Document BRJMaDDO36aBONJgv5ea9Ze1k

PLAINTIFF'S EXHIBIT DOW-1760 TOXICOLOGY RESEARCH LABORATcl_____________________ 1UIM< TT CO AY C MA ACC DATE October TMt' DOW CHEMICAL COMPANY tei / i, _ s HEt K-028126-(3) ( IV 23, 1974 K-028126 REPORTED BY- ; Mil S77TOXICOLOGY OF INGESTED ASBESTOS LITERATURE SURVEY JJulL' ChatleS T. Lithfy /C~ CHECKED BY: L. W. RjU&py iNfORMATlVC SUMMARY WITH CONCLUSIONS AASCO ON M( SAMFLC ACCC'VCO. AOO<TIONAL iNFOSMATtON INCUUO'NO Tm tmCTJ OP AEPCATXO CXPOSURC MAY C ACQUIACO AS SPECIFIC USES ANO FOANULATlON* A AC OCVCLOPCO OS IF FMOCCSS CHAN6CI OCCUR, A survey of the literature that is pertinent to the ingestion of asbestos was made. Asbestos is a ubiquitous mineral appearing everywhere - air, snow, rivers, drinking water, beverages, and drugs. Even control animals in one feeding study had asbestos particles in the several organs examined. Since it must be assumed that during inhalation, some portion of the mater ial must be swallowed, the incidence of gastrointestinal cancer in asbestos workers is pertinent to the ingestion of asbestos. Although the incidence of GI cancer in asbestos workers is relatively low in relation to the inci dence of lung cancer, studies have consistently shown GI cancer incidences of 2-3 times that expected in the general population. The incidence appears to increase with the duration of exposure and there is a long latent period for development. Feeding asbestos to animals has not increased the incidence of tumors. A study designed to determine the carcinogenicity of various sizes of as bestos and fiberglass particles when applied to the pleura of rats showed a definite relationship between carcinogenicity and size.--Fibers < 3 microns in diameter and > 20 microns in length are more carcinogenic than fibers with diameters > 3 microns regardless of length or less than 20 microns in length regardless of diameter. Most fibers found in water or beverages are indivi dual fibers less than 20 microns in length. In 1973 The Advisory Committee on Asbestos Cancer reported to the Director of the International Agency for Research on Cancer (a division of the World Health Organization). As part of their report they stated that, "such evidence as there is does not indicate any risk from asbestos fibers present in water, food, beverage, or drugs". S.M. Blcif 3.E. Bvryen 3.E. Crlten .JC. Fr#el N.L. Oerrfen, MO B. Mel4;. UD 8. Horvath D. MD C.E. Kimmel f F.C leovitt DISTRIBUTION sx.HeCu,cK.on D.D. McCall.ta. (J) R.J. Maalanaar Olaaa M.E Pruitt t. pyiiin L. Rimma V.B. Rofcimen RJ( Shavar RECEIVED OCT 0 61988 J. M. GOOTEE OO CD CD CD CD CO xa. cri (6i See attached sheet. RESTRICTED FOR USE OF OOw EMPLOYEES ONLY * STOOOOI 38 ut'Bb Oi To ( JftoT^Tl l>E ti TOXICOLOGY OF INGESTED ASBESTOS LITERATURE SURVEY Charles T. Lichy Toxicology Research Laboratory October 22, 1974 O'llOOOOlS TOXICOLOGY OF INGESTED ASBESTOS A survey of the literature that is pertinent to the ingestion of asbestos was made. Asbestos is a ubiquitous mineral appearing everywhere - air, snow, rivers, drinking water, beverages, and drugs. Even control animals in one feeding study had asbestos particles in the several organs examined. Since it must be assumed that during inhalation, some portion of the material must be swallowed, the incidence of gastrointestinal cancer in asbestos workers is pertinent to the ingestion of asbestos. Although the incidence of GI cancer in asbestos workers is relative ly low in relation to the incidence of lung cancer, studies have consistently shown GI cancer incidences of 2-3 times that expected in the general population. The incidence appears to increase wi the duration of exposure and there is a long latent period for development. Feeding asbestos to animals has not increased the incidence of tumors. A study designed to determine the carcinogenicity of various sizes of asbestos and fiberglass particles when applied to the pleura of rats