Document MGD96RGddapVob2G63KMDmrxj

FILE NAME: Union Carbide (UC) DATE: 1971 Sept 3 DOC#: UC043 DOCUMENT DESCRIPTION: Report from Carnegie-Mellon Univ. - Calidria Asbestos-Resin, Tracheal Insufflation of Rat Lungs Confidential Special Roport 34-70 7 Pages : .... ... . ' Chemical Hygiene Fellowship MELLON INSTITUTE * Carnegle-Mollon Unlverolty Il 9-3-71 . ` . Calldrin Aobcoton-Rcoin Credo RC 244 . i ' ' -- Tracheal Inoufflatlon of Rat Lungs with Interpretation . ' Editort Fort f Pathology after 30. 60 90 . C. P. Carpenter Contrlbutoroi . UNION CAKQIUK CORPORATION* Chomlcals and end 180 Dave D. L. Geary, Jr.# t. It* Kinksad, I* Ci Mycra, D* J* Machrslnsr Plastics Operations Division * -- : Sample ' ; -,. . / A 500-gram sample of Rein Crade RC 244 UCC Calldrla Asbestos ras received 11-30-70, from King City, Californio, pursuont to arrangement* Ciade by Paul McDaniel of the Mew York Office. The sample was identified by the Chemical Hygiene Fellowship #33-251* * * aw . Tracheal Inoufflatlon ; A IS (V/V) ouopenolon of the RC 244 sample vas prepared In 0*85Z saline* All needles, syringes and suspensions vers sterilised prior to tes* Cither 1 ml or 0*5 ml amounts of the sterile IS ouopenolon vers injected into the tat lung through the trachea, oxpooed by blunt'dlsoeetlon, aftor A midlino cervical incision* Following injection of these 200 to 300 gram, male albino, Harlan Mister rati the incisions were closod with Michael wound clomps until healing ensued* \ t t '' A total of 13 rats were doood with 1 sd and 15 with 0*5 id of tha It . suspension while 11 control rats rocelvod 1 ml of storlle 0.85Z MaCl. three rets from eaeh oobestos doood group and 2 controls wore killed for histopathologic examination of the lung after intervals of 30, 60 and 90 days which left .groupe of A, 6 and 5 rate on the 1 ml* 0*5 ml asbestos end control for the 180 dey secrifice* . Summary of Microscopic Pathology Found 30. 60 90 end j|Q Days Following Tracheal Inoufflatlon of Rato The 30.-day pothology was marked by the prooenca of. granulation tissue with thickening of.the structural element of the lung (attorns) and tha accumulation of giant cells often associated with foreign bodies* ' - | Report 34-70 *8 * .. . After 60 deyu one rot on tho 0.5 1 dooage level had inflssaatlon and In growth of connective tlouuc which blockod e torminnl bronchus. Tiro of 3 rata on both the 1.0 end 0.5 ul dosage level had otolcctooio (collepoe) of one or ore lobei of the lung. Flbrotlc foreign body uodulda were preoent In all caoea* After 90 dayo there woo chronic forolgn body pneumonia In 2 of 3 rota at both doougo levele, flbrotlc foreign noduleo in 3 of 3 end emphysema In 2 of 3. Chronic lnflaiiuatory cell foci end otclcctoolo woro preoont. Bronchloleo vara dllntod in 2 of 3 rots on both dooage levels and all but one on both dooaga levala bad ooce lung hoicorrhagc. ( the final 180 day oocrlflco rovealed intorotltlol pneumonia in 4 rate on tho 0.5 ml dose. Thio lo a chronic fora of pneumonio of interstitial tiesuo with docroaoc of the uornsl lung cluoua. Atoloctosie vao preoent in tho 4 rata on 1 ad and on 1 rat on the 0.5 ul dose of aobootoa with tho 5 controlo normal. Flbrotlc forolgn body tiocuo vao preoont in ell doood lungs vlth nono in tho controls. Fink hyalin uatorlsl was found in 2 of 4 lungo froo rate on tho 1 ul dooo While in 3 of * 4 thcro vao a bluish houogoncouo tutorial ovidont. ' . . " : . 