Document MG1xO64o3kgx299EmKLyjBa2z

INTESTINAL ABSORPTION OF LEAD L.8. Karhausen Association Euratom-CEA Eon tenay-aux-Roses France Our lot is cast in a perilous age ... But where shall we fly to escape from east winds and dogdays, from pesti lences that come and pestilences that dp not come, from ships that bring us yellow fever and quarantines that nourish and cultivate it, from cattle diseases that can only be exterminated by exterminating the cattle, from lead pipes for water contrived to kill every body except the animalcules, from fraudulent food and deleterious physic, from drugs that are poisonous and poisons that are adulterated, from infections patients whose pulses must be felt with a pair of tongs and their chest explored with a tarred stethoscope ? Jacob Bigelow Address at the Fourth National Quarantine and Sanitary Convention i860 N40774 INTESTINAL LEAD ABSORPTION \T _ 1 Lead has been known to be toxic for more than two thousand years and it continues to be the cause of numerous episodes of chemical intoxication of industrial and accidental origin as well as it remains a main problem of public health. Lead Ingestion Lead ingestion results from the contamination of food during its production, its prepration and during the storage of food ; air contamination from motor exhaust gases may deposit dry particles of lead on foods, or on other objects wich may be brought to the mouth especially in children. Drinking water may be rich in lead from the use of lead piping, particularly when combined with the use of a water-softener wich usually decrease the pH of water. Finally there are multiple circumstances which may increase the amount of ingested lead : glazed ceramic often release much lead when used for keeping acid beverages like fruit juices or cola-drinks. The paint covering of most pencils is a healthhazard for pencil ehewers (40). Some popular brands of toothpaste are potentially hazar dous as a result of the lead content in the tube, the tube coating and in the toothpaste itself (22bis). Lead intake ;some values Kehoe, 1$6l (26) (2?) Imamura, 1957 (22) Jaworowski, 1967 (23) Kehoe, 1962 (30) Patterson, 1965 (39) Schroeder, 1961 (43) Schroeder, 1968 (42) parry Howells, 1971 (37) Thompson, 1971 (47) Bogen, 1968 (3) Mean (mg/d) 0.30 0.15 (0.09-0.18) 0.30 (0.05-2.00) 0.33 (0.23-30) 0.33 O.I-O.54 0.44 0.27 0.27 The values for lead intake are obtained by different methods, measu rement of the actual content of foods, measurement of the lead content of feces with appropriate corrections to get back to intake e The amount ingested in fodd and in water has been studied by some authors : Lead content (mg/d) O.28O 0.410 Food (mg/d) 0.260 0.400 Water (mg/d) 0.020 0.010 Schroeder, 1968 (42) Patterson, 1965 (39) DUP050058874 Total lead content (mg/d) 0.093-0.187 V-S Food Water 0.089-0.127 0,004*0*033 (water) 0.027 (tea) Imamura, 1957 (22) Lead Intake : infants Lead intake in infants without evidence of pica, have been estimated by measuring fecal output of lead. If one uses an absorption coeffi cient of 35 % instead of 8 % as for adults, one gets approximately the following values : References Kehoe, 1953 (24) Baritrop, 1967 () Chisholm, 1956 () Fecal output 0.080 mg/d 0.123 0.132 Estimated intake 0.100 mg/d O.I5O O.I65 GASTROINTESTINAL ABSORPTION OF LEAD Methods of study Diftrent methods have been used to estimate the fraction of absorbed lead wich would correspond to the f^ factor of iCRP. 1. Intake and output studies (16) One measures the amount of lead in urine.and in stools and one calculates the ratio urinary lead fecal + urinary lead This method supposes 'that the equilibrium is reached i.e. that intake output that no lead is accumulated in the body that the amount of lead lost through sweat & hair is negligible Measurement of oral intake (food & water) as well as fecal output permits to calculate the ratio fecal output oral intake Finally, the urinary excretion of lead is a rough estimate of the amount absorbed. These differents methods do not allow to estimate how much lead is actually absorbed, how much is actually secreted by the liver & how much is secreted by the intestinal wall. It permits only to konw the net result of absorption and secretion. 