showed a definite relationship between carcinogeni city and size. Fibers< 3 microns in diameter and>20 microns in moooofs -2- length are more carcinogenic than fibers with diameters > 3 microns regardless of length or less than 20 microns in length regardless of diameter. Most fibers found in water or beverages are indivi dual fibers less than 20 microns in length. In 1973 The Advisory Committee on Asbestos Cancer reported to the Director of the International Agency for Research on Cancer (a division of the World Health Organization). As part of their report they stated that, "such evidence as there is does not in dicate any risk from asbestos fibers present in water, food, beverage, or drugs". STOOOOI 42 -3- TOXICOLOGY OF INGESTED ASBESTOS Introduction Although there is a large body of literature on the hazard of inhalation of asbestos, there is a dearth of definitive information on the hazard of asbestos ingestion. This report ignores literature on the inhalation hazard and focuses only on the data, theory, and conjecture dealing with the toxicology of ingested asbestos. How ever, since workers exposed to atmospheres containing asbestos ingest the material as well as inhale it, the literature relating to gastrointestinal cancer in asbestos workers is reviewed. Part of the difficulty in performing definitive ingestion studies has been the difficulty of asbestos analyses. The analysis for asbestos requires an electron microscope (at least for fibers less than about .3 microns in diameter) and the method usually requires a tedious fiber count from electron micrograph plates. In addition, the reproducibility from sample to sample is usually poor. The time required is about 11 man-hours per sample. Stan dard samples do not exist. This means that it is difficult to adequately characterize the samples of asbestos fed to animals and makes comparisons of studies difficult. Asbestos in Environment "Asbestos" is a generic term for a number of hydrated sili cates that, when crushed or processed, separate into flexible fibers made up of fibrils. There are many asbestos minerals, although only six are of commercial importance. Chrysotile, a ST0000143 1*ll000QlS ' -4- serpentine mineral, accounts for 95% of world's production. The other minerals are all amphiboles and include amosite, crocidolite, anthophyllite, tremolite, and actinolite. These asbestos minerals differ in chemical and physical characteristics which may affect .their biological reactivity. Rock outcrops of asbestos minerals and soils derived from asbestos minerals as well as commercial uses result in the material being ubiquitous. Water flowing over rock outcrops or soils can pick up the asbestos. The Ottawa river in Canada, for example, was found to contain asbestos particles (Table 1). .Cunningham and Ponte fract, (1971) examined twelve samples of Canadian beer and wine, six samples of U.S. beer, six samples of wine from around the world, and several Canadian soft drinks. All were found to contain asbestos fibers in the range of 1.1 to 12.2 million fibers per liter (mfl) . Samples of drinking water from Canadian cities which use surface water were also found to contain asbestos. Most of the fibers found in Cana dian beer and filtered city water were less than 1 micron in length whereas most samples of wine, some American beer and unfiltered water contained fibers ranging from 1-15 microns in length. Filter ing seems to help. The Ottawa river before filtering contained 9.5 mfl while the city of Ottawa tap water contained 2.0 mfl. The Detroit river contained 18-25 mfl while the city of Windsor tap water contained about 1.8 mfl (Kay, 1973). Samples of melted snow contained asbestos indicating asbestos in water may originate from dust. Wehman and Plantholt (1974) found asbestos fibrils ranging from 2.18 to 23.98 million fibers per liter of gin. Biles and Emerson (1968) also found asbestos fibers in beer. 5 TABLE 