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PRIVILEGED AND CONFIDENTIAL ATTORNEY WORK PRODUCT Historical Understanding of Toxicity of Lead 9506710 R91395R.DOC Prepared for Hawley, Troxell, Ennis & Hawley P.O. Box 1617 Boise, ID 83701 Prepared by Gradient Corporation 44 Brattle Street Cambridge, MA 02138 November 1995 Gradient Corporation Table of Contents PRIVILEGED AND CONFIDENTIAL ATTORNEY WORK PRODUCT Page 1 Executive Summary................................................................................................................ 1 2 Brief History of Bunker Hill Superfund Site........................................................................6 2.1 Mining and Smelting......................................................................................................................... 6 2.2 Impacts of Air, Soil, and Dusts on Community Blood Lead Levels.............................................7 2.3 Cleanup Levels in Soil...................................................................................................................... 9 3 Toxicology of Lead............................................................................................................... 11 3.1 Basic Concepts of Toxicology........................................................................................................ 11 3.2 Health Effects Associated with Exposure to Lead.......................................................................12 3.2.1 Health Effects in Children - Current Understanding.......................... 12 3.2.2 Health Effects in Adults - Current Understanding.......................................................15 4 History of Toxicology of Lead.............................................................................................17 4.1 Introduction...................................................................................................................................... 17 4.2 History of Lead Use.........................................................................................................................18 4.3 Use of Medicinal Lead.................................................................................................................... 19 4.4 History of Lead Toxicity in Adults................................................................................................ 20 4.4.1 16th Century through 19th Century.............................................................................. 21 4.4.2 Early 20th Century.........................................................................................................22 4.4.3 1940s- 1950s................................................................................................................ 24 4.4.4 1960s...............................................................................................................................28 4.4.5 Recognition of More Sensitive Indicators of Lead Absorption................................... 30 4.4.6 Lead Regulations in the Workplace.............................................................................. 31 4.5 History of Lead Toxicity in Children........................................................................................... 35 4.5.1 Discovery of Childhood Lead Poisoning in Australia..................................................35 4.5.2 Childhood Lead Poisoning in the U.S........................................................................... 36 5 Risk Assessment for Lead and Dust in Soil....................................................................... 41 5.1 Historical Understanding of the Effect on Animals of Ingesting Lead in Soil........................... 41 5.2 Ingestion of Lead in Soil by Children.............................................................................................44 5.2.1 Scientific Literature........................................................................................................44 5.2.2 Centers for Disease Control.......................................................................................... 47 5.3 Modem Risk Assessment Methods................................................................................................ 48 5.3.1 Introduction to Risk Assessment...................................................................................48 5.3.2 IEUBK Model.................................................................................................................50 5.3.3 Risk Assessment for Soil Ingestion.............................................................................. 51 6 Conclusions........................................................................................................................... 54 References.................................................................................................................................56 9506710 R91395R.DOC Gradient Corporation 1 Executive Summary PRIVILEGED AND CONFIDENTIAL ATTORNEY WORK PRODUCT The purpose of this report is to describe the historical understanding by the medical and scientific community of the toxicity of lead, especially forms of lead associated with mining operations, in children and adults. This understanding is compared with the present day understanding of the potential impacts of lead in soil and dust on subtle neurobehavioral effects in young children. Such present day concerns are the primary basis for remedial actions involving soil removal and replacement at the Bunker Hill Superfund site. The ultimate question is whether Hecla Mining Company and Day Mines Inc., at the time the mines were operating and through the late 1970s, could have foreseen the present day human health concerns requiring consideration of remedial activities. The report consists of six sections: Section 2 provides a brief history of the site, including mining and smelting activities, the baghouse fire in 1973, and the subsequent human health studies, including the blood lead measurements in children. A brief summary of the health-based cleanup goals for lead in soil is also provided. Section 3 provides an overview of today's understanding of the toxicology of lead to provide a context for the subsequent chapters. As with all chemicals, a key issue in understanding the toxicology of a compound is assessing the dose response relationship. The nature, likelihood, and magnitude of any effect of a chemical is dependent upon the dose of the chemical. Today's concerns for effects of lead are for relatively subtle effects at low dose levels (as compared to historical concerns), in particular neurobehavioral changes in children not associated with overt toxicity. These dose levels can be ascertained by measuring the lead concentration in blood. In adults, the effects of concern today for lead exposure include impacts on reproduction and hypertension, which generally occur at higher dose levels than in children. Again, such effects are not associated with overt toxicity. Section 4 describes the historical understanding of lead toxicity. Since antiquity lead has been known to be associated with obvious toxic effects in humans as a result of high exposure levels. The importance of the dose response relationship for lead was recognized historically, as reflected by the fact that lead was used medicinally, indicating that all exposures were not believed to pose harm. The historic industrial hygiene and occupational health literature provides multiple examples of health effects in workers 9506710 R91395R.DOC 1 Gradient Corporation PRIVILEGED AND CONFIDENTIAL ATTORNEY WORK PRODUCT due to lead exposure. These effects were overt, such as wrist and foot drop, stomach pains, anorexia, constipation, and convulsions. Readily apparent clinical signs such as the presence of bluish black lead lines on the gums were also noted. Cases were associated in particular with industries in which exposure to lead was especially high, such as battery manufacture, enameling, pottery manufacture, and smelters. It was generally believed that mining, particularly of lead sulfide ores, was associated with lower frequency of lead poisoning as compared to other lead industries. Over time, the medical and scientific community began to be concerned about effects of lower levels of lead in workers. This is reflected in the development of guidelines and regulations for the air concentration of lead in the workplace. Under the Occupational Safety and Health Administration (OSHA), the acceptable level was 0.15 or 0.2 mg/m3 from 1945 to 1979, when it declined to 0.05 mg/m3. Under the Mining Safety and Health Administration (MSHA), the acceptable level is still 0.15 mg/m3. In children, lead poisoning, as indicated by obvious toxicity, was described at the end of the nineteenth century in Australia. Lead poisoning in children was recognized later in the U.S. Individual cases, often ending in death, became more common starting in the mid-1920s. As reported poisoning rates increased, some urban cities instituted screening programs in the 1950s. As a result, many more children were diagnosed with overt lead poisoning. Most investigators pointed to lead paint as being a key source for lead poisoning. Subsequently, the combustion products of tetra-ethyl lead gasoline were identified as potential contributors to lead exposure in young children. Until the late 1960s lead poisoning was viewed as a clinical disease. Prior to 1970 excess lead absorption was defined as having a blood lead level exceeding 60 pg/dl. In 1970, the definition of excess lead absorption was reduced to a blood lead level exceeding 40 pg/dl. In 1975, this level was reduced to 30 pg/dl and in 1985 it was reduced further to 25 pg/dl. A series of prospective studies of neurobehavioral effects of lead in children beginning in the 1980s and continuing to the present, resulted in concern for potential impacts of lead at lower blood lead levels today - on the order of 10 pg/dl. Section 5 describes the development of the risk assessment process for lead in soil. In the risk assessment process, the potential adverse health effects of chemical exposure on humans is described. Risk assessment is critical to remedial decisions at Superfund sites, since risk assessment constitutes the basis for first determining whether exposures at a site, as may result from inadvertent ingestion of lead in soil and dust by young children, are associated with the potential for unacceptable adverse effects and, if so, the 9506710 R91395R.DOC 2 Gradient Corporation PRIVILEGED AND CONFIDENTIAL ATTORNEY WORK PRODUCT nature and extent of remediation required to reduce those risks. This chapter discusses how soil was recognized as a potential exposure pathway for lead in soil and cattle by the 1950s; however, soil was not recognized as an exposure pathway in young children until recently - beginning in the mid-70s - and even today there is much debate about how much soil children ingest and the bioavailability of different forms of lead. Most of the concern for lead in soil focused on paint and automobile exhaust as sources of lead. In the mid- to late-1980s U.S. EPA developed a model - the Integrated Uptake Biokinetic Model - to quantify the impact of lead in different environmental media, including air, water, soil and dust, on blood lead levels in young children. This model has been used at the Bunker Hill Superfund site to develop a target level of lead in soil for purposes of remediation to reduce the fraction of young children potentially experiencing a blood lead level greater than 10 pg/dl. Section 6 provides the conclusions for this analysis. Based on the historical medical and scientific literature on the toxicity of lead, as corroborated by site-specific information, I conclude that: Historic concerns for effects of lead in adults and children were for overt symptoms, such as colic, wrist drop, convulsions, and even death. A dose response relationship for lead was recognized historically as reflected in the use of lead for medicinal purposes in certain circumstances. It was generally believed by the medical and scientific community that the potential for adverse effects of lead in workers varied among industries, with lead mining being of relatively low hazard. Even among lead mines, the potential for hazard varied with the type of ore with lead sulfide ores being least toxic, and the amount of dust - less dusty environments being of lesser hazard. Most of the initial concern for children was for children with pica ingesting lead in paint. Concern for lead exposure from tetra-ethyl lead in gasoline developed later. 9506710 R91395R.DOC 3 Gradient Corporation PRIVILEGED AND CONFIDENTIAL ATTORNEY WORK PRODUCT Today's concerns for effects of lead in young children are based on subtle neurobehavioral effects that occur at blood lead levels much lower than those associated with overt poisoning. There is still vigorous debate as to what dose levels cause such effects, how long the effects persist, and which children are at risk. The awareness of soil as an exposure pathway did not begin to be developed until the mid1970s and even today the amount of soil ingested and the bioavailability of different forms of lead continue to be a source of debate. The IEUBK model, which is used by EPA to quantify potential impact of lead in soil and dust on blood lead levels, was not developed until the mid-1980s and not applied to lead in soil until later. This model forms the basis of risk assessments for lead in soil and, hence, risk management decisions regarding remediation. Historically and through the present, it has been recognized that different forms of lead are absorbed differently into the body, resulting in different levels of risk for the same amount of lead. For lead in tailings from lead sulfide ore, the large particle size, form of lead (lead sulfide), and associated matrix limits the uptake of mining lead when ingested in soil or dust. Thus, at the time that Hecla Mining Company and Day Mines Inc. were operating their mines and continuing through the 1970s, the medical and scientific community did not begin to be aware of the potential concern for lead in soil - namely the potential for subtle neurobehavioral effects in children from inadvertent ingestion of lead in soil. Although some scientists suggested a relationship between soil ingestion and neurobehavioral effects in children in the mid-1970s, scientific consensus accepting the importance of ingestion of lead in soil did not occur until the 1980s. Our knowledge regarding these effects continues to develop as new research is conducted to elucidate which effects occur, how long they persist, and what doses cause them. It is, therefore, unreasonable to conclude that the owners and operators of the Hecla Mining Company and Day Mines Inc. could, at the time the mines were operating and 9506710 R91395R.DOC 4 Gradient Corporation PRIVILEGED AND CONFIDENTIAL ATTORNEY WORK PRODUCT through the 1970s have anticipated the human health concerns of today which require consideration of remedial activities at the Bunker Hill site. 9506710 R91395R.DOC 5 Gradient Corporation PRIVILEGED AND CONFIDENTIAL ATTORNEY WORK PRODUCT 2 Brief History of Bunker Hill Superfund Site 2.1 Mining and Smelting The Bunker Hill Superfund Site encompasses 21 square miles along Interstate 90 in the Silver Valley area of Northern Idaho (Figure 1-1). The Site encompasses the now inactive Bunker Hill Mining Complex and former metallurgical and smelting facility (the Bunker Hill Complex); the cities of Kellogg, Pinehurst, Smelterville, and Wardner; and the residential areas of Page, Elizabeth Park, and Ross Ranch. The Bunker Hill Site is part of the Coeur d'Alene Mining District located in northern Idaho and western Montana. Mining of galena (lead sulfide), zinc, silver, and other metals began in 1883. The first mill for processing lead and silver ores at the Bunker Hill Complex was constructed in 1886 and had a capacity of 100 tons of raw ore per day. Other mills subsequently were built at the Bunker Hill Complex and the milling capacity ultimately reached 2,500 tons per day. Before the widespread use of ponds to contain milling waste products, tailings were often disposed of in local surface waters. The South Fork of the Coeur d'Alene River (SFCDR) received tailings in this manner from numerous mines and mills in the Silver Valley both in and upstream of the Site. Dams constructed to retain tailings within the floodplain of the SFCDR, as well as subsequent flooding caused the tailings to be spread throughout the valley floor. From 1886 until 1917, the lead and silver concentrates produced at the Bunker Hill Complex were shipped to offsite smelters for processing. Construction of the lead smelter began in 1916 and the first blast furnace went online in 1917 producing lead, cadmium, silver, and alloys. Over the years, the smelter was expanded and modified. At the time of its closure in 1981, the lead smelter had a capacity of over 300 tons of metallic lead per day. Smelting operations resulted in fugitive and stack emissions of sulfur dioxide and metals which were deposited throughout the Site. By the early 1970s, emissions from the lead smelter and zinc plant, including sulfur dioxide, total suspended particulates, lead and other heavy metals, contributed significantly to contamination of the surrounding area. Although both the lead smelter stacks utilized a baghouse to capture particulates, stack 9506710 R91395R.DOC 6 Gradient Corporation  BUNKER HILL SUPERFUND SITE LOCATION IN IDAHO FIGURE 1.1 PRIVILEGED AND CONFIDENTIAL ATTORNEY WORK PRODUCT lead emission rates at the facility averaged from 10 tons per month to about 15 tons per month through the 1960s. After a September 1973 fire in the baghouse at the lead smelter main stack, air pollution control capacity was severely reduced and there was a dramatic increase in emissions. Total particulate emissions of about 25 to over 140 tons per month, containing 50 to 70% lead, were reported from the time of the fire through November 1974. During the first three months of 1974, approximately 73 tons of lead per month were emitted into the environment, with airborne lead levels as high as 30 pg/m3 on a monthly average being reported. The baghouse was reconstructed in mid-1974 (Interim Site Characterization Report, 1986). In 1977, a 715-foot stack was constructed at the lead smelter and a 610-foot stack was installed at the zinc plant in an effort to disperse contaminants from the complex. The smelter and other Bunker Hill Company activities ceased operation in late 1981. At that time, portions of the smelter complex were salvaged for various materials and scrap. There are currently no active mining or other mineral production activities at the Bunker Hill Complex. Over the past 10 years, a variety of wastes have been shipped offsite for salvage, recycling, and disposal. Thousands of tons of sludge, tailings, flue dust, and other wastes remain at the complex. Contamination at the Site was characterized during Remedial Investigation/Feasibility Studies (RI/FS) conducted from 1987 to 1992. Risks to human health were evaluated through the Risk Assessment Data Evaluation Report (RADER), October 1990, and the Human Health Risk Assessment (HHRA), May 1992. Risks to the environment were evaluated in the Ecological Risk Assessment (ERA), November 1991. 