2. Measurement of f^ with Pb212 (20) An oral dose of Pb212 is administered and fecal and urinary excre tion are measured. 3. Measurement of the amount excreted via the bile (V) Measurement of the elimination of Pb21Q in the bile after IV injection of 100 jug of lead DUP050058875 4. Measurement of intestinal wall excretion of lead Measurement of fecal elimination of BaD after IV administration of a carrier-free tracer dose, taking account if necessary of bile excretion Urinary lead as an estimate of absorbed lead Usually 5-10 % of dietary lead is absorbed and the following values have been reported for lead in 24h urine output : Lead in 24h urine collection O.lPJO mg (0 #010-0.0.80) (0.00 -0.290) 0.030 (0.010-0.080) 0.044 (activation analysis) Authors Parry Howells (37) Horiuchi (17) Kehoe (30) Kopito (35) In children the 24h urinary excretion in subjects presumably free from pica was 0.026 mg Webster (4.9) Incidentally it may be mentioned that an international study cf uri nary lead concentration was published by Kehoe at al, 1940 (25) wich showed the following values : (see also (12)) Country France Mexico USA Germany Lead concentration (ug/liter) 0.020 0.022 0.029 0.027 In UK, we find a value of 0.050 (42), but the methods, the authors 8c the time being different it is difficult to draw firm conclusions. j* Anyway, lead concentration in urine in the absence of values for urinary volumes should be interpreted with caution. Urine and fecal lead as an estimate of absorbed lead Holtzman (16) calculates the ratio of the daily urinary output (which he gives as 0.057 mg), to the fecal output ; * 0.037/0.53 = 0.11. However, by accoating for the atmospheric lead contribution of 0.009 mg/d, we obtain, says Holtzman, f* * 0.08, The intake proposed by the author is 0.46 mg/d. The value calculated corresponds to the 8 % of ICPR (21). It seems preferable to me to use the ration U/U + F. This methodcan be criticized since it does not take account of sweat and hair loss which in basal conditions amount to about 0.1 mg/day. | DUP050058876 Absorbed fraction in adults V-4 Authors Method Kehoe (29) Kehoe (30) Patterson (39) Schroeder (42) Imamura (22) Hursh (20) Harrison (15) Horiuchi (17) (18) ihompsDn(47) Fairhall (IT) 0.10 Intake output 0.08-0.10 Same soluble (in water) : 0.10 insoluble (food) ! 0.05 0.10 0.20 to 0.40 Intake output 0.01, 0.08 & 0.16 Absorption of Pb212 0.06, 0.16 & 0.18 Absorption of Pb2Q3 0.06, 0.16 8c 0.18 Intake output 0.06 Intake output 0.08 intake output : Food-feces/ food 0.13 Intake-output : U/U + F 0.01 to 0.03 Intake-output Absorbed fraction in infants and children The date are very scarce* It is generally know that the absorbed fraction is higher in infants, for heavy metals like Sr or Ca. Moreover it has been shown that the absorbed fraction in the intestine is increased in the early stages of life (36) Applying the Intake-output method to Kehoe * s data (24), yields a ratio of 0.25 If calculated by age there are some variations but it does not seem there is an age trend* Variability of the absorption fraction 1 There are many factors of variation of the absorption fraction* Some are known, others are suspected or may reasonably be supposed to modify the intestinal absorption. Such studies must take account of the magnitude of salivary excretion of lead which adds up to the oral intake (41) } > There are good reasons to believe that some of the factors which regulate Ca (& Sr) absorption may play a role* it is not unlikely that the amount of vitamin D, of phosphate & of some complexant agents like inositohefcaphoephate in food are relevant* It has been shown that rats and men on a low Calcium diet absorb more lead, since their fecal output of lead was higher and the urinary output was lower than the controls* It is likely that pregnant women, growing children parti cularly in populations showing dietary deficiencies, are critical groups with a higher risk of increased absorption (45) (11). ! DUP050058877 TABLE 1 Belevant Physical Properties of Metallic Lead and Certain of Its Alloys and Compounds Material Melting Pouring Boiling point, tempera- point, 0C ture, C C Sc lubility. in 100 ml cold water hot water Acid Alkali Metallic lead (common) 327.4 362 152$ Insol lead acetate (anhydrous) 280 kk.3 lead arserate (Insecticide) mono, di, meta and ortho Decomp Insole Insol. 