FINAL Report on Carcinogens Background Document for Lead and Lead Compounds May 8, 2003 Prepared for the: U.S. Department of Health and Human Services Public Health Service National Toxicology Program Research Triangle Park, NC 27709 Prepared by: Technology Planning and Management Corporation Canterbury Hall, Suite 310 4815 Emperor Blvd Durham, NC 27703 Contract Number N01-ES-85421 05/08/03 RoC Background Document for Lead and Lead Compounds FOREWORD The Report on Carcinogens (RoC) is prepared in response to Section 301 of the Public Health Service Act as amended. The RoC contains a list of all substances (i) that either are known to be human carcinogens or may reasonably be anticipated to be human carcinogens and (ii) to which a significant number of persons residing in the United States are exposed. The Secretary, Department of Health and Human Services, has delegated responsibility for preparation of the RoC to the National Toxicology Program, which prepares the Report with assistance from other Federal health and regulatory agencies and nongovernmental institutions. Nominations for listing in or delisting from the RoC are reviewed by a formal process that includes a multi-phased scientific peer review and several opportunities for public comment. The review groups evaluate each nomination according to specific RoC listing criteria. This Background Document was prepared to assist in the review of the nomination of lead and lead compounds. The scientific information in this document comes from publicly available peer-reviewed sources. Any interpretive conclusions, comments, or statistical calculations made by the authors of this document that are not contained in the original source are identified in brackets [ ]. If any members of the scientific peer review groups feel that this Background Document does not adequately capture and present the relevant information, they will be asked to write a commentary for this Background Document that will be included as an addendum to the document. In addition, a meeting summary that contains a brief discussion of each review group’s review and recommendation for the nomination will be added to the Background Document, also as an addendum. A detailed description of the RoC nomination review process and a list of all nominations under consideration for listing in or delisting from the RoC can be obtained by accessing the NTP Home Page at http://ntp-server.niehs.nih.gov. The most recent RoC, the Ninth Edition, was published in May 2000 and may be obtained by contacting the National Institute for Environmental Health Sciences Environmental Health Information Service at http://ehis.niehs.nih.gov (800-315-3010). i 05/08/03 RoC Background Document for Lead and Lead Compounds ii 05/08/03 RoC Background Document for Lead and Lead Compounds Executive Summary Introduction Lead can be used in its pure form as a metal, alloyed with other metals, or used in chemical compounds. Inorganic lead compounds usually consist of lead in the divalent state. Organic lead compounds were used in automotive gasoline additives in the United States until 1996. Lead and lead compounds were nominated by the National Institute of Environmental Health Sciences based on the 1987 finding by the International Agency for Research on Cancer (IARC) of sufficient evidence of carcinogenicity in experimental animals to identify lead and inorganic lead compounds as possibly carcinogenic to humans (Group 2B) and the subsequent publication of additional human and animal studies of lead and lead compounds. Human Exposure Use. In worldwide metal use, lead ranks behind only iron, copper, aluminum, and zinc. Its greatest use is in lead-acid storage batteries found in motor vehicles and general industry. Other common uses of lead metal include ammunition, cable covering, piping, brass and bronze, bearing metals for machinery, and sheet lead. Lead oxides are found in paint, glass, and ceramics. Organic lead was used in motor vehicle fuels as an anti-knock additive in the United States until 1996, when it was banned by the U.S. Environmental Protection Agency, following a phase-out initiated in the 1970s. Organic lead still is permitted for use in gasoline for aircraft and in fuels for racing vehicles and for non-road vehicles such as farm machinery, marine vessels, construction equipment, and recreational vehicles. Despite reductions in some lead applications and the legislated end to use of lead as a gasoline additive, the overall consumption of lead is growing, mainly due to increased production of lead-acid batteries. Production. Lead is refined from mined ore. Lead ore occurs most frequently in the form of lead sulfide, also known as galena. As of 2000, 19 mines, employing approximately 1,000 workers, produced the vast majority of lead in the United States. Mined lead ore first is crushed and ground; then the various minerals are separated, resulting in a lead