9 - In essence, o total of 10 of.13 rats on tho 1 ad floes and 12 of 15 on the 0.5 ul dose hod flbrotlc forolgn body noduloo or tiesue. There vorp 3 caeoe of mphyoeiEa on the high dooo end 4 on tho low dooo and 1 in tho control. Atelectasis (essentially collapoo of lung elvooll) vas preoent in 9*rats on 1 ul end 6 on 0.5 ul of asbestos vlth none reportod in tho controls* In general, bocouso of the over whelming propondcronco of offoct in tho aobcotos doood lungoWoreus the controls, vo have sufficient evidence of dsmago to vdrn us to do bur boot to prevent inhalation of coscentratlons of eoboatos in excooo of tho Threshold Unit Value proposed for 197Q (Threshold Limit Values of Airborno Contominanto ind intended Changes. Adopted by ACGIII for 1970. American Conference of Governmental Hygienists, 1014 Broadway, Cincinnati, Ohio 45202). - . Summary Tables for each of tho four-aacrlflcoo ora ineludod. Dstailod pathology reports on each animal aro available end copies eon be furnished if the ood for then arloee. A literature review proporod in connection with Onothar requeot for information ia attached although not requested. Acknovlcdroonts: Inhalation Studies Charles F. Carpcnpdr, Fh.O. Adminiotratlva Fallow Daniel L. Ceary, Jr.* H.Ed. Reoearch Associate Edwin R. fcinkoad, B.S. Follow . Roy C. Myers, B.S. Rosoareh Aaolatant Donald J. Kachrolner, B.S. Research Assistant Report 34-70 c Rage 3 Toblo 34-19 . . Troehaal Inoufflotion to Roto Soerlficod 30 Doya Aftor Doping TOTAL NUMBER EXAMINED CROSSLY: 1AJNC: Number Examined Fnoumania llcmorrhago Pleural adheolona Stromal thickening . Foam cell occuiaulatlons . Cranulatiqn tlouue foci Multlnucloatcd giant colls Aboccsd.bronchopneumonia Round cell accumulations ' TRACHEA: Number Examined ' Chronic tracheitis CM) <G) <C)` (G) CM) CM) CM) CM) CM) CM) CM) V CM) Ml of IX Solution 1 0.3 0 .0 3 3 2 3 3 2 3 3 0 1 0 0 1 2 0 3 2 0 3 2 \ 0 3 3 0 3 2 0 0 1 0 0 O X 3 3 2 0 O 1 The following tlooueo vero examined microscopically on all animals: Lung, Livor, Kidney, Heart, Spleen, Adrenal, Thyroid, Parathyroid, Traehea And Esophagus. C " Cross M Microscopic Table 34-20 . Trachoal 'insufflation to Rate Sacrificed <0 Doyp Aftor Staging ` Ml o f 1 Z Solution TOTAL NUMBER EXAMINED CROSSLY: jLl'NGi Number Examined CM) Hemorrhage : Fucumonla Atclectaols Edema Hemorrhage * . CO . CC) CC) CG) CM) Atulectasle 00 Fibrotic foreign body nodulos CM) Bronchiolitis fibrosa obliterans CM) KIDNEY: Number Examined CM) Round cell occumuletlons 00 HEART: Number Examined ' . CM) Focal myocarditis CM) IUSCLE: Number Examined . CM) l'urulent mass (G) Large ouppurutlvo process, striated muscle CM) 1 M M 3 3 2 3 3 2 . 0 0 X * 3 3*# 0 0 '2 0 X 2* 0 X 0 0 2 2 0 3 3 0 0 X 0 3 3 2 X 0 0 3 3 2 0 X 0 X 0 .0 X 0 0 X The following tissues were examined microscopically on all animals: Lung, J _____ i.j < * s i ____ - (*_ 1 g j | A t a 1 ,T K tM *4 A l l a m a b k o r M f l . T p i a K s a am4 Report 34-70 Page 4 Tablo 34-21 Trochgal Inaufflotion to Roto Socrlflced 00 Povo Aftor PooInn x TOTAL NUMBER EXAMINED CROSSLY JLONCi Number Examined... Pleural udhoaiono ,Hemorrhage * Edema ;Pneumonia * Chronic foreign body pneumonia Flbrocic foreign body toduloa Emphysema . Chronic lnflancnatory call foci Round coll foci J Atelectasis " Bronchiectasis . Stromal thickening Hemorrhage - Inhaled blood . .