Document zQgjYarqDZrKoJdj3QeG8wp2n

RECEIVED 3^2 1979 IMPERIAL CHEMICAL INDUSTRIES LIMITED PLASTICS DIVISION NOTE FOR APME VCM COMMITTEE MEETING, LONDON 27 FEBRUARY 1979 PVC DUST I Hope this note will bring you up to date on what is happening on PVC dust in the UK. Tripartite Medical Meeting 24 January 1979 So for as PVC dust is concerned, this was a much happier meeting than we have had for 1/2 years because the Health and Safety Executive (HSE) and in particular its Employment Medical Advisory Service (EMAS) were satisfied that industry is giving serious attention to PVC dust. Industry may not yet be doing everything HSE would like to see us do but we have made a start. Work already initiated was reviewed and possible further work programmes were discussed as follows. Literature Survey Dr Greenberg of EMAS tabled the attached paper Appendix 1 noting work reported since we had met in May 1978. He included a personal communication from Dr Burrows of ICI on a survey of workers in an ICI PVC Fabrication unit regrettably this paper has not been accepted for publication because of defects in its protocol. This contrasts strangely with the ease with which Mapp et al and others of our antagonists can publish. EMAS and HSE continue to note that industry has not been able to disprove that long term inhalation of PVC dust is harmful to man. Dr Pigott of ICI's Central Toxicology Laboratory has had a literature search done on PVC dust. We have pruned the list because it contain d so much marginal material and we hope to have something better available soon. Survey of PVC Dust Exposed Employees at ICI's Hillhouse Works When Dr W G F Adams reviewed the work we had done in 1975/6 on Id's Hillhouse employees examined by the National Coal Board's Radiographic Unit, he found that he could not write a paper acceptable to a scientific,j urnal because of lack of'adequate control populations. Having met a somewhat similar problem in Dr Burrows' study and still being criticised by.th HSE that we commented adversely on already published pepers but published nothing ourselves. Id have asked an independent body, the Institute of Occupational Medicine (IOM) in Edinburgh to carry out a survey which could and would be published. . This work Is now under way. The IOM^are surveying 750 people out of a 2,400 population who have been at s me time employed at Hillhouse in the period since 1 January 1967. , The IOHhav been given a free hand in choice of exposed end unexpdsed, present- and former employees. In*-addition do &ill chesty-rays,j^spirometry,- gas,'transfer tests etc, the IOM's industrial hygiene team will./survey environmental conditions in the plant. The IOM are free to publish their survey in the medical and scientific pres* jond>.ipdeed ICI ^illyxpect: 9j4 C&p y-em bews-x et > Already there are some criticisms emerging about sampling/selection f people for inclusion in the survey. Regrettably the IOM could not d vote the resources to examine the total population. The entire matter f sampling/selection has been left to the IOM and has not bean influenced UCC 010890 2 by ICI. It is hoped thot the survey will be reported by mid-year though it may take longer than this to get into journals. We would plead that other companies who have done regular studies of their PVC dust exposed populations should publish their findings. If you have negative information, it is worth publishing!! 4 Improvement in PVC Dust Hygiene At some PVC plants, capital expenditure has been authorised to impr v dust hygiene and HSE are pressing us for details of results of monitoring in our plants. Visits by HSE and EMAS personnel have been made to mulsion PVC plants in particular to familiarise themselves with processes and conditions. They seem however more concerned about conditions in custom rs' premises and were pleased that the UK PVC producers have now revised their literature to re-emphasise to customers the need for care in handling PVC dust and for keeping as far as possible below 10 mg/m . Though th y did not say so explicitly, we believe that the survey they had asked the Medical Research Council's (MRC) Pneumoconiosis Research Unit (PRU) t carry out at a customer's premises had not revealed any respiratory disorders despite allegedly high PVC emulsion dust concentrations in th working atmosphere. The survey was led by Dr J C Wagner himself who is reputed to take the view that the exposures had not been long en ugh t show any physiological effect. 