1 Tebl, 1 Aitwstos Fibres in Beveragaa and Wattf Sample Source* Beer Beer Deer Ikcr Sherry Slierry Sherry Port Vermouth Vcrmouili Soft drink Soft drink Sort drink Soft drink Tap water Tap water Tap water Tap water Tap water Tap water Tap water Tap water Melted mow River water Canadian 1 Canadian 2 USA 1 USA 2 Canadian Spanish South African Canadian French Italian (ingcrale Tome water I Tonic water 11 Orange Ottawa. Ottawa river (F) Toronto. Lake Ontario (F) Montreal, St Lawrence river (F) Hull. Quebec. Ottawa river (NF) Bcauport, Quebec. St Lawrence river (6 km betow Quebec City) (NF) Drummondvillc. Eastern Townships. Quebec. St Francois river (F) Asbestos, Eastern Townships, Quebec. Nicolet nver (F) Thclford Mines, Eastern Townships, Quebec, lac 1 la Truite (NF) Ottawa, top 20 cm (2-3 weeks precipitation) Ottawa river, at Ottawa No. of fibres *10*1.*' 4.3 6.6 2.0 1.1 4.1 2.0 2.6 2.1 1.8 11.7 12.2 1.7 1.7 13 2.0 4.4 14 9.3 (.1 19 3.9 1717 33.3 9.5 * F, Filtration plant used; NF, no filtration plant used. Cunningham & Pontefract - 1971 ST0000145 -6- Nicholson, Maggiore, and Selikoff (1972) studied a number of samples of parenteral drugs and found asbestos fibers (Table 2). Based on their report, a study was undertaken by the FDA. Although the data are still preliminary (Fed Reg 38 (188) 9-28-73 pp 2707727081), 11 of 13 samples of parenteral drugs had clear-cut evidence of asbestos, one sample was questionable, and one was negative. Although these drugs are not ingested, they are examples of the widespread occurrence of asbestos. Perhaps the greatest concern of asbestos ingestion is that from drinking water. Studies have been made by several workers. Asbestos fibers have been found in practically every locale where sampling programs have been conducted and regardless whether the water source was surface or deep well. The levels seem to be higher in the coastal and mountainous regions where serpentine rock is indigenous, but asbestos has been- found through out the midwest as well. Fiber levels range generally from a few thousand fibers per liter to about ten million fibers per liter. For example, Sargent (1973) reported levels of asbestos in drinking water from Vermont which ranged from less than one thousand to 247 thousand fibers per liter (Table 3). Cunningham and Pontefract (1971) reported asbestos levels of 2-10 million fibers per liter except for an asbestos mining town in Quebec Province which regis tered 172.7 million fibers per liter (Table 1). Cook, Glass, and Tucker (1974) reported levels of asbestiform amphibole (not chrysotile) minerals of 1-30 million fibers per liter in the Duluth water supply. Kay (1973) reported levels of asbestos in ST0000146 -7 TABLE 2 Fibrous paniculate* seen in samples of parenteral drugs obtained during two periods of time. Observations were made by e?`.i:al mi- croseope (O) or electron imcracepe <). The optical determinations were made on one Quarter of each sample, the elccvon-microscope ^ter minations on 10*' of each sample. All drugs were labeled for intravenous use except those identified by IM (or intramuscular or l? fjr tmrspeotoneal. Amounts of samples are in grams unless specified otherwise. "Yes** after optical data indicates that some fibers in the sam ple were identified as chrysotik by optical microscopy; while many fibers seen in ill samples could have been asbestos, the majority cre not. All values of 27 X 10"* g or leu (or the estimated mass of asbestos could have resulted from the analysts background; N. number. Drue Amount. (!) Fibera by 0.1949 S-20 (N) 20-100 (N) >100 (N> Aabeatoi Chryutilc fibril* by E 1949 1970-71 <N) <N) Asbestos. estimated mass us total sample 0<^g) 1970-71 Sodium acciazolamide Sodium ampicUlin Cephaloridine Sodium ccphalothin Chloramphenicol Cortisone (IM) Lincolnrein Hd Sodium mclhkillia Neomycin udfaic* (IM) Neomycin aulfatc* (IP) Sodium oxacillin Streptomycin wUate* (IM) Streptomycin