* SIDNEYi Numbor Examined Hydronephroois Hydronephroolo ' Bound cell focuo yUAClIEAt * Number Examined Chronic tracholtla . HEART Humber Examined T Myxoid chango, interstitlum HI of IX Solution A 0.5 . -0 .0 3 3 2 CM) 3 3 2 cc) 0 2 .o CC) 0 2 0 <c) 3 * 3 *. 0 Cc) 3 3 0 CM) 2 2 0 00 ^3 CM) ' 'v - 2 CM) v, v j CM) t CM) S CM) 2 CM) 1 .3 2 v: 3 \] a as 3 ;2 0 0 * 0 .0 i i; :0 0 0 CM) 3. 2 0 CM) a o 1 0 . CM) 3 3 3 CO * 0 0 1 CM) 0 0 a CM) 0 : 1 c CM) '.3 y. *3 3 CM) 2 1 2 CM) 3. 3 3 CM) 0 1. 0 The following tloBuca vera examined microscopically oh #11 animals t Lung, liver, Kidney, Heart, Splaan, Adrenal, Thyroid, Parathyroid, Trachea and Esophagus C Cross M Microscopic ` i * Report 34-70 Ra 5 Tablo 34-22 ` Trnchoal Innnfflntlon to Rato Sacrificed ICO Dayci Aftor Dosing Ml of 1Z Solution TOTAL NIJMDER EXAMINED CROSSLY 1 LONG: Numbur Examined' EdcBS 1 0.5 ,0.0 4 6 5 CM) 4 6.* 5 (C) * 2 0 1 Pnoumonia . (C) 4 3 1 Atelectasis . (C) 2- 0 1 Emphysema . (G) 0 0 1 Emphysema . CM) 1 2 1* Atelectasis Inhalation pneumonia CM) 4 1 0 CM) 1 0 *0 Interstitial pneumonia . * CM) V 0 4 0 Abscess bronchopnouuorfla . ` > ; c m ) *j';0 Y/. C I Suppurative bronchiectasis Acute bronchitle - ' CM) . y - ''v y CM) . 1 ?v.o ' f -0 0 'v.kl Lymphoid cell accumulation* V ' -v' CM) 3 ; * o -o Foam cell accumulation* . . CM)- 2 {. .1 3 'Fibrotlc foreign body tissue * CM) 4; s 0 Cronulation tissue foci Fink hyalin material .* * . CM) 0 # i 0 CM) 2 0 0 Bluish homogeneous material CM) 3 1 0 numerous uononudoar cello CM) 1 0 o Mucoid infiltration . CM) 2 0 0 Proliferation bronchiole epithelium XtVERt Number Examinod Bile, duct proliferation Bound cell foci ; , . KIDNEY. Number Examined Uydronophroslo <M) CM) ;V -? JC H ) CM) CM) CC) 0 6 4 v 4 y 0 2 1 *0 4. 4 0 . 1 1 S 1 *0 ' 5 . .4 Sand calculi Hydronephrosis Sand calculi toilstod tubules Fink coots CC) 0 ` 1 0 CM) 0 1 r. 0 CM) . 0 i 0 CM) 0 2 . 2 CM) 0 li - 1 interstitial nophrltlo CM) 0 . l .0 Cellular infiltration CM) 1 0 Blight tubular regeneration CM) o 1 3 . Moderate tubular regeneration CM) 0 0 1 TRACHEA: Number Examinod Acute tracheitis * . - CM) 4 4 5 CM) i 0 0 Chronic tracheitis CM) 0 4 0 The following tissues were examinod microscopically on li animalst Luna, Liver, Kidneys, Heart, Spleen, Adrenal, Thyroid, Farethyroid, Trachea and Esophagus. c - Cross M * Microocopie . :j ' ' Report 34-70 . !' Page 6 ` A o b o o t o o .. ?'" .. ' * Addlnglcyj,..C, C. Aebcotoa Dust and Its Measurement. Ann, Occupy Hyg. I . . - 7 3 (19$(; Anon. Occupotional Hazards of Aobcotoo. CIS (International Occupational Safety and Health Information Centre.) (Abstracts on Aobeotos'io 1959 to 1967). Co11inn, T. F. Asbeotoo the Lethal Dust. S. Afr. Mod. J. 42i 218-9.(1968)1 As cited In Index Mcdlcus, 9(#8), 1968, 9. 70. ............ .. f Committee on Hygiene Standards. Hygiene Standards for Chryeotlle Aobestos Dust. Committee on Hygiene Standards of the British Occupational Hyglone Society. Enterllno, P. C. Asbestos-Dust Exposures at Variouo Levels and Mortality. Arch. Environ, Health. 15, p. 181, (1967). * . ' , . . I * ' Kogan, F. M.| Svlrokli, E. L.| Belebraglna, C. V. Cl*. Tr. Prof. Eabol. 13. fp. 9-1 (Hues) (1969). Hygienic Characteristics of thoDustGenerated in the production of Asbestos-containing Thermal Insulating Materials Asbeotot Vermlculite and * Asbestos Perlite. As c(ted in C.A. V. 72(26). p. 253(l36090y) 1970. Paratsl, Elena, at al. Cytotoxicity of Asbestos Dusts. "Mod. Lav. 1968. S9(10). 