lead. If such would be the case, and as we have seen, this is not unlikely, the remaining amount of blood lead would be very small.

As mentioned earlier, in the United States the average concentration of lead in blood is 0.25 ppm, yet the threshold for classical lead poisoning has been said to be 0.8 ppm (48, 62, 63), and most recently has been proposed to be 0.5 ppm (64). In view of the ready response of blood lead levels to changes in rates of lead ingestion and absorption, one may ask why is there so narrow a margin of safety and the body so poorly defended if natural blood levels are about 0.2 ppm.

Experimental checks could be made by determining, through ingestion over relatively long periods, the toxic thresholds of mercury, thallium, and bismuth in the blood of animals, together with natural levels, since contamination by these metals from industrial sources is a problem that can be handled with some certainty. The peculiar affinity of lead for the membranes of red blood cells in the contaminated state might also be utilized as a check. Although investigators have studied the distribution of lead between serum and the formed elements of the blood as a function of increasing concentration of lead, starting with the contaminated state, no one has studied what happens as a function of decreasing amounts of ingested lead over long periods. This could be done in humans by simply searching for and studying cases of low blood lead levels. Controlled animal studies of lead would be difficult because of contamination problems, but it would be interesting to follow the distribution of mercury, thallium, and bismuth between serum and formed elements of the blood in animals as a function of increasing metal concentration, starting at natural levels and ending at toxic thresholds and seeing whether the distribution changes with concentration.

CHRONIC LEAD INSULT

The latest view of existing lead states in this country, officially sanctioned by the United States Department of Health, Education and Welfare, is that they “*** are well within the presently accepted range of lead levels for humans and are not significant in terms of a threat of the occurrence of lead intoxication***" (95). This view has prevailed in the state and the Federal Public Health Services for decades. It is based upon a threshold for damage concept which has been applied to industrial workers, and which involves the axiom that a worker must be either perfectly healthy or classically intoxicated with lead but cannot be neither. This is a seriously unfortunate situation for the following reasons.

An average level of 0.25 ppm of lead in the blood of our population fails by an order of magnitude to provide an adequate margin of safety even from classical lead poisoning when the crudely significant range of lead levels in our population lies between 0.05 and 0.4 ppm and the threshold for acute lead intoxication lies in the uncertain range of 0.5 to 0.8 ppm.

The above acceptance of typical lead levels in humans in the United States today as normal and therefore safe or natural is founded on nothing more than an assumption that these terms are equivalent. No acceptable evidence exists which justifies this assumption. On the contrary, as this report shows, such an assumption may be in gross error. The 0.25 ppm level of lead in the blood, which has been and is still regarded with ill-founded complacency, actually seems to lie between an average natural level of about 0.002 ppm and an acute toxic threshold of 0.5 to 0.8 ppm. This suggests clearly and strongly that the average resident of the United States is being subjected to severe chronic lead insult. The threshold for damage concept, as it applies to lead, is an ill-defined opinion unsupported by any evidence. Our knowledge to date about classical lead poisoning is largely clinical and morphological, and it usually applies to combinations of rates and periods of lead adsorption which yield blood lead concentrations exceeding 0.5 to 0.8 ppm. Changes in cell morphology which result from lead poisoning are widespread throughout the body, but most are not recog nized as being specific for lead and nothing is known of the mechanisms which cause them. The evidence is therefore permissive for some lesions or altered cell metabolisms, which either have not yet been identified or have not been assigned to exclusive nonlead origins, to result from lead absorptions which correlate with blood lead concentrations considerably above a natural level, but less than 0.5 ppm, i.e., with typical levels of 0.2 ppm which now exist in the United States.

Economic pressures for expedient exposure to lead should be opposed and brought into suitable balance by pressures for healthy populations unafflicted by

lead poisoning. These latter pressures will originate from a thorough understanding of mechanisms of lead metabolism, but this kind of knowledge does not exist today and will be acquired slowly. It would be tragic if, many decades from now, it were recognized from accumulated evidence that large segments of populations in ours and other nations had suffered needless disability and torment because early warning signs like those recognized in this report went unheeded.