5 Animal Studies The UK PVC industry is divided on its view about the value of a dust inhalation study on animals. The cost would be at least 500,000 for an inhalation experiment and in ICI's experience the technical difficulties would be enormous. Moreover the choice of which "PVC Dust or Dusts" would be far from easy when one considers the differing particle sizes, surfactant coatings etc: our critics would say that Product XYZ proved to be all right but Product " with a different surface area/structure might not! After 3 years work and 0.5m expenditure, we could be left with an equivocal result which would overshadow even the most negative findings in an epidemiological survey. The question arises whether this money would be better spent in improving works hygiene. The HSE ere still clearly of the view that further animal work is.-, required here (but' it is of interest to note their, very firm view that enough animals had been sacrificed on VCM toxicity;work)*.C .Some UK companies are in favour since this could be one way of. .rebutting Wagner* s claims for his own work which he has not yet published in full and als it would obviate the criticism that industry experiments, on humans rather than animals. ; In addition to the technical difficulties of the inhalation experiment/ there are some cogent arguments against .the need for inhalation experiments* v.- ia'isj r.. .p - 1 ` 'jlir'i.* U,1 On frS r. v!'* r- *. (a) Only *one alleged pneumoconiosis xase hastbeen; reported.ifn any.,-.: t detair'(Amaud).--!* -a*-- - loit^ubni'VfiOl ................ I*''.'' t ,,:je sj.- (b) Many `companies `have `x-rayed employees segylarlAoiand <found jio .cases of pneumoconiosis. Selikoff has x-rayed -many US PVC workers and found no cases. .- (c) In the UK, suspected cases are referred to Pneumoconiosis Medical Panels - none attributable to PVC have been reported to our knowledge. UCC 010891 3 (d) Short term tests at ICI's CTL have not indicated fibrosis. (e) The NIOSH work on inhalation exposure of Geon 121 to monkeys, guinea pigs and rats gave no evidence of fibrosis. NIOSH say the exp rim nt was designed to test for fibrosis - they don't know how they would overcome the problems of design of such an experiment to test for carcinogenicity and indeed they say they would undertake such a study only if human epidemiology gave an equivocal result. (f) On the subject of carcinogenicity, Wagner's work on rats does not appear to indicate such an effect and neither Waxweiler nor any other epidemiologist has yet produced a well accepted study in this area. The UK industry is coming round to the view that they should ask a small group of experts to construct a protocol for a PVC Dust InhalationStudy to demonstrate whether PVC dust is carcinogenic and/or fibrogenic. The exercise of composing the protocol may help in deciding whether the study is practicable. This group has also proposed a protocol for studies to assess the validity of the intrapleural injection technique as a method for testing carcinogenicity of particulate matter but no decisions have yet been made whether to commission such a study or if we do, how widely to cost around "dusty" industries for financial support. 6 Epidemiological Studies Like ourselves, the HSE have tried to have a dialogue with Waxweiler post-Dubrovnik but failed. Everyone seemed to be agreed that Waxweiler had done an interesting but complex piece of work which deserves further study by people competent to do so. The HSE epidemiologists would like to try out the Waxweiler approach as another potential tool. They proposed a mortality study of workers exposed to PVC dust in the UK - this would be a naturol extension of the VCM study done in 1974/5. However the mixed exposure to VCM and PVC dust could be difficult to disentangle in job histories. HSE were adamant that a survey in PVC fabrication workers would be even more difficult. A small group of Government/industry biostatisticians will meet to discuss the feasibility of such a study. The HSE seem keen to do it but som industry representatives doubted whether the vast amount of work involved could be justified (if it avoided a whole-life inhalation study on rats it could be a worthwhile venture!) In July 1978 we found from Ethyl Corporation that Dr Patricia A Buffler of University of Texas would be publishing a paper which alleged an xeess of respiratory tumours in PVC workers. Though Dr Torkelson of Dow has asked that I should be given a pre-print, this has not yet been received. HSE didn't know Dr Buffler or of her work. However she is known to ICI's Dr Paddle who hopes he may Met her this month at Stanford. *2S' 7 Medical Research Council and University.Research ,.-nm nri* S1-: Dr Wagner of the MRC has been provided'with samples' of washed and z'*'n unwashed emulsion PVC powders for his aniMl work*_ /Some.samples Jbqye been, washed to remove surfactants.) The samples-are;from^P-iind~TCI^VirCTfev been supplied under Chemical Industry Association (CIA) Code Numbers. Th MRC claim that they can distinguish between the CIA codes and tell whose material they are examining.