2.2 Impacts of Air, Soil, and Dusts on Community Blood Lead Levels Contaminated air, soils, and dusts have been identified as contributors to elevated blood lead levels in children living in the Populated Areas of Site. Environmental media concentrations of Site contaminants of concern in the Populated Areas are strongly dependent on distance from the smelter facility and industrial complex. Residential areas nearest the smelter complex have shown the greatest air, soil, and lead concentrations; the highest childhood blood lead levels; and the greatest number of the studies conducted in the last decade. 9506710 R91395R.DOC 7 Gradient Corporation PRIVILEGED AND CONFIDENTIAL ATTORNEY WORK PRODUCT Health effects of environmental contamination were first documented following the smelter baghouse fire in 1973 and associated smelter emissions in 1973 and 1974. The U.S. EPA-Silver Valley Lead Health Studies, conducted in 1974 and 1975, documented elevated blood lead levels in a significant number of children. In an August 1974 survey, 98% of the 1 to 9-year-old children living within 1 mile of the smelter were found to have blood lead levels in excess of 40 pg/dl. (A pg (microgram) is 1/millionth of a gram, which is about 1/10-millionth of a Hershey's chocolate kiss. The unit of dl (deciliter or 1/10 liter) is equal to about 1/2 cup of liquid. Therefore, 40 pg/dl is equal to about 4 millionth of a Hershey's kiss dissolved in half cup of liquid.) The frequency of abnormal lead absorption (defined at the time as greater than or equal to 40 pg/dl) was found to decrease with increasing distance from the smelter. Several local children were diagnosed with clinical lead poisoning and required hospitalization. Lead health surveys conducted throughout the rest of the 1970s confirmed that excess blood lead absorption was endemic to the community. Concurrent epidemiologic and environmental investigations concluded that atmospheric emissions of particulate lead from the active smelter were the primary sources of environmental lead that affected children's blood lead levels prior to 1981. Contaminated soils were also found to be a significant, secondary source of lead to children. Following lead poisoning incidents in 1973-1974, a number of activities were instituted to decrease lead exposures and uptakes in the community. Emergency measures were initiated to reduce the risk of lead intoxication. These measures included: chelation of children with blood lead over 80 pg/dl, purchase and destruction of as many homes as possible within 0.5 mile of the smelter, distribution of "clean" soil and gravel to cover highly contaminated areas, initiation of a hygiene program in the schools, and reduction of ambient air lead levels through reduction of smelter emissions. Street cleaning and watering in dustproducing areas occurred during several periods in the late 1970s. Subsidies were provided by the Bunker Hill Company to residents for the purchase of clean top soil, sand, gravel, grass seed, and water; thereby promoting some yard cover in the community. No action was required by Hecla Mining Company and Day Mines Inc. Following smelter closure in late 1981, airborne lead contamination decreased by a factor of about 10, from approximately 5 pg/m3 to 0.5 pg/m3. (The unit of 1 pg/m3 is approximately equal to 1/10millionth of a Hershey's kiss dispersed throughout a cube in which the length, width, and depth are all 3 9506710 R91395R.DOC 8 Gradient Coloration PRIVILEGED AND CONFIDENTIAL ATTORNEY WORK PRODUCT feet.) A survey conducted in 1983 of children's blood lead levels demonstrated a significant decrease in community exposures to lead; however, the survey also found that several children, including some bom since 1981, continued to exhibit blood lead levels in excess of recommended public health criteria. Accompanying epidemiological analyses suggested that contaminated soils and dusts represented the most accessible sources of environmental lead in the community. Childhood mean blood lead levels have continued to decrease since 1983. These decreases are likely related to a nationwide reduction in dietary lead; reduced soil, dust, and air levels in the community; intake reductions achieved through denying access to sources; and the increase in family and personal hygiene practiced in the community. The latter is reflected in the implementation of a comprehensive Community Health Intervention Program in 1984, which was initiated specifically to reduce the potential for excess absorption and minimize total absorption in the population. The program encourages improved hygienic (housekeeping) practices and parental awareness, and provides special consultation on individual source control practices such as lawn care. Total blood lead absorption among the community's children has been reduced by more than 50 percent since 1983. For example, the number of children in Silver Valley with blood lead levels of greater than or equal to 25 pg/dl dropped from 50 (14% of those tested) in 1983 to 1 (0.2% of those tested) in 1994 (PHD1, 1994). Similarly, the number of children in Kellogg, Smelterville, Page, and Wardner (combined) with blood levels equal to ore exceeding 10 pg/dl decreased from 104 (45% of those tested) in 1988 to 59 (19% of those tested) in 1994 - a decrease of 43% (PHD1, 1994). Blood lead monitoring conducted in 1994 indicated that approximately 20% of area children surveyed exceed the blood lead level of 10 pg/dl. 2.3 Cleanup Levels in Soil The Site was placed on the National Priorities List (NPL) in September 1983 (48 FR 40658 as cited in USEPA, 1992). RI/FS activities were initiated in late 1984 following completion of the 1983 Lead Health Study. 9506710 R91395R.DOC 9 Gradient Corporation PRIVILEGED AND CONFIDENTIAL ATTORNEY WORK PRODUCT A 1991 ROD addressed contaminated residential soil within the populated areas of the site, provided for the excavation of soil with lead contamination above 1,000 ppm at 1,800 residential properties with disposal at an onsite repository, which was subsequently capped; and provided clean soil and sod to residents. (The unit mg/kg is equal to ppm, or parts per million. One drop of water in a full bathtub is roughly equal to 1 part in a million.) The 1992 ROD addresses a final remedy of the nonpopulated areas of the site and those aspects of the populated areas not addressed by the 1991 ROD. Chemical-specific soil excavation goals, which are based on health-risk levels, include a goal for lead of 1,000 mg/kg. Soil will be stabilized to meet RCRA LDR standards prior to disposal. Clean replacement soil will contain less than 100 mg/kg lead. 9506710 R91395R.DOC 10 Gradient Corporation 3 Toxicology of Lead PRIVILEGED AND CONFIDENTIAL ATTORNEY WORK PRODUCT 3.1 Basic Concepts of Toxicology Perhaps the oldest and most fundamental concept in toxicology is the concept that there are no `harmless" chemicals; there are only harmless levels of chemical exposure. This idea was first articulated by Paracelsus, the father of toxicology, over 400 years ago: "All substances are poisons; there is none that is not a poison. The right dose differentiates a poison and a remedy" (Paracelsus, 1567; as cited in Amdur et al., 1991) Although all chemicals are toxic at high doses, chemicals are an integral part of our environment. Our bodies are made of chemicals, and we are in constant contact with chemicals. We must breathe, drink, and eat chemicals in order to live. The human species has survived because it has maintained its level and frequency of exposure to chemicals within safe limits. As our ability to detect more subtle effects has evolved, our definition of what constitutes a safe limit has changed; for many chemicals the dose we consider safe has decreased markedly over time. Two basic toxicological concepts must be considered when evaluating the potential impact of exposure to chemicals: (1) the concept of a threshold dose level, and (2) the concept that qualitatively different biological effects are possible with different exposure levels. With regard to the first concept, empirical and scientific observations indicate that most biological effects occur only when the level of chemical exposure or dose exceeds a certain level, called the threshold dose level. The threshold dose level varies from chemical to chemical, and from person to person. At exposure levels ranging between zero and the threshold, some biochemical or physiological mechanism prevents any effects from being observed. As the level of exposure begins to exceed the threshold, however, these mechanisms become saturated and cannot detoxify the chemical or repair low-level damage. Consequently, the effect begins to appear at a rate which increases as exposure increases. All chemicals exhibit such a dose-effect relationship. With regard to the second concept, all substances possess some ability to produce bodily injury or death, including those we ordinarily think of as nontoxic. For example, table salt can be toxic if taken in large enough quantities. Its toxicity, however, is slight when compared to substances which are ordinarily 9506710 R91395R.DOC 11 Gradient Corporation PRIVILEGED AND CONFIDENTIAL ATTORNEY WORK PRODUCT considered toxic (Amdur et al., 1991). Even water causes toxic effects at high levels of exposure; excessive ingestion of water can lead to osmotic imbalances in the cells of the body, resulting in severe neurologic symptoms and even death (Ellenhom and Barceloux, 1988). Various exposure levels can elicit, qualitatively, different response or "effects." For example, high doses of lead cause convulsions and death in children while low doses cause behavioral problems and learning disabilities. Some chemicals may have beneficial health effects at some levels of exposure and harmful effects at other levels. A brief discussion of the toxicology of lead follows to illustrate some of these basic toxicological principles. (The historical understanding of lead toxicology is discussed in detail in Section 4). 3.2 Health Effects Associated with Exposure to Lead The toxic effects of lead range from overt life-threatening intoxication to subtle subclinical psychological and behavioral effects. With lead, as with other chemicals, the toxicological endpoints differ by level of exposure, and by duration of exposure. Also, the endpoints typically operate by different biological mechanisms. Thus, studies based on high-level chemical exposures must be used with caution when seeking to predict the health effects of the same chemical at low exposure levels, because the same effects are less likely to occur at low levels and, in some cases, may not occur at all. Further, the same level of exposure may cause qualitatively different toxicological effects in different target populations. Although overt poisoning still occurs from time to time, it is the effects of long-term low-level exposure that pose the greatest concern today. Exposure is typically measured by the levels of lead in blood, commonly referred to as blood lead levels. This section discusses the health effects from lead exposure on children and adults. 3.2.1 Health Effects in Children - Current Understanding Children experience most effects at lower lead exposure levels than adults. This is because children have a greater rate of lead absorption than adults, and because the developing tissues of children are more susceptible to the effects of lead. For example, while adults may absorb as little as 6-8% of lead ingested during non-fasting conditions, children may absorb 45-50% of lead similarly ingested (ATSDR, 9506710 R91395R.DOC 12 Gradient Corporation PRIVILEGED AND CONFIDENTIAL ATTORNEY WORK PRODUCT 1993). Also, it is believed that the immaturity of the blood-brain barrier may account in part for the greater sensitivity of the developing juvenile central nervous system effects (e.g., neurobehavioral effects) from low-level lead exposures, while adults initially manifest nervous system effects in the peripheral nerves (e.g., slower nerve conduction in the hands and feet) at higher levels of exposure (resulting in approximately 40 pg/dl). Overt central nervous system injury in children differs with the degree of exposure. At blood lead concentrations of about 100-150 pg/dl, lead encephalopathy occurs. Encephalopathy is a general term used to describe various diseases that affect brain function. Early symptoms that may develop within weeks of initial exposure include dullness, irritability, poor attention span, headache, muscular tremor, loss of memory, and hallucinations. The condition may then worsen, sometimes abruptly, to delirium, convulsions, paralysis, coma, and death (Kumar et al., 1987 as cited in ATSDR). Until the development of chelation therapy, about 65% of children with lead encephalopathy died. Children appear to be much more sensitive than adults to neuropathic effects of lead. Many children who survive lead encephalopathy have permanent neurologic effects including retardation and severe behavioral disorders (NRC, 1993). Childhood plumbism is also associated with kidney injury. In high-dose chronic lead exposure (50 pg/dl or more), aminoaciduria (excessive excretion of amino acids) is the most consistent finding in children. Anemia is also common in severe chronic poisoning. Other effects of high-level lead exposure include gastrointestinal effects such as colic. Colic is characterized by a combination of the following symptoms: abdominal pain, constipation, cramps, vomiting, anorexia, and weight loss. For children, EPA (1986a) has identified a LOAEL for colic of approximately 60-100 pg/dl. Lower levels of lead exposure can cause qualitatively different health outcomes in children. The average decrement of approximately 5 IQ points observed in studies by de la Burde and Choate (1972, as cited in ATSDR, 1993), and Rummo et al. (1979 as cited in ATSDR, 1993), represents a reasonable estimate of the magnitude of full-scale IQ decrements associated with markedly elevated blood lead levels (mean: approximately 50-70 pg/dl) in asymptomatic children. Lead exposures of perhaps 30 pg/dl, however, may cause a decrease in neurobehavioral functioning and academic achievement which persists into adolescence (Goyer, 1993). Exposures resulting in blood lead levels of 15-25 pg/dl may result in impaired vitamin D metabolism in children (impacting calcium balance in the body) and in an increase in 9506710 R91395R.DOC 13 Gradient Corporation PRIVILEGED AND CONFIDENTIAL ' ATTORNEY WORK PRODUCT erythrocyte protoporphyrin (an indication of an impact on heme-synthesis) in both children and adults (NRC, 1993). Even smaller lead exposures, resulting in blood lead levels of < 10-15 pg/dl, have been associated with deficits in neurobehavioral development, lower IQ, and growth retardation in infants exposed prenatally, and in children exposed postnatally (NRC, 1993; ATSDR, 1993). In response to this information, the Centers for Disease Control reduced the recommended maximum blood lead level in children from 25 to 10 pg/dl (CDC, 1991). In doing so, CDC stated that blood lead levels as low as 10 pg/dl, which do not cause distinctive symptoms, are associated with decreased intelligence and impaired neurobehavioral development, decreased stature or growth, decreased hearing acuity, and decreased ability to maintain a steady posture. Further, CDC stated that the concern about adverse effects on central nervous system functioning at blood lead levels as low as 10 pg/dl was based on a large number of rigorous epidemiologic and experimental studies, although researchers had not yet completely defined the impact of blood lead levels <10 pg/dl on central nervous system function. While many studies have tried to determine the public health implications of low-level lead exposure in children, the results are mixed. A recent study (Bellinger et ai, 1994) found only a modest association between children's postnatal lead exposure as measured in teeth, and the risk of behavior problems reported by teachers. However, as recognized by the researchers, the study does not elucidate the cause and effect relationship between tooth lead and behavior problems. For example, certain behavioral problems might increase the likelihood of lead exposure, or, alternatively, behavior problems among children with the highest tooth lead levels may be directly or indirectly related to lead-induced cognitive problems. Furthermore, when the researchers assessed the variance in the teachers' ratings using a model with as many as 30 sociodemographic and medical variables, the variables accounted for less than 10% of the variance. As the authors point out, this finding is not unique and raises several possibilities: that the major determinants of childhood behavior problems are not yet identified, or they are poorly measured, or-a more remote possibility--the association between the tooth lead and child behavior is attributable to confounding (i.e., an association with a variable not being studied). Pocock et al. (1994) evaluated the data from 26 epidemiology studies in order to quantify the magnitude of the relation between full scale IQ in children aged 5 or older and their body burden of lead. 9506710 R91395R.DOC 14 Gradient Corporation PRIVILEGED AND CONFIDENTIAL ATTORNEY WORK PRODUCT Although they were able to verify this relationship and found that the overall evidence shows a small but potentially important deficit in full scale IQ among children with raised body lead burden, `the inherent limitations of observational epidemiology in pinpointing the reasons for this association mean that uncertainty remains as to the real impact that lead makes on children's neuropsychological development." Pocock et al. conclude that `In the face of this doubt, the priority that should be devoted to detection and intervention on children with moderately increased blood lead, compared with other social influences on childhood development, is open to debate." 