This crucial problem has been a matter of concern to some toxicologists. Monier-Williams, for example, said "It cannot be emphasized too strongly that in discussing the amount of lead which may be considered as negligible in food, consideration of the toxic limits, so far as these are defined by the appearance of symptoms of poisoning, is beside the point, and tends to obscure the real question. What we want to know is not so much the toxic limit, as the safe limit, if indeed any limit, however small, for a cumulative poison can be regarded as safe. We cannot assume that there is a sharp dividing line between what is obviously toxic, giving rise to lead colic or other symptoms, and what is completely harmless. In all probability there is a range of lead intake between these two extremes in which some effects, however slight, are produced upon metabolism, effects which, clinically, may be difficult or impossible to detect or to ascribe to their real cause ***” (9).

The basic danger involved in lead pollution is not simply that, in common with some other kinds of technological filth, it may bring agony into our existence and shorten our lives. The course of human events is determined by the activities of the mind. Intellectual irritability and disfunction are associated with classical lead poisoning, and it is possible, and in my opinion probable, that similar impairments on a lesser but still significant scale might occur in persons subjected to severe chronic lead insult. It has recently been maintained, on the basis of experimental evidence from animals (96), that pathologic and histologic changes of the brain and spinal cord together with functional shifts in the higher nervous activity are induced by exposures to atmospheric lead concentrations corresponding to those exposures now experienced by dwellers in most large American cities.

These Russian investigations have been disparaged and discounted (97) by the same type of person who is largely responsible for the views outlined above in the opening paragraph of this section. Economic and ideological factors together with experimental uncertainties are involved here, but it cannot be denied that these kinds of investigation should occuply a legitimate and vital place in the research programs sponsored by the United States Health Service. Their absence is conspicuous and disquieting.

Civilizations and nations have waxed and waned. The Romans conquered Britain and Gaul partly to satisfy their demands for lead, which they used on a large scale to store and distribute potable liquids, for ointments and medicine, and to sweeten wines. In the last century, lead has been used in notoriously unhealthy ways on vast scales in Germany, France, and England. It is interesting and not at all unworthy to consider how the course of history may have been and is now being altered by the effect of lead contamination upon the human mind.

SUMMARY

There are definite indications that residents of the United States today are undergoing severe chronic lead insult. The average American ingests some 400 g of lead per day in food, air, and water, a process which has been viewed with complacency for decades. Geochemical relationships and material balance considerations show that this ingestion of about 20 tons of lead per year on a national basis is grossly excessive compared to natural conditions. It probably originates from the 1 million tons of lead dispersed yearly in such forms as lead alkyls, lead arsenates, and food can solder, and from the many millions of tons of lead accumulated throughout past decades and stored as paints, alloys, piping, glazes, and spent ammunition. Existing rates of lead absorption are about 30 times higher than inferred natural rates, yielding body burdens of about 200 mg Pb/70 kg body, and blood concentrations of 0.25 ppm Pb, which values are about 100 times above inferred natural levels of 2 mg Pb/70 kg body and 0.0025 ppm Pb in blood. Existing blood lead concentrations have for decades been regarded as natural, although it is well known that the average value lies only slightly below threshold levels for classical lead poisoning which are 0.5 to 0.8 ppm Pb. It appears that the following activities deserve serious

consideration and support: defining natural and toxic lead levels with greater care than in the past, investigating deleterious effects of severe chronic lead insult investigating the dispersion of industrial lead into food chains; elimination of some of the most serious sources of lead pollution, such as lead alkyls, insecticides, food can solder, water service pipes, kitchenware glazes, and paints; and a reevaluation by persons in positions of responsibility in the field of public health of their role in this matter.

(The preparation of this report was made possible by support from Atomic Energy Commission contract AT (04-3)-427 and United States Public Health Service grant No. AP0027. Dr. Harriet Hardy. Massachusetts Institute of Technology, and Prof. Arie Haagen-Smit. California Institute of Technology, provided essential source material for this work. work is based upon studies carried out earlier by T. J. Chow and M. Tatsumoto.)

REFERENCES

This

(1) Chow. T. J., and Patterson, C. C.: The Occurrence and Significance of Lead Isotopes in Pelagic Sediments, Geochim Cosmochim Acta 26:263, 1962.

(2) Tatsumoto, M., and Patterson, C. C.: "The Concentration of Common Lead in Sea Water," in Geiss and Goldberg (eds.): Earth Science and Meteoritics, Amsterdam: North-Holland Publ., 1963, chap. 4.