* Dr Wagner and his Director, Dr Elmes, hav visited ICI's plants and expressed disappointment that they had not been commissioned to carry out the Hillhouse study. UCC 010892 -vVrOtiij ... TMy-v-qJ 4 Dr Wagner does not disclose much about the progress of his own animal work where he must either be finding zero results or encountering pr bl ms he won't admit to us. Oddly enough in Appendix 1 Dr Greenberg does not refer to the paper Dr Wagner gave to the Pathological Society of Great Britain and Ireland in Southampton on 5 July 1978. The synopsis of the paper was as follows THE BIOLOGICAL EFFECTS FROM FINE POLYVINYL CHLORIDE PARTICLES J C Wagner MRC Pneumoconiosis Unit, Llandough Hospital, Penarth Attention.has been focussed, both in man and experimental animals, on the effects of inhalation of the gas monomer, vinyl chloride. Recently, note is being taken of the possible effects of the inhalation of the polymer in man. The particl s in question are those produced commercially as 'paste polymer', having an average diameter of 0.15 microns, and accounting for more than 10?S of the production in Britain. There are now strict regulations for the control of the monomer gas, but the particles are regarded as nuisance dust and their emission is not covered by specific legislation. Our studies on rats where both inhalation and implantation m thods of exposure have been used, and examination of tissue from human cases exposed to 'paste polymers', indicate that these small particles are not as benign as has been supposed. Techniques have been developed by which these particles can be demonstrated in ordinary histological preparations, and by transmission electronmicroscopy. " This is a fairly guarded statement which didn't attract any attention. The CIA samples^mentioned above will be used by Dr Wagner in injeeti n (presumably intro-pleural) experiments early 1979. He would like t d more PVC dust" inhalation studies and it is rumoured that he is trying t get a university*team (with no previous inhalation experienced) involved. .. Clearly progress is slow and this could in large part be related t th immense methodological problems in this area. My own layman's view is that Wagner .seems jto be trying to correlate intro-pleural or intro-trach al injection>ith^inhalation and set up say IP injection as a quicker, cheaper test for^carcinogenicity of particulates. V ` * *4 " * * ' t' r The CIA ere doing everything possible to provide Wagner end university researchers with materials':and-information. ._Is_thers.any_compq.robl. _ activity ugoiijjg on in .European universities or research institutes? .3 (vi It is interesting that neither the HSE nor the Trade Union Congr ss Medical Adviser is pressing us for an explanation of Foa et al or Mapp et al papers. Like ourselves, they seem to have concluded that if there had in fact been so many PVC attributable pneumoconiosis cases in Italy, we would have had much more informati n from the Italian companies cone rned and the press/scientific literature would have publicised th cases. UCO 010893 5 9 PVC Staining Technique Some time ago my colleagues Pigott and Wilson in our Central Toxicology Laboratory developed a staining technique for PVC particles. This t chnique has been made available to Wagner, Arnaud, Dr Torkelson of Dow and more recently to Dr Kammuller to be given to CIVO. We hope this technique will be subject of a paper in the Journal of Stain Technology and prove useful in identifying PVC particles in path slides. J Stafford Circulation APME VCM Committee UK CIA VCM Committee PVC Dust file JS (10) Mr C J Sleddon Dr B Bennett, Hillhouse Dr F W Best, Millbank Dr T R Torkelson, Dow Dr W Davis, Goodyear Mr R N Wheeler, UCC Dr M N Johnson, BFG Mr A G Wheeler Dr J Conbere ICI Americas Mr M J S Gibbons JS/MJE/DSO-107 6 February 1979 ' *"" j. ^ UCC 010894 i FULMOHARY DISEASE IN THF, V^/PVC TND'JSTRTks Some Further Reports Stnrtir-r? ``ince May Son* Biochemical and Histopathological Changes Induced by PVC Dust /5eon-l2i7in Rat Lung. Agarwnl, D.K. et al (1978). Environmental Research, 16, 3JV314. "Enzymatic and pathomorphologie alterations in rat lungs were studied at different time intervals up to 180 daya after a single intratracheal administration of 25 mg of polyvinylchloride dust. The activities of two energy-linked enzymes, succinic dehydrogenase (SDH) and adenosine triphosphatase (ATPase), and three lysosomal enzymes, acid phosphatase, glucuronidase, and ribonuelease, were significantly increased in the ear.lv period and then started to decline. The activities of SDH and ATPase reached control values at 150 days, while those of the lysosomal enzymes remained significantly higher up to this period. Histopathologically, the pulmonary response was in the form of acute inflammatory changes during the early stages of dust burden, followed by the development of granulomatous lesions containing small