sulfate* (IM) Sulfitoaa/ole diolamtnc Tetracycline HGt Tetracycline IICU Vancomycin HQ 1 32 33 7 I 10 13 3 Yea 2 11 21 4 2 44 22 5 2 0J23 6 2 1 11 2 4 0 2 91 51 10 1 21 4 1 J 101 37 31 Yen 2 24 33 II 1 IS 0 0 2 15 a 1 4 24* 7 1 i 24 14 7 Ya 03 1 14 7 1 Pota'uum penicillin G Sodium penicillin G Water control I0*unila 14 4 1 2 X 10-uoita 20 cm* 400 * fhiplicaid iuItm et nmrtet (na eUTcrot MMKmn of the line drag. t Duplicate udim of miMum.. I Avenge at arven samples rtaaing (mm 1.2 x SO-1 to 21 X MHg. 32 1 < 79 _ 30 S3 24 3 >100 2 13 6 i 2 4 22 2 1 >1004 g 13 30 12 9 7 1100 7A 210 . 7.7 14 <J 10 12 1.7 3.9 410 7J ;3 84 71 M 27 Nicholson , Maggiore, and Selikoff - 1972 ST0000I 47 -8- the drinking water of Canadian cities (Ontario Province) ranging from 2-4 million fibers per liter. He reported that the Ontario Ministry of Health has indicated that "ingestion of asbestos at these levels does not appear to present a health hazard at this time." STOOOOI 48 -9ASBESTOS IN VERMONT DRINKING WATER TABLE 3 Sargent - 1973 61I00001S -10- Ingestion During Inhalation Although this review does not deal with inhalation of asbestos fibers, the nose, throat, and trachea of humans is an efficient particle trap and any particle that is caught in the mucosa of these areas will pass through the gastrointestinal tract. Studies have shown that only a relatively narrow range of particles are inhaled and most efficiently at 0.25-0.50 microns (Hilding, 1963). The efficiency, of course, varies with the shape and density of the particles. Although asbestos, being fibrous, may be quite different in the size ranges, the majority of the particles must be swallowed. Selikoff and co-workers began in the early 1960's to study asbestos workers. On January 1, 1943, there were 632 members in the New York and New Jersey union local of the International Association of Heat and Frost Insulators and Asbestos Workers, AFL-CIO (IAHFIAW). Nine had died before reaching twenty years from first employment. The fate of the remainder through 1971 are shown in Table 4. The study was then expanded to include all of the workers in the IAHFIAW in the United States and Canada. These results are shown in Table 5. The results indicate an increase of GI cancer of 2-3 times that expected from national averages. It is, however, responsible for only about 5% of the total deaths. In a paper given in Lyon, France in 1973, Selikoff and co-workers reported on more studies. An entire work force of an amosite factory, which manufactured asbestos insulating ST00001 50 -11- materials, was studied. The group studied was selected from those first employed during 1941 - 1945 and consisted of 9 33 men who worked a range of one day to 20 years. These results are shown in Table 6. The incidence of cancer of the stomach, colon, and rectum was increased 2-3 times. Although the deaths from GI cancer were relatively few in relation to lung cancer, the consistency of the results suggest that the increase is real. Of course, the exposure to asbestos of the insulation workers is much higher than the ordinary population. In the United States, as a whole, the indidence of GI cancer has diminished from 5.3% of all deaths in 1960 to 4.9% of all deaths in 1970. The Advisory Committee on Asbestos Cancers reported in 1973 to the Director of the International Agency for Research on Cancer (part of the World Health Organization) and stated that a small excess risk of gastrointestinal cancer existed from asbestos inhalation, but was relatively small compared to bronchial cancer. McDonald, et al (1971) studied the mortality in workers from chrysotile mines in Quebec, Canada and found that although the respiratory cancer was higher than normal, the rate of gastro intestinal cancer was unrelated to the dust levels that the workers were exposed to. Enterline and Henderson (1973) reported a study of retirees from the asbestos industry. They found that men