(3) Tatsumoto, M., and Patterson, C. C.: Concentration of Common Lead in Some Atlantic and Mediterranean Waters and in Snow, Nature 199:350, 1963. (4) Chow, T. J.; Murozumi, M.; and Patterson, C. C.: Concentration Profiles of Lead and Barium in the Atlantic Near Bermuda, to be published.

(5) Murozumi, M.; Chow, T. J.; and Patterson, C. C.: Concentration Profiles of Lead and Silicon in Greenland Snow, to be published.

(6) Kehoe, R. A.; Thamann, F.; and Cholak, J.: On the Normal Absorption and Excretion of Lead: I. Lead Absorption and Excretion in Primitive Life, J Industr Hyg 15:257, 1933.

(7) Tilton, G., et al: Isotopic Composition and Distribution of Lead, Uranium, and Thorium in a Precambrian Granite, Bull Geol Soc Amer 66:1131, 1955.

(8) Analytical Methods Committee: The Determination of Lead, Analyst 84:127, 1959.

(9) Monier-Williams, G. W.: Trace Elements in Food, New York: John Wiley & Sons, Inc., 1949.

(10) Warren, H. V., and Delavault, R. E.: Observations on the Biogeochemistry of Lead in Canada, section 4, Trans Prog Soc Canada 54:11, 1960.

(11) Cannon, H. L., and Bowles, J. M.: Contamination of Vegetables by Tetraethyllead, Science 137:765, 1962.

(12) Poldervaart, A.: Chemistry of the Earth's Crust, Special Paper, Geol Soc Amer 62: 119, 1955.

(13) Mason, B.: Principles of Geochemistry, New York: John Wiley & Sons, Inc., 1958.

(14) I.C.R.P. Committee II: Report of I.C.R.P. Committee II on Permissible Dose for Internal Radiation, 1959, Health Physics 3: 1, 1960.

(15) U.S. Bureau of Mines Mineral Yearbook, 1962, and earlier years. (16) Ca at the surface of the earth's crust is 2.7 weight % (reference 12). (17) Ge in earth's crust is about 1 ppm.

Onishi, H.: Notes on the Geochemistry of Germanium, Chem Soc Japan Bull 29: 686, 1956; and El Wardani. S.A.: On the Geochemistry of Germanium, Geochim Cosmochim Acta 13: 5, 1957.

(18) Sn in earth's crust is about 4 ppm.

Onishi, H., and Sandell, E. B.: Meteoritic and Terrestrial Abundance of Tin, Geochim Cosmochim Acta 12: 262, 1957; and Barsokov, V. L.: The Geochemistry of Tin, Geochemistry, 1957, p 41.

(19) Rankama, K., and Sahama, T.G.: Geochemistry, Chicago: University of Chicago Press, 1950.

(20) Hg in earth's crust is about 0.5 ppm.

Goldschmidt, V. M.: The Laws of the Geochemical Distribution of the Elements, The Abundance of the Elements 9, Norske Videnskaps, akad. Oslo, Mat. Nat. Klasse. No. 4, p 1, 1937.

(21) Tl in earth's crust is about 1 ppm.

Shaw. D. M.: The Geochemistry of Gallium, Indium, Thallium: A Review, Physics Chem Earth 2: 164, 1957.

(22) Bi in earth's crust is about 2 ppm.

Noddack. I., and Noddack. W.: Die geoghimie des rheniums, Z Phys Chem A 154: 207. 1931: and Preuss, E.: Beitrage zur Specktralanalytichem Methodik:

II. Bestimmung von Zn, Cd, Hg, In, Ti, Ge, Sn, Pb, Sb, und Bi durch fractionierte distillation, Z Angen Mineral 3: 8, 1940.

(23) Ge has not been detected as a microconstituent of the body. Rosenfeld, G.: Metabolism of Germanium, Arch Biochem 48: 84, 1954 (Reports less than 0.4 ppm of rat tissue. If human body burden is about 20% of this upper limit, it equals about 6 mg Ge/70 kg.)

(24) Bone concentrations determine upper limit of tin body burden. Using bone and muscle values reported by Kehoe, R. A.; Cholak, J.; and Story, R. V.: A Spectrochemical Study of the Normal Ranges of Concentration of Certain Trace Metals in Biological Materials, J Nutr 19: 579, 1940; and remaining tissue values reported by Tipton (reference 14) the body burden of tin is about 12 mg Sn/70 kg. As a result of high exposure to industrial sources, one-half of this burden can be assigned to industrial sources.

