Document nND6nDE7vQV3k883JEjNnOgxX

Draft -- 11/6/75 Position Paper on Vinyl Chloride and Birth Defects Despite a number of alarming articles in the press over the past 15 months, the medical and statistical evidence compiled to date has failed to establish a relation ship between vinyl chloride exposure and birth defects in humans. Nevertheless, additional objective and thorough scientific investigation into this area of mutual industry and public concern is desirable. Background In January 1974, three cases of an extremely rare but always fatal type of liver cancer, angiosarcoma, were discovered among long term workers exposed to high concentrations of vinyl chloride monomer (VCM), the gaseous chemical used to produce polyvinyl chloride (PVC) resin. The relationship between heavy VCM exposure and angiosarcoma was subsequently confirmed through epidemiological studies of exposed worker populations and by animal research. In supplemental studies, VCM was shown capable of producing a mutagenic reaction in salmonella bacteria; and an increase in chromosonal breakage was found in a small number of heavily exposed PVC polymerization workers. Because of these isolated findings, concern was raised that VCM might also prove to be teratogenic, i.e. capable of causing malformations or birth defects. Study of Ohio PVC Plant Towns Undertaken In order to investigate this supposition, Dr. Peter F. Infante of the Ohio Department of Health examined the birth records of children born between 1970 and 1973 in three towns in eastern Ohio -- Painesville, Avon Lake and Ashtabula -- that RFGM^Q? 214U9001 o Not only was this discrepancy unexplained, but Dr. Infante then proceeded to lump cases of CNS malformations from one of these two communities -- North Ridgeville -- together' with those from the three plant towns in developing his statistics. Dr. Infante explained this unusual procedure by stating that North Ridgeville was 'proximate" to one of the plant towns. In reality, the two are nearly 10 miles apart. In addition, if one examines the data from the four towns separately, rather than in combination as Dr. Infante did, the fact emerges that while one of the plant towns -- Painesville -- did have over half of the observed CNS birth defects, the non-PVC town had 25 percent of the total. Another of the plant towns -- Avon Lake -- v which has had a PVC facility in its midst for the longest period of time of all three communities, had no CNS defects at all. Nearly the same situation applied in the case of CNS cancers among adults.. Dr. Infante, once again, added cases from North Ridgeville to the three plant towns. When examined separately, only Painesville and North Ridgeville, which has no PVC facility, showed an excess of adult CNS cancer deaths. The other two PVC plant towns showed no excess. When the hard data from the three PVC plant towns and North Ridgeville are examined Individually, more unexplained differences than similarities in CNS malformation and adult cancer rates emerge. Dr. Infante's unorthodox procedure of "lumping" data from three widely separated communities -- Painesville is located about 30 miles to the west of Ashtabula and Avon Lake lies another 50 miles west of Painesville -- plus a town without a PVC facility, effectively obscured these significant differences. BFG14399 2148S003 - 5- The second part of the CDC study involved a thorough investigation of the 15 cases of CNS malformation recorded at the Painesville Hospital from 1970-1974. For each malformation case, two normal births were investigated as ''controls'' for comparison purposes. The results of this research, which was totally absent from Infante's original work, can be summarized as follows: 1. None of the interviewed parents of the children with CNS birth defects ever worked at either of the two PVC polymerization plants in Painesville (one set of parents could not be located, but records show they did not work at the plants at the time of their infant's birth). 2. In the "control" group, two of the fathers of "normal" children were working at one of the PVC plants at the time of their infant's birth. 3. Neither of the parents in either group lived within two miles of either of the two plants. 4. A statistical analysis of the actual distances between the two PVC plants and both residences and workplaces of the parents of "cases" and "controls" showed no difference between either group. The CDC concluded, on the basis of its own investigations and a thorough analysis of the existing research data, that while the possibility could not be ruled out that VCM might be teratogenic, the evidence to date did 'taot establish any association between (birth defect) cases and vinyl chloride exposure. " Provocative Statements Still Continue Despite the research and analysis done by CDC, some individuals continue to make provocative but superficial statements based on inaccurate interpretations of the Infante BFG14401 21489005 Applied Microbiology, Nov 1975, p wi7-Hl() Copyright D 1975 American Society l<o VIi< r'lhiiilcigv V..I :tll V. { ' N AP'inl< ,t 1n Prodiginine (Prodigiosin-Like) Pigments from StreptoverticiUium ruhrireticuli* an Organism That Causes Pink Staining of Polyvinyl Chloride NANCY N. GKKltKK anm DONALD P. STAHI.Y' Institute of Microbiology. anthers University, The State University <</ ,Weic Jersey . AW Hrunsicick. A'< i: Jersey OKMXi, and Department of Microbiology, ('allege of Medicine, University of imi'n. fount City. Iowa 5T2J2' Received for publication 1 April 1975 Rod pigments were oxl meted from Strcptorciiicillium rubrircticnh strain 10019, an organism frequently incriminated in pink staining of pnlyvinvl chloride These pigments were identified its undocylprodigininr and butyleveloheptylprodiginine. Pink discoloration of polvvinvl thloritle due tn microbial growth has frequently plagued I lie plastics industry MV 18' Such discoloration oc curs on vinvl-covcred furniture, vinyl wall cov ering. and vinyl doors. In an attempt to induce artificially the pink discoloration of vinyl plastic. Yeager 07) bur ied vinyl in soil and observed production of pink spots on the vinyl. Of the many organisms iso lated. only one. StreptoverticiUiurn ruhrircticuli fformerly Strcptomyces rubrirotirit/iy pro duced the pink discoloration of vinyl. Because of the lack of information in the literature on the nature of the pink pigments produced by S. rubrireticuh, a study was initi ated to characterize these substances and to determine cultural conditions suitable for their formation. The evidence presented indicates lat the pink pigment is actually a mixture of two prodiginine pigments, undecylprodiginine and butvlcvcloheptylprodiginine.' MATERIALS AND METHODS Organism. S. ru6n>ehcu/i strain 100-19. an orga nism kindly provided by G Tirpak. Tenneco Chemi cals. inc , was used in this study. It was originally isolated from pink-stained vinyl. Solid media. Five different media solidified with 15 g of agar per liter lUSP no. 1. Meer Corp.. New York. N Y.i were used. These included M` Bennett's medium '5k Mi) yeast-Czapek medium <5a>: (iii) Pablum medium containing 60 g of Pablum mixed cereal per liter (Canadian Pablum, Mead Johnson Co., Toronto, Ont.) in tap water, no pH adjustments; (iv) malt medium containing 10 g of malt extract per liter 'Fisher Chemical Co., Pittsburg. Pa.) in tap water; and <v) nutrient glycerol medium contain ing 60 ml of glycerol. 