561-76 (Eng). As cited in C.A. Vol. JNL, #2, p . 256(6374nT ll&9). Kaport from a Working Croup of the International Union Against Cancer. The Association of Exposure to Asbestos.Dust end Cancer. Ann Occun. Bt r .'8, p 267, (1.965). * ., * * ~ loach, 8. A. Hygiene Standards for Asbestos. Ann. Occun. Bye. 13. pp. 7-15,' (1970) . ' Selikoff, Irving J., et el. Asbestos Exposure, Smoking, end Neoplasia. JAMA. 204. #2, p. 106/104, 1968. . ' *--- * -- * ] * j Timbrcll, .V,, ot al. A Simple Dispenser for Cenerstlng Dust Clouds from Standard Reference Semples of Asbestos. Ann. Occup. Hvn. 11. pp. 273-281*1968. * I Aobeotosls * ' ./ ' . Baiter, J. LcRoy. Industrlol Hygiene fpr Insulation Workers. J. of Occun. Med. 10, #1, (1968). . Cross, Paul and R. T. r. dcTreville. Experimental Asbaetosls. Arch. Environ. Health 5, p. 638 (1967). . ---: Crooa, P. and R. T. P.'dcTrcvillc, Experimental Asbestoois. Studies on the Progres- alvcness of the Pulmonary Fibrosis Causod by Chrysotilc Dust. Arch. Environ. ! Health| 15,. (1967). .As cited Ac Industrial Hygiene Digest. 32 ; May 1968, #449. , McDonald, J. C., at al. Mortality in Chryeotlle Asbestos Mines and Mills of Quebec, Arch, Environ. Health. 22 677-86, June 1971. As reported in the JAMA p. 1658. June 7, 1971, Vol. 216 No. 10. Report 34-70 Page 7 Editorial* Aobcotc... I.n Urban Populations* JAMA 196i 732 (1966)* ' Gross* Paul* et al* Asbestos Versus Nonesbestos Fibers* Arch* Environ*. Wealth* 20, pp. 571-578 (19/0). * Holt, P. F.* J. Mills, ami D. K. Young. The Early Effoots of Chrysotlle Asbestos Dust on the Hat Lung* J* Pathol* A Boctorlol*. Jj7t 15-23 (1964)* . Hygienic Standards. Ind* live. J** 19(82). p* 161* (1958). Harr, William T. Aobcstos Exposure During Navel Vesool'Overhaul* AIHAJ* 25 (#3), pp. 264-268, May-June 1964* * . * Thomson, J. C., and W, M. Groves* . ' * . Asbestos as an Urban Air Contaminant** Areh* Pathol* 81: 458 (1966). . Westlake, Ceorgc E., Marlon J, Spjut, and Marilyn N* Smith* Penetration of Colonle . Mucosa by Asbestos Particles* An Electron Microscopic Study in Rats Pad Asbestos Dust* tab* Investigation* 14t 2029 ( 1 9 6 5 ) * ' Analytical ^ # . Crable, John V* Quantitative Determination of Chrysotlle, Amosltjs and Crocldollte by X-ray Diffraction. A1UA, Vol* 27 (13), May-June, 19j66 p. 293-298* * . Crable, John V., and Marta J* Knott. Application of X-ray Diffraction to the , Determination of Chryootlle in Bulk or Settled Dust Semplii* A1HA, Vol* 27 (#4),' July-Aug.,1966 - p. 383-387, * . 1 * . . . . Crable, John V*, and Marta J* Knott* Quantitative X-Ray Diffraction Analysis of Crocldollte and Aaoslte in Bulk dr Settled Dust Samples* AXUA, Vol* 27 (15), Sept*-Oct*`, 1966 - p* 449-453* . ' Lynch, Jeremiah R*, and llovard E* Ayor* Measurement, of Dust RxpOSurSs In the . Asbestos Textile Industry* AXHA, Vol* 2f (#5), Sept*-Oct*, 1966 p* 431-437* The Method For Determining Asbestos Dust Concentration* This publication sells for $1.00 and may be obtained from the Asbestos Textile Institute, P, Q* Box 239, Pompton Lakes, New Jersey 07442* AXHA, Sept*0ct*, 1965* * . * Tlseua Response to Asbestos (Report of a Meeting by C* N* Davies)* ' Ann. Occup* Hyg* Vol. 13 pp. 241-245* Porgammon Preso, 1970* I e?* ,^' R eport mailing list b Medical Directors 4 - C... Dernchl 1 - E. Q. Hull 1 R. E. Joyner 1 - K. J. Sexton 1 - I. N. 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