(25) Hg has been found in the body to the extent of about 0.002 ppm. Stock, A.: Mercury in the Tissues of Man, Z Biochem 316: 108, 1944.

(26) Tl and Bi have not been detected as microconstituents of the body. Using upper limits reported by Tipton (reference 14), 3 mg T1/70 kg and 2 Mg Bi/70 kg are obtained as upper limits, and if human body burdens are about 20% of these values, they are 0.6 Mg Tl and 0.4 Mg Bi in a 70 kg body.

(27) Turekian, K., and Kulp, J. L.: The Geochemistry of Strontium, Geochem Cosmochim Acta 10: 245, 1956.

(28) Heide, F., and Christ, W.: On the Geochemistry of Strontium and Barium, Chem Erde 16: 327, 1953.

(29) Bowen, H. J. M., and Dymond, J. A.: Strontium and Barium in Plants and Soils, Proc Roy Soc 144: 355, 1956.

(30) McLester, J. S.: Nutrition and Diet in Health and Disease, Philadelphia : W. B. Saunders Co., 1940.

(31) Rivera, J.: Stable Strontium in Tri-City Diets, Health and Safety Laboratory Fallout Program Quarterly Summary Report, US AEC Health Safety Lab 131: 230, 1962.

(32) Sr-90 in Human Diet in the United Kingdom 1958, Agriculture Des Council Radiobiol Lab, Department 1, Her Majesty's Stationary Office, 1959. (33) Grummitt, W. E.: "Strontium and Barium in Bone and Diet," in Radioactive Fallout From Nuclear Weapons Tests, A. W. Clement, Jr. (ed.) New York: Proceedings of Conference at Germantown, Md, 1961, book 2, p 376.

(34) Aarkrog, A.: Environmental Radioactivity in Denmark, RISO, Department 41, 1962.

(35) Henderson, E. H.; Parker, A.; and Webb, M. S. W.: Barium in Bones and Foodstuffs, UKAEA, Research Group Chemical Division Woolwich Outstation, AERE-R-4035, 1962.

(36) Thurber, D. L., et al: Common Strontium Content of the Human Skeleton, Science 128:256, 1958.

(37) Sowden, E. M., and Stitch, S. R.: Estimation of the Concentrations of Stable Strontium and Barium in Human Bone, J Biochem 67:104, 1957.

(38) Sherman, H. C.: Chemistry of Food and Nutrition, ed 8, New York: Macmillan Co., 1952.

(39) Nicolaysen, R.; Eeg-Larsen, N.; and Malm O. J.: Physiology of Calcium Metabolism, Physiol Rev 33:424, 1953.

(40) Comar, C. L., and Wasserman, R. H.: "Strontium," in Comar, C. L., and Bronner, F. (eds.): Mineral Metabolism, on Advanced Treatise, New York: Academic Press, Inc., vol 2, pt A, 1964.

(41) Langham, W., and Anderson, E. C.: Environmental Contamination From Weapon Tests: Entry of Radioactive Fallout Into the Biosphere and Man, US AEC, Health Safety Lab 42:282, 1958.

(42) Bureau of the Census: Statistical Abstract of the United States, US Department of Commerce, Bureau of the Census, US Government Printing Office, 1963.

(43) Bureau of Census: United States Census of Population: 1960, Department of Commerce, Bureau of the Census 1, US Government Printing Office. (44) Wright, F. W.; Hodge. P. W.; and Langway, C. C.: Studies of Particles for Extra Terrestrial Origin, J Geophys Res 68:5575, 1963.

(45) Reed, G. W.; Kigoshi, K.; and Turkevich, A.: Determinations of Concentrations of Heavy Elements in Meteorites by Activation Analysis, Geochim Cosmochim Acta 20:122, 1960.

(46) Patterson, C.: The Pb207/Pb206 Ages of Some Stone Meteorites, Geochim Cosmochim Acta 7:151, 1955.

(47) Monier-Williams, G. W.: Public Health Reports, Ministry of Health, Her Majesty's Stationary Office, 1938.

(48) Kehoe, R. A.: The Metabolism of Lead in Man in Health and Disease: The Harben Lectures, 1960, J Roy Inst Public Health 24:81-97, 101-120, 129–143, 177-203, 1961.

(49) Schroeder, H. A., and Balassa, J. J.: Abnormal Trace Metals in Man: Lead, J Chronic Dis 14:408, 1961.