221.20 HN03 Acetic SI .sol. Sol. Sol. lead bromide |ead carbonate p(white lead) 373 Decomp. 916 0.4$$ Insol. 4.71 Insol. Sol. Sol. Sol. Sol. lead chloride /lead chromate (chrome yellow) $01 m lead fluoride 8$$ jad nitrate tW:'lid sesquioxide led oxide (red lead) monoxide l^d suboxide dioxide peroxide) |*d silicate glazes) id sulfate Decomp, at 470 Decomp, at 360 Decomp. at $00 888 Decomp. Decomp. at 290 766 1170 |d sulfide 1114 id tetraethyl - 130 id tetramethyl - 27.$ 9$4 0.673 Decomp. 0.0000$ 1290 0.064 Decomp. 38.8 Decomp Insol. Decomp. Insol. 0.0017 Insol. Insol. t Insole 3.34 138.8 Sol. Sol. (Insol. acetic) Sol. HNO3H2SO4 Sol, Decomp. Spl. Insol. Sol. Insol. Sol. Sol, Sol. Sol. Insol. Sol. Sol, Insol. Sol. Sol. Sol. Decomp. Sol. * 200 * 110 0*0028 Essentially insole Insol. Insol 0.00$6 Insol. Insol. Sol .cone`. f insol. acetic Sol. Insol. Insol. Insol. Inso l * Insol. ------ --------- DUP050058878 Lead seems to be more readily absorbed from water than from food and Patterson (39) suggests the following factos : Absorbed fraction Food Water 2 $ 10 Some physiological factors are probably relevant, like the fraction secreted by the liver and the fraction secreted by the intestinal wall (19). There have been some contradicting reports in the literature as whether bile or intestinal wall are a more significant pathway of lead excretion. In sheep and in rats, about 8 to of the IV dose of lead acetate was excre ted throug the biliary tract which was about hundred times more than through the walls of the intestines (4) Two human subjects who received an IV injection of Pb212 excreted 0.29 & 0.23 Per cent dose in the 0 to 48 h fecal collection (20). Inhalation of particulate lead-212 was followed by a fecal excretion of 2-3 % in the 0 to 72 hours collection, while inhalation of lead-212 as a vapour showed an excretion of 37 # during the same period. It is not known whether the swallowed fraction differed in the two situations (4l), Constipation increases the absorbed fraction (24). The chemical form of the ingested lead is probably very important. Table 1, taken in part from Kehoe (30) shows the some of the chemical and physical chemincal characters of the main compounds of lead. However, solubility is not the whole story. For instance, lead sulfide is not absorbed in the lungs but is readily absorbed in the gastro intestinal tract if gastric acidity is present. Lead sulfide is converted to lead chloride which is readily abosrbed before it reaches the colon, where it reverses back to sulfide. The lead compounds which are absorbed are those which are soluble or which are converted to absorbable compounds. Experimental ingestion of lead arsenate showed that the arsenate was completely broken down in the body and the lead was poorly absorbed : 1.3 % to 3*2 % of the ingested lead appeared in the urine (11). The following compounds are readily abosrbed through the gastrointes tinal tract : Lead acetate, Lead chloride, Lead oxide & Lead tetraethyl ; less soluble but still absorbed are othe compounds like Chromate, Sulfide, Sulfate and Carbonate* Nothing is known regarding the mechanism of absorption trough the intestinal wall# Is there a protein which limits the amount absorbed (like irons) ? What is the role of complexants and ligands ? All the konwn biological ligands contain dissociable protons which may be replaced by heavy metals in complex formation, Metal binding by biological ligands is not specific ; the order of affi nities and the relative concentrations of the different ligands only count. DUP050058879 On the other hand, chelation