5 g of Wilson's peptone 851, 5 g of NaCl, and 3 g of meat extract iDifco Labora tories, Detroit, Mich.) per liter of tap water. Liquid media. The five liquid media used were li) Bennett's, >ii yeast-Czapek. iii' modified yeast-Cza pek in which l Iv phosphate .salt was replaced by calcium carbonate Mb glileri. <iv veasl-dextnisr i5i. and i vt soybean media to). The sovhean meal in the latter medium differs from that used previously i5i in that it contains 49'-; solvent-extracted soybean meal from Central Soya (Fort Wayne. Ind.i. It con tains not less than 49M crude protein: the ingredi ents are solvent-extracted dchullod soybean meal with added kaolin. Cultural conditions. Slant cultures on solid me dia were maintained at 2S C. Growth in liquid me dia was in 50-ml hatches in 250-ml Lrlonmeyer flasks shaken on a New Brunswick model V rotary shaker at 180 to 220 rpm When the organism was grown for extraction and purification of the pig ments. a slant culture was inoculated into soybean medium or Bennett's broth, shaken 3 days at 28 C. and then transferred into 10 flasks of soybean me dium. After 3 days, the cells were harvested In filtration. Extraction and purification of the prodiginine pigments. The following steps were taken M) The cells were shaken overnight with acetone. Spectrophotometric assay at 530 nm <5i. the wavelength at which maximum absorbance occurred, indicated about 4 mg of prodiginine pigments in the acetone extract, (ii) This acetone extract was concentrated and poured into water and the mixture was exracted twice with chloroform. Before the second extraction the aqueous lavtr was made strongly acid and the shaken mixture w as allowed to stand over night before the lower, pigment-containing chloro form layer was withdrawn. This procedure was known from previous work with other microorga nisms to result in higher yields of chloroform-extractable pigments, iiii > The pigment mixture wn further purified and resolved into two fractions by column chromatography on alumina and silica gel <5*. Techniques for characterization of the pig ments. Procedures for spectrophotometric analysis thin-layer chromatography iTLC). and mass spec troscopy were described previously'5'. Mass spectra were obtained at 2 kV with an inlet temperature of 240 C. 807 21490001 808 GKRHKK AND STAHLY ArpL. Microbiol KFSUI.TS I'lgmentalion and cultural conditions. S. rubrireticuli gruwn on five solid media, previ ously found useful for eliciting prodiginine pig ments. showed strong rod nundiffusing pigmen tation on nutrient-glycerol agar only. Weak red pigmentation was observed in the growth on Bennett's agar, but it was nearly obscured by the intense dark diffusing pigment that was also produced. Only the dark diffusing pigment was observed when this organism was grown on mail. Pablum. or yeast-Czapek agar. During ihe past 2 years une of us iN.N.G.) has studied 12 Xtreptumyces or Slreptouerticdliuni strains that produce prodiginine pigments. S- rubrireticuii strain 100-ID is the first such strain that failed to show red pigment on yeast-Czapek agar. In shaken broth cultures, strain 100-19 grew well in yeast dextrose and soybean media, less well in Bennett's broth, and poorly in the two types of yeast-Czapek broth. Red pigmentation was most noticeable in cells grown in soybean medium. Some pigmentation was apparent in cells from Bennett's and yeast-dextrose media, but it was absent from cells in the two yeastCzapek media. More pink pigment was produced at 28 to 31 C than at 22 C. At 38 C pigment production was slight to none. Maximum pigment accumu lation occurred during the early stationary phase of growth. Characterization of the prodiginine pig ments. The pigments extracted from cells were purified and resolved into two fractions (A and B> as described in Materials and Methods. The purified pigments were compared with authen tic samples of the nine known, fully character ized, naturally occurring prodiginines. Figment A exhibited visible absorption max ima at 528 nm in acid-CHCL and at 525 nm in acid-ethanal. These maxima as well as the ob served TLC behavior (color, fluorescence, and Rf) were identical with those of authentic sam ples of undecylprodigimne and nonylprodiginine (4). Mass spectroscopy indicated that pig ment A was undecylprodigimne (Fig. IA; Fig. 2). The molecular ion was clearly 393 mass units, and the spectrum closely resembled that ofauthentic undecylprodiginin*' (M), Nonylprodiginine has a molecular ion at 3^5 mass units. Figment II was identical with authentic butvlcycloheptylprodiginine (Fig tB) in visible absorption maxima 1542 nm m ai id-CHCl3 and 536 nm in acid-ethanol) and TLC behavior (5a). On the TLC plate, spots of piirment B were slightly behind those of authr*'r.ic metacycloprodigiosin (15) and pinker lie-'; orange). Spots of pigment B were the same c"*or as those of authentic prodigiosin (10, l';' but slightly ahead. The structure was vrnfied by mass spectroscopy (Fig. 2). The mayi spectrum was similar to that obtained previously for butylcycloheptylprodiginine (5a) and dearly different from that of metacycloprodigiosin, which does have the same molecular formula but a differ ent structure. DISCUSSION Two prodiginine pigments have been identi fied as products of S. rubrireticuli, undecylprodiginine and butylcycloheptylprodiginine. These pigments were recently found by Gerber (5a) to also be produced by Streptomyces sp. Y-42, a strain isolated from leaf and grass com post. Several other members of the order Actinomycetales have been found to be capable of producing prodiginine pigments (l-5a, 7-9, 11-15). it is probable that the "pink staining" of poly vinyl chloride caused by S. rubrireticuli is due to the prodiginine pigments produced by the organism. Yeager 118) reported that "the pres ence of the organism in the vinyl system is not necessary to produce the stain. Instead, the discoloration is caused by a migration of the stain from a nearby substrate on which the organism is growing." The prodiginine pig ments ofS. rubrireticuli are soluble in diisode* cyl adipate, one of the plasticizers used commer cially by some vinyl manufacturers. Exposure of the plasticizer to red mycelia resulted in ex traction of the pigment iStahly, unpublished data). Thus, the plasticizer is the probable vehi- AB Fic. 1. Prodiginine pigments ofS. rubrireticuli. lAI Undecylprodigimne, (5) butylcycloheptylprodiginine. 21490002 BFG14404 Vol. 30, 1976 PKODK'.ININK PIGMENTS FROM S. RUBRWETICWA 809 I Frc. 2. M&ttbspfctra ofpradiginine pigments of S ruhrireticuli. (A) Pigment A, undecylprodiginine; (B) pigment B, L$tjtlcyctoheptylprodiginme. cle through vyftich the pigment is transported from S. rubrityticuli throughout the vinyl sys tem. The mass, spectrum of pigment A with its strong moloc^iar ion at 393 mass units is clearly different from that of nonvlprodiginine. the moleculafcidn of which is 28 mass units less. Both show th<j';252 mass unit peak caused by /j cleavage of tJ3? aliphatic side chain. Although both metacydfftprodigiosin and butylcycloheptylprodiginiqtf'.have strong molecular ions at 391 mass unftjt the next largest peaks are 307 and 320 for tw former and 348 and 334 for the latter. S Literature cited 1. Arctmone. (e^A. Di Marco. M. Ghione. and T. Scocti 1957. Studltfj] ptgmento si mile alia prodigiosina prodotto da al^u actinomiceti. G. Microbiol 4:77-85 2. Dietzel. E. 1w Uber das Vorkommen von prodigiosinahnlichiflprbetofTen bei Actinomyceten Naturwi*. senechaften 35:345 3. Dietzel. E. 1949 Uber prodigiosinahnliche Farbatoflfe bei Actinomyceten Koppe-Seyier's Z. Phyaiol. Chem. 284:282-271. 