45

My own experience of obtaining NPS for virological diagnosissuggests very wide variation in consistency: some children havevery watery secretions, often further diluted by tears, while othersproduce small volumes of viscid secretion. The dilution ofinterferon by watery secretions could be so great as to render itundetectable even in a normal child. Without an effective means ofstandardisation one may be left with "presence" or "absence" as theonly way of expressing results.

I am not sure whether the sibling controls were also followed upprospectively, whether NPS were taken at each infective episode inthese children, and how often interferon was present or absent inthese specimens. It would be reassuring to know that it is veryunusual to fail to detect interferon in NPS of normal children andeven more interesting to see what scatter of interferon concen-trations is detected in them, before suggesting that the failure todetect interferon in these four children might reflect a primarydefect contributing to their undue susceptibility to infection.

Sidney Farber Cancer Institute,Charles A. Dana Cancer Center,Boston, Massachusetts 02115, U.S.A. MICHAEL M. REID

**This letter has been shown to Dr Isaacs and colleagues, whosereply follows.-ED L.

SiR,-Dr Reid is right in saying that it is difficult to quantitate theinterferon activity of nasopharyngeal secretions (NPS). The NPS ofnormal children with colds showed titres between 10 and 320, andwere usually between 40 and 80. We accept that the exact valuemight be affected by the profuseness of nasal discharge and bediluted with tears, but it is not true that the "deficient" childrencried while the others did not-and in fact they yielded particularlygood samples of sticky secretion.We agree that it is difficult to say for certain by examining titres

whether the "deficient" children represented the end of a normaldistribution or a separate subgroup. What is clear is that the failureto detect interferon was a consistent finding in nasal secretion andcultured white cells and on repeated testing and not just the result ofrandom fluctuations in collecting NPS or in the performance ofcertain interferon assays. We combined results from both the

siblings (who were indeed visited prospectively) and the "non-defective" index cases, and we referred to these children as "normalinterferon producers". We found interferon in the same proportionof NPS in both groups, namely in 86% of incidents in which arhinovirus was isolated and in 6% of those in which no virus wasisolated. Thus we failed to detect interferon in only 14% of theseproved viral colds and this reassured us that with the methods weused we might expect to detect interferon.in at least some specimensfrom all children.

Clinical Research Centre,Harrow, Middlesex HA1 3UJ

D. ISAACS

J. R. CLARKED. A. J. TYRRELLA. D. B. WEBSTERH. B. VALMAN

HEALTH HAZARDS OF FORMALDEHYDE

SIR,-Your issue of Oct. 31 (p. 980) carried a letter entitledCarcinogenicity of Formaldehyde co-signed by Dr David Groth ofthe National Institute for Occupational Safety and Health

(N.I.O.S.H.). The implication of the letter is that formaldehyde isan established human carcinogen. That is not the position of thisInstitute. As expressed in our Current Intelligence Bulletin no. 34(April 15, 1981) animal experimental data are supportive of theposition that formaldehyde is a potential human carcinogen. Theuse of Dr Groth’s name as coauthor of the letter was not authorised

by N.I.O.S.H.National Institute for

Occupational Safety and Health,Centers for Disease Control,Atlanta, Georgia 30333, U S A J. DONALD MILLAR

SIR,-The views expressed in our Oct. 31 letter represent ourpersonal opinions, we having been involved in evaluating over 200carcinogen bioassays. 1 These opinions do not necessarily reflect theviews of the National Toxicology Program or the National CancerInstitute.

National Toxicology Program,National Institute of Environmental Health Sciences KENNETH C. CHU

Laboratory of Comparative Carcinogenesis,Frederick Cancer Research Center,National Cancer Institute,Frederick, Maryland, U.S.A. JERROLD WARD

*** The Lancet does not usually publish disclaimers and printed thetwo provided in the typescript of the letter referred to only becauseof the difficulties Dr Peter F. Infante had been facing. Thisinsistence on further disclaimers may disturb those who believe inthe free exchange of scientific views. Would the director ofN.I.O.S.H. have written differently had he got the title of the letterright, as above?-ED. L.