3.2.2 Health Effects in Adults - Current Understanding In adults, who have been studied in occupational settings, encephalopathy occurs at higher blood lead levels than it does in children - 120-150 pg/dl. The symptoms include irritability, headaches, hallucinations, progressing to convulsions, paralysis, and even death. More typically, the neuropathologic outcome of adult lead poisoning is peripheral polyneuritis involving sensory and motor nerves; wrist drop and foot drop may occur in advanced cases. At lower exposures (30-70 pg/dl) nerve conduction velocities may be impaired. Colic is a consistent early symptoms of lead poisoning in adults, where it typically occurs at blood lead levels of 100-200 pg/dl, although it has been noted in workers with blood lead levels as low as 40-60 pg/dl (ATSDR, 1993). Renal dysfunction including chronic nephropathy, has been documented in lead workers, many of whom had no history of prior lead poisoning (NRC, 1993). Lead workers often show evidence of both marked impairment of heme biosynthesis and increased erythrocyte destruction. The threshold for a decrease in hemoglobin in occupationally exposed adults is estimated to be 50 pg/dl, while in children it is 40 pg/dl (ATSDR, 1993). A large body of literature clearly indicates that high levels of lead cause adverse effects on both male and female human reproductive functions. Women who are exposed during pregnancy, in particular, have experienced miscarriages and stillbirths. The results of two recent studies in females with blood lead levels of 10 pg/dl indicate no effect on the rate of spontaneous abortions. One study in males indicate that at moderate blood lead levels (40-50 pg/dl) sperm production may be affected. While the concern for lowlevel lead exposure in children is for impacts on cognitive development, in adults, the critical effect is on 9506710 R91395R.DOC 15 Gradient Corporation PRIVILEGED AND CONFIDENTIAL ATTORNEY WORK PRODUCT blood pressure (Goyer, 1993). There is evidence suggesting that blood lead levels of 10-15 pg/dl are associated with hypertension in adults, including pregnant women (NRC, 1993). However, for individuals who ingest large quantities of salt, the effect of lead on blood pressure may be less important. 9506710 R91395R.DOC 16 Gradient Corporation 4 History of Toxicology of Lead PRIVILEGED AND CONFIDENTIAL ATTORNEY WORK PRODUCT 4.1 Introduction Lead has been used since antiquity. Consequently, its toxicity has been understood, to some extent, since then. However, until recently, lead toxicity was only recognized when symptoms were overt (e.g., encephalopathy, wrist drop, foot drop). In the last 20 years, the effects of low-level exposure to lead (where symptoms are not overt) have been recognized and it is these effects that current regulatory efforts seek to prevent. Today, health concerns associated with lead focus on lower level environmental exposures, which are much lower than historical exposure levels associated with overt toxicity. Although the toxicity of lead has been known for centuries, this toxicity is not equally conferred on all forms of lead. It was recognized by the 1920s that lead toxicity varied considerably by lead compound, occupation (miner vs. smelter), particle size, route of administration, and exposed population (/. e., children vs. adults). Lead sulfide, the predominant lead compound in Silver Valley, was considered to be the least toxic ore and it was much less toxic than other forms of lead used in industry such as lead oxide and lead carbonate. Further, lead sulfide was known to be relatively insoluble in the human stomach and associated with low levels of poisoning, even in miners exposed in the early 1900s when controls were virtually nonexistent. By the 1950s, no accounts of poisoning from lead sulfide in the U.S. are found in the literature. This is in stark contrast to the incidence of poisonings for other more toxic lead compounds such as lead carbonate, lead oxide, and tetra-ethyl lead. In fact, blood lead levels are not regulated by the Mining Safety and Health Administration (MSHA) as they are by the Occupational Safety and Health Administration, further testament to the lack of toxicity of lead ores, especially lead sulfide, the most frequently mined ore in the U.S. The purpose of this section is to present and contrast the types of health effects which were of concern historically, to those of concern today. Historically, concern was for the overt lead poisoning observed first in occupationally exposed adults, and then in children exposed to lead in paint. Overt lead poisoning is defined as absorption of lead in sufficient quantity to produce subjective symptoms and readily 9506710 R91395R.DOC 17 Gradient Corporation PRIVILEGED AND CONFIDENTIAL ATTORNEY WORK PRODUCT apparent clinical signs of anemia, peripheral neuropathy, encephalopathy, colic, and impaired kidney function. Today's concerns center primarily on neurobehavioral effects in children and on subtle reproductive and blood pressure effects in adults. Both types of effects are believed to occur at very low levels of exposure. 4.2 History of Lead Use Despite its recognized toxicity, lead has been used for thousands of years. The discovery of lead, one of the seven metals of antiquity, dates back to at least 3500 B.C. (Lin-Fu, 1985). Its use in civilization is documented by a wide variety of artifacts discovered by archaeologists. In 2500 B.C., the discovery that silver could be recovered from lead ores, resulted in a large increase in the amount of lead mined and smelted. However, the real boost to lead production came with the Romans who used massive amounts of lead in their aqueducts. It is estimated, for example, that 12,000 tons of lead were used in the construction of a single siphon unit in the aqueduct at Lyons. The Romans reportedly produced an average of 60,000 tons of lead per year for 400 years. (It is from this Roman use of lead in plumbing that we get the term plumber.) During medieval times lead production decreased to only a few thousand tons per year, but production rebounded quickly with the exploitation of the lead-silver mines in Mexico and Peru by the Spaniards between about 1550 and 1750. The advent of the large country house in Europe increased the demand for lead, which was used for roofing, piping, and statuary. Until the 17th century the skills necessary to make large structures in lead were not widely known, but the use of alloys and supporting framework were widely known by the 17th century and were used to produce a wide variety of statuary and ornamentation that can still be seen in cities, towns, and gardens. In the last half of the 17th century, John Roebuck invented the lead chamber process for the manufacture of sulfuric acid. An improved method for making lead shot was developed by William Watts, a plumber in Bristol. The first lead storage battery was made in 1859 when Gaston Plante used two lead plates in a bath of acid. (Lead is still used in batteries and their manufacture is associated with relatively high lead exposures.) With the initiation of the Industrial Revolution, world production soon reached a million tons per year. In 1970, worldwide production was estimated at 3.5 million tons per year (Woolley, 1984). By 1982 production had increased to 5.2 million tons per year with about 20% of consumption in 9506710 R91395R.DOC 18 Gradient Corporation PRIVILEGED AND CONFIDENTIAL ATTORNEY WORK PRODUCT / the U.S. Nearly all lead mined in the U.S. comes from mines in Missouri, Colorado, Idaho, and Montana (Matte et al., 1992 in Needleman). 4.3 Use of Medicinal Lead Until 30 years ago, lead toxicity was termed plumbism, after plumbum, the Latin name for lead. Lead poisoning was also called saturnism, a term for lead poisoning coined by Medieval alchemists because lead `absorbs and devours, so to speak, all other imperfect metals in its scorification' (Aub et al., 1926). According to the literature, colic, encephalopathy, and paralysis were recognized symptoms of lead poisoning about 200 years ago (Johnson and Mason, 1984). Despite its known toxicity, lead was recognized to be of medicinal value at certain prescribed levels, even in children. Doctors prescribed lead for a variety of aliments up until at least the 1920s. The treatment for cholera in 1835 was lead pills (Wedeen, 1984). The 1883 edition of United States Pharmacopeia (Edes, 1883), for example, prescribed the use of lead carbonate to dress bums. It stated that lead acetate, one of the most poisonous lead compounds, "is used as an astringent in diarrhea and dysentery, and has the great advantage, especially for children, that its taste is not disagreeable." In addition, lead acetate was employed as a styptic in hemorrhages from the lungs, kidneys, uterus, and bowels and it was said to have cured aneurysm. Externally it was used as a lotion for bruises and abrasions, but its long-term use was cautioned against due to the fear of absorption. The author also noted the toxic effects of lead acetate when taken in large doses or over a long period of time. Such usage led to the typical symptoms of chronic lead poisoning: blue line on the gums, colic, paralyses, and cerebral symptoms; however medicinal use of lead acetate rarely resulted in poisoning, according to Edes. The recommended doses for adults were 1 to 5 grains, 6 to 30 centigrams (0.06 to 0.30g) every hour for hemorrhage; for diarrhea 1 grain (6 centigrams) every 2 or 3 hours in pill, or for children a fraction of this dose in powder with sugar of milk was recommended. (One centigram is 1/100 of a gram, while 1 microgram (pg) is 1/millionth of a gram. Thus a centigram weighs 10,000 times more than a microgram.) In 1905, the British physicians found it necessary to alert the public to the severe consequences of using lead compounds for "female irregularities" and to induce abortions (Wedeen, 1984). But in 1915 lead acetate was still be prescribed for diarrhea (Hatcher and Wilbert, 1915). Bell, in 1924, used lead as therapy for cancer (Hardy, 1965). This is the last documented medicinal use of lead. 9506710 R91395R.DOC 19 Gradient Corporation PRIVILEGED AND CONFIDENTIAL ATTORNEY WORK PRODUCT 4.4 History of Lead Toxicity in Adults The presently accepted signs of lead poisoning have been recognized since at least 1914. In a book on lead poisoning published in that year, effects of lead on the digestive, reproductive, cardiovascular, and nervous system were described (Johnson and Mason, 1984). Both blood effects and reproductive effects were described. It was known that women who worked with lead especially in potteries and lead paint factories often could not continue pregnancy to term and that babies bom alive had a very poor prognosis (hence the use of lead to induce abortion). The 1926 publication by Aub et al. entitled Lead Poisoning provided a lengthy and sophisticated treatment of the subject. The authors, citing 500 references, made a distinction between acute and chronic poisoning and gave the four early signs of lead poisoning: ashen skin color, lead line on the gums, stippling of red blood cells, and indications of red blood cell destruction such as mild secondary anemia and hematoporphyrin in urine. Arteriosclerosis and chronic nephritis were noted as late effects of chronic lead poisoning. Although methods were available for measuring lead in urine and feces, their diagnostic value, except to prove lead absorption, was debated (Johnson and Mason, 1984). Significant steps that have occurred since then in the ability to detect lead toxicity include the ability to measure lead in blood (beginning in the late 1920s but not generally available until the 1940s), identification of the heme biosynthesis pathway; inhibition of this pathway by lead, with consequent ability to monitor subclinical effects, and increased ability to measure functions of both the peripheral and central nervous systems (Johnson and Mason, 1984). The use of blood lead levels to evaluate the extent of lead absorption is now routine, and their use is based on the knowledge that blood effects are the first effects to be detected subsequent to lead exposure and absorption. This section describes, in detail, the growth of knowledge regarding the toxicity of lead in adults. Current occupational standards for lead include: biological monitoring (blood lead and zinc protoporphyrin) is prescribed for all employees who are exposed to lead in air at levels higher than the action level of 30 pg/m3 for more than 30 days in the year, while medical examination is mandatory for any worker whose blood lead level exceeds 40 pg/100 g (OSHA-29 CFR-1910.1025) (40 pg/100 g is 9506710 R91395R.DOC 20 Gradient Corporation PRIVILEGED AND CONFIDENTIAL ATTORNEY WORK PRODUCT equivalent to 40 (xg/dl). These standards are presented here as points of reference; their basis is discussed in Sections 4.4.6 (Occupational Standards). 4.4.1 16th Century through 19th Century Lead poisoning in adults has occurred historically from two separate routes of exposure - through ingestion of lead in food or drink and through occupational exposures. The first written documentation of lead toxicity came in the 16th century when Agricola wrote a classic treatise on mining and metallurgy in which he provided excellent descriptions of illnesses of workers exposed to various metals, including lead (Lin-Fu, 1985). In 1567, Paracelsus, a Swiss physician, who had worked as a mining and smelting as a laborer for 10 years and then several years later returned to the mines to get material for his treatise on occupational diseases, described various miners diseases such as disturbances of the lungs, stomachs, and intestines from mining and smelting ore (Patty, 1948). In the following century Vematti, a noted physician, noted the toxic effects of lead in white lead (lead carbonate) workers. In 1713, Ramazzini, a physician who taught at the University of Modema and Padua, wrote his famous treatise on the diseases of workers in which he listed 54 occupations associated with lead poisoning. Despite this knowledge concerning lead poisoning, mass epidemics of lead poisoning were not recognized as such. For example, in 1616, Francois Citois published an account of an epidemic in Poitou, France characterized by symptoms of pallor, insomnia, stomach pains, loss of appetite, convulsions, and paralysis. This became better known as Poitiers colic, which was caused by wine contaminated by lead from lead storage vessels; however its cause was not recognized for 150 years (Smith, 1986). With the advent of the Industrial Revolution, industrial lead use increased dramatically and new processes were introduced, such as the manufacture of lead storage batteries, where lead exposures were very high. As a result, occupational lead poisoning became an extremely grave problem by the early 19th century. Tanquerel des Planches wrote a treatise in 1839 providing a meticulous and detailed account of a large number of patients admitted with extremely overt lead poisoning to a Paris hospital between 1831 and 1839. In Britain, lead was made a notifiable disease in 1899 under the influence of Sir Thomas Legge, the first appointed Inspector of Factories. In the United States, cases of lead poisoning were noted during the 17th and 18th centuries in the pottery, pewter-making, shot-dropping, and lead smelting industries (Freeman, 1969 as cited in Needleman et al., 1992). 