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August 21, 1990 Lead CAS #7439-92-1 (1) Molecular Weight: 207.2 (1) Criteria and Standards EPA. Group B2 Carcinogen Cancer Potency Factor (CPF): None established due to uncertainty and importance of other health effects at low levels (2) Reference Dose (RfD): No threshold level established, since very low levels are known to cause adverse health effects, especially in children. Current risk assessment methodology involves calculating the pr;Pcted population distribution of blood lead levels associated with various exposure scenarios. (2) (15) Maximum Contaminant Level Goai: 20 Ecg/I, proposed (drinking water) (2) Ma)dmum Contaminant Level: 50 ,gg/1, pro:.aulgated (drinking water) (2) Ambient Water Quality Criteria: 50 ltg/1, based on ingesting aquatic organisms and drinking water (2) Ambient Water Quality Criteria: 50 gg/l, adjusted for drinking water only (2) Acute Intake Chronic: 1.4 x 10'3 mg/kg-day, oral (3) 4.3 x 10'4mg/kg-day, inhalation (3) Health Advisory: 20 µg/day (lifetime, drinldng water) (3) American Conference of Government Industrial Hygienists: Threshold Limit Value-Time Weighed Average: 0.15 mg/m3, airborne inorganic dust and fumes, as Pb (4) r821h!0.006

Centers for Disease Control: Elevated Blood Lead Level for Children: 25 pg/dl (associated with a blood erythrocyte protoporphyrin level of 35 µg/dl or greater (11) Chenlista and Uses Lead is a heavy metal that exists in one of three oxidation states 0, +2, and +4. Metallic lead and common lead minerals are relatively insoluble in water, however, organic lead compounds are water soluble (5). Metallic lead is used as a major component of many alloys such as solder, print-type metal, and many bronzes. Lead compounds also have a wide variety of uses as paint pigments, in storage batteriesm, and in ceramics (1). Phannacaldnetics Appro;cimate3y 8% of the lead ingested by human adults is thought to be absorbed. Absorption rates in children are higher, for example, children are thought to absorb as much as 45-50% of lead in foods (8). This absorption level is generally higher in animals or humans that have been fasting. The absorption rate for human infants is approximately 50%. Lead is also absorbed after inhalation; reported pulmonary deposition rates as range from :30% to 50%. After being absorbed by the body, most lead compounds dissociate, yielding inorganic lead. Tetrac;tbyl and tetramethyl leads are dealkylated to tri- and di- alkyl compounds which are more tcWc than the parent compounds. In human adults, under conditions of long-term exposiu°e, approximately 95% of the total amount of lead found in the body is localized in the skeleton. In the blood, most- lead is found in the erythrocytes. Lead also readily crosses the placenta. In most species, the main route of excretion is through the bile. However, in babo=s and humans, urine appears to be the primary route (5,8). T2 2 r821h!0.006

At high exposure levels, lead produces encephalopathy, gastrointestinal effects, anemia, nephropathy, and electrocardiographic abnormalities. These effects are primarily seen in acutely poisoned children or in adults from occupational exposures. Lower level exposure to lead in all humans can affect the synthesis of heme, which, in turn, affects metabolic processes and decreases vitamin D circulating in the body, reducing calcium stability in the body. Inhalation of airborne lead is generally a minor exposure pathway for children, but ingestion of lead-containing particles in dust can contribute significantly to children's lead exposure (11). Effects of great concern from low level lead exposure include neurobehavioral decrement and growth rF tardation in infants exposed prenatally and children exposed postnatally. . Based on blood lead concentrations, no clear threshold for neurobehavioral effens has been shown from low level lead exposures resulting in blood lead levels < 10-15 ug/dI (9). Increased blood pressure from low level lead exposure in middle aged men has been observed following low level lead exposures. An effects threshold for increased blood pressure in men has not been defined; several studies have failed to find one while one longitudinal study suggests of threshold of 30 {tg(dl (16). T'2 3 r821h!0.006