exposed only to ST0000I 5 I -12- chrysotile asbestos had a respiratory cancer mortality rate 2.4 times the expected; whereas men exposed to both chrysotile and crocidolite had a respiratory cancer mortality rate 5.6 times the expected. In no case, however, was the gastrointestinal -cancer rate significantly higher than expected. There seemed to be a trend toward increasingly higher incidence among older people (75 + years) but the values are not statistically significant. ST0000152 -13- TABLE 4 Exoected* and observed number of deaths among 623 New York-New Jersey asbestos insulation workers 1 January 1943-31 December 1971. twenty or more years after onset of first exposure to asbestos Total cancer: all sites Lung cancer Pleural mesothelioma Peritoneal mesothelioma Cancer of stomach, colon, oesophagus Cancer all other sites Asbestosis All other causes Total all causes rectum. Person-years of observation 1943-51 1952-61 1962-71 Expected Observed Expected Observed Expected Observed 11.3 28 18.3 1.5 13 3.5 a` 1 n-- n.a. 1 n.a. 57 17.6 104 23 5.1 48 2 n.a. 5 3 n.a. 20 4.1 5.7 n.a. 65.1 76.4 7 6 1 44 73 3726 5.0 9.8 n.a. 89.4 107.7 18 11 10 94 161 j 4406 3.9 8.6 n.a. 78.3 95.9 16 IS 22 61 187 2898 Total. 1943-71 Expactad Obstrvad 47.2 10.1 n.a. n.a. 13.0 24.1 n.a. 232.8 280.0 189 84 8 24 41 32 33 199 421 11.030 * 632 memoers were on the union's roils on 1 January 1943. Nine died before reaching 20 years from firs: employment. these calculations uoon reaching me 20-year from onset of first exoosure point. * Expected rales are based upon aoe-soecific death rate data of the US National Office of Vital Statistics from 1949-67. polated 1943-48 from rates for 1949-55. and for 1968-71 from rates for 1961 -67. * US death rates not available, but these are rare causes of deatn in the general population. All others enteied Rates were extra Selikoff, Hammond, and Seidman - 1973 TABLE 5 06001$ Expected* end observed deaths among 17.800 asbestos insulation workers in the United States and Canad 1 January 1967-31 December 1971 Total daatha Cancer: all salts Lung cancar Pleural mesothelioma Pentonaal mesothelioma Cancer of stomach Cancer of colon, rectum Cancer of oesophegus All other cancers Asbestosis All other causes Number ol men Person-years of observation Total Expecttd Observed 905.63 1*4.09 44.42 nj.* rta. 6.62 17.51 3.21 7243 n.a. 661.54 1092 459 213 26 51 16 26 13 114 78 555 17.800 86400 Distribution by duration from onset of exposure Leu than 20 years 20 years ana mors Expected 178.94 2641 7.03 n.a. n.a. 047 2.51 0.44 1548 n.a. 152.63 Observed 211 51 22 2 3 1 3 1 19 5 155 Expected 626.69 117.78 37.39 n.a. n.a. 5.65 15.00 2.77 56.97 n.a. 508.91 Observed 881 408 191 24 48 15 23 12 95 73 400 cn co 12.681 62.673 5.119 23.627 * Expected deaths are besed upon age-specific death rata data of the US National Office of Vital Statistics. Rates for 1968-71 wars extrepolatad from rates for 1961-67. * US death rates not available, but these ere rare causes of death in the general population. Selikoff, Hammond, and Seidman - 1973 TABLE 6 Expected* and observed deaths amono 933* amostte asbestos factory workers first employed 1941-45. and ooserved to 31 December 1971 Total deaths Total cancer: all sites Lung cancer Pleural mesothelioma Peritoneal mesothelioma Cancer of stomach Cancer of colon, rectum Cancer of oesophagus All other cancers Asbestosis AH other causes Before 1952 Expected Observed 69.98 9.81 1.49 n.a.* n.a. 1.45 1.56 0.27 5.04 n.a. 60.17 68 15 3 1 0 3 2 0 6 3 70 1952-61 Expected Observed 108.27 18.72 3.71 n.a. n.a. 1.84 2.61 0.45 10.11 n.a. 89.55 146 44 23 0 0 4 5 0 12 7 95 1962-71 Expected ! Observed 121 24 21.63 6.21 n.a. n.a. 1.29 2.88 0.51 10.74 n.a. 99.61 250 84 47 2 4 4 8 0 19 17 149 Total. 