QUARTZ AND PNEUMOCONIOSIS IN COAL MINERS

SIR,-Dr Seaton and colleagues (Dec. 5, p. 1272) continue thecontroversy concerning the role of quartz (silicon dioxide) in coalworkers’ pneumoconiosis. As cited, during the last 50 yearsnumerous studies have suggested that either coal dust or quartz isthe pathogenetic agent. However, as yet there is no agreement.Seaton acknowledges that airborne coal-mine dust is a complex andvariable mixture of coal, quartz, and other minerals. One possibleexplanation for the continuing lack of agreement is that neither coaldust nor quartz is the significant factor and that instead anothermineral is responsible.Our department frequently receives material from fatal cases of

pneumoconiosis in South Yorkshire and Derbyshire, and during thepast 3 years lung tissue has been examined by transmission electronmicroscopy with energy dispersive X-ray microanalysis (EDAX).All cases have been found to contain variably sized fibres andparticles which consistently contain aluminium, potassium, silicon,and occasionally iron (see figure). Despite an extensive search, freesilicon (consistent with silicon dioxide/quartz) has not beendemonstrated. The material analysed corresponds to the

birefringent "silica" particles and fibres seen by light microscopyand a direct correlation seems to exist between the severity ofpneumoconiosis and the number of particles. Although similarresults’have recently been reported by other workers using scanning

1. Chu K, Cueto C, Jr, Ward J. Factors in the evaluation of 200 NCI carcinogen bioassays.J Toxicol Envir Health 1981; 8: 251-80

X-ray microanalysis of a "silica" particle demonstrating thepresence of aluminium, silicon, potassium, iron, and a peak ofosmium due to the fixative.

46

electron microscopy and EDAX, 1,2 it must be emphasised that thefindings are not original. As early as 1932, jones3 demonstrated thatsilicotic lungs contained acicular fibres of sericite-a hydratedsilicate of aluminium and potassium. He also presented evidence toshow that the different incidence of silicosis in the gold-bearingquartz areas of the Transvaal and India and in the anthracite coalfields in Wales and Scotland correlated with the sericite rather thanquartz content of the rock. Sericite is usually found in rocks whichalso contain a high percentage of free silica in the form of quartz, butit is not present in all rocks that contain quartz.These findings indicate that any study of pneumoconiosis should,

if possible, include an analysis of all components of coal-mine dustand not merely quartz and coal. It is unclear from Seaton’s paperwhether sericite is included in the figures representing quartz (dueto its silicon content) or in the presumably heterogeneous non-quartz mineral. It is of crucial importance to know whether thesericite content of the dust in the controls and cases was significantlydifferent before quartz is regarded as the pathogenetic factor.

Royal Hallamshire Hospital,Glossop Road,Sheffield S10 2JF

DAVID SLATERTERENCE DURRANT

**This letter has been shown to Dr Seaton and colleagues, whosereply follows.-ED L.

SIR,-Any sericite in the dust we sampled was included in ourmeasurements of the non-quartz mineral fraction. Table III in the

paper shows that the average difference between cases and controlsin their exposures to this part of the dust was small and could easilyhave arisen by chance.

4Our earlier epidemiological work has suggested an interactionbetween the effects of quartz and the clay minerals kaolin and mica,the latter including sericite; increasing effects of quartz on simplepneumoconiosis risks were reversed in the presence of high claymineral exposure. The result was consistent with animal and invitro studies.5-8 Necropsy cases7,10,1 have consistently shown thepresence of quartz in coalminers’ lungs and we will shortly bereporting a further study which confirms this.We have observed only trace quantities of fibrous particles in

colliery airborne dusts. These vary considerably in composition andinclude aluminosilicates. Scanning electron microscopy/energydispersive X-ray studies have shown that plate-like illite-sericite

clay minerals may be judged as "fibres" unless the basal plane of theplate is approximately normal to the angle of view.The case-control study described in our paper represents an

addition to a long series of papers on the relation between dust

1. Roub LW. Pulmonary silicosis. A case diagnosed by needle aspiration biopsy andenergy-dispersive X-ray analysis. Am J Clin Pathol 1979; 72: 871-75.

2. Vallyathan NV, Green FHY, Craighead JE. Recent advances in the study of mineralpneumoconiosis. In: Sommers SC, Rosen PP, eds. Pathology annual, vol. 15, part 2.New York: Appleton-Century-Crofts, 1980: 77-104.