4. Gerber. N N 1969 Prodigiosin-like pigments fromAcfinomaduro ' Nocardla> pelletieri and Actinomaduro rnadume Appl. Microbiol. 18:1-3. 5. Gerber, N N. 1973 Minor prodiginine pigments from Actinomaduro madume and Actinomaduro pelletieri J. Heterocycl. Chem. 10:925-929. 5a. Gerber, N. N. 1975 A new prodiginine (prodigiostnlike! pigment from Streptomycea. Antimalarial activ ity of several prodiginines. J. Antibiot. 28:194-199. 6. Girard, T. A., and C F Koda. 1959 Pink discoloration of vinyls. Mod. Plast 36:148 7. Haraahima, K . N Tsuchida. and J. Nagatau. 1966 Prodigiosin-25 C. A new prodigiosin-hke pigment. Agric- Biol. Chem 30:309-310. 8. Haraahima. K , N. Tsuchida, T. Tanaka, and J. Na gatau. 1967. Prodigiosin-25 C. Isolation and chemical structure. Agric. Biol Chem. 31:481-489. 9. Khoklova, I. M., A. V. Puchnina, and 0 I. Artamova 1964. Chemical study of the chief components of vitamycin. Biokhimiya 29:841-845. ' t .7 \ rrf*?-' j *, v- -3Xi jam BFG14405 810 GERBER AND STAHLY Appl. Microbiol. 10. Morgiin. fci N.. and E. M. Tanner. 19S5. Prodigiosin. J. Chem Sue. I9*>':33(I5. 11. Perry. .1. ) 1961 Prodigiosin in an actmomycete. Na ture i London) 191:77-78. 12. Washerman. H. H . D. J Friedland. and D. A. Momson 1968. A novel dipyrrolydpyrromethane prodig iosin analog from Serratia marcescens. Tetrahedron Lett 1968:641-644. 13. Wasserman, H. H.. J. Keggi, F Bohlmann, and W. Luders. 1960. Struktur eines prodigiosin-ahnlichen PilzfarbstofTs aus Streplamyces iongisporus ruber. Angew. Chem. 72:779. 14 Wasserman, H H.. G. G. Rodgers, Jr., and D. D. Keith. 1966. The structure and synthesis of undecylprodigiosin. A prodigiosin analogue from Slreptomycex. Chem. Commun. 1966:825. 15. Wasserman. H. H . G. C. Rodgers, and Keith- 1969. Metacycloprodigiosin. a tripyrflR* pigment from StreptomYies Inngtsporut ruber. J A'n. Chem. Soc 91:1263-1264. 16. Williams. R. P., and W. R. Hearn. 1967. Pzp^igioain. p. 410-432. 449. In D. Gottlieb and P. D. Stlaw <ed.|. Antibiotics, vol. 2. Biosynthesis. Springer-Verlag. Inc . New York. 17. Yeager. C. C. 1962. Pink staining in polyvinyl chloride. Plast World 20:14-15. 16. Yeager, C. C. 1968. Deterioration of vmgFvesin sys- tems-special considerations, p. 222-225 -In Develop ments in industrial microbiology, vol. tf. Am. Inst. Biol. Sci . Washington. D C. v- BFG14406 _____ A*)* a?a dJJhXuC. PB-249 412 HEALTH HAZARD EVALUATION/TOXICITY DETERMINATION REPORT H.H.E. 74-61-232, GATES RUBBER COMPANY, DENVER, COLORADO Bobby J. Gunter, et al National Institute for Occupational Safety and Health Cincinnati, Ohio November 1975 BFG14407 21491001 4 sOhiaeUeGtCS. AHMICDATA NIOoh-TR-KuhuEc 77/41-6C1l-2?3V2> * 4, litlc jrJ bcb(t;li Health Hazard Evaluation/Toxicity Determination Report H.H.E. 74-61-232 Gates Rubber Company Per.ver. Colorado 7. 4wHo(.)Bobby 0. Gunter, Ph.D. and James B. Lucas, M.D. 9- Hectorraio j Organization Name and AdJ*e National Institute for Occupational Safety and Health Hazard Evaluation Services Branch, Div. of Tech. Services 508 U. S. Post Office Building ..'**'* Cincinnati, Ohio 45202 12 Spoesorcaj Orfrnaizzfioe Nui and Addin* National Institute for Occupational Safety and Health " Parklawn Building 5600 Fishery Lane Rockville, Maryland 20852 .....................-* -- IS. Sappln<wfry Nmm PB 249 &. itjc.t Orr Nov. 1975 s. 412 3- ?ntcraia OrjiaiaciM Ktpr. 74-M-W 10. Proicct/Iiik/.otk Laic N,. 11. Casnct/Graac No. n IX Type e* Repeat S pjtioi Cotrt4 Final.June 1974-May T97 U. . IS. A^KCMtS 5 i Determination: A plant manufacturing extruded hose, principally frofl'the *' extrusion of`polyvinyl chloride, was investigated by NIOSH to eyaluat^.. employee exposures to cyclohexanone, TDI, trichloroethylene, Estane* thermoplastic polyurethane, methvlene chloride, Niqrosrine, Di-2-ethyl hexyl phthalate (DOP oil), dust, and vinyl chloride. It was determined that a potential health hazard may exist from exposure to cyclohexanone, and that several cases of primary irritant dermatitis had occurred following repeated exposure to solvents. Although only one of 38 vinyl chloride samples was found to exceed the Federal Standard action level, it was recommended that airborne concentrations be reduced to levels not detected bv the recommended analytical techniques. r ^ ~ ' | Ilf. Omy Wocda aad Qbcihmnr AaadyzU. 17^ Dweripm, .. . -- [Hazardous- cgtartals, Toxicity, Toxicology, rrfl-rtir. Tn~prrtfnn. Tfnnr'Tir Tt, TT rni mm IndostrlaT hygiene:, * vinyl Chloride, Isocyanates, Dust, Cyclohexanones, > - Plastics. . ' ` ' _ '. . _ . ... " : ; ./ '"'.`V..... ' ;7. -V I". . ` - _. ---------- j, .\Q-f.>'44' ' _ ` rtf7 --,. - ; , . * ' ; *: v i~--'W - ' -- - . -- , 'V| ; "`^VT J ----. ' .tc- i- ,' - jJt'I&gifim/OpM'EMlwLTgnw " `.""ill'' ' - iHeeith hazard evaluation. Toxicity determination. Occupational Safety and Health Act y\1970. Toluene dlisocyanate, TDI, Nigrosine, Methylene Chloride, Di-2-ethyl hexyl - <*';** . . phthalate, Estane, Nuisance dust, DOP oil. Extruded hose. Polyvinyl . . chloride extrusion. Garden hose manufacture . V. . - r\ jlTe-CCSATT FIrW/Groy Jl* iiiry Scimmt \ : Available to the public lapfodvtd by NATIONAL TECHNICAL INFORMATION SERVICE U $ Dpo<l.- el CTm.rf Vi ??l$l PRICES SUBJECT TO tHAKSI I9.5ew(7 Ciaa* (TaL* SeMn) 'i-\v-r 20- icR:r CUm lists ___ i,~yrT_455fy;TQ 2L .Va. m P.-- /*? 22. Fc.ce %3.Z>-J.2Sl C BFG14408 050050 U.S. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE CENTER FOR DISEASE CONTROL NATIONAL INSTITUTE FOR OCCUPATIONAL SAFETY ANO HEALTH CINCINNATI, OHIO 45202 HEALTH HAZARD EVALUATION DETERMINATION REPORT 74-61-232 GATES RUBBER COMPANY DENVER, COLORADO NOVEMBER 1975 I. TOXICITY DETERMINATION From the results of environmental and medical evaluations conducted by the National Institute for Occupational Safety and Health (NIOSH) on June 4 and 7, 1974; July 11, 1974; November 11, 1974; December 3, 1974; March 20, 1975; April 10, 1975; and May 5-7, 1975, it has been determined that a potential health hazard may exist from exposures to cyclohexanone in the Extruded Hose Department(Department 60) of the Gates Rubber Company, Denver, Colorado. This determination is based on airborne measurements of cyclohexanone which exceeded recomnended hygienic standards for this substance. In addition several workers within this Department were found to have primary irritant contact dermatitis from repeated exposure to solvent containing solutions. All environmental measurements for toluene diisocyanate (TDI), trichlorethylene, and total dust were below NIOSH recomnended standards and established OSHA Federal Standards. Only one of 38 vinyl chloride samples was found to exceed the Federal Standard action level of 0.5 ppm. It Is NIOSH's policy to reject the concept of a threshold limit for _y1nyl chloride jas or any other carcinogen. NIOSH recommends that the employer reduce airborne concentrations of vinyl chloride to levels not detectable by the reconmended analytical techniques. On three of four occas ions when measured all vinyl chloride concentrations were below detection limits. II. DISTRIBUTION ANO AVAILABILITY Copies