1 941-71 Expected Observed 299.49 50.16 11.41 n.a. n.a. 4.58 7.05 1.23 25.89 n.a. 249.33 484 143 73 3 4 ii 15 0 37 27 314 * Expected rates are based upon age-specific death rate data of the US National Office of Vital Statistics from 1949-57. Rates were extra polated for 1941-48 from rate: lor 1949-55. and for 1968-71 from rates lor 1961-67 * 933 men were employed. In 5 cases, ages were not known and these men have been excluded from these calculations. 877 men were traced to death or to 31 December 1971. 51 men were partially traced and rema-n in tne calculations until lost to observation. * US deatn rates not available, but these are rare causes of death in the general population. Selikoff Hammond and Seidman 1973 -15- Ingestion Studies In a study by Bonser and Clayson (1967) forty rats were maintained on a diet for 75 weeks which contained 1.5 grains of asbestos per Kg of food. No tumors of any kind resulted nor were there any lesions on the intestinal wall which might have suggested a previous absorption of asbestos fibers. There was, however, a high mortality rate in the study: only 38% of the controls and 30% of the treated rats survived the 75 weeks. In an unpublished study by L.M. Swinburn (personal commun ication to FDA) asbestos particles were fed once a week to an unspecified number of SPF Wistar rats for 16 to 18 weeks, admin istered in butter. Although the asbestos particles were of the size range known to produce tumors by other modes of administration, no tumorgenic effect was noted. This was, however, a very short study. With a single large dose, the fibers were totally cleared by the gastrointestinal tract in 48 hours and no asbestos was detected in the animal tissues at the end of one week. The gastro intestinal tract of the rat seemed to provide an effective barrier to penetration. In another study, W.E. Smith, et al (1965), reported that hamsters maintained on a diet of one percent chrysotile or amosite throughout their life had no gastrointestinal tumors. Harley, Gross, and Greene reported at the 1974 Annual Meeting of the International Academy of Pathology (US-Canada Div.) on rat feeding studies. In one study ten rats were fed 5% asbestos for 59 I00001S -16- 21 months. In another study, ten rats were given intragastric injections of asbestos and taconite (an iron ore containing asbestos). In a third study, 20 rats were fed asbestos and tac onite mixed in butter and were examined at weekly intervals for : five weeks. Although occasional mineral fibers were found in :the tissue digests of seven animals from all of the studies, only one of the fibers was consistent with the ingested test material. Also similar fibers were found in the control animals. Electron microscopic examination of the gut wall disclosed no evidence of tissue invasion by fibers except for the presence of a fiber in a vacuole of a phagocytic cell in the intestinal submocosa of one animal. Pontefract and Cunningham (1973) reported intragastric injections of asbestos resulted in asbestos being found in the Q C_ blood. Rats given 9.4 x 10 fibers had 4.65 x 10 /g in the blood two days later (Table 7) . Four days after treatment with 9 94 x 10 (10 x the first dose) fibers the blood levels were 1.19 x 106/g. This indicates that there is a mechanism for clearance of fibers from blood. Assays of other tissues revealed asbestos fibers but in numbers similar to the controls. Apparently, the body contains asbestos particles from air, food and water contam ination. Most of the fibers found were 0.2-2.0 micrometers in length. In early 1974, as a result of a water pollution suit brought by the Environmental Protection Agency (EPA) against the Reserve Mining Corporation, the water of Duluth, Minnesota, was found to STOOOO!56 17 TABLE 7 Numb** el Ashosio* Fibre* Recovered from Treeied and Non-Traatad Rala mood Spleen Onicnlum Heart Brain Lungs Controls mean* 0.00 _ 133 0.675 :.4h 0.46 109 0 41 0.05 0.02 1.06 0.26 Croup 1 f mean 4.651 1.02 4.11 0.49 174 0.17 0.3 III 0.19 I.SO 0.54 Group 2) mean* 1.19 3.45 19.25 128 0.29* 1.74 0.77 1.20 7.79 0.40 0.11 0.26 Average of