British Journal of Industrial Mediine 198;37:19-113 In-vivo determination of lead in the skeleton after oupational exposure to lead L AHLGREN,' BIRGITTA HAEGER-ARONSEN,2 S MATTSSON,' AND A SCHUTZ3 From the Radiation Physis Department,' University oflund, Lund, Department of Oupational Mediine,2 Malmo General Hospital, Malmo, and Department of Oupational Mediine,3 University Hospital, Lund, Sweden ABSTRACT The onentrations of lead in the phalanges and in the blood were determined in 22 subjets who had formerly been exposed to lead in a storage battery plant, whih had been losed for seven s. The bone lead onentration was measured in vivo using an x-ray fluoresene tehnique in whih two 57Co y-ray soures were used for generating the harateristi x-rays of lead, whih were measured with a Ge(Li) detetor. In three subjets the variation of the lead onentration along the forefinger was measured together with the lead onentration in the tibia. The measured lead onentrations in the phalanges were between 2 lug/g (our detetion limit) and 118,ug/g. The lead onentration in the phalanges was found to inrease with the length of employment, but no simple relation was found between the lead onentrations in the blood and in the phalanges. The derease in the blood lead onentration after the essation of exposure was followed in four subjets. Seven s after exposure had ended, the blood lead onentration was found to be more dependent on the daily intake of lead than on the release of lead from the skeleton. These experimental results ould be explained by a two-ompartment model using exhange rates given in publiations. This model has also been used to alulate the blood lead onentration that ould be ahieved after a sudden release of lead from the skeleton. The skeleton ontains about 9-95% of the total body burden of lead.'2 Measurements of the lead onentration in the skeleton are therefore of fundamental importane for estimating the total body burden of lead. In earlier publiations3-5 we have reported the in-vivo detetion of lead in the skeleton of lead workers using x-ray fluoresene analysis. This paper deals with a omparison between the lead onentrations in the blood and in the skeleton as determined in the phalanges by x-ray fluoresene analysis in vivo. The determinations were arried out on subjets whose oupational exposure to lead had ended seven s before the study. Materials and methods Twenty-two men aged between 27 and 75 s (mean 57), who had earlier worked in a storage Reeived 9 May 1979 Aepted 4 June 1979 battery plant for periods from -8 to 45 s (mean 22) were studied. At the time of the measurements the fatory had been losed for seven s, sine whih time none of the subjets studied had been oupationally exposed to lead. Blood samples for determination of the lead ontent were olleted at the time of the in-vivo measurement and analysed by atomi absorption spetrophotometry.6 For some of the subjets studied, the variation in the blood lead onentration had also been followed during the first after the losing down of the fatory. In our determination of lead in the skeleton the lowest detetion limit (2,ug Pb/g fresh weight) is reahed when the measurements are arried out on the fingers. The lead onentration in the seond phalanx of the left forefinger was therefore determined for all the partiipants in this study. The fingers were arefully washed with water and detergent before measurement to remove any lead whih might have been ontaminating the skin. For three of the subjets, the proximal and distal joints of the left forefinger as well as the upper part of the tibia 19 Br J Ind Med: first published as 1.1136/oem.37.2.19 on 1 May 198. Downloaded from http://oem.bmj.om/ on 13 July 218 by guest. Proteted by opyright.