of this hazard evaluation determination are available upon request from the Hazard Evaluation Services Branch, NIOSH, U.S. Post Office Building, Room 508, Fifth and Walnut Streets, Cincinnati, Ohio 45202. Copies have been sent to: fa) Gates Rubber Company (b) United Rubber Workers, Local #154, Denver (c) U.S. Department of Labor - VIII (d) NIOSH - Region VIII For the purpose of informing the approximately 60 "affected employees'* this report should be posted in a prominent place accessible to the workers for a period of approximately 30 days. I- i j t t 21491003 BFG14409 t Page 2 - Health Hazard Evaluation Determination Report 74-61 III. INTRODUCTION Section 20(a)(6) of the Occupational Safety and Health Act of 1970, 29 U.S.C. 669(a)(6), authorizes the Secretary of Health, Education, and Welfare, following a written request by any employer or author ized representative of employees, to determine whether any substance normally found in the place of employment has potentially toxic effects in such concentrat.ons as used or found. The National Institute for Occupational Safety and Health received such a request from the President of United Rubber Workers, Local #154, Denver, Colorado, to evaluate the hazards associated with various chemical substances used in the manufacture of extruded hose and dust generated by this manufacturing process. IV. HEALTH HAZARD EVALUATION A. Plant Process The Extruded Hose Department of Gates Rubber Company produces garden hose principally from the extrusion of polyvinylchloride (PVC). Other plastics are used infrequently in this process. Other chemicals used in preparing nylon cords for reinforcing the hose include cyclohexanone, TDI, trichloroethylene, Estane* thermoplastic polyurethane, methylene chloride, di-2-ethylhexyl phthalate (OOP oil), and nigrosine. Various combinations of these chemicals have been in use during the Health Hazard Evaluation study period. During the period of the medical evaluation two principal formulations were in use and designated numerically as compounds 10127 and 10139. While containing common ingredients the former compound also contains methylene chloride and DOP oil while the latter contains nigrosine. Only small quantities of compounds 10127 and 10139 are utilized. Nylon thread Is passed through these mixtures, which serve as bonding agents, prior to entering knitting machines that produce a reinforcing matrix surrounding the hose core. Knitting machine operators, who for safety reasons cannot wear protective gloves, are the principal Department personnel exposed to these materials. Other major activities within the Department include plastic blending, extrusion, and hose finishing or colling. Personnel per shift normally include two stockmen, one blender, four extruder operators, two knitting operators and seven or eight hose finishers. B. Evaluation Design The Extruded Hose Department normally works three shifts, with a 40-hour work week per shift. At the time of this evaluation A- BFG14410 21491004 'm a cta^r2ft2r!E. Page 3 - Health Hazard Evaluation Determination Report 74-61 there were usually 17-18 employees per shift. Environmental evaluations were performed on all three shifts. Environmental samples were analyzed in both HIOSH Salt Uke City and Cincinnati laboratories. Employees from all shifts also participated in the medical evaluation which was principally conducted in the offices of Local Union No. 154, United Rubber, Cork, Linoleum and Plastic Workers of America - AFL-CIO. C. Evaluation Methods Vinyl chloride, cyclohexanone, and trichloroethylene were collected on organic vapor sampling tubes and analyzed by gas chromatography. TD1 samples were collected in all glass midget impingers and analyzed by the Marcali method. Total dust samples were taken on pre-weighed filters and re-weighed in the laboratory. Non-dlrected medical interviews and, when deemed advisable, limited physical examinations were carried out privately by a N10SH physician. These examinations when indicated included cutaneous* eye, nose, throat, blood pressure, chest, heart, and hearing assessments. Bulk samples of compounds 10127 and 10139 along with the individual ingredients of each mixture were obtained and concentrations suitable for patch testing prepared. The following concentrations and vehicles were utilized: Patch Test Materials 1. Estane^, IX in acetone 2. Nigrosine, IX in petroleum 3. OOP oil, 1% in petroleum 4. Mixture 10127, 5X in acetone 5. Mixture 10139, 5% in acetone These concentrations are known to be sufficently low to preclude irritant reactions. Standard patch test procedures were followed in testing four wrrker volunteers, each of whom gave histories compatible with repeated episodes of irritant or allergic contact dermatitis. Appropriate acetone and petroleum control patches were also applied. Cyclohexanone and methylene chloride were not tested Individually since they have never been reported to cause allergic sensitization and were already present in formulas 10127 and 10139. In addition, a reactive patch test to either or both these formulas plus the reaction pattern tc the other materials tested would permit the identification of either of these solvents in the 5- \ j j 21491005 BFG144U Page 4 - Health Hazard Evaluation Determination Report 74-61 unlikely event that they were causing sensitization. Patch test sites were carefully examined 48 hours after application and volunteers were urged to report promptly any reactions which might appear subsequently. D. Evaluation Criteria Vinyl chloride is considered a carcinogenic agent. It is suspected of being an etiologlc agent in the development of angiosarcoma of the liver (a rare form of liver cancer). As stated in NIOSH's Recommended Standard for Occupational Exposure to Vinyl Chloride, "there is probably no threshold for carcinogenesis although it is possible that with very low concentrations, the latency period might be extended beyond the life expectancy." In view of these considerations and NIOSH's inability to define a safe exposure level the concept of a threshold limit for vinyl chloride gas in the atmosphere is rejected. As a result, the NIOSH Recom mended Standard for Occupational Exposure to Vinyl Chloride states that exposure to vinyl chloride monomer she .Id not exceed levels that are detectable by the recommended methods of sampling and analysis. These views are not universally held and as will be subsequently presented the OSHA Federal Standard for vinyl chloride has been set at 1.0 ppm. Cyclohexanone is commonly used as a solvent and chemical Inter mediate. It is considered to be low in degree of hazard to health under the usual conditions of use. While capable of causing narcosis and even death at very high levels Its low volatility at room temperatures renders this possibility negligible. Definite eye, nose, and throat irritation have been reported at levels of 75 ppm. Since cyclohexanone is an excellent lipid solvent it is very likely that repeated contact will result in skin irritation.. It has a TLV of 50 ppm. Trichloroethylene Is conmonly used as an industrial solvent particularly in degreasing metal parts. It has narcotic effects In high concentrations and was fairly widely used as a surgical anesthetic in the past. Chronic exposure has been reoorted to cause abnormal fatigue, increased need for