concentrate, which is shipped to a primary smelter for refining. At a primary smelter, lead concentrates are sintered, then roasted and subjected to a series of refining steps, resulting in lead metal that is 99.99% pure. In 2001, two primary lead smelter-refineries were operating, employing a total of approximately 400 people. Secondary smelters (recycling smelters) use scrap lead, mainly from used lead-acid batteries, as their supply. As of 2001, 26 secondary lead smelters were operating within the United States, employing approximately 1,600 workers. In 2001, the United States produced 1,375,000 tons of lead, used 1,687,000 tons of lead, and recycled 1,099,000 tons of lead. Environmental exposure. Environmental exposure to lead results in absorption of lead into the body via inhalation (approximately 30% to 50% absorbed into the bloodstream), via ingestion (approximately 8% to 15% absorbed into the bloodstream) and, to a limited extent, through the skin. Air lead concentrations may be > 10 μg/m3 near industrial sources such as smelters. A 1991 survey of lead levels in U.S. urban air revealed a maximum quarterly mean concentration of approximately 0.08 μg/m3. Rural iii 05/08/03 RoC Background Document for Lead and Lead Compounds concentrations typically are lower, bringing the estimated U.S. mean air lead concentration to 0.04 μg/m3 in 1995. The average intake of lead by inhalation is estimated at 2 μg/day for an adult living in a U.S. urban setting. Lead concentrations in U.S. drinking water generally are below 5 μg/L. Lead also is found in food, cigarette smoke, and alcoholic beverages. In 1990, the estimated daily intake of lead from consumption of food, water, and beverages was approximately 4 μg/day for children 2 years of age and younger, 6 to 9 μg/day for children aged 14 to 16, 6 to 9 μg/day for adults aged 25 to 30, and 2 to 8 μg/day for adults aged 60 to 65. The most common source of environmental lead exposure for young children is direct ingestion of paint chips and leaded dusts and soils released from aging painted surfaces, which can contribute an additional intake of 5 μg/day for a toddler engaging in normal hand-to-mouth activity. Occupational exposure. The most common route of occupational exposure to lead is inhalation of lead fumes or leaded dusts in air and absorption of lead through the respiratory system. Lead also may be ingested and absorbed in the gastrointestinal tract. The National Institute for Occupational Safety and Health has estimated that more than three million Americans potentially are occupationally exposed to some form of lead. Many occupations have the potential for high exposure to lead. Occupations having frequent high exposure to lead include battery-production workers, battery-recycling workers, foundry workers, lead chemical workers, lead smelter and refinery workers, leaded-glass workers, pigment workers, and radiator-repair workers. Occupations with moderate frequency of high exposures include firing-range instructors, house renovators, lead miners, newspaper printers, plastics workers, rubber workers, and steel welders and cutters. Occupations with low frequency of high exposure include automobile-repair workers, cable-production workers, construction workers, demolition workers, firing­ range participants, flame-solder workers, plumbers and pipe fitters, pottery-glaze producers, ship-repair workers, and stained-glass producers. Mean lead air concentrations in U.S. industries, as monitored by the Occupational Safety and Health Administration, ranged from 165 μg/m3 (secondary smelters) to 200 μg/m3 (storage-battery plants and brass, bronze, and copper foundries). Human Cancer Studies IARC reviewed lead and lead compounds in 1987 and concluded that the evidence available at that time, which was very limited, was inadequate to demonstrate human carcinogenicity. The number of epidemiologic studies on the potential role of lead exposure in cancer has expanded since the last IARC update; 17 case-control and 17 cohort studies have been published, as well as updates on previously studied populations and meta-analyses. Steenland and Boffetta (2000) calculated a fixed-effects rate ratio of 1.04 (95% confidence interval [CI] = 1.00 to 1.09) for all cancers combined (N = 1,911) based on eight cohort studies of highly exposed workers. Lung cancer. Meta-analyses performed since the IARC review have reported significantly elevated relative risks (RRs) for lung cancer and lead exposure. Fu and Boffetta calculated RRs of 1.24 (95% CI = 1.16 to 1.33) based on 15 studies and 1.42 (95% CI = 1.05 to 1.92) based only on studies of battery and smelter workers, who were iv 05/08/03 RoC Background Document for Lead and Lead Compounds considered to have the highest exposure. Steenland and Boffetta (2000) calculated an RR of 1.30 (95% CI = 1.15 to 1.46; 675 lung-cancer deaths) based on eight cohort studies in which lead was the predominant exposure.