11 were also measured. In normal measurements a small volume (about 1 m3) of the seond phalanx of the left forefinger was irradiated for 4 minutes with two ollimated 57Co soures (-6 and -2 GBq) as shown in fig 1. The ount rates of harateristi x rays emitted from lead in the irradiated bone volume were measured with a Ge(Li) spetrometer (16 mm diameter x 5-2 mm; energy resolution: FWHM = 75 ev at 75 kev). The angle between the inident and measured radiation was about 9. The ollimator in front of the detetor and the radiation shield was made of high purity tin partly overed with gold (fig 1). The mean diameter of the bone measured was alulated from two radiographs taken in orthogonal projetions. To relate the ount rates of the harateristi lead x rays to the lead onentration in the bones of the finger, measurements on finger-like phantoms with known onentrations of lead in their bony part and with various bone diameters were arried out as desribed by Ahlgren and Mattsson.5 Radiation dosimetry-the absorbed dose rate to the finger was measured with small (2 x 2 x 1 mm3) extruded LiF dosimeters. The absorbed dose at the surfae of the skin was 5 5 mgy (55 mrad) and to the entre of the finger it was 2-5 mgy (25 mrad) per 4 minutes. Sine the total volume of the finger (bone and soft tissue) irradiated was always less than 3-5 m3, the total absorbed energy was muh 3 Sn * Au ni PerSDex S:57Co- soure D: Ge(Li)-detektor " IC-rI:), VI I İ mm 5 Fig 1 Arrangement for determination of lead in phalanx by x-ray fluoresene analysis. Radiation shield, two 57CO soures, detetor ollimator with its gold-overed opening, and perspex-holder for finger are shown. Table 1 Ahlgren, Haeger-Aronsen, Mattsson, and Shlitz Mean absorbed dose and absorbed energy Type of investigation Mean absorbed dose Absorbed energy mgy mj x-ray fluoresene analysis of finger 2-5 1-2 x-ray examination of hand -65 (1-25) x 1-2 smaller than in hand (table 1). Results and disussion an ordinary radiograph of the It is important to know how well the lead onentration in the phalanges represents the mean lead onentration in the skeleton and thus the total body burden of lead. Figure 2 shows the results ofmeasurements of the lead onentration in different parts of the skeletons of three highly ontaminated subjets. The onentrations in three different regions of the left forefinger are not signifiantly different, and a signifiant differene between the lead onentration in phalanx and the tibia ould be deteted only for one person (No 1, fig 2). It must, however, be pointed out that the unertainty in the tibia measurements was onsiderably larger than that in the finger measurements. This means that differenes of up to 5% between the lead onentration in the phalanx and the tibia ould be present without their being registered as being signifiant. Of the 22 men studied, 15 (7 %) had lead onentrations in the phalanx above 2,tg/g, whih was the limit of detetion. The lead onentration in the phalanges inreased with the length of employment in the battery fatory (fig 3). The variation of the exposure to lead, with time, and from worker to worker, is only very poorly known, although inreased health are ertainly lowered the exposure to lead during the last s of the exposure period. The shortest period of exposure giving a measurable lead onentration in the fingerbones was three Fig 2 Lead onentrations (,ug/g ± I SD) in phalanx and tibia. Br J Ind Med: first published as 1.1136/oem.37.2.19 on 1 May 198. Downloaded from http://oem.bmj.om/ on 13 July 218 by guest. Proteted by opyright.
In-vivo determination of lead in the skeleton after oupational exposure to lead. a, C C a- nui - 1 2 3 4 5 6 Exposure time Fig 3 Measured lead onentration in phalanx of subjets with different periods of oupational exposure. s. Figure 4 shows the lead onentrations in the skeleton and the blood for 15 workers, the periods of employment being roughly indiated in the figure. 15 1 a, 5 a E I- 15 1 5 5.L i 1 n I~ 15 Exposure time: 3-15 s a -T MA 16 3-1 *B 1 31-45 1 J, ~ I J 5 I I I _+~~ + + ++_ T *DO 5 1 15 2 Pb-on in blood,umol/l.1.1~~~~~~~~~~~~~~~~~ 2 3 4 Pb-on in blood,ugig Fig 4 Measured lead onentrations in phalanx and blood for oupationally exposed subjets. Total body burden of lead is estimated assuming that lead onentration in phalanx represents lead onentration in whole skeleton. E represents these values for non-oupationally exposed people. Indiated unertainty is due to ounting statistis. The mean blood lead onentration for men from the same part of Sweden but with no known oupational exposure to lead is 4,umol/l (range -2-9,umol/1).7 From lead onentrations in the skeleton derived from neropsy samples taken from 126 non-oupationally exposed Danes, the total body burden of lead has been estimated to be 22mg.8 Assuming that the lead onentration in the phalanx reflets the body burden, fig 4 indiates that even seven s after the end of exposure to lead there is no simple relation between the total body burden of lead and the blood lead onentration. Three subjets (A, B, and C) deviated from the rest of the group in having ratios between the lead onentrations in the skeleton and in the blood whih are two to three times greater than for the other subjets. Subjet A had been exposed to lead oxide dust for 43 s, while B had been highly exposed to the same dust during the first 2 s of his employment. During this period he had several times shown aute symptoms of lead poisoning, but for the last 2 s of employment his exposure to lead had been very low. Subjet C was exposed for 35 s, but the degree of his exposure annot be reliably estimated. The last of this group, (D), worked for 45 s, being mainly onerned with the melting of metalli lead. Figure 5 shows the variation in the blood lead onentration of A, B, C, and D after their exposure was disontinued. The rapid derease in the blood lead onentration may represent the washout of lead from the pools of soft tissue. The figure suggests that seven s after exposure had ended the blood lead onentration of these highly ontaminated people was dependent.c' 4. 3. 2k 1 Pb on in fingerbone Exposure time o Subjet pu/g O A 112 43 B 12 4 \ 87 35 'IO ~~~ D 3 4.5,......... 1 2 3 4 Time after end ot exposure 5 6 7 8 9 -Jig 5 Measured blood lead onentrations at different times after end of oupational exposure. Mean value and range of lead onentration in blood for nonoupationally exposed subjets is indiated. 111 Br J Ind Med: first published as 1.1136/oem.37.2.19 on 1 May 198. Downloaded from http://oem.bmj.om/ on 13 July 218 by guest. Proteted by opyright.
