Document 6bdgNbr8Rm24D1x88Z4DgVod3

TO: Dick Conrad-LCVCM J&k. JCl: MMG: RF XF: ---------------- Interoffice Communication FROM: DATE: SUBJ: T. G. Grumbles July 27, 1989 VISTA LITERATURE RESULTS OF BRAIN TUMORS AND VCM EXPOSURE STUDIES Attached is an example of what papers summarizing the literature say. In general, excesses have been seen but the excess is probably not significant, or in other words no more than the normal population. These pages are from a "summary" paper that will go in the book. I think we want to put this type of paper first and direct their attention to them. T. G. Grumbles dlj Attachment VVV 000009422 41 CONCLUSION Occupational exposure to concentrations of VC of the order of 1,000 ppm has caused the classical 'vinyl chloride Illness1. Exposure to such levels, or perhaps lover levels of the order of several hundred ppm, has caused angiosarcoma of the liver after a latent period ehec Is seldom less then 15 years, _r~> The evidence now available from following up many thousands of men occupationally exposed_ to vinyl chlpride_sugg9ats,,_th4t__e _small_risk of lung cancer may alao_have been produced, which must, however, have been substantially leas (in absolute terms) than the risk of angiosarcoma of the liver* The balance of evidence\does not support the idea chat VC has caused cancer In any other organ^ but It Is impossible to state categoric ally that it has not. Clearer evidence, one way or the other, could be obtained If the various Investigators would present their results in comparable forma that would allow them to be combined and subjected to the standard taata for an occupational hazard. Thera la no evidence that exposure to VC has caused any other disease. Suggestive evidence has bean obtained that peat levels of environmental pollution with vinyl chloride may have caused a few cases of canear In the general public. VVV 000009423 28 German and tha Swedish studies derived the expected number* of deaths from oaclonal mortality races for a stogie year towards the end of the study period. The expected numbers of deaths are likely, therefore, to have been overestimated and the SMRs correspondingly underestimated as the mortality from lung cancer had been rising throughout the period of observation. The Idea that VC eight cause brain cancer wee suggested by Monson et al. (1974), when they reported 5 cases against 1.2 expected. In the ease paper In which they suggested that VC eight cause lung cancer. The coablned data that are shown in Table 4 provide soee support for this hypothesis. Honson et al.*s cases were, however, observed in US workers and oust be presueed to be Included in the total reported by Environmental Health Associates (1986), in which case they will have contributed a substantial proportion of the total in Table 4. To test the hypothesis we ought, therefore, to subtract Honson et al.'s data. Their study was not a cohort study and thalr expectsd deaths do not corrtspond exactly to those in Table 4; we can, however, only subtract both the observed end the expected cases from the present totsls. This leaves 24 observed against spproxleately 18.3 expected, a difference which eight easily occur by chance (P, one-tailed, 0.1).* Additional information from two ottaar sources Is given In Table 5. The small axceta reportad provides llttls further tvldenca of an occupatlonal hasard, as ona of tha two daatha observed In the Swedish study oceurrsd In s young man who had been employed for lees than a year whan the diagnosis was mads, while the excess death rata for brain cancer observed If we regard Vaxweiler et sl.'s (1976) study as tha origin of tha hypothesis we should be left with 26 deaths sgalnst 18.94 expectsd (P, one-talltd, - 0.07). VVV 000009424 29 la the German study vet Lett than that observed In chemical workers not exposed co vinyl chloride (2.9 deaths oftor allowance for deaths from unknown causes against 1.6 expected) and In workers in the PVC fabrication Industry (5.9 deaths after allowance for deaths from unknown causes against 1.1 expected). Cancers of lymphatic and Haematopoietic Tissues The idee Chat VC might cause cancer of ehe lymphatic and haemato poietic tissues - and more specifically the lymphatic tissue - was suggested by Tabershew end Gaffey (1974) and by Waxveller et al. (1976) when they found, respectively, in two cohort studies (1) 5 deaths from lymphomas in the most heavily exposed workers against 2.54 expected, and (it) 4 deaths from cancers of the lymphatic and haematopoietic tissues against 2.5 expected. These smell excesses might have been Ignored if the laboratory findings had not bean interprettd as suggasting that lymphomas were produced experimentally in animals exposed to vinyl chloride by Inhalation (Kaltoni end Lefamine, 1975)* On this basis, the idee that similar exposure might also cause lymphomas in Han needed serious consideratlon. The date from the four principal