may be highly specific and introduces exceptions to the rule of relative affinities (38). The effect of lead on epithelial membranes is restricted, as fas as we know, to the affect on the cells of the renal tubule, where it produces a pattern of aminoaciduria which is rather specific (aluninuria) (38). The load of lead may probably raise the value of the absorbed fraction (50) (.2.6) (27) (28) (29). The size of the lead particles which is very important in inhalation is probably irrelevant in the case of oral intake. Are lead blood levels a good index of absorbed lead ? ( 6) (1,3) (48) Blood levels of methylmercury are a reasonable good estimate of chronic exposure but the same is not true for lead. Ninety per cent of blood lead is fixed on the red cells (bound by the ligands of the cell membrane or rattached on the surface as a phosphate colloid). A small amount of lead is within the red blood cells themselves * Anyway, the lead which is fixed on the erythrocytes is not in equili brium with the plasma. Plasma lead is probably of two types, like calcium, a diffusible and a non-diffusible form. The diffusible fraction is very small, contrary to calcium* It probably accounts for the lead excreted : through the kidneys. Blood levels show some correlation with absorbed lead in the case of exposure to inorganic lead. No such relation has been shown in the case of organic lead exposure. It must be kept in mind that blood level is not the most sensitive index of the total body burden of lead. Are, there other qualitative indices of lead absorption ? ! It is not the purpose of this discussion to develop the systemic effects! of lead absorption. jStill one should mention that lead once abosrbed into the body, interferes with some blood enzymes and with the sinthesis of hemoglobin. There is a correlation between blood lead levels and the blodd activity of d-aminolevulinic acid dehydrase while the enzyme substrate 3-amino levulinic acid accumuiates in the urine. There is a close relationship between the latter's amount in the urine and the blood levels* Urinary excretion of coproporphyrin may also be used as an estimate of absorbed lead. I t 't; DUP050058880 ORAL VERSUS RESPIRATORY INTAKE OF LEAD Today in the USA, high levels of blood lead indicating high intake of lead are most frequently found in ghetto children. However more recently, high blood levels or slightly increased levels have been described in middle-class children. Geochemical evidence suggests that human lead levels may well have been a factor of 100 below current levels (39) and that almost half of the increase occurred within the last 50 years, i.e. since the intro duction f tetraethyl lead into gasoline in 1923* In the USA, 25 % of the total lead used consisted in gasoline additives in 1968. The average content of the earth's crust is about 10 to 15 ppm, but the dust which deposits in cities contains about 1 which is near the concentration in lead ores. Lead in urban air ranges between 1 to 10 jug per m3, but near highways it reaches 40 jug per m3. In Los Angeles at peak traffic hours it reaches 71*3 jug per m3. Moreover urban air lead & lead in rainfall correlates with local gaso line sales. Goldsmith & Hexter have estimated that about 30 to 60 # of the body burden of lead comes from the atmosphere. Lead inhaled Inhaled lead depends mostly on atmospheric lead. Lead intake is distributed as follows : Oral intake food : fluids s Amount inhaled 0.4o mg 0.01-0.09 mg Respiratory urban (20 m3/dt 1*3T/m3) rural (20 m /d, 0#05T/ra3) 0.01-0.04 mg 0.026 mg 0.001 mg Reference (23) (23) (20) (23) (20) (34) (34) Absorption of inhaled lead Respiratory absorption of lead is sure to be a significant factor, as shown by recent studies suggesting that blood lead levels parallel the atmospheric concentrations of lead in the area where the exposed popu lation lives (10), Inhaled lead in industrial surroundings is more readily absorbed than ingested lead. The absorption coefficient is about 25 to 60 %, (10) (23) (26) (30) (39) (42) 04). DUP050058881 