Animal In experimental animals, effects associated with exposure to lead and lead compounds are similar to those in humans. Observed effects have included weight loss, decreased survival, and neurological, cardiovascular, and Iddney effects. Several studies with experimental anina,als suggest that lead may interfere with the immune response (5). Can:inog_enicity Humen The EPA has classified lead as a Group B2 Carcinogen. Data concerning the carcinogenicity of lead in humans are inconclusive. There is no evidence that oral exposure produces a tumor response. Although studies of occupational inhalation exposure have produced largely negative results, increases in cancer of the digestive organs, respiratory system and kidney have been reported (2,6,19) Aninial There is evidence in experimental animals that lead salts are carcinogenic in both mice and rats, resulting in tumors of the lQdneys after either oral or parenteral administration. Most of the investigations found a carcinogenic response only at the highest -dose. It is unclear how this effect relates to the lower level exposures typical to humans. Metallic lead, lead oxode. ;md lead tetralkyls have not been tested adequately. No studies are available on the carcinogenic potential of lead compounds via inhalation (2). N ~ Mutagenici ~ ~ ~ In a number of DNA structure and function assays, lead has been shown to affect the ~ molecular processes associated with the regulation of gene expression. Lead acetate induces ~ T2 4 r821h!0.006

cell transformation in Syrian hamster embryo cells and enhances the incidence of simian adenowirus induction. Lead oxide demonstrates a similar enhanced adenovirus induction. Under certain conditions, lead compounds may induce chromosomal aberrations in vivo and in tis sue cultures. One study showed a relationship between sister chromatid exchange and lead exposure in exposed workers (2). Repnyluctive Effects In exp,crimental animals, various non-teratogenic reproductive effects have been observed including developmental delays, decreased fertility, and fetotoxicity. No reproductive effects from human oral exposure to lead have been reported; however, occupational inhalation exposures have been linked to altered testicular function, increases in spontaneous abortion, premature delivery, and early membrane rupture (5). Basis tor Lead Criteria The classification of lead as B2, probable human carcinogen, is based on sufficient animal data • nd insufficient human data. Ten rat bioassays and one mouse assay showed statistically significant increases in renal tumors with dietary and subcutaneous exposure to several soluble lead salts. The most characteristic cancer response is bilateral renal carcinoma, however; there is some evidence of multiple tumor sites (2). Cance:r risk due to exposure to lead involves many uncertainties, such as age, health, nutritiicnal state, body burden and exposure duration which influence the absorption, release and excretion of lead. In addition, current knowledge of lead pharmacokinetics indicates that an estimate derived by standard procedures would not truly describe the potential risk. Therefore, the EPA does not currently recommend a specific cancer potency factor (2). The water quality criteria of maximum contaminant level goal (MCLG) is based on neurological effects of lead in infants and adverse effects associated with blood lead levels T2 5 r821 h! O.00b

of 15 i!tg/dl. Using a conversion factor of 6.25 to convert from blood lead concentrations to drinldng water lead concentrations and an uncertainty factor of 5, the MCLG of 20 ug/l was proposed (2). The Centers for Disease Control (CDC) has defined an elevated blood lead level for children, which reflects excessive absorption of lead, as a confirmed concentration of lead in wihole blood of 25 pg/dl or greater (11). This level is based on several studies. For example, a study of children living near a lead smelter found an erythrocyte protoporphyrin (EP) response at blood lead levels ranging between 10 and 20 jLg/dl. Although the biologic threshold for lead toxicity, based on an EP response, is thus less than 20 µgJdl, CDC set the criteria for screening based on several additional factors including acceptability, cost- effectiveness, and the feasibility of effective intervention and follow-up. Thus, the CDC- recommended intervention lead level is 25 pgidl, associated with an EP level of 35 ug/dl or greater. The CDC is currently reviewing the blood lead level of concern; the guideline is expected to be revised downward, but it is unclear whether CDC will consider the distinction between blood lead levels associated with prenatal, and, hence, maternal exposures and those associated with post-natal exposures. (17). Risk characterization of lead exposure generally involves using mathematical models to predict blood lead levels that will result from any given range of lead uptake rates. These models allow blood lead levels to be related quantitatively to uptake rates and can provide estimates of the frequency distribution of blood lead levels associated with any given uptake lead e;irposure scenario. The Integrated Uptake/Biokinetic (ItJBK) Model, developed for of the U.S. Environmental Protection Agency, accepts either monitoring data or estimated values for the levels of lead in various media. The model predicts mean levels of lead in blood, bone, liver, and kidney for children of different ages. These mean blood lead levels and an estimated geometric standard deviation for blood lead levels in humans can be combined to predict the frequency distnlb ution for population blood lead levels (15). T2 6. r821h!0.006