amounts of stromal elements." No significant difference was stated to have been observe^ in the rate of mortality of control and PVC/Administered rats, no details are given of population sizes, pattern and causes of death or histooatv,ology other than of lung tissue. Malignant Tumours of the Liver and Lungs in an Area with a PVC Industry. Saric, M. et at (1976). Environmental Health Perspectives, '<7, *89-19? **T-' "The incidence of malignant tumors of ths lung and bronchus and of cytologically confirmed primary malignant tumor of the liver was analyzed for a 4-year period in a city with several factories, including a PVC industry. Prior to the study of two cases of angiosarcoma of the liver were diamnored in workers employed in PVC production. The total incidence of analyzed tumors was only slightly higher than predicted. The tumors of the liver recorded did not show any dependence on place of work or residence. During the neriod of observation, malignant tumors of the bronchus (lung) were not recorded in the PVC industry. Their rate in the area in which the PVC industry is situated was approximately the son#* as that for the entire city area. The study does not indicate that the occurrence of malignant tumors other than angioaarcomn is associated with exposure to v'.-vl chloride." ucc 010895 -z- Tha period of observation was too short for n !>'rinitive conclusion to be reached: w fUr.thermore^a substantial proportion of perse: ; with lung cancer could not be ( adequately investigated. Chemical*Plant 1 `Waxweiller, R.J. et al (1978) NT05K While this does not conclusively demonstrate a causal relationship between exposure to PVC dustpnd lung cancer, it indicates such a possibility and' merits further consideration. Works of Wagner, J.C In a series of personal communications, he has reported the presence of PVC particles in lung sections obtained from PVC workers* In his animal studies, intra- pleural instillation has shown there to be dissemination with evidence of particles present in lung sections. Bis inhalation study on rats showed there to be pulmonary fibrosis and multiple granulomas. Pathology of Polyvinyl Resins. Broussard, G. (1969) Folia Medica 92, 102-108 This paper claims that PVC resin powder on inhalation accumulates in the lung with a consequent loss of alveolar surface. He considers the powder insoluble and inactive. He further considers that when mixed powders are inhaled oulmonary fibrosis may develop with a restricted ventilation defect, alteration in the alveolar-capillary permeability, and an obstructive or combined type of defect in the ease of pulmonary fibrosis. The radiological appearance is said to be reticulation with enlargement of the hilar lymph nodes or a mieronodular fl-pearance without enlargement of the hilar lymph nodes* Clinically, chronic bronchitis with progressive respiratory insufficiency, alternating with periods of remission of the .'.ymptoms are said to occur. Unfortunately there am no hard data to support these contentions and although several references are listed at the end of the paper it is uncertain aa to what support they give to the asseverations of this paper. Radiological and Lung Function Studies of Workers Exposed to Polyvinyl Chloride Dust. Burrows, G.E. et al (19?8?) Personal Communicntion Summary " The results of a number of studies on the effects of PVC dust both in vitro and ucc 010896 1 n nninm and nnn have !)<?or: corfi.ctir". rrcscn'. sUnlio.r performed in loyp nmd 1977 connint of chord. '-'v1 >. o1 orv<~ri' *'*1'1 .ur.p f'motion 'innonnmont of male workers exnoned to HVC dust. in ''970 Chert x-rays were taken on 179 men exposed ancl 97. men not exposed to IJVC dust. In "'-t77 >09 men; ">0^ exposed to PVC dent only, IV exposed to .'solvents only end 79'. eyoosed to a mixture of both, agreed to fill in the MRC questionnaire on respiratory function and Performed simple snirometric tests. *IT>e radiological survey showed no pneumoconiosis and the proportion of all abnormalities was the same in the two proms. Lung function, forced expiratory volume (FEV, q) and forced vital capacity (FVC) were determined for members of each of the three groups. No differences were found after allowance was made for ape, height and smoking. When service and smoking effects were separately considered, the latter is shown to be the dominant cause of reduced function. Work with PVC dust has not produced deleterious effects on lunp; function in this study." There are a number of observations one might make on this study. Thus it would be helpful to know more about the background to the x-ray study in terms of response rate, turnover of employees etc., Although the MRC questionnaire was employed, (the method of administration was not a standard one) the results are not discussed. The pulmonary function study reveals