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M Davies, T.A.L. (Dept. Employment and' Productivity, London, Engta^^4*1 Hunter, C.G. (Tunstall Lab., Sittingbourne, Kent, England): Williams, M.K.(London School Hyg. and Trop. Med., England): THE EARLY DETEC TION OF ABSORPTION OF TOXIC MATERIALS. Proceedings of the Royal Society of Medicine 61:911-2; 913-5; 915-6(Sept.), 1968. N36917 / Volume61 September l%8 91 i Section of Occupational Medicine President W Melville Amou t o mic p Meeting February 81968 The Early Detection of Absorption of Toxic Materials [Abridged] Dr T A Lloyd Davies {Department of Employment & Productivity* London) Control ofToxic Hazards The anecdotal collection of cases of poisoning is no longer a sufficient index of industrial environmcni. Because of the lack of screening tests, we may be compelled (for diseases such as anthrax or oc -ijr.rio.iitl ameer) to rely on the diagnosis of overt disease. So far as cancer is concerned, the safety of environment can only be determined by lifetime studies of *at rink1 populations. An cxample of a lifetime study is the register of 42,105 men (after excluding those born outside UK) who were aged 35 years and had been employed for one year or more in 380 rubber and cable fac tories (of which 128 hud used renal tract carcino gens), which was established by a census on February l, 1967. The experience of these men will be followed by watching removals from the NHS register (lo determine the cause of death) and registrations with cancer bureaux for defined cancers (JCD (Eighth Revision) 150, 155, 188, 189, 191, 192, 204-7). Other registers established by the Medical Branch of HM Factory Inspec torate concern workers exposed to benzene (though it is recognized that the past wide spread use of benzene renders the completeness of this register questionable), blowroom and card-room operatives in coarse cotton mills in Lancashire, persons reported as suffering front or dying of mesothelioma, and chrome platers in selected areas. The traditional example of success in reducing poisoning is the reduction from 1,058 noli lied eases of lead poisoning in 1900 to a current yearly . total of 80-100 notified eases. Quite apart from considerable undcr-notilication, it will be shown that the more rclincd screening tests are used, the greater is the iceberg below the surface. 1.000 lf<0 PV 40 73 kCWV 54 U>a R 4COOCOM 043 WO pM 30 IIS 4.M 34 Fig 1 Distribution of normal and abnormal dial observ ation in relation to symptoms of htemogiobiu,-tn-ittarycoproporphyrin and blood had in haft workers, phenolic bodies in urine ofworkers absorbing benzene and X-ray score btfoundry workers Fig 1 shows the distribution of vital observa tions in persons not exposed and occupationally exposed to various toxic agents. Any person having relevant vital observations outside the normal range must be regarded as showing a metabolic response to environment. This is clearly demonstrated by the distribution of hemoglobin in asymptomatic lead workers (Fig 3). Clearly, when overt symptoms and signs develop - which may be predicted if individual and group observa tions exceed defined levels - poisoning occurs. Between symptomatic poisoning and the accepted higher limit of normality there is an area of abnormality which, if not justifying the term symptomatic poisoning, represents a departure from normal, often a potentially hazardous departure, for which the term asymptomatic poisoning is suitable. The difficulty is to judge what is significant; it may he argued that blood load up to 80 jig/100 ml. or an X-ray score1 in foundrymen from 0-63 to 10, represents no more than retention. Further, retention above these levels may not cause immediate harm, but no ono 1\ suorc bused on rending* by three observess, using intcrobscrvcrdiftfcrenccs r DUP050312625 S K tto n o fOccupational Medicine tti v.?s4 & "5 c'a-Q .= 2 -a -S ,o .5 1 O c 0 O S|| -s? s-8 a~ **. V, ts S' So & S * ^c*s. sj u "5 &! s s < . . I Is tsM -S^ |s5iwei'1*?S'sN:!o?>s 35 & * - .s M*5 c & a ! SS's.-c. s?s ,o e 2 =._ .S >s 2 ? 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During the second week six biological tests were each estimated daily. Blood lead was found to have thegreatest merit followed by urinary lead and coproporphyrin together. Urinary S-ammokcvulinic acid was of less merit, the punctate basophil count of little merit and haemoglobin of no merit at the level of exposure studied. Urinary coproporphyrin had the greatest merit per unit cost. Perhaps the method has other applications. Dr J R Glover {Institute of Preventive Medicine, Cardijff )stxi*l there appeared to be some confusion between absorption of toxic substances and poisoning by those toxic substances. The position was shown diagramnwtically in Fig 1. REFERENCE Williams M K. Kins E& Walfon) J (1966) Brtt. nttif. J. i, 18 Dr H Locwenthal {London) said that no laboratory test on its own could distinguish between exces sive and early toxic absorption oF lead. Even very high blood lead levels did not necessarily indicate lead poisoning, but hromatological and biochem ical tests token together would facilitate diagnosis by the factory doctor. The wider use of the polarographic method of lead estimation and the use of the micro-method for the packed cell volume estimation would require smaller quantities of blood and this would help to allay the apprehen sion of the lead worker who did not object so much to the withdrawal of blood from his vein as to the amount which had to be lakcn if stan dard methods were used in the laboratory. Dr Owen MeGirr {London Airport) asked Dr Hunter if his Fig 1, demonsiniling twentyfour-hour excretion of phenols after a relatively short inhalation of benzeno,.could be considered as an expression of a logarithmic relationship indicating a time-dose relationship. If so, this was perhaps comparable to biological responses to some physical exposures such as ionizing radiations and intense noise. He noted that even at twenty-four hours there remained a (small) body burden of phenols and wished to know whether successive exposures would increase the phenolic body burden. Dr Hunter, in reply,.said that after a single inhalational exposure to benzene vapour only onethird of the absorbed dose was eliminated in the form of urinary phenol. The urinary phenol fell to within the normal range within 24~36 hours. Therefore the residual burden of benzene must be metabolized very slowly and the body must retain a burden of benzene for each exposure rather than a burden of phenol. The benzene dose/ phenol excretion time relationships were not known and relationships in Fig 1 were those for ' t. - Fig l A model to lilustraic the relationship between absorption andpoisoning Almost every hazard had a group of the popu lation who were particularly susceptible to it and a group who were particularly resistant to it. The `susceptible' graph was therefore S-shaped. For example, the maximum allowable concentration (MAC) of selenium was. 0-1 mg Sc/ma, However, a parson susceptible to skin contact with selenium dioxide would show skin signs in atmospheres where selenium was so low that it could not be measured. 'Morbidity* on Fig 1 might be defined as signs and symptoms caused by the toxic hazard. This type of diagram was useful for deciding whether a test of biological dysfunction was too sensitive or loo late in picking up early eases ofpoisoning by the toxic hazard. MeetingJune 23 1967 The meeting took the form of a visit to the Victoria Line, London Transport, which is under construction, and included Oxford Circus Station, Cobourg Street switch house, substation and con trol room, and Easton. Station. Meeting October 26 1967 Professor W Melville Arnott {Queen Elizabeth yioxpind, Birnjbighani) delivered his Presidential Address which was entitled Caring for the Worker, Meeting December 141967 A discussion was held on the subject of The Early Recognition of Environmental Hazards. The opening speakers were Dr A M Adelstdn, Dr H H Pilling and Dr J C Gilson. DUP050312627