112 15,ug/day Daily exhange rate 2 A12 1 Io 65 x12 Blood -3 Skeleton liver r21-1 x 1 musle 2 x1 A21 A12 161 x 12 N ( -4 t A1 A21*.4 x 1 xj1* 729 x 1-3 Fig 6 Two-ompartment model used to desribe kinetis of lead transfer between skeleton and blood. Two different exhange rates A21 and A21* for transfer of lead from skeleton to soft tissue pool orrespond to ly turnover rates for skeleton of 3 5 % and 1-5 % respetively. more on their normal daily intake of lead than on the total body burdens. This result an also be predited using a two-ompartment model desribing the kinetis of lead in the body as shown in fig 6. Compartment 1 represents the blood, liver, and musles and ompartment 2 the skeleton. The exhange rates A12 (from ompartment I to 2) and A1o have been alulated assuming the steady state ondition desribed by the ICRP9 with 11 mg lead in the skeleton, 6-2 mg lead in the blood, liver and musles (of whih 1-4 mg is in the blood), and a daily absorption of 4 jug. Two different exhange 1 1 1 1 IP,A Skeleton A2 21 A21 SlZe-let-opnqn--oqupgtionaL Blood non -oupational 1 2 3 4 5 6 7 8 9 Year after end of exposure Fig 7 Lead onentrations in skeleton and blood at different times after end of oupational exposure as alulated from two-ompartment model. El represents mean value of measured blood onentration offive people having about 7,ug/g in their skeletons seven s after end of exposure. Calulated lead onentrations in skeleton and bloodfor non-oupationally exposed people are also given. A21' Ahigren, Haeger-Aronsen, Mattsson, and Shlitz rates (A21) from the skeleton to the blood have been used, one being taken as the mean skeletal turnover rate of 3-5 % a 1 and the other as the turnover rate for femur-like bones, 1P5 % a.1 Using these alulated exhange rates and a daily absorption of 15,ug, it an be shown that after 55 s the blood will reah a value of -43,tmol/I (-9,ug/g) and that the skeleton will ontain between 2 and 3,ug/g (fig 7). These values are in good agreement with the orresponding values for non-oupationally exposed subjets in Sweden. These results further indiate the validity of the alulated exhange rates. The same kineti model has been used to predit the derease in the lead onentration in the blood after the end of a long oupational exposure. For this alulation, the lead onentration in the skeleton at the end of the exposure was taken to be 8,ug/g, with a blood lead of 3-4,Lmol/l ( 7 )ug/g). These values are typial for the most highly exposed subjets in our study. Our kineti model predits that seven s after the end of exposure the lead onentration in the skeleton will be 68-74,ug/g and in the blood between 1 9 and 1-2,umol/l, assuming transfer rates of lead from the skeleton to the blood of 3-5% and 1-5% a respetively. In fig 7 the mean value (EO) is shown for the measured blood lead onentration for five people having about 7,tg/g in the skeleton seven s after the exposure. The blood lead onentration that originates from the skeletal pool is very dependent on the exhange rate from the skeleton. The low onentrations in the blood of these formerly oupationally exposed subjets indiates an exhange rate from the skeleton of 1-2% a. This low exhange rate an be explained by the fat that most of the lead in the skeleton of the subjets was aquired during the first part of their 3- exposure, when lead exposure in the fatory was very intense. The lead in the more easily exhangeable parts of the skeleton may therefore already have been released. The large amounts of lead stored in the skeletons of these subjets represents a potential risk should it be suddenly released. In table 2 we have alulated the blood lead onentration after a release of 1-1% of the lead in the skeleton during one, six, or 12 months. The alulations have been arried out using the kineti model in fig 6 with A12 = and with values for A21 and A1 as given in table 2. The alulated blood level after a sudden release is high in omparison with the limit value for oupational exposure, 3-4,umol/l ( 7,ug/g). These values are theoretial alulations and may represent an upper limit for lead onentration in blood. The exponential inrease in lead exretion in urine with inreasing Br J Ind Med: first published as 1.1136/oem.37.2.19 on 1 May 198. Downloaded from http://oem.bmj.om/ on 13 July 218 by guest. Proteted by opyright.