sleep, irritability, headache, and decreased tolerance to alcohol. Ventricular fibrillation resulting in death has been related to trichloroethylene exposure in several reports. Adverse kidney and liver effects were noted in the older literature, but are thought to be due to other chlorinated hydrocarbons present as contaminants. Very recently it has been reported that large amounts of trichloroethylene when fed to rats resulted In cancer development in high percentage of animals. The relevance of such 4- BFG14412 21491006 Page 5 - Health Hazard Evaluation Determination Report 74-61 experiments to the usual types of human exposure remains to be determined. To date there are no studies suggesting that trichlorethylene is a human carcinogen. TDI is the most conmonly used isocyanate and is widely used in the manufacture of "polyurethanes" or "polyurethane plastics." In higher concentrations it is a potent pulmonary tract Irritant. It is also capable of inducing an allergic pulmonary sensiti zation which results in an asthma-like syndrome. This sensiti zation occurs in only a small proportion of exposed individuals* but once developed precludes any further contact with the unreacted substance. The current standard is thought to be sufficently low to prevent the occurrence of sensitization. Estane^ is a trade mark of the B.F. Goodrich Co. for a group of theroplastic polyurethanes. Presumably any toxic properties would be due to any unreacted isocyanate present and might* In general, be expected to resemble those of TDI. Nigrosine is a widely used black dye. While unconmonly a cause of dermatitis it is a known skin sensitizer. Most cases have been reported from handling "carbon paper." Methylene chloride is another widely used industrial solvent and is widely used in de-greasing metal parts. Since it is non-flamable Its use appears to be growing. In high concentra tions it has anesthetic action manifest by headache, giddiness, stupor* Irritability* sensations of "drunkenness", and loss of coordination. It is moderately irritating to the skin upon repeated contact. Di-2-ethylhexyl phthalate (dioctyl phthalate) Is one of the most widely used plasticizers and as such as received fairly extensive toxicologic investigation. Based on these studies it may be concluded that the hazard to workers under the usual conditions of use would be extremely low. Patch tests with undiluted material do not cause irritation nor has it been reported to cause sensitization. Three sources of criteria were considered in assessing the workroom concentrations of air contaminants encountered in evaluation. These are: (1) Recommended and proposed threshold limit values (TLY's) and their supporting documentation as set forth by the American Conference of Governmental Industrial Hygienists (ACGIH) (1974); (2) Occupational health standards as promulgated by the U.S. Department of Labor (Federal Register* June 27, 1974, Title 29, Chapter XVII, Sabpart G); and (3) NICSH recommended criteria for occupational exposures. S- i i ' c n > iu v wru*,'.wi 21491007 BFG14413 K+\*> 1 Page 6 - Health Hazard Evaluation Determination Report 74-61 In the following tabulation criteria, the most appropriate value in the opinion of the authors is presented with its reference footnoted. Substance Permissible Exposures 8-Hour Time-Weighted Exposure Basis Winyl Chloride ........................ 2 Cyclohexanone .......................... (a) 3TDI .............................................. (b) ^Trichloroethylene .................. Total Dust ................................ (c) (a) ppm = parts of vapor or gas per million parts of contaminated air (b) C = celling value; this concentration shall not be exceeded for any period (c) mg/M3 = approximate milligrams of substance per cubic meter of air ^Reference: current OSHA standard. As previous discussed NIOS'i has reconmended that exposure to VC should not exceed levels that are detectable by reconmended methods of sampling and analysis. ^Reference: 1974 ACGIH TIV and current OSHA standard. 3Referemce: 1974 ACGIH TLV and current OSHA standard. ^REference: 1974 ACGIH TLV and current OSHA standard. ^Reference: 1974 ACGIH TLV Occupational health standards are established at levels designed to protect individuals occupationally exposed to individual toxic sub stances on an 8-hour per day, 40-hour per week basis over a normal working lifetime. U- 21491008 BFG14414 Page 7 - Health Hazard Evaluation Determination Report 74-61 E. Evaluation Results and Discussion The environmental measurements are presented in Tables I-IV. Only one vinyl chloride sample exceeded 0.5 ppm out of 38 samples submitted for analysis and all values are within the current Federal Standard (OSHA) for this substance (Table I). Nuisance dust levels obtained by personal breathing zone collection and general area sampling methods were found to be well under the hygienic standard (Table II). The blender operator was felt to be the only Individual potentially exposed to excessive dust based on a careful walk through assessment of the Department. Cyclohexanone levels were found to exceed the recctrcnended standard for three of the four samples analyzed for this substance (Table III). In view of the restricted usage of this solvent to the knitter operation sampling was limited to those employees working in Immediate proximity to that process. All samples for trichloroethylene (Table III) were reported as being less than 0.05 mg/M , the limit of sensitivity for the method employed. TDI sample results (Table IV) were also less than the sensitivity of the current analytic proceedure. A total of 18 Department 60 employees (4 women and 14 men) participated In the medical portion of the evaluation* The average age was 42 (range 28-60 years). The average duration of employment by Gates was 14 years (range 3-29) and most had spent a majority of this employment (average 10 years) in Department 60. It should be pointed out that these employees were not randomly selected for participation In the study, but rather represent a group who voluntalrly came forth on learning that a medical evaluation was planned. It is probably valia to conclude that such a group would contain those employees who are the most likely to have symptoms or complaints which they attribute to their work or who have other health problems and concerns. This sample represents about 30-35% of the total Department work force. As might be anticipated from the age and size of this group a wide range of symptoms, chronic illnesses, and physical complaints were identified. The most common symptom elicited was headache with five employees mentioning this as a problem. In most instances the headaches were occasional in incidence and not related to any particular department process. One individual did attribute his headaches to the process of purging the tubing extruder. BFG14415 Page 8 - Health Hazard Evaluation Determination Report 74-61 Four cases of dermatitis were identified and characterized as ezematous in type. The hands were the most common site involved and in several workers the problem had been intermittently present for several years. While the limited distribution to the hands, wrists, and arms suggested primary irritant dermatitis, allergic contact dermatitis could not be excluded on clinical grounds. These four individuals were therefore patch tested as outlined In Section C. The results of these tests were entirely negative confirming the probable irritant nature of the dermatitis. Three of the four employees with dermatitis work as knitter operators in which some exposure to cyclohexanone and methylene chloride, agents easily capable of defatting the skin, is essentially unavoidable since safety considerations preclude the use of gloves. Other signs, symptoms, and conditions encountered were: asthma-1; allergic rhinitis-2; deafness-1; nose bleeds-1; eye irritation-2; shortness of breath-1; cough-1; arthritis-1; cataract-1; sub cutaneous lipomatosis-1; prostatitis-2; cystitis-1; high blood prcssure-1; hypercholestrolemia-1; diabetes-1; seizure disorder-1; and post operative status (lipoma excision). The diversity and low frequency of these, not uncommon medical problems, make it quite unlikely that they are related to current occupational exposure. G. Recommendations 1, Adequate ventilation should be provided during hose extrusion. 