3. Jones WR. Silicotic lungs. J Hyg 1932; 32: 307-29.4 Walton WH, Dodgson J, Hadden GG, Jacobsen M. The effect of quartz and other non-

coal dust in coalworkers’ pneumoconiosis In: Walton WH, ed. Inhaled particlesIV. Oxford: Pergamon Press, 1977 vol 2, 669-90

5. Robock K, Klosterkolfer W The cytotoxic action and the semi-conductor properties ofmine dusts. In: Walton WH, ed Inhaled particles III. Old Woking: Unwin Bros,1971: vol 1, 453-64

6. Schlipkoter WH, Hilscher W, Pott F, Beck EG Investigations of the aetiology of coalworkers pneumoconiosis with the use of PVN-oxide. In: Walton WH, ed. Inhaled

particles III. Old Woking Unwin Bros, 1971: vol 1, 379-90.7. Le Bouffant L, Daniel H, Martin JC Quartz as a causative factor in pneumoconiotic

lesions in coal miners. Commission of the European Communities—ECSC. IndHealth Med Ser no 19, Luxembourg, 1977

8 Reisner MTR, Robock K. The results of epidemiological, mineralogical andcytotoxicological studies on the pathogenicity of coal-mine dusts In: Walton WH,ed Inhaled particles IV. Oxford: Pergamon Press, vol 2, 1977. 703-16

9. Carswell C, Bergman I, Rossiter CE The relation of radiological appearance in singlepneumoconiosis of coal workers to the content and composition of the lung InWalton WH, ed. Inhaled particles III. Old Woking: Unwin Bros, 1971 vol 2,713-26.

10. Bergman I, Carswell C Lung dust and lung iron contents of coal workers in differentcoalfields of Great Britain. Br J Ind Med 1972; 29: 160-68.

11 Davis JMG, Ottery J, Le Roux A The effect of quartz and other non-coal dusts incoalworkers pneumoconiosis. In Walton WH, ed. Inhaled particles IV OxfordPergamon Press, 1977: vol 2, 691-702

exposure and coalminers’ pneumoconiosis. It describes a specialcase where a group of miners, at a colliery with no history ofpneumoconiosis during the past 20 years, was exposed to dust with ahigh quartz content for a relatively short period. Most Britishcoalminers are exposed to dust containing relatively low levels ofquartz, seldom exceeding 8% of the respirable fraction. In thesecircumstances the best single index of the hazard is given by themass of respirable mixed dust.4,12,13

Institute of Occupational Medicine,Edinburgh EH8 9SU

ANTHONY SEATON

J. A. DICKJ. DODGSONM. JACOBSEN

DIALYSATE ALUMINIUM CONCENTRATION ANDALUMINIUM TRANSFER DURING HAEMODIALYSIS

SIR,-Hodge et al. recommend a lower than 15 pg/l (0 - 4 mol/1)concentration of aluminium in the dialysis bath solution to avoidaluminium transfer to patients during haemodialysis, but they donot refer to the principles acting on aluminium transfer duringhaemodialysis.We have shown2 that aluminium in patients on chronic

haemodialysis is highly protein bound, the fraction of free diffusibleplasma aluminium being about 20%, and that the determiningdriving force for aluminium transfer is the effective concentrationgradient between dialysate aluminium and the free diffusibleplasma aluminium concentration (fig. 1).That this principle is valid can be illustrated by dialysing patients

against different dialysate aluminium concentrations. Aluminiumkinetics during haemodialysis were studied with flameless atomicabsorption spectrophotometry in twenty-four dialysis patients at alow dialysate aluminium of 0-2 mol/1 (dialysis 1) and at a highconcentration of 1 pfmol/1 (dialysis 2). The results are shown in fig. 2.In dialysis 1, when the dialysate aluminium concentration wasalways below the patient’s free diffusible plasma aluminium,aluminium was removed during haemodialysis in all patients, theeffective concentration gradient being directed from patient todialysate. In dialysis 2, however, only patients whose free diffusibleplasma aluminium (20% of total) was equivalent to a predialysis total

12. Jacobsen M, Rae S, Walton WH, Rogan JM The relation between pneumoconiosisand dust exposure in British coal mines In Walton WH, ed. Inhaled particles III.Old Woking: Unwin Bros, 1971. vol 2, 903-19.

13. Hurley JF, Burns J, Copland L, Dodgson J, Jacobsen M. Coalworkers’ simplepneumoconiosis and dust exposure at 10 British coalmines. Br J Ind Med (in press)

1. Hodge KC, Day JP, O’Hara M, Ackrill P, Ralston AJ. Critical concentrations ofaluminium in water used for dialysis. Lancet 1981, ii: 802-03.

2. Graf H, Stummvoll HK, Meisinger V, Kovarik J, Wolf A, Pinggera WF. Aluminiumremoval by hemodialysis. Kidney Int 1981; 19: 587-92.

Fig. I-Mean predialysis total plasma aluminium concentration oftwenty-four patients on haemodialysis and effective concentrationgradient (eff) between free diffusible plasma and dialysatealuminium.