V-* The following table is obtained from Patterson (39) ) Substance Intake/d Pb concen*tration Pb ingested fPb/'d Fraction absorbed Food 2 kg 0.2 ppm 400 0.05 Water 1 kg 0.01 ppm 10 0.1 Urban air 20 m3 1.3Vm3 26 0.4 Rural air 20 m3 0,05'r/m3 1 0,4 Tobacco smoke 30 cigarettes 0.8r/icig. 24 0.4 Pb absorbed TPb/d 20 1 10 0,4 10 Pb ingested means lead getting entrance into the gastrointestinal or the respiratory tract. If we accept 0.030 to 0.04Q mg of lead as the amount absorbed through the intestine, it appears that if the air in urban communities contains 1.5 to 2.0 jig per m3, an adult would retain and absorb 0.015 to 0.020 mg of lead, assuming 50 % absorbed and respiring 20 m3. These values may show some variation : absorbed fraction may be low, but air concentration may be higher (9.8 pg/m3) in Paris in 1966* It should be remarked that blood lead shows a definite correlation with lead in the air (and presumably with lead intake through the respira tory tract) 5 however if lead in the air Increases by hundred times * blood lead only doubles. What does all this mean for children ? It seems there is some suggestive epidemiological evidence that inhaled lead is an important path of intake. Exposure to 6 /ig/m3 results in increased coproporphyrin excretion. In Sofia, it has been shown that a group of 48 children aged 5 to 7 years excreted more coproporphyrin than a control group in the suburbs. It seems that the amount of inhaled lead is lower than the amount absorbed from oral intake. However the above values are only represen tative and it is clear that in many situations absorbed lead from the atmosphere may equal that absorbed from the gastrointestinal tract. ? One may of course object that the above values for absorbed fraction was obtained with the traditional methods of toxicological investiga tions, i.s. by means of balance studies or Of epidemiological studies relating blood levels to atmospheric lead concentration. Horiuchi 09) administered RaD acetate intratracheally intoguinea-pigs and observed that 11 % was eliminated through the kidney, 34,8 % through the stools and 31 % remained in the body. It means that about 77 % was absorbed through the respiratory tract.. Size of the particles and respiratory absorption Particles of less than Ip diameter are better retained and 50 % of the lead is absorbed. Particles which have more than 2 jx diameter are depo sited on the mucous lining and are transported through the mucociliary flows to the esophagus and swallowed. DUP050058882 V-l* Seventy five per cent of exhaust gases particles carrying lead are less than 0.9 P diameter , which suggests that most of the atmospheric lead from automobile exhausts is deposited in the respiratory tract which is a system with a high absorption coefficient* Is research needed and what research ? The first question is ; is further research necessary ? Do we know enough on the problem of intestinal absorption of lead for the purposes of public health and preventive medicine ? Any new research should use radionuclides and apply a metabolic model fitted to the data. If such is the case, one should thereafter study the effects of diffe rent factors on the different parameters : growth, gastric acidity, dietary composition and phytine content, intake of phosphate and calcium, chemical form of the ingested lead compound, dietary deficiencies. A second aspect which needs to be clarified is to know what happens to the lead compounds once ingested ? What are the effects of the different biological ligands and complexants present in the lumen of the GI tract ? Finally, the mechanism of lead transfer through the intestinal wall is unknown. Extrapolation of data from rodents, or dogs is questionable in view of the known species differences of the metabolism of bone seeking radioisotopes* DUP050058883 v-it Summary 1# Oral intake of lead amounts to about 0.44 mg in adults and 0.15 mg in children. 2. The coefficient of intestinal absorption is around 0.08 in adults and 0.25 in children. However the value for children is questionable and needs confirmation. 