2. Exhaust ventlaltion should be provided above the hopper where powdered and chipped PVC is hand poured and mixed. 3, Adequate ventilation should be installed in the vicinity of the knitter machines to control cyclohexanone exposure. 4. Knitter machine operators should be supplied with barrier creams formulated to resist organic solvents. Examples of such products are: (1) PLY 9 (Mtlburn Co., 3246 E. Woodbridge, Detroit, Michigan 48207) (2) West No. 411 (West Chemical Products, 42-16 West St., Long Tsland City, New York) (3) FEND $-2 (Mine Safety Appliances Co., Pittsburgh, Pa.) (4) Kerodex 51 (Ayerst Laboratories, 685 Third Ave., New York, N.Y. 10017) (5) MAN-0 (MAN-0 Products, 3710 Floral Ave., Cincinnati, Ohio 45207) BFG14416 Page 9 - Health Hazatd Evaluation Determination Report 74-61 V. AUTHORSHIP AND ACKNOWLEDGMENT Report Prepared By: Bobby 0. Gunter, Ph.D. Regional Industrial Hygienist NIOSH - Region VIII Denver, Colorado James B. Lucas, M.D. NIOSH Medical Officer Cincinnati, Ohio Study Participant: Raymond L. Rube NIOSH Industrial Hygienist Cincinnati, Ohio Originating Office: Jerome P. Flesch, Chief Hazard Evaluation Services 8ranch Cincinnati, Ohio BFG14417 B F G 14418 TABLE I Breathing Zone and General Roan Concentrations of Vinyl Chloride (VC) Gates Rubber Company Denver, Colorado June and July 1974 Date June 4H , 1974 ii ii it ii M II It II II II June 7, 1974 n n ii it K Job Blender Operator Tti>er Operator Hose Finisher Knitter Operator Blender Operator Tuber Operator Hose Finisher Knitter Operator Blender Operator Tuber Operator Hose Finisher Knitter Operator Knitter Operator Insulator Hose Finisher Insulator BLANK BLANK Sample VoUcc) 377 599 494 794 479 590 611 874 426 1306 1155 1520 1958 927 1015 1166 Sample Nimber 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 Vinyl Chloride (VC] ppm None Detected i n ii H ii II IK n II ti < 0.2 < 0.2 < 0.2 < 0.2 < 0.2 < 0.2 i i OTStTZ (continued) /O- I I f I I i T TABLE I (continued) Gates Rubber Company Denver, Colorado Date July 11, 1974 h II ii Nov. 11, 1974 ii h ii n ii Simple Job Vol(cc) Tuber Operator 41OQ Tuber Helper 390 Tuber Operator 4000 Blender Operator 9500 Tuber Operator 2300 Hose Manager 6500 Knitter Operator 4400 General Blender Area 3200 BLANK Tuber Operator 7100 Tuber Helper 10100 Tuber Operator 7100 Blender Operator 9500 Tuber Operator 4000 Hose Manager 2000 Knitter Operator 9300 6eneral Blender Area 2300 Tuber Operator 8953 Tuber Operator 4239 Tuber Operator 9826 Tuber Operator 4483 Tuber Operator 3686 BLANK BLANK Tuber Helper 1922 HYGIENIC STANDARD Sample Number 1 2 3 4 5 6 7 8 \3 18 17 20 11 23 22 19 21 1 2 3 4 5 6 7 8 Vinyl Chloride ppm < 0.2 < 0.2 < 0.2 0.25 0.25 < 0.2 0.21 0.25 < 0.2 < 0.2 < 0.2 < 0.2 < 0.2 0.29 0.46 < 0.2 0.52 < 0.2 < 0.2 < 0.2 < 0.2 < 0.2 None Detected None Detected < 0.2 1.0 The lower limit of detection of vinyl chloride In the NIOSH Salt take City laboratory Is 0,2 ppm. UQT6nZ A wffiggiBOfi it B FG 14420 'I f'T*MA* / &* **i* rrv'# > TABLE II Breathing Zone Concentrations of Nuisance Dust Gates Rubber Company Denver, Colorado June 7, 1974 Job Blender Operator Blender Operator General Blender Area Sample Vol(L1ters) 180 456 456 Sample Number E-24 31 38 HYGIENIC STANDARD Nuisance Dust mq/M^ 2.2 5.2 2.1 10.0 >TOT6frTZ /-2. .:XTJ-5S i BFG14421 TABLE III Breathing Zone Concentrations of Cyclohexanone and Trichloroethylene Gates Rubber Company Denver, Colorado ' July 11, 1974 Sampl e Job Volfilters) Knitter Operator 10.5 ttiltter Operator 9.5 Knitter Operator 20.0 Knitter Operator 39.0 Sample Number 9 10 14 15 HYGIENIC STANDARDS Cyclchexanone mq/M3 36.0 68.0 68.0 8.0 50.0 Trichloroethylene mg/M3 < 0.05 < 0.05 < 0.05 < 0.05 100.0 >. TABLE IV Breathing Zone and General Room Concentrations of TDI April 10, 1975 Location Sample VoULIters) Sample Number TDI3 mg/M'5 Knitter Operator General Room Knitter Operator General Roan BLANK 68 1 61 2 66 3 63 4 5 HYGIENIC !STANDARD < 0.02 < 0.02 < 0.02 < 0.02 0.12 The lower limit of detection of TDI by. current NIOSH analytical methods Is 0.02 mg/M . B F G 14422 BFG14423 ' 1- SEE DISTRIBUTION LIST I I IDM W. C. BACHTEL buiur., t BFfi TECHNICAL DQffiSESNi' illo rn 'injt 11 n ofr li -T. Cc. Mmiinni: MmUu.. B DEPT. 0020, BLDG. 5-H (AKRON) 11-5-75 Toxicity studies have been performed on samples rff "purified". These studies were performed by Indu using standard test methods. th raw and o-Test Laboratories I have prepared for your information and use a summary of test results, appropriate precautionary statements and discussion. I. Summary of Results TOXICOLOGY FILE COPY Return To. R. K. Hinderer D/5456 Cleveland Test - Raw 10A "Purified" 10A Acute Oral LD50 (rats) >15,380 mg/kg relatively harmless >15,380 mg/kg relatively harmless Acute Dermal LD50 (rabbits) >3,000 mg/kg practically non toxic >3,000 mg/kg practically non toxic Eye Irritation (rabbits) minimally irritating extremely irritating Primary Skin Irritation (rabbits) minimally irritating minimally Irritating Inhalation LC50 (rats) > 0.72 mg/L air >0.43 mg/L air II. Applicable Precautionary Statements A. Eye - Skin 1. Code 10A'Purified" Danger causes eye burns Do not get in eyes, avoid contact with skin Avoid breathing dust Keep container closed Use with adequate ventilation Wash thoroughly after handling First Aid: In case of contact - immediately flush eyes with plenty of water for 15 minutes. Call a physician. Flush skin with water. 2. Code 10A Raw WARNING causes irritation Avoid contact with eyes, skin and clothing Wash thoroughly after handling First Aid: In case of contact, immediately flush eye with plenty of water. Call a physician. Flush skin with water. 