9506710 R91395R.DOC 21 Gradient Corporation PRIVILEGED AND CONFIDENTIAL ATTORNEY WORK PRODUCT Nonetheless, it was recognized that mining carried less risk of poisoning than most other leadrelated industries and that lead sulfide was the least toxic lead compound used in industry. During the early 20th century, the focus was still on overt lead poisoning, as painstakingly documented by Dr. Alice Hamilton. Since physicians were advised that nonovert effects, such as lead nephropathy, could not occur in the absence of overt symptoms of lead intoxication such as colic, palsy, or encephalopathy (Smith, 1925, as cited in Wedeen, 1984), overt poisoning remained the focus until the 1970s. 4.4.2 Early 20th Century Lead is discussed in the occupational health literature of the U.S. as early as 1914 (Thompson, 1914). Thompson reported that in a Bulletin of the United States Bureau of Labor (1911) that "men mining lead ores, such as galena or sulphide, do not suffer from plumbism" and noted that this referred to the British industry. By contrast, he stated that lead smelting gives rise often to most acute forms of lead intoxication, to the extent that it is sometimes immediately fatal. In 1918, Rosenau (Rosenau, 1918) recognized that different forms of lead were associated with different toxicities: carbonate was much more poisonous than sulphate (so much so that Rosenau recommended the cessation of carbonate in industry); carbonate, oxide, and chromate were the most serious, because they were most used in industry; and soluble salts were more readily absorbed than insoluble salts. Dr. Alice Hamilton, Assistant Professor of Industrial Medicine at Harvard, was the first American to comprehensively study the lead toxicity in American industries. She noted that at the time U.S. industrialists believed their workplaces to be free of the hazards reported in European lead industries. Dr. Hamilton surveyed those industries with particularly high lead exposures and found the following prevalence of lead poisoning: in storage battery manufacturing (18% of workers had lead poisoning), potteries (23% lead poisoning) (1934), typefounding (1917), smelting (14-63% lead poisoning) (1934), enameling of sanitary ware (1919), and pigment production (1934) (Matte et al., 1989 as cited in Matte et al., 1992). In the 1925 edition of her book, Industrial Poisons in the United States, Hamilton discussed lead mining, smelting, and refining. Dr. Hamilton noted that lead poisoning prevalence amongst miners varied with the type of ore being mined. At the time, lead mining was carried out chiefly in Southeastern Missouri, in Utah, Idaho, and Montana. Dr. Hamilton noted that in Utah, where large quantities of 9506710 R91395R.DOC 22 Gradient Corporation PRIVILEGED AND CONFIDENTIAL ATTORNEY WORK PRODUCT carbonate ore were produced, a high prevalence of lead poisoning of miners was documented in a survey conducted by Arthur L. Murray for the Bureau of Mines. Murray found that of reported cases of lead poisoning in Utah from 1919-1920, 76-83% of those poisoned were miners. Hamilton notes that "the rate of lead poisoning in a mining community depends upon the dryness of the mines and on the proportion of carbonate and oxide ores, which are more soluble than sulphide ore and therefore more poisonous" (Hamilton, 1925). The rate also depended on the depth of the mine, because as the depth increased, the greater the proportion of sulfide ore and the smaller the proportion of more toxic ores such as lead carbonate and lead sulphate. In Leadville, Colorado, for example, Hamilton reports that poisoning in miners decreased from 40 to 50 miners a year in 1880, 8 in 1910, and none in 1912. She reported a similar trend in Utah. She notes that cases of lead poisoning occur in the galena (lead sulfide) ores of Southern Missouri, "although their number is probably not great." Dr. Hamilton does not mention any lead poisoning in Idaho. Investigations into the occupational health problems facing miners did not focus on lead poisoning. They focused on silicosis, the second highest cause of death amongst miners (accidents from explosions and falls were first). Although silicosis in miners had been recognized for centuries, it only became a widespread occupational health problem as a result of the technological changes of the 19th century. The development and adoption of power drills of mining generated greater quantities of dust and smaller particles capable of reaching the innermost part (alveoli) of workers' lungs. In the 1910s, the Bureau of Mines - Public Health Service (BOM-PHS) conducted studies in Joplin, Missouri and Butte, Montana. At both locations, the average concentrations of silica in dust were 100 times the 1988 federal limit on exposure. In Joplin, the BOM-PHS found that 60% of the miners had silicosis; in Butte, 43% were silicotic. Lead poisoning was documented in hardrock miners but to a much lesser degree than silicosis. Conditions in the Park City (Utah) area were perhaps the worst in the industry but lead hazards also existed in the Sanford area, in the Coeur d'Alenes, and other lead centers (Derickson, 1988 based on citations primarily from 1880-1921). However, it should be noted that although lead poisoning in Missouri, Colorado, and Utah was written about fairly frequently, this is the only reference to poisoning in the Coeur d'Alenes area we could find. 9506710 R91395R.DOC 23 Gradient Corporation PRIVILEGED AND CONFIDENTIAL ATTORNEY WORK PRODUCT In 1934, Alice Hamilton's Industrial Toxicology was published. It contained a very detailed account of the signs and symptoms of overt lead poisoning. They included anemia, basophilic stippling of red blood cells, anorexia, colic, constipation, encephalopathy, palsy, and arthralgia (pain in the joints). In addition, Dr. Hamilton reported that lead was well known to induce abortions and to injure the germ cells of both sexes. She also described the occupations and types of lead most frequently associated with lead poisonings, since "their dangerous character ... varies greatly, and it is a mistake to assume that every lead occupation carries with it a serious risk of plumbism." The greatest risk was from lead suboxide in the smelting and refining of lead due to exposure to the dust and fumes. Next in risk was lead burning in which a blowtorch was applied to a lead surface, creating a lead oxide. A much slighter danger from lead oxide was smelting zinc ore containing lead; in typefounding; in foundry work where a high proportion of lead is present in the alloy; in soldering by hand; in making molded lead goods, and finishing them; and the printers trade. The higher oxides, litharge, red lead, and orange mineral were used in making pottery glazes and enamels, batteries, paint, and lead glass; the occupations were associated with high rates of plumbism. Dr. Hamilton notes, however, that white lead - lead carbonate - "is the most notorious source of plumbism" (lead poisoning). It was readily soluble in gastric juice (60 to 78%) and was responsible for lead poisoning in plumbers, painters, and pottery workers. In her 45 pages of text on lead, Dr. Hamilton includes but one paragraph on lead poisoning from mining ores. She observes that in Missouri, only lead sulfide ores are found, and since it dissolves only to a slight extent in human gastric juice (in the stomach), lead poisoning among miners of galena is rare. (Lead sulfide is the type of lead ore mined at Bunker Hill.) By contrast, lead mining was one of the chief sources of industrial plumbism in Utah, because mines in Utah were nearer the surface and contained oxidized ores such as sulphate and carbonate, which were far more soluble than lead sulfide (Hamilton, 1934). 4.4.3 1940s - 1950s In 1949, the second edition of Industrial Toxicology, which was co-authored by Alice Hamilton and Harriet Hardy, was published. The chapter on lead emphasized the variables that affected toxicity: the solubility in the body fluids; the fineness of the particles (the finer they are the more quickly they dissolve); and the particular lead compound. Hamilton and Hardy reported that Fairhall and Sayers had recently (1940) published the results of exhaustive tests on animals to determine the relative toxicity of the most 9506710 R91395R.DOC 24 Gradient Corporation PRIVILEGED AND CONFIDENTIAL ATTORNEY WORK PRODUCT important lead compounds (Fairhall and Sayers, 1940 as cited in Hamilton and Hardy, 1949). From the inhalation experiments with guinea pigs they made qualitative judgments as to which compounds were most toxic, but could not make quantitative evaluations. They concluded that the carbonate, monoxide, and sulphate were more toxic than metallic lead or other compounds. They also noted that lead arsenate was very toxic. Lead chromate, which was tested by other workers who injected animals intraperitoneally, was observed to be of low toxicity to man. As reported by Hamilton and Hardy, Harrold and colleagues determined that the level of lead was normal in the blood and urine of 185 men using lead chromate paint in a paint spraying booth (the concentration of lead in air was 1.6 to 7.3 mg/m3, as compared to the present standard of 30 pg/m3, equivalent to 0.03 mg/m3). Hamilton and Hardy noted that the compounds differ decidedly in their toxicity, "an important point in the prevention of lead poisoning in industry." As in the previous edition, they state that the risk of poisoning in mining galena is minimal while the risk of lead poisoning to miners of oxidized ores, sulphate, and carbonate, is one of the chief sources of industrial plumbism in Utah. It is not nearly so necessary to guard against dust in the lead mines of Missouri, they state, because the ore is lead sulphide, which is very slightly soluble (as recently documented by a journal article reporting the results of an experiment by Carlson and Woelfel), unlike the mines of Utah, which carry the much more soluble carbonate and sulphate. Fairhall (1949) concurred, stating that "the low incidence of lead poisoning among miners in galena mines is probably due to the insolubility of lead sulfide in the tissue fluid of the lungs." Meanwhile, Kehoe stated that the sulfides of ore were not readily absorbed', and therefore, had a relatively low toxicity (Patty, 1949). These findings were bolstered by an industry hygiene survey conducted in 1947 in the mills of the St. Joseph Lead Company in Missouri where the concentrates of ore contained up to 75% lead sulfide. The concentration of lead were measured in air and in the blood and urine of the workers. The results of the atmospheric study determined that the lead concentration greatly exceeded the generally accepted safe limit (1.5 mg/10 m3), while the average blood lead levels were well below the limit of intoxication, although they were suggestive of lead absorption (Belden and Garber, 1949). An entire section of the 1949 edition of Industrial Toxicology is devoted to tetraethyl lead, whose acute toxicity and use in industry had already resulted in over 100 cases of severe poisoning, including at 9506710 R91395R.DOC 25 Gradient Corporation PRIVILEGED AND CONFIDENTIAL ATTORNEY WORK PRODUCT least 11 deaths. The action of tetra-ethyl lead was known to differ markedly from that of other lead compounds, because it was more rapidly absorbed and more soluble in fats, resulting in its concentration in the central nervous system and in the liver. Poisoning takes place through inhalation and through the skin (a route considered unimportant for other lead compounds). The symptoms of poisoning from tetra-ethyl lead were also recognized to be quite different from those associated with other lead compounds: there were not any severe gastric and intestinal cramps or constipation or diarrhea, the blue lead line on the gums was not found nor did stippling usually occur. By this time, it was also recognized that the forms of lead poisoning differ according to the degree of exposure and the solubility and fine division of the particles. Dr. Hamilton and Dr. Hardy stated that a very severe acute attack, which was common in the early years of the century among smelter, sanitary-ware enamellers, and white lead and red lead workers, was seldom seen by 1949 and that exposure to heavy doses of soluble lead compounds now only occurred as a result of accident or an unusual degree of neglect. The authors reported that physicians now expected to see an early stage of a slowly developing lead toxicity. However, the diagnosis of lead poisoning was based on the presence of one or more of the following symptoms: the lead line (a bluish-black stippling which appears along the margin of the gums); the ashen color of skin; tremors of fingers and tongue; the evidence of blood effects such as stippling, an increase in reticulocytes, and anemia; lead in the urine and blood exceeding normal values; hematoporphyrinuria; and perhaps a slowed "chronaxia." Chronaxia is the minimal length of time a galvanic current of standard strength takes to induce muscular contraction; a reaction slower than normal, showing a fall in muscle excitability, is the danger signal. In addition to these signs there must clinical symptoms involving the gastrointestinal tract - anorexia, abdominal pain, constipation; less often the nervous system - insomnia, headache, tremors, loss of muscular strength; and least often arthritis-like symptoms or myositis. By modem standards, finding these objective signs and symptoms constitute severe and overt poisoning. Today we use much more sensitive indicators of lead absorption (such as blood lead levels) to identify people at risk of poisoning so that poisoning can be prevented. Scientists also recognized that the route of exposure resulted in markedly different levels of toxicity. The most severe poisoning occurred when lead was inhaled - absorption was very rapid from the 9506710 R91395R.DOC 26 Gradient Corporation PRIVILEGED AND CONFIDENTIAL ATTORNEY WORK PRODUCT respiratory tract and severe symptoms appeared quickly. Dr. Hamilton and Dr. Hardy reported that the greater rapidity of absorption by inhalation as compared to ingestion was in part, because lead enters directly into the general circulation instead of passing through the liver as in gastrointestinal absorption. They concluded, consequently, that lead poisoning varied with the amount of lead in the air, the size of the particle, and the form of lead. In Colorado smelters. Dr. Hamilton found that 90% of the lead poisoning occurred in the men on the furnaces who constituted only one-half the work force. In Utah, where the lead is fairly soluble, workers in smelters were poisoned to the extent of 14.3%, while the men cleaning dust (consisting of very fine particles) from the flues were poisoned at a rate of 62.5%. By comparison, 13% of miners who worked in the Park City and Tintic mines in Utah were lead poisoned while 27% of the miners in Frisco, Utah were poisoned. According to Hamilton and Hardy (1934) the difference was due to the dustiness of the work environment: Park City and Tintic were only `fairly dusty" while Frisco was `Very dusty." When red lead paint was heated by torches, creating fumes consisting of tiny particles, an astonishing 69% of the workers were lead poisoned (Hamilton, 1934). The importance of dust levels was also demonstrated by contrasting lead poisoning rates in potters in the U.S. (23%) where dust levels were little controlled to potters in England where only 0.9% were poisoned because dust was "strictly prevented" (Hamilton, 1934). In the 1950s, scientists continued to write of lead poisoning in mining being dependent on the type of ore mined. Hunter (1955), for example stated that blasting and shoveling galena "rarely gives rise to plumbism," although he noted that silicosis was usually a hazard. Further, he stated that lead poisoning at the Broken Hill Mines of Australia, a site where many lead poisoning had been observed in the past (11 deaths from lead poisoning were reported at the facility in 1891 (Cumpston, 1968)), was no longer a problem, because the lead sulphate, which had been the cause of the poisonings, had all been mined and the subjacent galena "caused no trouble." The cessation of smelting in Broken Hill in 1897 and the compulsory use of water sprays also contributed to the decrease in poisonings (Cumpston, 1968). Men involved in occupations other than mining were in much greater danger of lead poisoning. Occupations with high lead exposures were lead burners, chemical plumbers, and shipbreakers using torches in their work. In addition, foundry work, smelting, and milling, carried a risk of lead poisoning. 