studies that are summarised in Tabla 4 provide littla support for the hypothesis when all cancers of the lymphatic and haematopoietic tissues are considered together (57 deaths against 50*87 expected, SMR 112) and very little more is obtained from the I separate data for cancers of tha lymphatic system (using Tabershew end Gaffey's definition of ICD list numbers, 8th revision, 200-203 and 205) i ii that are shown In Table 1 (35 deaths against 29.40 expectad). The position la, moreover, hardly altarad by subtracting the data in Tabershew and Gaffey's initial report (29 deaths against 23*36 expected, SMR 124)* Some little additional information is provided by tha results of the German study, some of which ere shown In Table 5* This obtained an SMR of 214 for exposed workers (based on 15 observed deaths, increased to 16*5 VVV 000009425 36 absolutely aloose as large as the risk of developing the normally very rare angiosarcoma* One of the many hazards that have been suggested can be dismissed, as there Is no evidence to support It: namely, the Idea that VC causes any cancer of the digestive tract ocher than angiosarcoma of che liver* Two hazards (of aelanoma and cancer of Che thyroid) have been suggested only very recently and few of the available studies have provided information about them. Thera la no good theoratlcal reason or laboratory evidence to suggest that either should be produced by VC and, on present evidence, the simplest explanation Is that ths reported excesses are the chance effects that muat be expected when many different types of eaneer are studied in several different populations. So far as melanoma is concerned It has to be remembered that the disease has become much more common in recent years la Scandinavia (where the excess has been reported) due, it Is believed, to the popularity of sunbathing and the increased opportunities for Scandinavians to travel to the warmer parts of Southern Europe and North Africa* The extent Co which this may have affected the observation In Norway neads to be examined. ________ JZT} Two other hazards (of lymphoma and oiChrallUcanceT^ were suggested by the early results of some of the American studlas. That VC might produce a hazard of lymphoma was Initially supported by Che preliminary results of animal studlas, but the complete results of Che many studies that have now been undertaken (see Neltonl and lefamine, 1984) do not suggast that lymphoma or any other cancer of the haematopoietic system is liable to be produced. There la, however, some evidence that brain tumours esn be produced In rats (sat Haltoni and Lefamine, 1964). The hypotheses that lymphomas and brain cancers might be produced by VC have been supported by the observation that both these types of cancer have caused death more often than might be expected from national mortality rates, but the VVV 000009426 37 excmtt observed In the combined data from the four principal studies are small and not statistically significant and the hypotheses remain unproven. The small excess of brain cancer is particularly difficult to evaluate as mortality rates from this disease have changed rapidly over time In company with Improved methods of diagnosis and the suspicion of an occupational hazard (which was raised in 1975) could have influenced the findings. What excess has occurred has been limited to the USA and Cermany and the German findings carry little weight, as the excess was found in each of the three occupational groups studied, irrespective of the chemicals to which they were exposed. The supplementary data from the German study showing an Increased mortality from lymphatic and haematopoietic cancers are more Impressive, particularly ae the excess was most marked for men who had been employed for at least 5 years. In these clrcumstsnees, we must still suspend judgment until the data for each study are analysed for each specific type of cancer, by intensity snd duration of exposure, end time since exposure began. There remains the suggestion that VC might cause lung cancer. At first sight, this is ruled out by the SMR of 97 for the combined data for respiratory cancer for the four principal studies. Lung cancer Is, however, normally eo co--on (accounting for about M of Che expected deaths) that an Increase in mortality that was half as Important (numerically) as the mortality from angiosarcoma of the liver might easily be overlooked (95X confidence limit of the SMR, 85*112). The Incidence of the disease Is moreover very variable within a country and there must be doubts whether the national experience provides a suitable control for men employed in plants Chat are not evenly distributed about the country. In these circumstances we cannot exclude an occupational hazard unless lc can be shown that the mortality within the exposed men la independent of the factors that might be expected to Influence it, If some of it were WV 000009427