21492001 ' /4 \ lTM: O'!ft BFG14424 BFG TECHNICAL DOCU -2- B. Inhalation WARNING harmful if inhaled Avoid breathing dust Keep container closed Use only with adequate ventilation III. Discussion A. Acute Oral Toxicity No deaths were recorded during the 14 day observation period at any of the dose levels of either the raw or purified Code 10A. Solidified test material was found in the stomach of the rats at the 15,380 mg/kg dose level on autopsy. No unexpected reactions or other gross pathological changes were noted with either material. These materials are apparently not readily absorbed through the gastrointestinal tract. Consequently it can be assumed that the probable acute lethal oral dose for a normal 70 kg man of either material would'be in excess of 2 lbs. B. Acute Dermal Toxicity All animals survived application of these materials to intact skin at a level of 3000 mg/kg. The materials were applied as an aqueous slurry. No systemic or behavioral reactions were noted. Both materials, however, did cause slight reddening and swelling of the skin. No pathological changes were noted. These results indicate poor dermal absorption. The probable lethal dose via dermal exposure for a normal 70 kg man would be between a pint and a quart of either Code 10A raw or purified. C. Acute Inhalation Toxicity A definitive LC50 could not be determined for either material. The greatest dust concentration obtainable under the test conditions was 0.72 mg/L air for the purified and 0.43 mg/L air for the raw sample. There were no untoward reactions during or after exposure, weight gains were normal and no gross pathological changes were noted. The particle sizes concentrations of the two materials were markedly different. The raw Code 10A contained 46.2% respirable particles while the purified 10A contained 77.1% respirable particles (particles <.10 microns). The data presented in these studies would not indicate that these materials are highly toxic by inhalation. However, since no definitive LC50 could be as certained and since a large percentage of the materials are of a particles size that is respirable both 10A raw and purified should be . handled as though toxic by inhalation. D. Eye Irritation Installation of the normal 100 mg sample of Code 10A raw and purified into BFG 14425 21492002 BFG TECKfiiCAL liCaV;'liLr. -3 rabbits eyes caused irritation. The purified material was considerably more irritating than the raw material. The purified material caused corneal density starting within one hour and lasting through the test period with vascularization of the cornea by the seventh day in all rabbits. Hie irris was severely affected through seven days. By the 14th day no affects was seen in the irris of five of the six animals. The purified material also produced conjunctivitis with swelling redness and discharge throughout the 14 day period in three of the six animals and through seven days in the others. Code 10A purified is extemely irritating to the eye with a good possibility of permanent eye damage resulting from contact. Clearly, eye protection must be worn by persons who may handle Code 10A purified. The raw Code 10A caused mild irritation to the rabbit eye consisting of conjunctivitis lasting through 24 hours.one animal showed some corneal clouding at 24 hours. By 48 hours all irritation was absent. Consequently, raw Code 10A would be considered to be minimally irritating to the eye. One would not expect to see permanent eye damage result from contact with this material. Eye protection, should be worn' when handling raw Code 10A. E. Skin Irritation When both materials were applied to intact and abraded skin only a small amount of reddening was observed at 24 hours. By 72 hours no irritation was noted. Neither of these materials would be considered primary skin irritants. However, one should wash thoroughly after handling them. Use of Code 10A If either Code 10A raw or purified is used widely in the polymerization of PVC resins one must consider their potential as an indirect food additive. These materials appear to be innocous by ingestion and skin absorption. If as presently stated the residual level of Code 10A in the resins is in the range of 300 to 800 ppb and extraction into food simulating solvents is less than 50 ppb, I see no need for further chronic testing at this time. If, however, usage levels increase with corresponding increases in extractables (i.e. above 50 ppb in any food simulating solvent) then further studies maybe warranted. At this time we would consider Code 10A as a necessary adjuvant In the polymerization process not reasonably expected to migrate into food. As far as employee exposure, I feel no further chronic studies are warranted due to the apparent low acute toxicity of these materials. The greatest concern is for the extreme eye irritation caused^by the "purified" Code 10A. Bachtel L. Cohen J.B. Haehn DISTRIBUTION LIST F.E. Krause T.W. Boyer D.E. WItenhafer L.M. Puckett/A. Hastings E.G. Schwaegerle B.M.G. Zwicker BFG 14426 21492003 ( 9nduAtiUiL BIO -TEST 1810 FRONTAGE ROAD 3nc. NORTHBROOK, ILLINOIS 60062 September 9, 1975 Dr. W. C. Bachtel Toxicologist The B. F. Goodrich Company 500 South Main Street Bldg. 5-H - Dept. 0020 Akron, Ohio 44318 Dear Dr. Bachtel: Re: IBT No. 663-07243 - Acute Dust Inhalation Toxicity Study with TA5D0I-Raw and TA5DOI-Purified in Albino Rats l We are submitting herewith our laboratory reports prepared in connection with the above study. Very truly yours, JCC/fd J . C . Calandra President 21493001 BFG14427 l i Onduibuol 3 I O - T E S T lali&iai&ued., 9*tc. REPORT TO THE B. F. GOODRICH COMPANY ACUTE DUST INHALATION TOXICITY STUDY IN RATS Test Material.: TA5DOI-Raw Strain: Charles River Rats Form Administered: Dust Exposure Time: 4 hours Acute LC50: > 0. 72 mg/1 air Observation Period: 14 days IBT No. 663-07243 Generation of Material Exposure: The dust was suspended by passing a stream of clean dry air (-40C dewpoint) through a dust shaking mechanism. The resulting air-dust mix ture was then introduced into the exposure chamber. Chamber Conditions Size Group No.______(liters Atmospheric Pressure Temperature Air Flow (inches Hg)_____________(C )______________(l/min) I 80 30.03 24 15 Results Group No Total Number of Animals Male /F emael Average Analytical Concentration Weight Gain Mortality Male-F emale Male-Female_______(grams ) I 5/5 0. 72 mg/l air* 0/5 - 0/5 ^Maximum attainable concentration at conditions stated. 87-34 Remarks There were no untoward reactions during exposure or the 14-day observa tion period which followed. The average 2-week body weight gains were with in the normal limits. Necropsy... performed on all rats at the end of the obser vation period, did not reveal any gross pathoLogic alterations. The particle size distribution data is presented on Table I. Respectfully submitted. INDUSTRIAL BIO-TEST LAB ATORIES, INC : .T.wVy 1V ik/UcZ/L Prepared by App roved by: A!L Larry |. Horath, B. S. Johii W. Goode, Ph. D. Assistant Toxicologist /Manager Inhalation Toxicology catur Research Laboratories mk 9/9/75 21493002 BFG14428 9rtdu4rt`Ual 3 I O - T E S T lakyiat&iied., 9nc. Particle Size Distribution A sample of airborne dust was collected from the test atmosphere for the purpose of conducting a microscopic determination of particle size distribution. Particles were counted with respect to 4 size ranges, viz. 5 microns or smaller, 6 to 10 microns, 11 to 25 microns and larger than 25 microns. Particles less than 10 microns are generally considered to be respirable. The smallest particle which can be detected by the lightfield technique employed is approximately 1 micron. The smallest and largest particles observed were also recorded. TABLE I TEST MATERIAL: TA5DOI-Raw Particle Size Distribution Data Particle Size Range (microns) 1-5 N Limb e r of Particles Counted 36 86 o i ^o 11-25 90 > 25 52 Percent of Total Counted 13. 6 32. 6 34. 1 19. 