9506710 R91395R.DOC 27 Gradient Corporation 4.4.4 1960s PRIVILEGED AND CONFIDENTIAL ATTORNEY WORK PRODUCT With the 1960s, the debate about lead contamination of the environment began. The debate had several aspects: what was the background level of lead in the environment and in man, what was the health significance of increased environmental levels of lead (due to the use of tetra-ethyl lead in gasoline), what was the risk of lead poisoning from ingestion (an issue raised by the increased reports of child lead poisoning from ingestion of paint), what was the significance of the increased ambient levels of lead in air; what were the best ways to measure lead toxicity; and what levels of lead in blood and urine were safe. In addition, some raised the possibility that low-level effects were possible and recommended additional research (Hardy, 1965). (Hardy's implicit definition of low-level effects was effects that may occur at levels lower than those presently recognized as causing lead toxicity.) In a conference sponsored by the Public Health Service in 1965, these issues were hotly debated. Although occupational exposures to lead were not a focus of the conference, they were discussed. Stokinger (1965) analyzed data for concentrations of lead in air and urine in industries representing the major uses of lead: automobile manufacture and repair; foundries; electrotype printing; storage battery manufacture and rebuilding; and secondary smelters (the large category of munitions was not included). They found a tremendous decrease in exposure to lead in industry from 1934 through 1965 based on data documenting lead concentrations in air and urine for 21 plants in Detroit. The decrease continued but at a slower rate since 1945 "at which time the average exposure in most work categories was below the acceptable limits owing to the introduction of safe work standards for lead in air and in urine." Others argued, however, that although the trend toward overall improvement in occupational exposure was downward, the number of workers exposed to high levels of lead had probably not decreased significantly in 20 years due to the increase in small, poorly controlled establishments (Horton, 1965). Stokinger also reviewed blood lead data in 86 surveys of 26 different operations over a 4-year period. He found indications of excessive exposure to lead in 10-35% of exposed workers, as judged by blood analysis (the allowable limit was 100 p.g/100 g blood). Stokinger's data were not based on systematic sampling, but represented the blood samples of persons thought to be suffering from lead poisoning, and workers possibly suffering from lead absorption but no overt toxicity were not sampled (NAS, 1972). The U.S. has never collected data on lead poisoning in adults in a systematic way, so it is not possible to determine the exact magnitude of poisoning in adults in the past (NAS, 1972) or the present (Johnson and Mason, 1984). 9506710 R91395R.DOC 28 Gradient Corporation PRIVILEGED AND CONFIDENTIAL ATTORNEY WORK PRODUCT To assess toxicity from lead ingestion, experiments were conducted in which adults were administered lead in soluble form by mouth, in three doses of equal size, taken with meals (Kehoe, 1965). The four subjects took the following doses: one took 3 mg of lead chloride daily for 18 weeks (in addition to the background lead in his diet); the second took 2 mg daily for 2 years (in addition to the background lead in his diet); the third took 1 mg daily for somewhat more than 4 years; and the fourth took 0.3 mg per day plus the mean quantity of 0.32 mg taken in the diet, over a period of 60 weeks. There was a progressive increase in the output and concentration of lead in the urine and blood of the subjects and in the quantity of lead retained in their bodies (the difference between the intake of lead and the output of lead in feces and urine); the accumulation progressed essentially at constant individual rates throughout the study. Kehoe concluded that ingestion at the levels of 3, 2, and 1 mg daily would eventually lead to dangerous levels of lead in the body in 8 months, 4 years, and 8 years, respectively, based on extrapolating from the curve of blood lead levels achieved over the course of the study. Kehoe further noted that the lethal dose was unknown but that oral doses of several hundred milligrams can cause acute but not fatal illness in the adult. In 1968 at a conference in Amsterdam authorized by the Permanent Commission and International Association on Occupational Health, lead was also an important topic. In an article summarizing the conference's findings with regard to the standards for the prevention of occupational lead poisoning, Kehoe writes that biochemical alterations in the blood were the subject of several papers and that it was generally agreed that the concentration of lead in the blood was the most important measure for the control of hazard and for the prevention of lead poisoning in the inorganic lead industries. Although the analysis of lead in blood had difficulties, he recommended a threshold value for the detection of hazard and the avoidance of lead poisoning of 60 to 80 pg per 100 ml of whole blood. Participants generally agreed that the value of 80 pg per 100 ml could be trusted as the earliest indication of the existence of individual hazard only when multiple analyses could be made promptly by trained and experienced technicians; the measurement under the best of circumstances was associated with an error of 10%, and sometimes somewhat more (Kehoe, 1971). 9506710 R91395R.DOC 29 Gradient Corporation PRIVILEGED AND CONFIDENTIAL ATTORNEY WORK PRODUCT 4.4.5 Recognition of More Sensitive Indicators of Lead Absorption In 1972, the NAS noted that derangement in heme synthesis was almost always associated with blood lead levels above 80 pg/100 g of whole blood. In terms of subclinical effects, they reported that for renal and nervous system function, while the thresholds for clinical correlation with the biochemical effects were not known for lead, significant impairment of renal and nervous system function was unlikely in persons whose blood lead content dose not exceed about 50 or 60 pg/100 g (equivalent of 50 or 60 pg/dl) of whole blood. Subclinical effects are now the basis of the standard for inorganic lead exposure, which went into effect in 1979. The standard, promulgated by the Occupational Safety and Health Administration (OSHA), is based on reproductive effects in men (decreased sperm count), which was found to be the most sensitive indicator of lead absorption. As discussed in more detail in the following subsection, the current standard for mines, which are regulated under the Mining Safety and Health Administration (MSHA), was revised in 1973, as was OSHA's. However the MSHA standard was not revised in 1979 (as OSHA's was), and it therefore does not mandate measurement of blood lead levels in workers in the mining industry. More recently, surveys have been conducted to determine the blood lead levels of miners. In 1980, the National Institute for Occupational Safety and Health performed a health survey at two galena mining and milling facilities in southeastern Missouri. The goal of the survey was to determine if lead absorption was occurring and if there was evidence of an acute or chronic lead intoxication problem. They determined that none of the mine workers examined (a total of 86) had elevated blood lead levels (>40 pg/dl) or free erythrocyte protoporphyrin (FEP) (>120 pg/dl), although the mean blood lead levels for both the mine worker group and the mill worker group for exceeded that of the office and supervisory workers (level of significance, if any not reported) (NIOSH, 1984). In 1986, the results of a study on lead absorption in the mineral extraction industry in Derbyshire, England were reported. The ore mined in the region consists primarily of lead sulfide. Lead poisoning was found amongst the workers in the floatation and grinding/bagging departments, where lead carbonate and lead oxide formed as a result of exposure to the elements; lead concentrations in air reached 20 times the 9506710 R91395R.DOC 30 Gradient Corporation PRIVILEGED AND CONFIDENTIAL ATTORNEY WORK PRODUCT control limit of 0.15 mg/m3. However, lead poisoning was not found amongst the miners, because they were exposed solely to insoluble lead in the form of lead sulfide (Doman, 1986). Thus from the turn of the century to the present, lead sulfide has been considered to present little risk to miners. As a result, it has never been extensively studied and even today, the measurement of blood lead levels of workers in the mining industry is not required by the federal government. 4.4.6 Lead Regulations in the Workplace Permissible lead levels in the workplace have declined dramatically over time. Just 25 years ago the recommended limit of lead in air was five times higher than today (0.15 mg/m3 as compared to 30 pg/m3, which is equivalent to 0.03 mg/m3). In 1923, Hutton summarized the laws relating to lead poisoning for 16 political entities and the United States (Hutton, 1923 as reported by Johnson and Mason, 1984). Hutton's report indicates that Great Britain had the most comprehensive regulations to curtail lead exposure. The Factory and Workshops Act of 1901 in Great Britain specified ventilation and required the reporting of lead poisoning cases, stipulated suitable washing and separate eating facilities, and prohibited employment of children in the manufacture of white lead (lead carbonate). The Workman's Compensation Act of 1906 in Great Britain included lead poisoning as a compensable occupational disease. A 1920 act placed restriction on employment of women and people less than 18 years of age in lead industries. Subsequent orders under this act defined lead compounds as any substance containing more than 5% lead, prescribed medical examinations every three months, and required that separate, clean rooms be available for nonwork clothing. Hutton (1923 as cited Johnson and Mason, 1984) also reviewed the lead laws of the British Dominions and India, France, Germany, Austria, Switzerland, Belgium, the Netherlands, Russia, Greece, Sweden, and the recommendations of the International Labor Organization. France, for instance, prohibited painters from using white lead to paint either the interior or exterior of buildings. The U.S., in contrast, had no federal regulation of lead exposure and 24 states had no regulations. Some states required that lead poisoning be reported, such as New York, Ohio, Pennsylvania, Missouri, Illinois, Massachusetts, Minnesota, Wisconsin, California, Connecticut, Louisiana, and North Dakota. At this early time, methods of monitoring the air to evaluate compliance with regulations were available, but exposure limits had not been established. 9506710 R91395R.DOC 31 Gradient Corporation PRIVILEGED AND CONFIDENTIAL ATTORNEY WORK PRODUCT The Public Health Service study conducted in 1928 of a battery manufacturing plant, found that lead exposures reached about 20 mg/m3 (Johnson and Mason, 1984). The report concluded that 'Except for prolonged exposure, it appears that the limit of safety under the conditions encountered in this study is an atmospheric concentration of lead dust or fiimes of less than 0.15 mg/m3 of air' (as quoted by Johnson and Mason, 1984). This standard was designed to protect against overt lead poisoning, the only lead poisoning recognized at the time. Kehoe and other members of the Committee on Lead Poisoning of the American Public Health Association recommended 0.15 mg/m3 as a time-weighted average (TWA) exposure limit. By 1945, this recommendation (0.15 mg/m3) of the Public Health Service was generally accepted in the U.S., and was adopted by the American Conference of Industrial Hygienists (ACGIH) in 1946 (ACGIH, 1991). A number of investigators found 0.15 mg/m3 difficult to achieve in many industries, and observation of workers, lead urinalysis, and similar studies suggested that the recommended 0.15 mg/m3 value could not be justified (ACGIH, 1991). On the basis of these reports and unpublished data from several sources, ACGIH increased the TLV for lead in 1957 to 0.2 mg/m3 where it remained until 1972 (ACGIH, 1991). This was significant because: 1) there was no federal occupational safety and health law in the U.S. and several states adopted the TLVs as legal standards; 2) the TLVs were adopted as standards by the federal government under the Walsh-Healy Public Contracts Act (1936, amended 1947) and the McNamaraO'Hara Service Contract Act (1965); and 3) after passage of the Occupational Safety and Health Act (Public Law 91-596), the Occupational Safety and Health Administration adopted the 1968 TLVs as federal standards. Thus, the first Federal regulations in the U.S. to limit occupational exposure to lead had a limit of 0.2 mg/m3, which was greater than what had been accepted by the U.S. Public Health Service more than 20 years before. Moreover, comprehensive standards regarding work practices and biological monitoring were still missing from U.S. federal regulations. In 1971, the ACGIH's TLV Committee recommended reducing the limit to its former value of 0.15 mg/m3 on the basis of the recommendations of the 1968 Amsterdam meeting of the International Subcommittee on Occupational Health of the Permanent Commission, and a study by Williams et al. of British battery workers in whom a high correlation was found between air levels and blood and urine Pb values, and urinary coproporphyrins and ALA. For each correlated parameter, the 9506710 R91395R.DOC 32 Gradient Corporation PRIVILEGED AND CONFIDENTIAL ATTORNEY WORK PRODUCT upper 95 percent confidence limit exceeded the safe limits of 0.20 mg/m3 but approximated it when the limit was 0.15 mg/m3 (Stokinger, 1981). In 1971, the National Institute for Occupational Safety and Health (NIOSH), an agency of the U.S. Public Health Service, recommended a comprehensive lead standard to the Occupational Safety and Health Administration (OSHA). This recommendation included an air limit of 0.15 mg/m3, as well as medical monitoring, reporting, and work practices. The air value was based on NIOSH's goal of keeping workers' blood lead levels from exceeding 80 pg Pb/100 g whole blood. In 1978, NIOSH revised its recommended standard to limit exposures to 0.1 mg/m3 to limit blood lead concentrations to 60 pg/100 g (NIOSH, 1978). In 1979, the current OSHA standard came into effect. It limits exposures of workers to 0.05 mg/m3 (8 hour time-weighted average (TWA)) and requires the employer to make available to workers biological monitoring (blood lead and zinc protoporphyrin levels) when airborne lead levels reach 0.03 mg/m3 as an 8hour TWA (OSHA, 1978). The intent of this permissible exposure limit (PEL) is to maintain average blood leads of workers below 40 pg/100 g whole blood to protect against hematologic consequences, peripheral nerve damage, and effects on reproduction and fertility. Other federal regulations in the U.S. assigned to control lead exposure are summarized in Table 4-1. All were promulgated in 1973 or thereafter. 9506710 R91395R.DOC 33 Gradient Corporation PRIVILEGED AND CONFIDENTIAL ATTORNEY WORK PRODUCT Table 4-1 U.S. Agencies having Lead Regulations and Date Law First Promulgated 1. Environmental Protection Agency 40 CFR -- National Interim Primary Drinking Water Standards Sec. 141.80 - December 7, 1992 40 CFR -- Primary Lead Smelters Sec. 421.70-March 8, 1984 40 CFR -- Secondary Lead Smelters Sec. 421-130-March 8, 1984 40 CFR -- Lead Content of Discharge Water Sec. 261-32 - January 16, 1981 40 CFR -- Fuels and Fuel Additives Sec. 80.25 - December 6, 1973 40 CFR -- Primary and Secondary Ambient Air Quality Standards Sec. 50.12 - October 5, 1978 2. Consumer Product Safety Commission 16 CFR -- Products Subject to Other Acts (Pb paint, primarily) Sec. 114.5 - September 1, 1977 16 CFR -- Ban on Pb-Containing Paint and Certain Consumer Products Containing Lead (toys, furniture) Sec. 1303 - September 1, 1977 3. Small Business Administration 13 CFR -- Lead-based Paint (residential structures) Sec. 116.20 - October 28, 1977 4. Housing and Urban Development 24 CFR -- Lead-based Paint Poisoning Prevention Act Sec. 200.800 - January 15, 1987 5. Food and Drug Administration 21 CFR -- Color Additives Sec. 70-March 22, 1977 Source: Adaptedfrom Johnson amiMason. 1984. 9506710 R91395R.DOC 34 Gradient Corporation 4.5 History of Lead Toxicity in Children PRIVILEGED AND CONFIDENTIAL ATTORNEY WORK PRODUCT For centuries, lead poisoning was viewed as a disease of adults exposed in the workplace. Although some older literature refers to illness in newborns and children of lead workers, they were presented as byproducts of their parents' exposure to lead at work (Lin-Fu, 1992). Overt childhood lead poisoning was first recognized as an important distinct entity at the turn of the century and was, for many years, viewed as rare. As it became more recognized, case numbers increased, but the concern was focused on children with pica exposed to lead paint in deteriorating housing in the urban northeast. Only in the last 20 years or so has it been recognized that lead poisoning results from ingestion of lead in dust, soil, and paint that stick to children's hands or toys and are subsequently ingested through normal hand-to-mouth activity. Behavioral effects in children resulting from low-level exposure have been described even more recently. Based on these effects, CDC now recommends that children's blood lead levels be kept below 10 pg/dl (CDC, 1991). 