicine (Chicago) , 2_(2) ;15 (1941) (from Registry of Toxic Effects of Chemical Substances, ETECS). 9. Kobayashi, N. and T, Okamoto, J, Natl, Cancer Inst., 5(2):1605-10 (1.974) . : '" 10, Kaminski, E. J. et al., Brit, J, Exp, Path,, 58(1):9-12 (1977) (from Toxline HEEP/77/9633), 11, Tesic, P. and p, Labudovic, Acta. Vet., 14_(3) :179-83 (1964) (from CA 63:12214h), 12, Nezel, K. and H, Vogt, Arch.. Gefleugelkd., 40_(5) % 188-92 (1976) (from CA 86.;70268t), 13, Griffin, T, B, et a.L, , Envlr. dual, Saf. Supp.l., 2_:202-20 (1975) (from CA 84:1313 8k).. 14, Griffin, T. B. et al., Arh. Hig. Rada. Toksikol., 26:191-208 (1975) (from CA 85:10 4885:p)Y : ~-- -- 15, Bruch, J. et al.. Comm, Eur, Communitus, Vol. 2:781-91 (1975) (CA 87:128290h), 16, Zharkova, N. S., Tr. Nauch,-issled. Inst. Rraer. Patol, Ama Ata., 22:85-96 (1971) (from CA 81:115510f). 17, Unpublished Haskell Laboratory Data: .MR-10--50, HL-104-66. 18, Unpublished Haskell Laboratory Bata? .MR-2712-001, HL-142-77, - 10 - DUP040010875 REFERENCES (CONTD) 19. Unpublished Haskell Laboratory Data: MR--2712-GP1, HL-143-77, 20. Unpublished Haskell Laboratory Data: MR-2712-001, HL-176-77. 21. Unpublished Haskell Laboratory Data: MR-2712-001, HL-253-77. 22. Unpublished Haskell Laboratory Data: MR-2712-001, BLt 6|4-77. 23. Unpublished Haskell Laboratory Data: MR-170, HL-41-6S, 24. Bruch, J. et al., Proc. Int. Symp. Envir. Health Aspects Lead, 221-30 (1972) (from CA 79 :88049n). 25. Feldman, R. G. et al./ Lancet., (January 8, 1977). 26. S.chwanitz, G., Dtsch. Med. Wochenschr ., 95J32) : 1636-1641 (1970) (from Toxline CARC/71/112)> ~ 27 Tox-T.ips, August 19 77 (15-25) . 28. Garza-Chapa, Raul, et al., Arch. Invest. Med., 8/1):11-20 (1977). (from CA 87;43485 a). Pamela J. Gort:md March 22, 1978 - 11 DUP040010876