7 The total number of particles counted was 264. The smallest and largest particles observed were 2 and 65 microns, respectively. eOO6frTZ BFG14429 9ncLdttial 3 1 O - T E 5 T laJt&ta&vti&i, $hc. REPORT TO THE B. F. GOODRICH COMPANY ACUTE DUST INHALATION TOXICITY STUDY IN RATS Test Material: TA5DOI-Purified Form Administered: Dust Strain: Charles River Rats Exposure Time: 4 hours Acute LC^q: > 0.43 mg/1 air Observation Period: 14 days IBT No. 663-07243 Generation of Material Exposure: The dust was suspended by passing clean, dry air (-40C dewpoint) through a dust shaking mechanism. The resulting air-dust mixture was then introduced into the exposure chamber. Chamber Conditions Size Group No,_______(liters Atmospheric Pressure Temperature Air Flow (inches Hg)_____________(C)_______________ (1/min) I 80 30. 03 24 15 Results Group No Total Number of Animals Male/Female Average Analytical Concentration Mortality Male-Female Weight Gain Male-F emale (grams) I 5/5 0. 43 mg/lair* 0/5 - 0/5 ^Maximum attainable concentration at conditions stated. 86-34 R emarks There were no untoward reactions during exposure or the 14-day observa tion period which followed. The average 2-week body weight gains were with in the normal limits. Necropsy, performed on all rats at the end of the ob servation period, did not reveal any gross pathoLogic alterations. The particle size distribution data are presented on Table I. Respectfully submitted. INDUSTRIAL BIO-TEST LABORATORIES, INC. Prepared by: ^ ^ ihl pult/]4. Approved by; j ^ Larr^//L. Horath, B.S. ^/Joh/n^W. Goode, Ph. D. Assistant Toxicologist Inhalation Toxicity VJ^Ianager Decatur Research Laboratories mk 9/9/75 tc cc o BFG14430 9ftdtiiiciai S 1 O - T E S T Jlakyiattyiiei, 9tic. 2 of 2 Particle Size Distribution A sample of airborne dust was collected from the test atmosphere for the purpose of conducting a microscopic determination of particle size distribution. Particles were counted with respect to 4 size ranges, viz. 5 microns or smaller, 6 to 10 microns, 11 to 25 microns and larger than 25 microns. Particles less than 10 microns are generally considered to be respirable. The smallest particle which can be detected by the lightfield technique employed is approximately 1 micron. The smaLlest and largest particles observed were also recorded. TABLE I TEST MATERIAL: TA5DOI-Purified Particle Size Distribution Data Particle Size Range (microns ) Number of Particles Counted 1-5 6-10 94 75 11-25 35 > 25 15 Percent of Total Counted 42. 9 34. 2 16. 0 6. 9 The total number of particles counted was 219. The smaLlest and largest particles observed were 1. 5 and 50. 0 microns, res pecti ve Ly. s o o e e fc T Z BFG14431 9ruSu6t/iLoi BIO T E S T -Zk&m&toedv 9nc. 1810 FRONTAGE ROAD NORTHBROOK, ILLINOIS 60062 -TOXICOLOGY RLE COPY 'Return To. R. K. Hinderer D/5456 Cleveland REPORT TO THE B. F . GOODRICH COMPANY ACUTE TOXICITY STUDIES WITH TA5DOI - PURIFIED AUGUST 29, 1975 IBT NO. 601-07242 BFG14432 21433006 Sfl/SjAbt/Luil BIO -TEST 1810 FRONTAGE ROAD NORTHBROOK. ILLINOIS 60062 August 29, 1975 Dnc. Dr. W. C. Bachtel Toxicologist The B. F. Goodrich Company 500 South Main Street Bldg. 5-H - Dept. 0020 Akron, Ohio 44318 Dear Dr. Bachtel: Re: IBT No. 601-07242 - Acute Toxicity studies with TA5DOI - Raw and TA5DOI - Purified We are submitting herewith our laboratory reports prepared in connection with the above study. Very truly yours JCC/fd J. C. Calandra President 21493007 BFG14433 BIO-TEST ^a&o'iato'ued., 9ttc. REPORT TO THE B. F. GOODRICH COMPANY ACUTE TOXICITY STUDIES WITH TA5DOI - PURIFIED AUGUST 29, 1975 IBT NO. 601-07242 I. Introduction At the request of The B.. F. Goodrich Company, the following studies were conducted with a brown powder identified as TA5DOI-Purified: Acute Oral Toxicity Study - Albino Rats Acute Dermal Toxicity Study - Albino Rabbits Eye Irritation Test - Albino Rabbits Primary Skin Irritation Test - Albino Rabbits BFG14434 21493008 HtuLtdbUal B I O - T E S T J.ai&iat&ue&; 9nc. 2 II. Summary The results of the acute toxicity studies with TA5DOI-Purified are summarized below: Test Results Acute Oral Toxicity Study Albino Rats Acute Dermal Toxicity Study Albino Rabbits Relatively Harmless ld50 > 15'380 mg/kg Practically Nontoxic LD5q > 3,000 mg/kg Eye Irritation Test Albino Rabbits Extremely Irritating (59.3/110.0) Primary Skin Irritation Test Albino Rabbits Minimally Irritating (0.4/8.0) Respectfully submitted, Report prepared by: INDUSTRIAL BIO-TEST LABORATORIES, INC. \Z-J- lobert J. CSuinn, B . S. Technician Acute Toxicit^ A Helfried Paa Assistant Group Leader Acute Toxicity Report approved by: C. W. Mastri, B.S. Section ^Head, Acute Toxicity Florence K. Kinp^hita,//Rh.l5T' Technical Manager, Toxicology M. . Keplingeis Ph.I^r Manager, Toxicology gb BFG14435 21493003 Undudt/UaL B I O - T E S T Jlahyiat&U&i, 9*tc. 3 III. Results A. Acute Oral Toxicity Study - Albino Rats 1. Mortality and Body Weights Individual mortality and body weight data are presented in Table I. 2. Reactions and Pathology Hypoactivity was observed in the rats dosed at 15,380 mg/kg 3 hours following oral administration of TA5DOI-Purified Diarrhea was observed in the rats of this dose level after 6-22 hours. These symptoms had subsided within a day. Necropsy examination revealed solidified test material in the stomachs of rats dosed at 15,380 mg/kg level. No other gross pathologic altera tions were observed in any of the other animals. T 0 6 frT Z BFG14436 i ^iidu&bual B I O - T E S T J.a&&ujt&iie4-r 9nc. 4 TABLE I Acute Oral Toxicity Study - Albino Rats Mortality and Body Weight Data IBT No.: 601-07242 Classification: Relatively Test Material: TA5DOI-Purified Harmless Form Administered: As a 40.0 percent Acute Oral LD^q > 15,380 mg/kg (w/v) suspension in 2.0 percent (w/v) aqueous methylcellulose Dose Level Cms/kB) Animal Number and Sex Individual Body Weights (grams) Test Day Number: Number Dead 0 14 Number Tested Percent Dead 1,350 1-M 2-M 3-F 4-F 232 230 240 204 290 0/4 0 290 280 244 4,556 5-M 6-M 7-F 8-F 240 232 190 220 320 0/4 0 310 210 240 15,380 9-M 10-M 11-F 12-F 218 250 188 190 260 0/4 0 320 200 210 21493011 BFG14437 !)HdUufrtial BIO-TEST Jtalx>/iat<yUe&, 9*tc. 5 B. Acute Dermal Toxicity Study - Albino Rabbits 1. Mortality and Body Weights Individual mortality and body weight data are presented in Table II. 2. Reactions and Pathology No pharmacotoxic symptoms were exhibited by any of the rabbits following dermal exposure to TA5DOI-Purified. The test material was slightly irritating to the skin of the albino rabbit. Pale red erythema and slight edema were observed at 24 hours, while no skin reactions were noted at the test skin sites at 7 and 14 days. Necropsy examination did not reveal any gross pathologic altera tions in any of the rabbits. 21493012 BFG14438 Duduifrual B I O - T E S T Jakwa&ued, 9hc. 6 TABLE II Acute Dermal Toxicity Study - Albino Rabbits Mortality and Body Weight Data IBT No.: 601-07242 Test Material: TASDOI-Purified Form Administered: As an aqueous slurry Classification: Practically Nontoxic Acute Dermal LD^q > 3,000 mg/kg Dose Level (mg/kg) Animal Number and Sex Individual Body Weights (kg) Test Day Number: Number Dead Percent 0714_________________ Number Tested_____ Dead 3,000 1-M* 2-M 3-F* 4-F 2.70 2.70 2.68 2.72 2.70 2.84 3.08 2.90 2.84 3.18 2.90 2.660/4 0 * The skin at the site of application was abraded. (X o HU BFG14439 DfuLubUol B I O - T E S T Jla&yiattyU&i., 9*tc. 7 C. Eye Irritation Test - Albino Rabbits The results of the eye irritation test are presented in Table III C trtosstrtz BFG14440