4.5.1 Discovery of Childhood Lead Poisoning in Australia The first cases of childhood lead poisoning were reported in Australia at the turn of the century. In 1890 and again in 1891, A. Jefferis Turner encountered foot drop and wrist drop in three children; he admitted two of them to the hospital under the care of J. Lockhart Gibson, who agreed with the tentative diagnosis of lead poisoning (Lin-Fu, 1992). In March 1892, Gibson presented the cases to the Medical Society of Queensland; his colleagues were exceedingly skeptical of the diagnosis. Gibson pursued the investigation and later that year reported 10 more cases of lead poisoning seen at the hospital between December 1891 and July 1892 (Gibson et al., 1892 as cited in Lin-Fu, 1992). Gibson et al. published their findings in the Proceedings of the Intercolonial Medical Congress of Australia in 1892 (Lin-Fu, 1992). They noted that no other cases of lead poisoning had been recognized in Brisbane children, that the diagnosis appeared to have been frequently overlooked, and the chief reason was that lead poisoning was never thought of as a possible cause of the symptoms. In 1897, Turner published a comprehensive review in the Australasian Medical Gazette in which he analyzed 76 cases of lead poisoning in children treated at the Brisbane Children's Hospital in the previous 6 years; 7 of the cases ended fatally (Turner, 1897 as cited in Lin-Fu, 1992). Turner observed 9506710 R91395R.DOC 35 Gradient Corporation PRIVILEGED AND CONFIDENTIAL ATTORNEY WORK PRODUCT that lead poisoning was related to habitation, since symptoms recurred after children returned to their homes. Although testing of tank water used for drinking revealed the presence of lead, doctors could not understand why adults were not similarly affected (Lin-Fu, 1992). In a paper published in 1899, Turner stated that children were misdiagnosed because textbook descriptions of lead poisoning were based on findings in adults. The source of the lead poisoning was finally solved in 1904 when Gibson discovered that a majority, and probably all of the affected children, lived in houses with lead paint, and that both fresh paint and old powdery paint adhered readily to children's hands (Lin-Fu, 1992). Since most of the poisonings occurred during the hottest months, he suggested that outdoor activities contributed to a greater exposure. However the elucidation of the cause of lead poisoning in children did not decrease its incidence. In 1908 Turner reported that since 1891, 262 children had been treated at the hospital and that 20 children per year were still being admitted Lin-Fu, 1992). Turner believed the only way to decrease the poisonings was through legislative action. In 1920 the Australasian Medical Congress passed a resolution to prohibit the use of lead paint on verandahs and surfaces within the reach of children {Med. J. Australasia, 1922 as cited in Lin-Fu, 1992). 4.5.2 Childhood Lead Poisoning in the U.S. In the U.S. in early 1900s, some considered childhood lead poisoning to be unique to Australia (Thomas and Blackman, 1914, as cited in Lin-Fu, 1992). Nevertheless reports of childhood lead poisoning in the U.S. were soon published. In 1917, Kenneth Blackman, a physician at Johns Hopkins Hospital recommended that in all patients with convulsions where the cause was not clear, lead should be suspected (Rabin, 1989). In 1924, Ruddock reported that lead poisoning in children may be easily overlooked because `the average physician has never had his attention called to the fact, and also because the clinical picture is usually very different from that in similar poisoning in adults." Ruddock observed that "A child lives in a lead world" (Ruddock, 1924). He listed multiple sources of lead exposure, which included lead paint on windowsills, porch railings, toys, crib railings, and furniture as well as lead in food and water containers, lead cosmetics, lead solutions used to treat poison oak, lead ointments on mothers' breasts, and lead dye in buns and candies. From the mid-1920s on, childhood lead poisoning was increasingly reported. Between 1924 and 1933, for example, 89 children were treated at the Boston Infant's and Children's 9506710 R91395R.DOC 36 Gradient Corporation PRIVILEGED AND CONFIDENTIAL . ATTORNEY WORK PRODUCT Hospital for lead poisoning. Many articles, mostly case studies, followed in the 1930s identifying leadbased paint in the home as the source of child lead poisoning (Rabin, 1989). Nevertheless, many cases went undiagnosed by doctors unfamiliar with the symptoms of lead poisoning. To add to the diagnostic confusion, the symptoms of lead poisoning (e.g., vomiting, abdominal pain, constipation, irritability), were common to other childhood diseases (Rabin, 1989). Some lead poisoning cases, for example, were originally reported as brain tumors. In addition, diagnostic tools at the time were poor. Blood lead testing was not widely available until after 1940 (Rabin, 1989). The use of xrays to reveal excess levels of lead in bone was suggested in 1930 as a means to diagnose lead poisoning in children. Using this rather crude technique, the doctors found three to four more times lead poisoning than before - much more than they expected. A 1930 report of the Metropolitan Life Insurance Company concluded that a majority of pediatricians agreed that chronic lead poisoning in infancy and childhood was by no means rare (Metropolitan Life Insurance Co., 1930 as cited in Rabin, 1989). Increasing numbers of reports of severe lead poisoning among children in the 1930s and 1940s led several cities to initiate case finding activities. The Baltimore City Health Department began to investigate deaths in children from lead poisoning on a routine bases in 1932. The health department established a free blood lead laboratory service for physicians and hospitals in 1935 (Rabin, 1989). Other cities such as New York, Philadelphia, and Chicago initiated case finding activities and as activities intensified, more lead poisoning was found in children. Yet lead encephalopathy, which indicated acute toxicity from very high lead exposures, continued to occur with a high frequency and even with chelation treatment, 25% to 30% of these children died. Many considered the problem to be solely one of poor children who lived in slums where they ingested lead paint (Lin-Fu, 1972). In 1966, Chicago began the nation's first mass screening program and many other cites such as Baltimore, New York, and Philadelphia followed. In 1967, the Children's Bureau in the U.S. Department of Heath, Education, and Welfare, now the Department of Health and Human Services, issued a publication entitled Lead Poisoning in Children that called attention to lead poisoning as a preventable cause of death, mental retardation, and neurological handicaps. Three years later in November 1970 the U.S. Surgeon General issued a statement on the problem which recommended screening of children to identify those with excess lead absorption, which was defined as a confirmed blood lead level of 40 pg/dl or 9506710 R91395R.DOC 37 Gradient Corporation PRIVILEGED AND CONFIDENTIAL ATTORNEY WORK PRODUCT more (Lin-Fu, 1972). Prior to this statement, 60 pg/dl had been considered the upper limit of normal blood lead levels in children. The following year the Lead-Based Paint Poisoning Prevention Act was passed, which mandated, among other things, the mass screening of children. The screening yielded surprising results: 20 to 45% of the children tested had blood lead levels exceeding 40 pg/dl (Lin-Fu, 1972). Contrary to earlier findings, many of these children did not live in slums or have pica (a condition in which children place an abnormal number of objects in their mouths, increasing their exposure to lead in paint chips). In 1965, the Public Health Service sponsored a symposium on Environmental Lead Contamination. The most contentious topic was whether tetra-ethyl lead in gasoline should be curtailed or eliminated altogether. It was recognized that gasoline was the biggest contributor to lead in air (Horton, 1965) but the consequences of this on blood lead levels and health were at the time unrecognized, especially since lead poisoning in children was viewed as a direct result of eating paint (Horton, 1965). Speakers agreed that lead exposure occurred through air, food, and beverages, but only one speaker - Dr. Harriet Hardy - listed soil as a medium of lead exposure. In the context of recommending well-designed prospective studies of sensitive populations to study low-level effects. Dr. Hardy stated that such studies would establish how these populations "tolerate the extra burden of lead in air, water, soil, food" (Hardy, 1965). Dr. Hardy was also the only speaker who recommended testing to determine whether or not low-level effects did occur; most speakers were skeptical or hostile to the idea of low-level effects. Lead poisoning continued to be viewed strictly as a clinical disease until the late 1960s when most children with elevated blood lead levels (then defined as 40 pg/dl or more) identified through screening programs were found to be "asymptomatic." With this finding, research on lead toxicity shifted from clinical studies to investigation of psychoneurological effects in children. Although as early as 1943, Byers and Lord reported that children thought to have recovered from lead poisoning later demonstrated behavioral and learning disorders that contribute to poor school performance, the significance of this paper, like the findings of Gibson, was rediscovered only in the 1970s (Lin-Fu, 1992). Additional research revealed effects on children of low-level exposure to lead. In 1979, Needleman et al., using dentine lead content as marker of past exposure, reported that children with high dentine lead levels scored significantly less well in the Wechsler Intelligence Scale for Children than those with low 9506710 R91395R.DOC 38 Gradient Corporation PRIVILEGED AND CONFIDENTIAL ATTORNEY WORK PRODUCT levels; none of the children were ever reported as having clinical lead poisoning. During the 1980s, many papers reported toxic effects of lead at lower and lower blood lead levels (Lin-Fu, 1992). Prospective studies revealed a correlation of the pregnant women's blood lead levels with preterm delivery and reduced birth weight and delayed development of infants. While a 6 point difference in the Mental Development Index (MDI) in the Bayley Scale at 6 months was found between the high and low in-utero exposure groups, (the mean blood lead level of the high exposure group was only 14.6 pg/dl and that of the low exposure group was 1.8 pg/dl). A follow-up study of these infants at 12, 18, and 24 months showed a persistent difference of 4 to 8 points in the MDI. Because of concerns for health effects at these low levels, the limit of blood lead for children has been reduced three times in less than 20 years. In 1975, the Center for Disease Control lowered the limit to 30 pg/dl, and in 1985, further lowered the limit to 25 pg/dl. Most recently (1991), CDC further lowered the recommended limit of lead in blood to 10 pg/dl (CDC, 1991). As shown in Table 4-2, CDC recommends follow-up activities based on blood lead level. The lowest blood lead level at which intervention is recommended is 15 pg/dl. However, as discussed in more detail in Section 3, more recent findings have been inconsistent and there continues to be significant debate regarding the existence and persistence of neurobehavioral effects at or below blood lead levels of 10-15 pg/dl. 9506710 R91395R.DOC 39 Gradient Corporation PRIVILEGED AND CONFIDENTIAL ATTORNEY WORK PRODUCT Table 4-2 Interpretation of Blood Lead Test Results and Follow-up Activities: Class of Child Based on Blood Lead Concentration Class Blood Lead Concentration (pg/dl) Comment I <9 A child in Class I is not considered to be lead-poisoned. IIA 10-14 Many children (or a large proportion of children) with blood lead levels in this range should trigger community-wide childhood lead poisoning prevention activities. Children in this range may need to be rescreened more frequently. IIB 15-19 A child in Class IIB should receive nutritional and educational interventions and more frequent screening. If the blood lead level persists in this range, environmental investigation and intervention should be done. III 20-44 A child in Class III should receive environmental evaluation and remediation and a medical evaluation. Such a child may need pharmacologic treatment of lead poisoning. IV 45-69 A child in Class IV will need both medical and environmental interventions, including chelation therapy. V >70 A child with Class V lead poisoning is a medical emergency. Medical and environmental management must begin immediately. Source: CDC, 1991. 9506710 R91395R.DOC 40 Gradient Corporation PRIVILEGED AND CONFIDENTIAL ATTORNEY WORK PRODUCT 5 Risk Assessment for Lead and Dust in Soil The focus of concern at the Bunker Hill Superfund Site is lead in soil and dust. This concern is based on the risk of ingesting lead in soil and dust. Current regulations and guidelines seek to protect sensitive populations (primarily children) from the effects of low-level exposure to lead in soil and dust, which is inadvertently ingested by children when they put their fingers in their mouth. However the realization that this was a pathway of exposure to children did not begin until the 1970s and was not generally recognized until the mid-1980s. The risk assessment procedures used to assess this risk are of even more recent vintage; the first risk assessment guidelines for ingestion of soil were not available until 1989. This section discusses the historical knowledge concerning soil and dust as a pathway of exposure first in animals, then in children - and then discusses the history of the development of risk assessment methodology, especially as it relates to soil ingestion. 5.1 Historical Understanding of the Effect on Animals of Ingesting Lead in Soil Although claims of livestock damage in the area immediately surrounding the Bunker Hill complex began as early as 1915, effects in livestock were not thought to be indicative of health effects in humans. In 1932, the Idaho state legislature authorized the formation of the Coeur d'Alene River and Lake Commission to study the harmful effects of discharge of tailings. The Commission reviewed a number of reports and letters submitted to them alleging the poisoning of livestock and swans from lead tailings. However the Commission did not comment on possible health effects to livestock and were skeptical of effects in swans, although they noted that the polluted section of the Coeur d'Alene River was `practically devoid of fish fauna, bottom fauna, or plankton organisms" because the bottom portion of it was "deeply covered with shifting deposits of very fine rock powder which...prevented the development of any bottom consocies of animals either adult or immature" (Babcock et al., 1933). The Commission, which primarily addressed the problem of excessive silt in the river, came to the following conclusions: 1) that the use of the dredge may be very effective in cleaning the deposits of Climes" [fine particles] from the Coeur d'Alene River and 2) that the most efficient method of handling the slimes was to transport them to the settling beds by some method other than using the river channel. At no time did the commission express concern for human health effects. In fact one of the members of the Commission reported that `ft is a most 9506710 R91395R.DOC 41 Gradient Corporation PRIVILEGED AND CONFIDENTIAL ATTORNEY WORK PRODUCT significant fact that in none of the reports submitted to this Commission is it claimed or even suggested that any person has been poisoned by drinking any of the water of the Coeur d'Alene River or of the Coeur d'Alene Lake, or that any miner who has mined the ores or any mill man who has worked in the mills where such ores are treated and where he is constantly in contact with them has been poisoned" (Taylor, 1933). The next mention of lead poisoning in livestock in the Coeur d'Alene Valley was in the 1970s. By this time all of the tailings were being contained in tailing ponds and were not being released to the Coeur d'Alene River (USEPA, 1992). Weatherhead (1986) documented a series of horse deaths from 1974-1975 which were attributed to lead poisoning from grazing on lead-contaminated grass and soil pasture areas. As a result, the Bunker Hill Company sent a letter to landowners in the Kellogg area advising them that grazing livestock (especially horses) on pastures in the area should be avoided. No other report on livestock deaths from lead in the Coeur d'Alene Valley are reported in the literature. Although no more information regarding the ingestion of soil by livestock in the Coeur d'Alene area was available, the topic is discussed to some extent in the scientific literature. Literature in the 1950s reported that farm animals, especially young calves, were extremely susceptible to lead poisoning (Allcroft, 1950). Based on the literature and his own calculations Allcroft estimated that humans appeared to absorb about 50% of ingested lead while ruminants (grazing animals) absorbed about 1 to 2%. Allcroft also noted that finely ground galena was much less well absorbed than lead acetate, phosphate, carbonate, oxide, or wet and dry lead paint. However, Allcroft does not suggest that humans could be exposed to lead through the ingestion of soil. In a dissertation completed in 1955 in Germany, the author reported that since the metalworks had begun to emit flue dust and gases through stacks, the surrounding grasses and livestock had died (Gunther, 1954). To determine the cause, Gunther fed two horses and one sheep with the flue dust from the lead works and the resultant symptoms were classic symptoms of lead poisoning. According to Gunther, the pharynx paralysis of one of the test animals and the results of the blood and liver test results point to lead as the major agent. However Gunther does not speculate on the possible significance this may bear on human health. 