5. Absorption in the intestine depends on known factors (chemical form, dietary Ca) and presumably significant factors (vitamin D intake, diet composition, load of lead, gastric acidity ...). 4. Inhaled lead contributes a significant part to lead intake. It varies mainly with the atmospheric concentration of lead, the size of the particles and some physiological factors. 5. Further studies, if necessary, should concentrate on the fractions absorbed and secreted at the different levels of the GI tract, on the effect of biological eomplexants and ligands in the intestinal lumen and on the mechanism of transfer through the intestinal wall. DUP050058884 1. P.L. Altmar and D.S, Dittmer, Editors (1968), Metabolism, Fed. Am. Soc. Exptl. Biol., Belhesda 2. D. Barltrop and N.J.P. Killala (1967)1 Faecal excretion of lead by children. Lancet (II) : 1017-1019 3 Bogen, D.C. Stable Lead Investigations at HASL, pp, 4-12, in Pro ceedings of the Annual Bioassay and Analytical Chemistry Meeting, A. de G. Low-Beer, Ed., USAEC Contract W-7405~eng~48. 4. N. Castellino, P. Lamanna and B. Grieco (1966), Biliary excretion of lead in the rat, Brit. J. Industr. Med. 23- 237-239 $. J. J. Chisolm, dr. and H.E. Herrison (1956), The exposure of children to lead. Podia tries, _l8 : 943-957 6. Clarkson, T.W. Epidemiological and Experimental Aspects of Lead and Mercury Contamination of Food, Fd. Cosmet. Toxicol., 9 : 229-243, 1971 7. E.C. Cogbill & M.E. Hobbs (1957)* Transfer of Metallic Constituents of Cigarettes to the Main-Stream Smoke, Tobacco Science, 144 : 68-73 r;\ 8* 8. N. Cohen & G. Parry Howells (1969), A brief Review of Pb210 Metabo lism, HSL-204 : 81-97 9. Elkins, H.B. (1959) The Chemistry of Industrial Toxicology, Wiley & Sons, New York 10. J.R. Goldsmith and A.C. Hexter (1967), Respiratory exposure to lead ; Epidemiological and experimental dose response relationships, Science 158 : 132-134, 11. L.T. Fairhall (1938), The absorption and excretion of lead arsenate in man, Public Health Reports : 1231-1245. J 12* J.R. Goldsmith and A.C. Hexter (1968), Lead intake from food and from the atmosphere, Science, 159 5 1000. 13. V.F. Guinee (1972), Lead poisoning, Amer. J. Med. 2 : 283-288. 14. T.J. Haley (1966), Chronic lead intoxication from environmental contamination Myth or Fact ? Arch. Environ. Health 12 t 761-78$ 15. C.E, Harrison, T.E.F. Carr, A. Sutton, E.R. Humphreys & J. Rundo (1969), Effect of Alginate on the Absorption of Lead in Man, Nature ; 224 : III5-III6 16. R.B. Holtzman (1961), Critique on half lives of lead and RaD in the human Body, Radiological Division Semiannual Report July through December i960, ANL-6297 s 67-80. DUP050058885 V~ti 17* K. Horiuchi and I. Takada (1954), Studies on the industrial lead poisoning* I* Absorption* transportation * deposition and excretion of lead, I* Normal limits of lead in the blood* urine and feces among healthy Japanese urban habitants, Osaka City Med* J. 1 : 117-125. ~ 18. K. Horiuchi* I. Takada. (195*0, I* Absorption* transportation, deposition and excretion of lead. I. Normal limits of lead in the blood, urine and feces among healthy Japanese urban habitants, Osaka City Med. j J, : 117-125 19* K. Horiuchi & S. Horiguchi (1968), Studies on the Industrial Lead Poisoning. 1 Absorption, Transportation and Excretion of Lead. (5) An experimental Study with radioactive Lead (Radium D)* Osaka City Med. J., 4 : 159-1?0 20. J.B. Hursh and J. Suemela (1968), Absorption of ^2Pb from the gastrointestinal tract of mail,Acta Radiol. : 108-120. 21. International Commission on Radiological Protection (1959)* Recommanda'tions of the International Commission on Radiological Pro tection, Report of Committee II on Permissible Pose for Internal Radiation, ICRP Publication 2, Pergaraon Press (19S0). " F" ' 22. Y. Iraamura (1957), Studies on industrial lead poisoning, I. Absor ption, transportation, deposition and excretion of lead, 3 An experimental study of lead intake in human being, Osaka City Med. J. 2 : 167-194 22 International Herald Tribune* (June 28* 1972), Best selling U.S. bis Toothpaste found potentially hasardous, p. .25* 23. 