five rat* in all case* except where noted, f Animal* injected with 9.4 x 10* fibres and tissues examined 2 d later. J Ani mals iniected with 94* 10* fibres and tissues examined 4 d later. I Standard error of the mean. || Four rats only. T FcO.Ol; F < 0.05. (The figures in the table are fibres g-'x 10"*.) Pontefract and Cunningham - 1973 ST0000157 -18- contain asbestos fibers. Although the EPA felt that asbestos fibers constituted a hazard to health and the U.S. District Court in Minnesota concurred, most of the evidence appeared to be based on inhalation studies. Masson, McKay, and Miller (1974) studied "the patterns of cancer in the Duluth, Minnesota, area and found no increase in the incidence of cancer among persons of all ages including children, but noted that the period of observation (15 years) was short relative to the latent period for asbestos-induced carcinogenesis. In 1971, Merliss suggested that the high rate of stomach cancer in Japan was a result of using talc, which may be con taminated with asbestos, as a coating on rice. The rate of stomach cancer appears to follow roughly the rice-eating habits of people in various areas within Japan. Japanese _who migrated to the U.S. and do not routinely eat talc-coated rice do not have the high incidence of stomach cancer. Other Asians who do not eat talc-treated rice also do not have high incidence of stomach cancer. Smith, 1973, reported a study in which ham sters were fed talc containing fibrous materials. No tumors were found and Smith suggested nitrosamines as the causative agent for stomach cancer in Japan rather than talc-treated rice. The Advisory Committee on Asbestos Cancer reported in 1973 to the Director of the International Agency for Research on Cancer (a Division of the World Health Organization) . As part of their report they stated that, "such evidence as there is does not indicate any risk from asbestos fibers present in water, food, beverages, or drugs". ST0000I 58 -19- Mechanics of Asbestos Toxicity A theory has been postulated in recent years that the principle mechanism of action of asbestos is mechanical rather them chemical and depends on its fibrous character (length to diameter ratio). Stanton and Wrench of the National Cancer Institute reported in 1972 on an extensive study comparing various types and sizes of asbestos and fiberglass when applied to the pleura of rats. Asbestos, inducing a high incidence of mesotheliomas, caused fewer mesotheliomas when reduced to submicroscopic fibrils by milling. Fiberglass did not cause meso theliomas except when reduced to sizes resembling asbestos fibers. Metals and hydrocarbons have been postulated to cause tumors or at least enhance the activity of asbestos. (Harington,-1965, Harington and Roe,-1965). Neither fine particulate nickel or nickel-chrome steel or oil showed any tumorigenic effects. In an editorial in the Journal of the National Cancer Institute in 1974, Stanton postulated that fibers< 3 microns in diameter and > 20 microns in length are more carcinogenic than fibers with diameters larger than 3 microns regardless of length or with lengths less than 20 microns regardless of diameter. Short fibers are probably not carcinogenic because they are effectively disposed of by overt or intracellar phogocytic activity. Since asbestos found in liquids are short individual fibers less than 20 microns in length, their presence may constitute a minimum hazard if the studies of Stanton and Wrench are reliable. ST0000I 59 -20- One report (Cunningham and Pontefract - 1973) comments that the more time that fibers remain in water, the more their magnesium is leached out and the central canal begins to disappear. The electron diffraction pattern also begins to fade. This may indicate a slow solubilization of the fibers in water. However, no other report makes this comment. ST00001 60 -21- Asbestos References 1) Asbestos - Cement Water Pipe and Health