9506710 R91395R.DOC 42 Gradient Corporation PRIVILEGED AND CONFIDENTIAL ATTORNEY WORK PRODUCT Although lead poisoning of livestock continued to be reported, especially in cattle, the source of the lead remained illusive. In 1968, for example, an outbreak of lead poisoning was reported in 10 3-monthold calves (Harboume and Watkinson, 1968). The authors submitted samples for chemical testing of roofing felt on top of a gate-post, scrapings from a metal gate and a wooden gate, water from the trough, soil, and pasture samples. Of these samples, only the water and the pasture samples contained lead; less than 0.05 ppm lead in water and 12 to 350 ppm lead in pasture. The authors remained doubtful as to the cause of the poisoning because it was possible that the calves could have consumed lead from the numerous shallow veins of lead ore (lead sulphate and lead carbonate) in the area. In 1974, Thornton reported that recent measurements in southwest England indicated that the amount of soil ingested by grazing cattle over the winter months varied from 140 to 1,400 g/day (Thornton, 1974). Since lead in soil reached levels of 1,700 ppm in past mining and smelting areas in England, Thornton speculated that this accounted for the good correlation between geochemical reconnaissance data and the distribution of livestock disorders relating to trace-element imbalance in the United Kingdom. Thornton did not raise the possibility of humans ingesting lead in soil. Almost 10 years later, Thornton and Abrahams (1983) reported the results of a study in which they found that grazing cattle involuntarily ingest from 1 to 8% of their dry matter intake as soil and that, based on their calculations between 9 to 80% of the lead intake into cattle on contaminated land is due to ingested soil. The authors did not relate their findings to humans. In a study on lead poisoning in cattle in 1980 (Bhat and Krishnamachari, 1980), the authors determined that the cattle drank water from a stream which was downstream from a mining operation. The water contained as much as 75 ppm of lead while the soil contained 24-183 ppm of lead; the cows' milk and dung both contained high concentrations of lead (0.05-0.15 ppm and 4.7-38 ppm, respectively). The authors reported that there was no evidence of poisoning in humans, who used a well that was uncontaminated. The authors noted that while children living in areas with elevated lead levels in soil are exposed to an increased burden of lead, it is insufficient to constitute a serious hazard. Thus, although it was known that livestock, especially cows, were poisoned by lead, it was not known that they were exposed to lead in soil until relatively late (1983). Furthermore, this finding was not inferred to indicate that humans, too, might be exposed to lead through soil ingestion. 9506710 R91395R.DOC 43 Gradient Corporation PRIVILEGED AND CONFIDENTIAL ATTORNEY WORK PRODUCT 5.2 Ingestion of Lead in Soil by Children 5.2.1 Scientific Literature Although Dr. Harriet Hardy raised the possibility that humans were exposed to lead in soil in 1965, lead in soil was still not recognized as a pathway of exposure in 1972. The NAS wrote that `Today in the United States, lead poisoning in children is believed to be due almost entirely to the repetitive eating of leaded house paint" (NAS, 1972). The NAS described available data as being based on retrospective analyses of small groups of cases from cities in which childhood lead poisoning was a reportable disease New York City, Chicago, Philadelphia, and Baltimore. The NAS described the `Well established" epidemiologic features of lead poisoned children as: prevalence of pica (the repetitive ingestion of nonfood items such as string, dirt, paint), seasonal features (between 85 to 90% of all known cases were recognized during the period of May through October), age distribution of cases (80 to 85% of cases occurred in children 12 to 35 months old), and association with dilapidated and deteriorating housing. The NAS believed that street dust was a potential source of ingested lead in children. However, based in the available data, ingestion of lead in dust did not appear sufficient to cause poisoning on its own, but that combined with paint ingestion may `Well account, in large part, for the higher mean blood lead content in urban children and the rather large fraction whose blood lead content falls in the range of 40-60 pg /100 g"(NAS, 1972). Nevertheless, NAS concludes: `Even so, the direct ingestion of lead-pigment paints is clearly the principal environmental source in cases of severe acute lead in young children." In 1973, Dr. Lin-Fu, an expert on childhood lead poisoning, wrote that `)jica has a most important role in causing excessive lead intake among children, but normal oral exploration and hand-to-mouth activities in some may also be contributory" (1973 b). She noted that Sayre et al. had measured the lead content of dust found on the hands of inner-city children, lending support to the suggestion that a substantial amount of lead could be introduced into the body through the hand-to-mouth activity of children. Based on these findings, Sayre et al. had suggested that among inner city children, hand-to-mouth activity could easily result in ingestion of a considerable amount of lead. (She also noted that several recent studies suggested that gastrointestinal absorption of lead may be age-dependent and that children 9506710 R91395R.DOC 44 Gradient Corporation PRIVILEGED AND CONFIDENTIAL ATTORNEY WORK PRODUCT appeared to retain significantly higher rates of lead than adults.) Based on lead screening programs which had recently begun and included children from outside the "inner city," she further states that, contrary to earlier literature, the problem of lead poisoning is not confined to the inner city of slums, or to large urban areas, nor is it confined to the eastern part of the United States (Lin-Fu, 1973a;b). In 1971 and 1972, 38% of the children with blood lead levels of 40 pg/100 ml or more came from outer areas (Lin-Fu, 1973a). Therefore, it was not until this time--the early to mid-1970s--that lead poisoning started to be associated with nonurban areas, such as the Bunker Hill area of Idaho, and that lead poisoning from normal hand-tomouth activities was considered possible. In 1977, the World Health Organization (WHO) discussed at length the issue of whether dust and soil was a major source of lead exposure for infants and children. When homes of children with lead poisoning were surveyed, most had flaking paint but others had none, indicating that another source of lead must be present. The information available at the time was contradictory. Griggs et al. (1964) found a significant positive correlation between the presence of elevated urinary lead and the presence of flaking paint inside the homes, but also reported that there was no flaking paint indoors for about a third of the children with elevated urinary lead. In 1973 Guinee reported that in surveying homes where children had blood lead levels of 60 pg/100 ml or more (defined as lead poisoning), the largest number of cases occurred during the summer. In addition, of the children poisoned, 7% were found to be without any apparent source in the home. Of the remaining 93%, 75% of them had at least one surface in which the paint contained more than 1% lead (Guinee, 1973). Another study published that same year (Greenfield et al, 1973 as cited in WHO, 1977), found accessible painted surfaces in only 60% of the homes of inner city children with excessive lead exposure. WHO noted that investigators often overlooked the fact that lead painted surfaces on the outside of houses are potential sources of lead or, `for that matter, that the soil surrounding the houses may have accumulated substantial concentrations of lead from the weathering outer walls." They reported that Fairey and Gray (1970, as cited in WHO, 1977) had reported that the concentration of lead in the soil near homes where pediatric lead poisoning had occurred was over 1,000 mg/kg in 27 out of 30 cases. When soil samples were collected from yards at random, only 30 out of 170 soil samples had concentration of lead in excess of 1,000 mg/kg (Bertinsuon and Clark, 1973 as reported by WHO, 1977). 9506710 R91395R.DOC 45 Gradient Corporation PRIVILEGED AND CONFIDENTIAL ATTORNEY WORK PRODUCT In addition to exterior lead paint as a source of ingested lead, WHO (1977) reported that lead in soil from combusted alkyl lead from car exhaust was also a possible source of lead, based on the data of Ter Haar and Aranow (1974). Street dust, they note, had been found to contain high concentrations of lead. Recent data from 77 midwestem cities in the U.S. indicated that the average concentration of lead in ,dust was 2,413 mg/kg in commercial areas, 1,512 mg/kg in industrial areas, and 1,636 mg/kg in residential areas. But WHO notes that for soil or street dust to be a significant source of lead exposure, it must be inhaled or ingested and that `Evidence regarding the likelihood that young children would ingest soil or street dust is extremely fragmentary." Although one study of 58 children with increased lead burdens had found that 37 had a history of eating dirt and sand, 34 had eaten plaster, and 20 had eaten paint flakes, another had found that children living on soils containing average lead levels of 10,000 mg/kg (in a village near extensive old mine workings) showed no statistically significant elevation in blood lead concentrations when compared to children living on soils with average lead concentrations of 500 mg/kg (Barltrop et al., 1974). Although dust and dirt occur indoors as well as outdoors, only scant attention had been paid to the significance of indoor dust. Sayre et al. (1974) were the first to demonstrate the transfer of lead-bearing house dust of the hands of young children. Sayre found that the dust in older homes of the inner city contained more lead that the dust of suburban homes. In addition, the hands of the children living in the inner city houses were heavily contaminated with lead while the hands of the suburban children were not. Sayre et al. further noted that the lead-containing dust could be rubbed easily from surface with a moist towel and that this, coupled with the correlation between the amount of lead on household surfaces and the hands of children living in the homes, provided further support for the idea that lead on children's hands might be of importance. In 1980, Chamey et al. published the results of a study in which they explored the hypothesis that lead-contaminated household dust was a major source of lead for children with moderately (30 to 80 pg/100 ml) elevated blood lead levels. Forty-nine inner city children with blood lead levels of 40 to 70 pg/100 ml were matched with 50 children with blood lead levels of less than or equal to 29 pg/100 ml. They reported that house dust lead and lead on hands were found in significantly great quantity among the children with the higher blood lead levels (Chamey et al., 1980). They concluded that although the cause 9506710 R91395R.DOC 46 Gradient Corporation PRIVILEGED AND CONFIDENTIAL ATTORNEY WORK PRODUCT of blood lead elevation was multifactorial, lead contamination of house dust and hands appeared to be a major factor in this condition. 5.2.2 Centers for Disease Control The Centers for Disease Control have played the leading role in the U.S. Government in terms of formulating policy and guidelines on safe levels of lead. The policies of the Centers for Disease Control (CDC) largely mirrored the scientific findings reported in the literature. In 1975 CDC published its first monograph on childhood lead poisoning; updated monographs were published in 1978, 1985, and 1991. Commonly known as the `CDC Lead Statements"the document provides guidelines for screening children, definitions of an elevated blood lead level and lead toxicity, recommendations for medical evaluation and management of lead-poisoned children, and guidelines for environmental investigation on lead-hazard abatement. In 1975, CDC stated that dust and dirt may constitute `intermediate dose' sources of lead when contaminated by lead-based paint (CDC, 1975). In 1978 the CDC Lead Statement characterized the contribution of soil and dust to childhood lead exposure this way: `Lead contained in air, dust, and soil may also constitute a hazard for children....Lead in dust and soil is becoming increasingly suspect as a source of lead exposure for young children, especially that within 3 feet of the house's foundation, inside the house, along the heavily traveled roadways, or in vacant lots where housing has been removed" (CDC, 1978). In the 1985 edition, CDC provided an entire section on soil and dust. It stated: `Soil and dust that contain lead are often an important source of lead exposure for children....Children appear to obtain lead from dust and soil as a result of their normal exploratory behavior, coupled in some instances with pica. Because of those mouthing tendencies, young children who live near major sources of airborne lead pollution must be considered at risk of exposure both by inhalation of airborne lead and by ingestion of deposited lead from soil and dust. In general, lead in soil and dust appears to be responsible for blood lead levels in children increasing above background levels when the concentration in the soil or dust exceeds 500-1,000 ppm." This is the first government publication to state unequivocally that lead exposure is related to soil and dust ingestion by children. However the document states that the sources of this lead are airborne lead that is deposited, and flaking lead paint in and around houses; it does not even raise the possibility of other sources of lead in soil such as tailings or fines. 9506710 R91395R.DOC 47 Gradient Corporation PRIVILEGED AND CONFIDENTIAL ATTORNEY WORK PRODUCT In 1991, CDC first included industrial sources as sources of lead in soil and dust. The Lead Statement published that year states: `Soil and dust act as pathways to children for lead deposited from paint, gasoline, and industrial sources." CDC goes on to say that since lead does not dissipate, biodegrade, or decay, the lead deposited into dust and soil becomes a long-term source of lead exposure for children. This is the first CDC Lead Statement in which industrial sources are implicated as contributors to the lead that children ingest in soil and dust. 5.3 Modern Risk Assessment Methods Today, risk assessment is used to quantify the health risks of populations exposed to chemicals in environmental media. The science of risk assessment, as we know it today, is a very new discipline. Quantitative site-specific risk assessment -- the technique used to evaluate health risks associated with the chemicals found at hazardous waste sites today -- has only been in existence since the late 1970s to early 1980s. Prior to the 1980s, the necessary technical foundation had not yet been developed. Risk assessment techniques for soil and dust ingestion are even more recent--EPA first provided recommended soil ingestion rates in 1989. This section describes the basic principles of human health risk assessment and reviews its historical development, especially as it relates to soil and dust ingestion. 5.3.1 Introduction to Risk Assessment Today, much of the concern at hazardous waste sites focuses on exposure to low levels of chemicals in the environment, because we now understand that long-term, low-level exposure to some chemicals may be associated with subtle or latent adverse health impacts or a probability for a no-threshold effect such as cancer. Risk assessment, which is defined as "...the characterization of potential adverse health effects of human exposure to environmental hazards" (NRC, 1983) is used to predict potential effects from these low-level environmental exposures. The term "quantitative risk assessment" is often used synonymously with the term "risk assessment," to indicate that quantitative estimates of risk are being developed. Regulatory agencies frequently employ risk assessments in selecting the appropriate regulatory response to a potential health hazard. Risk assessments have been used by the government to establish water quality criteria, select acceptable levels of contaminants in soil, regulate the level of pesticides and additives in food, and determine cleanup criteria for specific hazardous waste sites. 9506710 R91395R.DOC 48 Gradient Corporation PRIVILEGED AND CONFIDENTIAL ATTORNEY WORK PRODUCT Risk assessment involves the following four steps, which were first presented as a framework by the National Academy of Sciences in 1983 (NRC, 1983): 1. Hazard identification: first, the potential hazard is identified; this involves determining if a particular chemical is causally linked to health effects. 2. Dose-response assessment: a dose-response assessment is performed to determine the relationship between the magnitude of exposure and the probability of the occurrence of the health effect. 3. Exposure assessment: the level of human exposure to the hazard is estimated. 