large standard deviations suggesting that the study was not adequate for detecting moderate differences in lung function between the exposure groups even if these had been present. If pneumoconiosis under the circumstances of this particular study had a low prevalence, it would be easily be missed in a study of this nature. Ideally, one would have wanted a total population study with standardised methods of observation (x-ray reading, symptomatic enquiry and lung function) and analyses admitting the moat heavily exposed to be studied separately. This paper does not resolve the position vis-a-vis the respiratory effects of ,PVC inhalation. Various Studies of Meat Workers Asthma , ^*i s, While these relste to emissions from heated labels and wrapping material,' there is disease evidence in some casesjthat/rsay be due to components such.a''pbthalledanhydride, 2, 1 .tOinhooO .*.A) T ucc 010897 concluded that there was no inflammatory or otherdet.eteri.Qjfi effects neen ir. the lung of exposed animals that could 'c attributable to PVC inhalation. Male guinea pigs were similarly exoosed for a 1? month period (T.6 exDosed, control '7'ri). As with the rats there were more rj'^-nnhnres norcthseernt in the lungs of exposed animals but it was concluded that no inf'nTratory or/rieleterious effects seen m the lungs of these animals could be attributable to PVC inhalation. 10 male Cynomolgus monkeys were exnosed to similar levels for almost 22 months. It was concluded that the only contribution of the inhaled PVC dust deposition and retention to pulmonary tissue mornhology, was numerous aggregations of PVC-containing macrophages. The report of plant material in the lungs of oroosed animals could have affected interpretation in certain circumstances. I", ir : ficult1 to '"r'-oneile the results of these experiments with others reported. The studies wer' c-,t set up to determine carcinogenic properties of PVC du3t, which incidentally is not specified in the documents available. In a letter to the Chief of the Pathology section at NIOSH, B.F.Goodrich Chemical Company, both Geon 121 and Geon 92 are referred to. Which was used in these studies was not specified in the papers available. PVC Chronic Inhalation Toxicology Study * r' - *f' 1 fJ, ^ , *, A document which is a photocopy of two pages of typescript and one table with no attribution is present on the department files. The clue to its origin lies in the following quotation: - , o. - ................... "In light of the relationship unequivocally established between occupational exposure to vinyl chloride-monomer and liver angio-sarcema and the concern expressed;onopotenfcialsriak to human health from exposure to pblyvinyl* chloride Studies and Tests of Validity of Industrial Air Standard! ` ilation * t tf, exposure study with'.PVC.dust. Actual exposure* to a representative material (B.F. Goodrich Company .(Geon 121) began in February 1976 utilising j5 species of animals - monkey, guinea nig and rat.................." uoc 010898 I Although 'her*' nr cr"-!" i'- ''c-.-.-een this xniarent summary pacer and t^n 7 Irii,.1'i stndv . -- `'Tor,H. i* is rossih'.e that bh.cv , refer to the same study. Never* r.e - s -t^act refers to further data not included \n t1"" NIOdH f-nnort*' ;r.','iu - "'.nnnarv function of the monkeys and hionhemicfii/n'tnin-i' crnnisfy on <- nn n-e c-d rat. Tests for liver riamn-'o were relative1 y insensitive so thn* is nn* possible to conclude that there was no liver damage but on.lv that no pv- -.rive n~tion*` liver damage occurred. The monkey pulmonary function tests ....... 'oss of lung recoil pressure oronablv as the res':1 t of ageing an" there wn nnrr : ".cation of small, air-way obstruction o^ non-shntisiicn' ri'*ri'riraprn. At '*'' - pp cocmrpt; with ore-exposure data of lung function no significant differences wp"p observed. Functional Respiratory Changes upon Chronic Exposure to Monomeric and Polymeric Vinylchloride. Mapp, C (19?8) Isfcituto Medicins del Lavoro, 69, Ifil-ifiP workers producing nolyvinyl chloride were studied by respiratory symptom questionnaire, lung function radiorraphy etc. In their conclusions the authors consider that vinylchloride monc-e* 'oar adverse effect on lung function which is generally moderate :r. terms of nrc. '.lone'' and severity as distinct from a foreign body type reaction due to po'vmer. "ne" raise the Possibility of a potentiation of effects between monomers,nolymer nowoera and tobacco which can lead to obstructive disease and symptoms of chronic bronchitis. CONCLUSIONS * h The additional studies reviewed do not disprove f*o suggestion that the long term inhalation of PVC dust ('pure' and compounded) may be a hazard to man in terms of respiratory disease (malignant and non-malignant) or disease of other systems. I M GREENfERG JANUARY IOTP h*C t*Vr uoc 010899