The Society of Environmental Geochemistry and Health (SEGH)'I'ask Force has developed a statistical model for estimating acceptable soil lead levels based on a desired mean and range of blood-lead levels. This model utilizes statistical relationships (developed from epidemiological analyses) to describe the contn'bution of soil sources and non-soil sources to blood lead. Unlike the IUBK model, the SEGH model does not require the use of assumptions for soil-dust transfer coefficients, soil ingestion rates, and lead bioavailability. Instead, the SEGH model utilizes site-specific environmental health data, such as individual- specific soil lead and blood lead levels, to determine the slope relationship between soil lead and blood lead in the population being studied (18). Once the slope relationship has been established, the frequency distnbution of blood lead levels associated with given soil-lead levels can be determined. T2 7 r821hI0e006

References (1) ACGIH, 1986. Documentation of the Threshold Limit Values and Biological Exoosure Indices. Fifth Edition. Cincinnati, OH: American Conference of (2) Governmental Industrial Hygienists. ISBN-0-36712-68-6. U.S. 'EPA (Office of Health and Environmental Assessment). December 1989. Integrated Risk Information System (IRIS). Washington, DC EPA/600/8-86-/032b. (3) U.S. EPA (Office of Emergency and Remedial Response). October 1986. Superfund Public Health Evaluation Manual. EPA 540/1-86/060. (4) ACGIH, 1988-87. Threshold Limit Values and Biological Exposure Indices for 1987- 1988. Cincinnati, OH: American Conference of Governmental Industrial Hygienists. ISBN: 0936712-72-4. (5) Clement Associates, September 27, 1985. Chemical, Physical and Biological Properties of Compound pound Present at Hazardous Waste Sites. Final Report for U.S. (6) EPA. U.S. EPA (Environmental Criteria and Assessment Office). 1984. Health Effects Assessment for Lead. Cincinnati, OH. Final Report. (7) U.S. EPA (Environmental Criteria and Assessment Office). 1980. Ambient Water QualitX Criteria for Lead. Cincinnati, OH. NTIS PB 81-117681. (8) Doull, J., C.D. Klaassen, M.O. Amdur; 1980. Casarett and Doull's Toxicology: The Basic Science of Poisons. Second Edition. Macmillan Publishing Co., Inc. ISBN 0- 02-330040-X. (9) Agency for Toxic Substances and Disease Registry (ATSDR). July 1988. The Natur= and Extent of Lead Poisoning in Children in the United States: A Report to Con ess. U.S. Department of Health and Human Services. (10) Agency for To)ac Substances and Disease Registry (ATSDR). February 19g8. Toxicological Profile for Lead. U.S. Public Health Service: Atlanta, GA. Draft for (11) Public Comments. January 1985 Preventine Lead Poisoning in Centers for Disease Control (CDC) . . , Your Children. U.S. Public Health Service, Atlanta, Georgia. N O (12) W W and Sherlock Smart Forbes J Patterson J G G I M R Moore Richards N N ~ . . , , . , , ., . , . . . . , . ~ T.S. Wi2son. 1982. "Assessment of Lead Intakes and Dose-response for a Population in Ayr Exposed to a Plumbsolvent Water Supply." Human Toxicol. 1: 115-122. ~ 1V ~ T2 8 r821h!0.006

(13) Cools, A., J.A. Salle, M.M. Verberk, and R.L. Zielhuis. 1976. "Biochemical Response of Male Volunteers Ingesting Inorganic Lead for 49 Days." Int. Arch. Occup. and Environ. Health. 38: 129-139. (14) Harley, N.H., and T.H. Kneip. 1985. "An Integrated Metabolic Model for Lead in Humans of All Ages " Final Report to the U.S. EPA, Contract No. B44899 with New York University School of Medicine, Dept. of Environmental Medicine, January 30, 1985. (15) U.S. EPA (Office Of Research & Development). March 1990. Technical Support Documentaion Lead. Cincinnati, OH. EPA ECAO-CIN-757. (16) U.S. EPA (Office of Air Quality Planning and Standards). March 1990. Review of The National Ambient Air quality Standards for Lead: Assessment of Scientific and Technical Information. Research Triangle Park, NC. (17) Steele, M.J. August 1990. Personal communication - Gradient Offices. Cambridge (18) MAe Gradient Corporation. August 15, 1990. Evaluation of Two Methods to Determine Cleanup Levels for Lead in Soil. Cambridge MA. (19) Selevan, S.G., P.J. Landrigan, F.B. Stern and J.H. Jones. 1985. "Mortality of Lead Smelter Workers." Am. J. Epidemiol. 122: 673-683 dV O ~ ~ ~ ~ ~ ~ ~ ~ T2 9 r821h!0.006