4. Risk characterization: finally, the estimated exposure level is then compared with the value obtained from the dose-response assessment and characterized in a risk estimate, with an assessment of the magnitude of uncertainty. Site-specific human health risk assessments, which are used to estimate the potential hazard to human health from chemical exposures at a particular site, were developed by the U.S. Environmental Protection Agency (USEPA) in compliance with the Comprehensive Environmental Response, Compensation and Liability Act (CERCLA) of 1980. CERCLA mandates the USEPA to assess the hazards associated with waste sites and to take remedial action, if necessary, to protect human health and the environment. Under CERCLA, site-specific risk assessments are used to evaluate potential human health effects associated with the sites, in order to aid in making decisions about remedial alternatives. Modem site-specific risk assessment is a well-defined process that is the result of decades of development. For noncancer health effects, EPA has developed reference doses for most chemicals frequently found at hazardous waste sites. There are two kinds of reference doses: oral reference doses (RfDs) and inhalation reference concentrations (RfCs). An RfD or RfC "is an estimate ... of a daily exposure to the human population (including sensitive subgroups) that is likely to be without appreciable risk of deleterious effects during a lifetime" (USEPA, 1995). The RfD or RfC is then compared to the estimated chemical intake from sources such as those present at a hazardous waste site, to determine if the estimated intake 9506710 R91395R.DOC 49 Gradient Corporation PRIVILEGED AND CONFIDENTIAL ATTORNEY WORK PRODUCT exceeds the RfD or RfC. If it does, a more detailed evaluation is conducted; the results are considered in determining whether remediation is necessary. However, EPA has not developed a RfD or RfD for inorganic lead due to fact that RfDs/RfCs are based on the assumption that there is a threshold for the toxic effects; since EPA has concluded that the existence of a threshold for toxic effects on children is uncertain, EPA has not developed a RfD for lead. For sites where lead is present, EPA has used two approaches to assessing risk: it has invoked lead concentrations in soil that CDC has determined do not appear to be associated with excess lead absorption, and it has used the Integrated Exposure Uptake Biokinetic (IEUBK) Model for Lead in Children. EPA has also concluded that lead is a probable human carcinogen, based on 10 rat bioassays and 1 mouse assay, which showed statistically significant increases in renal tumors with dietary and subcutaneous exposure to several soluble lead salts (e.g., lead phosphates and acetates) (EPA, 1995). However, human data are inadequate and EPA has not developed a cancer slope factor. However, cancer effects are essentially irrelevant, since the effects of concern are neurobehavioral effects believed to occur at low exposures in children. 5.3.2 IEUBK Model The IEUBK Model uses data of environmental lead to estimate blood lead levels in young children. The model includes an exposure component in which a daily absorbed value of lead from all sources, including their diet, ingestion of water, inhalation of air containing lead, and ingestion of lead-bearing soil and dust, is calculated, along with a pharmacokinetic component that estimates the impact on blood lead levels of absorbed lead. The IEUBK Model was developed by EPA in the mid- to Iate-1980s based, in part, on the pharmacokinetic parameters developed by Harley and Kneip in 1985. The model was validated using three blood lead studies in which there existed an active emitter of lead into air: Silver Valley Lead Study conducted in 1974 and 1975 by CDC and the Idaho Department of Health and Welfare, study results reported by Yankel et al., 1977; 9506710 R91395R.DOC 50 Gradient Corporation PRIVILEGED AND CONFIDENTIAL ATTORNEY WORK PRODUCT East Helena, Montana, Child Lead Study, Summer 1983, conducted by the Montana Department of Health and Environmental Sciences, et ai. Final Report July 1986; and Omaha Study conducted form 1971 and 1977, results reported by Angle and Mclntire, 1979. The first documentation of the model was published in 1990 (USEPA, 1990). Since then EPA has continued to revise the model. The current version of the Model contains four components: exposure, absorption, biokinetics, and variability. The exposure component relates concentrations of lead in the environment to the amount of lead that is taken into the body and is available in the gut or the lungs for absorption. The absorption component relates the amount of lead in the gut to the amount of lead absorbed through the gut and into the body's circulatory system. The biokinetic component models the distribution of lead in the body between blood, liver, kidney, other soft tissues, and other body fluids. And last, the variability component provides a measures of how different children exposed to the same environmental levels of lead may have different blood lead levels. Using this model, EPA has recently calculated a residential screening level for lead of 400 ppm. According to guidance distributed by EPA in 1994 (USEPA, 1994), levels of contamination above the screening level would not automatically require a removal action, nor designate a site as "contaminated." EPA recommends the use of the model to assess site-specific exposures. The model evaluates multimedia exposure, incorporates absorption and pharmacokinetic information, and allows the calculation of the potential distributions of exposure and risk likely to occur at the site. Therefore EPA judges this approach `to be superior to the more common method for assessing risks of non-cancer health effects which utilizes the reference dose (RfD) methodology" (USEPA, 1994). 5.3.3 Risk Assessment for Soil Ingestion One of the most important potential exposure pathways for contaminants at hazardous waste sites, namely inadvertent soil ingestion by children on a regular basis, was not addressed by EPA until 1989. As described in detail in the previous section, soil ingestion, as a potential exposure route in young children, did not begin to be recognized by the general medical and scientific community until the early to mid1970s. At about the same time (between 1971 and 1974), soil was also recognized as a potential source of 9506710 R91395R.DOC 51 Gradient Corporation PRIVILEGED AND CONFIDENTIAL ATTORNEY WORK PRODUCT exposure for hazardous materials other than lead when soil in Times Beach, Missouri was tested and found to be contaminated with tetrachloro-dibenzodioxin (TCDD or dioxin). Some of the contaminated soil was removed in an attempt to limit human exposure, although the pathway of exposure was not stated (Carter et al., 1975). In 1984, after a detailed soil study of Times Beach, Kimbrough et al. (1984) proposed the first level of concern for a chemical in soil, setting 1 ppb of TCDD in soil as a level at which to consider limiting human exposure. Because of the increased understanding of the significance of soil contamination, Hawley (1985) undertook a detailed soil exposure analysis and established a lifetime exposure model to assess human health risk from exposure to contaminated soils. In this same year, CDC recognized the importance of lead in soil and dust as an exposure route for childhood lead poisoning. Estimates of soil ingestion rates based on empirical studies began to be published at this time (Binder, et al., 1986; Calabrese et al., 1987). EPA first recommended soil ingestion rates in 1989 when it recommended an intake value of 200 mg/day of soil for children under the age of 6, and 100 mg/day for individuals, including adults, above this age. Based on a study by Calabrese et al. (1990), EPA adopted a default value of 50 mg/day for adult ingestion of soil and dust in the "typical" workplace. Today there is still much debate regarding how much soil is inadvertently ingested by individuals (Sedman and Mahmood, 1994; Calabrese and Stanek, 1993), and more recent work indicates that EPA's default values may be too high. For example, when the results from Calabrese et al. (1989) and Davis et al. (1990) studies are averaged, the overall estimate of childhood soil ingestion is 77 mg/day. Calabrese's most recent work is in agreement with this ingestion rate. Using tracer studies, Calabrese (1994) calculated median and arithmetic average values of 40 and 83 mg/day, respectively, for central tendency soil ingestion rates in children. A recent re-analysis of the Calabrese data corroborates these values (Stanek and Calabrese, 1995). Calabrese and Stanek are now analyzing the concentrations of tracer metals by size of soil particle so that they can take into account the fact that certain metals are disproportionately represented in the smaller sized particles (E.J. Calabrese, personal communication). Research into the bioavailability of lead in soil and dust is also being conducted. Since lead in soil is much less bioavailable than lead in other media, research has been conducted in order to characterize that bioavailability. Lead in soil and dusts is less available biologically than lead in food and water, because it 9506710 R91395R.DOC 52 Gradient Corporation PRIVILEGED AND CONFIDENTIAL ATTORNEY WORK PRODUCT reacts with soil to form insoluble salts (Lansdown and Yule, 1986). For example, one group of researchers compiled information on residents of several different communities, all of whom lived in close proximity to mill tailings; they found no evidence of health effects or elevated blood lead levels due to the tailings. The authors concluded that metals in tailings or soils, unlike fine metallic dusts, are unlikely to be bioavailable to humans because of large particle size, adsorption to soil, entrainment in a rock matrix, and low intrinsic solubility (Danse et al., 1991). In another study, researchers reported that the bioavailability of lead from soils at the Butte, Montana site was reduced because the soil contained adsorbing surfaces which reduced the absorption of lead in the small intestine (Freeman et al., 1992). Other researchers have found that the particles size greatly impacts intestinal absorption - the larger the particle, the less well-absorbed it is (Barltrop and Meek, 1979). For lead sulfide, in particular, it was found that the larger particles took a much longer time to solubilize than smaller particles, indicating that they could pass through the gastrointestinal tract before being converted to a more readily absorbed form (Healy et al., 1982). 9506710 R91395R.DOC 53 Gradient Corporation 6 Conclusions PRIVILEGED AND CONFIDENTIAL ATTORNEY WORK PRODUCT Based on the historical medical and scientific literature on the toxicity of lead, as corroborated by site-specific information, I conclude that: Historic concerns for effects of lead in adults and children were for overt symptoms, such as colic, wrist drop, convulsions, and even death. A dose response relationship for lead was recognized historically as reflected in the use of lead for medicinal purposes in certain circumstances. It was generally believed by the medical and scientific community that the potential for adverse effects of lead in workers varied among industries, with lead mining being of relatively low hazard. Even among lead mines, the potential for hazard varied with the type of ore with lead sulfide ores being least toxic, and the amount of dust - less dusty environments being of lesser hazard. Most of the initial concern for children was for children with pica ingesting lead in paint. Concern for lead exposure from tetra-ethyl lead in gasoline developed later. Today's concerns for effects of lead in young children are based on subtle neurobehavioral effects that occur at blood lead levels much lower than those associated with overt poisoning. There is still vigorous debate as to what dose levels cause such effects, how long the effects persist, and which children are at risk. The awareness of soil as an exposure pathway did not begin to be developed until the mid1970s and even today the amount of soil ingested and the bioavailability of different forms of lead continue to be a source of debate. 9506710 R91395R.DOC 54 Gradient Corporation PRIVILEGED AND CONFIDENTIAL ATTORNEY WORK PRODUCT The IEUBK model, which is used by EPA to quantify potential impact of lead in soil and dust on blood lead levels, was not developed until the mid-1980s and not applied to lead in soil until later. This model forms the basis of risk assessments for lead in soil and, hence, risk management decisions regarding remediation. Historically and through the present, it has been recognized that different forms of lead are absorbed differently into the body, resulting in different levels of risk for the same amount of lead. For lead in tailings from lead sulfide ore, the large particle size, form of lead (lead sulfide), and associated matrix limits the uptake of mining lead when ingested in soil or dust. Thus, at the time that Hecla Mining Company and Day Mines Inc. were operating their mines and continuing through the 1970s, the medical and scientific community did not begin to be aware of the potential concern for lead in soil - namely the potential for subtle neurobehavioral effects in children from inadvertent ingestion of lead in soil. Although some scientists suggested a relationship between soil ingestion and neurobehavioral effects in children in the mid-1970s, scientific consensus accepting the importance of ingestion of lead in soil did not occur until the 1980s. Our knowledge regarding these effects continues to develop as new research is conducted to elucidate which effects occur, how long they persist, and what doses cause them. It is, therefore, unreasonable to conclude that the owners and operators of the Hecla Mining Company and Day Mines Inc. could, at the time the mines were operating and through the 1970s have anticipated the human health concerns of today which require consideration of remedial activities at the Bunker Hill site. 9506710 R91395R.DOC 55 Gradient Corporation References PRIVILEGED AND CONFIDENTIAL ATTORNEY WORK PRODUCT Agency for Toxic Substances and Disease Registry (ATSDR). 1993. Toxicological Profile for Lead Update. Atlanta, GA: Agency for Toxic Substances and Disease Registry. National Technical Information Service. PB 93-182475. Albert, R.E. 1994. Carcinogen risk assessment in the U.S. Environmental Protection Agency. Crit. Rev. Toxicol. 24(l):75-85. Allcroft, R. 1950. Lead as a nutritional hazard to farm livestock. IV. Distribution of lead in the tissues of bovines after ingestion of various lead compounds. J. Comp. Path. 60:190-208. Amdur, M.O., J. Doull, and C.D. Klaassen, eds. 1991. Casarett and Doull's Toxicology: The Basic Science ofPoisons. Fourth Edition. Pergamon, NY. 1033 pp. American Conference of Governmental Industrial Hygienists (ACGIH). 1991. Documentation of Threshold Limit Values and Biological Exposure Indices, Sixth Edition with updates through 9/1/94. Cincinnati, OH: American Conference of Governmental Industrial Hygienists. Aub, J.C., L.T. Fairhall, A.S. Minot, and P. Reznikoff. 1925. Lead poisoning. Medicine 4(1-2): 1-250. Babcock, F.J., E.O. Cathcart, and J.H. Taylor. 1933. Report and Recommendations of the Coeur d'Alene River and Lake Commission to the Twenty-Second Session of the State Legislature of Idaho. Barltrop, D. and F. Meek. 1979. Effect of particle size on lead absorption from the gut. Arch. Environ. Health 34:280-285. Barltrop, D., C.D. Strehlow, I. Thorton, and J.S. Webb. 1974. Significance of high soil lead concentrations for childhood lead burdens. Environ. Health. Persp. May:75-82. 9506710 R91395R.DOC 56 Gradient Corporation PRIVILEGED AND CONFIDENTIAL ATTORNEY WORK PRODUCT Belden, E.A. and L.F. Garber. 1949. Health of workers exposed to galena. J. Ind. Hyg. Toxicol. 31(6):347-351. Bellinger, D., A. Leviton, E. Allred, and M. Rabinowitz. 1994. Pre- and postnatal lead exposure and behavior problems in school-aged children. Environ. Res. 66:12-30. Bhat, R.V. and K.A.V.R. Krishnamachari. 1980. Environmental lead toxicity in cattle. Bull. Environ. Contam. Toxicol. 25:142-145. Binder, S., D. Sokal, and D. Maughan. 1986. Estimating soil ingestion: The use of tracer elements in estimating the amount of soil ingested by young children. Arch. Environ. Health 41(6):341-346. Calabrese, E.J. 1994. Presentation to U.S. Environmental Protection Agency. Amherst, Massachusetts. September 28. Calabrese, E.J. and S.J. Stanek, III. 1993. An improved method for estimating soil ingestion in children and adults. J. Environ. Sci. Health A28(2):363-371. 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Center for Disease Control. 1975. `Increased Lead Absorption and Lead Poisoning in Young Children." U.S. Department of Health, Education, and Welfare." Public Health Service, Center for Disease Control. Bureau of State Services. Environmental Health Services Division, Atlanta, GA. Chamey, E., J. Sayre, and M. Coulter. 1980. Increased lead absorption in inner city children: Where does the lead come from? Pediatrics 65(2):226-231. Cumpston, A.G. 1968. Health and disease in the mining industry. Med. J. Australia 1(22): 1143-1144. Danse, I.H.R., L.G. Garb, and D.H. Moore. 1991. Metal-containing mill tailings in or near residential soils: Implications for health of nearby communities. Arch. Environ. Health 46(3): 187. Davis, S., P. Waller, R. Buschbom, J. Ballou, and P. White. 1990. Quantitative estimates of soil ingestion in normal children between the ages of 2 and 7 years: Population-based estimates using aluminum, silicon, and titanium as soil tracer elements. Arch. Env. 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Hamilton, A. 1925. `Chapter 10: Lead Mining, Lead Smelting and Refining, Zinc Smelting, Metallic Lead." In: Industrial Poisons in the United States. The MacMillan Company, New York. pp. 124-139. Harboume, J.F., C.T. McCrea, and J. Watkinson. 1968. An unusual outbreak of lead poisoning in calves. Vet. Rec. 83:515-517. Hardy, H.L. 1965. `Lead." In: Symposium on Environmental Lead Contamination. U.S. Department of Public Health Service. December 13-15. pp. 73-86. 9506710 R91395R.DOC 59 Gradient Corporation PRIVILEGED AND CONFIDENTIAL ATTORNEY WORK PRODUCT Hatcher, R.A. and M.I. Wilbert. 1915. `Chapter XI. The Heavy Metals and their Salts. In: The Pharmacology of Useful Drugs. American Medical Association, Chicago, pp. 354-382. Hawley, J.K. 1985. Assessment of health risk from exposure to contaminated soil. Risk Analysis 5(4):289-302. Healy, M.A., P.G. Harrison, M. Aslam, S.S. Davis, and C.G. Wilson. 1982. 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