2. Jaworowski, (1967)* Stable and Radioactive Lead in Environment and Human Body, Nuclear Energy Information Center, Review Report N 29, Warsaw. 24. R.A. Kehoe, F. Thamann and J. Cholak (1933), On the normal absorb ption and excretion of lead, IV. Lead absorption and excretion in infants and children, J * Ind. Hygiene Jj5 i 301-305 i 2$. R.A. Kehoe, J. Cholak and R.V, Story (1940), A spectrochemical study of the normal ranges of concentration of certain trace metals in biological materials, J. Nutr. Ijj) : 579-592 26. R.A. Kehoe (1961), The metabolism of lead in man in health and disease, j. The normal metabolism of lead, J. Roy, Inst. Public Health 24 : 81-97. 27. R. Kehoe (1961) The metabolism of Lead in Man in Health and Disease, II The Metabolism of Lead under abnormal Conditions, J. Roy, Inst. Public Health 24 : 101-121 28. R. Kehoe (19-61) The Metabolism of Lead in Man in Health and Disease II (part 2) The Metabolism of Lead under abnormal Conditions, J. Roy Inst. Public Health, 24 : 129-143 29. R. Kehoe (1961) The Metabolism of Lead in Man in Health and Disease Present Hygienic Problems relating to the Absorption of Lead, J. Roy Inst, Public Health, 24 : 177-203. DUP050058886 v-n H.A. Kehoe (1962), 11 Industrial Lead Poisoning", Chapter XXVI, pp, 941*985, in Industrial Hygiene and Toxicology. Interscience Publishers, New-York, Vol, II, Second revised edition. Edited by F.A. Patty 1* Kehoe, R. (1964), Normal Metabolism of Lead, Arehiv. Env. Health, 8 s 232-235 Xehoe, H. (1964), Metabolism of Lead under abnormal Conditions, Arch. Env. Health, 8 : 235-243 R, Kehoe (1968), Lead Intake from Food and from the Atmosphere, Science, 159 s 1000 R. Kehoe, (1969), Toxicological Appraisal of Lead in Relation to the tolerable Concentration in the ambient air, J. Air Pollut Control Assoc., 19 * 690-700 35 L. Kopito and H. Schwachman (1967), Determination of lead in urine by atomic absorption spectroscopy using coprecipitation with bismuth, J. Lab. Clin, Med. 22. * 326-332 K. Kostial, I. Simonovic & M. Pisonic (1971), Lead Absorption iron the Intestine in the Nexborn Rats, Nature, 235 : 564. G. Parry-Hove11s, Report of the Standard Man Task Group for the Internation Commission of Radiological Protection, W.S. Snyder, Chairman, personal communication H. Passow, A. Rothstein & T.W. Clarkson (1961), The general Pharma cology of the heavy Metals, Pharmacological Reviews, 13 : 185-224 C.C. Patterson, (1965), Contaminated and natural lead environments of man, Arch. Environ, Health 2X 5 344-360. j. Pichirallo (1971), Lead Poisoning : Risks Ibr Pencil Chewers ? Science, 1?3 : 509-310. D.V. Pooker, A.C. Chamberlain, D. Newton (1969), Uptake of radio active lead following inhalation and injection, Bit. J, Radiol. 42 : 457-466 H.A. Schroeder and I. H. Tipton (1968), The human body burden of lead, Arch, Environ. Health : 965-978 H.A. Schroeder and J.J. Balassa (1961), Abnormal trace metals in man : Lead, J, Chron. Dis. j4 :408-425 N.I, Sax (1964) Dangerous Properties of Industrial Metals, Rheinhold Publishing Compagny, New York KM Six & R.A. Goyer (1970), Experimental Enhancement of Lead Toxi city by Tow dietary Calcium, J. Lab. Clin. Med., 76 ; 933-942 Special Article (1971), Medical Aspects of Childhood Lead Poisoning, Pediatrics, 48 ; 464-468. DUP050058887 -r 47. j.A. Thompson (197l)i Balance between Intake and Output of Lead in normal Individuals Brit* J* Industr. Med* 28 : 189-194 48. Tsuphiya, K. Some industrial Problems in Absorption and Excretion s of Metal ions, in Intestinal Absorption of metal ions. Trace Elements & Radionuclides, Skoryna, S.C. Waldron, E., Ed. Pergamon, 1971 49. S.H, Webster (194l), The lead and arsenic content of urines from 46 persons with no known exposure to lead or arsenic, U.S. Public Health Report : 1953-1961 50. Working Group on Lead Contamination (1965), Survey of Lead in the Atmosphere of three Urban Communities, U.S Department of Health, Education & Welfare, n PB 170 739* DUP050058888