A/C Pipe Producers Assoc. Suite 1113, 1875 Conn. Ave. N.W. Washington, DC 20009 2) Federal Register 38 (188) 27076-27081 September 28, 1973 3) Report of the Advisory Committee on Asbestos Cancers to the Director of the International Agency for Research on Cancer. Brit. J. Industr. Med. 30: 180-186 1973 4) Biles, B and Emerson, T. R. Examination of Fibers in Beer Nature 219:93 1968 5) Bonser, G. M. and Clayson, D. B. Feeding of Blue Asbestos to Rats British Empire Cancer Campaign for Research Annual Report 1967 6) Cook, P. M., Glass, G. E., Tucker, J. H. Asbestiform Amphibole Minerals: Detection and Measurement of High Concentrations in Municipal Water Supplies Science 185:853-855 1974 7) Cunningham, H. M. and Pontefract, R. Asbestos Fibres in Beverages and Drinking Water Nature 232:332-333 1971 ST000016 I ST0000I 62 -22- Asbestos References Continued 8) Cunningham, H. M. and Pontefract, R. D. Asbestos Fibers in Beverages, Drinking Water, and Tissues: Their Passage Through the Intestinal Wall and Movement Through the Body. Journal AOAC 56(4) 976-981 1973 9) Enterline, P. E. and Henderson, V. Type of Asbestos and Respiratory Cancer in the Asbestos Industry. Arch Environ Health 27: 312-317 1973 10) Harington, J. S. Chemical Studies of Asbestos Ann N.Y. Acad. Sci 132: 31-47 1965 11) Harington J. S. and F. J. C. Roe Studies of Carcinogenesis of Asbestos Fibers and Their Natural Oils Ann N.Y. Acad. Sci 132: 439-450 1965 12) Harley, R. S., Gross, Paul, and Greene, William B. Transmigration of Asbestos across the Gut Wall. Abstract of Paper presented at International Academy of Pathology (U.S.-Canadian Div.) 63rd Annual Meeting, San Francisco, March 1973 13) Hilding, A. C. Phagocytosis, Mucous Flow, and Ciliary Action Archives of Environmental Health 6: 67-77 1963 14) Jackson, J. C. Asbestos in Drinking Water Paper presented to New England Water Works Association Feb. 21, 1974 ST0000I 63 -23- Asbestos References Continued 15) Kay, G. Ontario Intensifies Search For Asbestos in Drinking Water. Canadian Journal of Water Pollution Control Ills 33-35 1973 16) Merliss, R. R. Talc-treated Rice and Japanese Stomach Cancer Science 173: 1141-1142 1971 17) Merliss, R. R. Talc and Asbestos Contamination of Rice JAMA 216: 2144 1971 18) McDonald, J. C., et al Mortality in the Chrysotile Asbestos Mines and Mills of Quebec. Arc Environ. Health 22: 677-686 1971 19) Masson, T. J., McKay, F. W., and Miller, R. W. Asbestos-like Fibers in Duluth Water Supply JAMA 228(8) 1019-1020 1974 20) Nicholson, W. J. (Ed) Insulation Hygiene Progress Reports 4 (4) 1972 21) Nicholson, W. J., Maggiore, C. J., and Selikoff, I. J. Asbestos Contamination of Parenteral Drugs Science 177: 171-173 1972 22) Pontefract, R. D., and Cunningham, H. M. Penetration of Asbestos Through the Digestive Tract of Rats. Nature 243: 352-353 1973 23) Sargent, H. E. Asbestos in Drinking Water Journal New England Water Works Assoc. P 43-57 1973 -24- Asbestos References Continued 24) Selikoff, I. J., Hammond, E. C., and Seidman, H. Cancer Risk of Insulation Workers in the United States in Biological Effects of Asbestos International Agency for Research on Cancer Scientific Publication No. 8 World Health Organization 197 3 25) Smith, W. E. Asbestos, Talc, and Nitrites in Relation to Gastric Cancer Industrial Hygiene Journal P 227-228 May 1973 ST0000I 64 26) Smith, W. E. ; Miller, E. L.; Elsasser, R. E.; and Hubert, 0. 0. Tests for Carcinogenicity of Asbestos Ann. N.Y. Acad. Sci 132: 456-488 1965 27) Stanton, M. F. Fiber Carcinogenesis: Is Asbestos the Only Hazard Journal of the National Cancer Institute 52: 633-634 1974 ~ 28) Stanton, M. F. and Wrench, C. Mechanisms of Mesothelioma Induction with Asbestos and Fibrous Glass Journal of the National Cancer Institute 48(3) 797-816 1972 29) Wehraan, H. J. and Plantholt, B. A. Asbestos Fibrils in Beverages. I. Gin Bulletin of Environmental Contamination and Toxicology 11(3) 267-272 1974