(50) Chambers, L. A.; Foster, M. J.; and Cholak, J.: A Comparison of Particulate Loadings in the Atmosphere of Certain American Cities, read before the Third National Air Pollution Symposium, Pasadena, Calif, 1955.

(51) Public Health Service: Air Pollution Measurement of the National Air Sampling Network, Public Health Service publication 978, 1962.

(52) Durum, W. H.; Heidel, S. G. ; and Tison, L. J.: World Wide Runoff of Dissolved Solids, IASH Commission of Surface Waters, publication No. 51:518, 1960. (53) Turekian, K. K., and Kleinkopf, M. D.: Estimates of the Average Abundance of Copper Manganese, Lead, Titanium, and Chromium in Surface Waters of Maine, Bull Geol Soc Amer 67 :1129, 1956.

(54) Kleinkopf, M. D.: Spectrographic Determination of Trace Elements in Lake Waters of Northern Maine, Bull Geol Soc Amer 71:1231, 1960.

(55) Kehoe, R. A.; Cholak, J.; and Largent, E. J.: The Concentrations of Certain Trace Metals in Drinking Water, J Amer Water Works Assoc 36:637, 1944. (56) Braidech, M. M., and Emery, F. H.: Spectrographic Determination of Minor Chemical Constituents in Various Water Supplies in the US., J Amer Water Works Assoc 27:557, 1935.

(57) US Public Health Service: National Water Quality Network, Annual Compilation of Data, US Public Health Service publication 663, 1959-1962.

(58) Langham, W. H.: "Radioisotope Absorption and Methods of Elimination: Relative Significance of Portals of Entry," in Caldecott, R. S. and Snyder, L. A. (eds.): Symposium on Radioisotopes in the Biosphere, Minneapolis: University of Minnesota Press, 1960.

(59) Alimentary absorption of water-soluble lead is about 10% (reference 48). Food lead is less readily absorbed, and the value may be closer to 5%, a value which has been observed for soluble barium (reference 41).

(60) The concentration of lead in American tobacco has decreased from a high of about 130 ppm during the early 1950's to an estimated 20 ppm today. These values are inferred from arsenic values.

Satterlee, H. S.: The Problem of Arsenic in American Cigarette Tobacco, New Eng J Med 254:1149, 1956; Weber, J. H.: Arsenic in Cigarette Tobacco, J Sci Food Agriculture 8:490, 1957; Guthrie, F. F.; McCants, C. B.; and Small, H. G., Jr: Arsenic Content of Commercial Tobacco, 1917-1958, Tobaco Sci 3:62, 1959; Tobacco 148:20, 1959.

Most of the lead originated from lead arsenate insecticides, and its decrease was caused by the substitution of organic for metallic insecticides. The transfer factor from cigarette to smoke is 4%.

Coghill, E. C., and Hobbs, M. E.: Transfer of Metallic Constituents of Cigarettes to the Main-Stream Smoke, Tobacco Sci 69:24, 1957.

(61) Brecher, R., et al: The Consumers Union Report on Smoking and the Public Interest, New York: Consumers Union, Inc., 1963.

(62) Hamilton, A., and Hardy, H. L.: Industrial Toricology, New York: Paul B. Hoeber, Inc., a division of Harper & Brothers, 1949.

(63) Cantarow, A., and Trumper, M.: Lead Poisoning, Baltimore: William & Wilkins Co., 1944.

(64) Egli, R., et al: Die verbreitung der chronischen bleivergiftung in Akkumulatoren und bleifarben fabriken, Schweiz Med Wschr 87:1171, 1957.

(65) Hofreuter, D. H., et al: The Public Health Significance of Atmospheric Lead, Arch Environ Health 3:568, 1961.

(66) California State Department of Public Health: Health Effects of Atmospheric Lead in Los Angeles, preprint, part of program for survey of lead in three urban communities by the Working Group on Lead Contamination, composed of representatives of the U.S. Public Health Service, the California State Department of Public Health, the Ethyl Corporation, the E. I. du Pont de Nemours & Co., Inc., the G.M.C. Technical Center, the A.P.I., and the Kettering Laboratory, University of Cincinnati.

(67) Krause, D. P.: Stable Lead in Human Bone, ANL-6398, pp 77, 1961. (68) Bruderold, F., and Steadman, L. T.: Distribution of Lead in Human Enamel, J Dent Res 35:430, 1956.