In-vivo determination of lead in the skeleton after oupational exposure to lead Table 2 Calulated blood lead onentrations after release ofpart of total skeletal lead. Calulations have been arried out for a person with an initial lead onentration of 7 pg/g in the skeleton, and 14 pmol/l in the blood, with an exretion rate (Alo) of -65 x 1-2 a day Perentage of Period during Exretion rate Maximal alulated total lead whih the lead A21 (a day) blood lead released is released (d) onentration (,umol/l) 1 3-33 ± 1-3 2-5 5 3-167 ± 1-2 7.3 1 3 33 ± 1-2 12-8 1 18-556 ± 1-3 8 2 1 36 278 1-3 54 onentration of lead in the blood noted by Shutz and Skerfving6 indiates that the exretion rate, A1o, inreases with inreasing blood lead onentration, thus lowering the real blood lead onentration. Conlusion The onentration of lead in the skeleton of 22 oupationally exposed men was determined in vivo in the phalanges and ompared with the blood lead onentration seven s after their exposure to lead had ended. In three subjets, the onentration of lead along the finger and in the tibia was also studied. No statistially signifiant variation of the onentration along the phalanx bone ould be deteted. Fifteen of the 22 men had a lead onentration in the phalanx exeeding the detetion limit of 2,ug/g, and the onentration was found to inrease with the length of employment in the lead fatory. No simple relation between the onentrations in the blood and skeleton was found. A two-ompartment model desribing the kinetis of lead in the body has been used to verify the measured lead onentrations in the blood and skeleton several s after the end of an oupational exposure. The results of this work indiate the neessity of arrying out in-vivo measurements of skeletal lead onentrations in order to have a valid estimate of the total body burden of lead and hene information on the potential risk assoiated with a partiular degree of lead ontamination. This investigation was supported by grants from the Swedish Work Environment Fund. Referenes 113 Barry PSI, Mossman DB. Lead onentrations in human tissues. Br J Ind Med 197;27:339-51. 2 Shroeder HA, Tipton IH. The human body burden of lead. Arh Environ Health 1968;17:965-78. 3 Ahlgren L, Liden K, Mattsson S, Tejning S. X-ray fluoresene analysis of lead in human skeleton in vivo. Sand J Work Environ Health 1976;2:82-6. 4 Ahlgren L, Liden K, Mattsson S. In vivo X-ray fluoresene analysis of lead in human bone. Digest of the ninth Nordi meeting on linial physis, Gothenburg, Sweden. 1977:155-7. Ahlgren L, Mattsson S. An X-ray fluoresene tehnique for in vivo determination of lead onentration in a bone matrix. Phys Biol 1979;24:136-45. R Shutz A, Skerfving S. Effet of a short heavy exposure to lead dust upon blood lead level, erythroyte S-aminolevulini aid dehydratase ativity and urinary exretion of lead, 3-aminolevulini aid and oproporphyrin. Sand J Work Environ Health 1976;3:176-84. 7 Haeger-Aronsen B, Shutz A. Zin protoporphyrin in the blood-a new variable for assessment of the influene of lead. Lakartidningen 1978;75:3427-3. 8 Grandjean P. Bly i danskere, en historisk-toksikologisk undersogelse. Copenhagen: Trykteknik A/S, 1973. (Summary in English.) 9 International Commission on Radiologial Protetion. Report of the task group on referene man. Oxford: Pergamon Press, 1975. 1 Rivera J. Human bone metabolism inferred from fall-out investigations. Nature 1965 ;27:133-2. Br J Ind Med: first published as 1.1136/oem.37.2.19 on 1 May 198. Downloaded from http://oem.bmj.om/ on 13 July 218 by guest. Proteted by opyright.