Lead is a ubiquitous metal in the environment, and its adverse effects on human health are well documented. Lead interacts at multiple cellular sites and can alter protein function in part through binding to amino acid sulfhydryl and carboxyl groups on a wide variety of structural and functional proteins. In addition, lead mimics calcium and other divalent cations, and it induces the increased production of cytotoxic reactive oxygen species. Adverse effects associated with lead exposure can be observed in multiple body systems, including the nervous, cardiovascular, renal, hematologic, immunologic, and reproductive systems. Lead exposure is also known to induce adverse developmental effects in utero and in the developing neonate.
Lead poses an occupational health hazard, and the Occupational Safety and Health Administration (OSHA) developed a lead standard for general industry that regulates many workplace exposures to this metal. The standard was promulgated in 1978 and encompasses several approaches for reducing exposure to lead, including the establishment of a permissible exposure limit (PEL) of 50 μg/m3 in air (an 8-hour time-weighted average [TWA]), exposure guidelines for instituting medical surveillance, guidelines for removal from and return to work, and other risk-management strategies. An action level of 30 μg/m3 (an 8-hour TWA) for lead was established to trigger medical surveillance in employees exposed above that level for more than 30 days per year. Another provision is that any employee who has a blood lead level (BLL) of 60 μg/dL or higher or three consecutive BLLs averaging 50 μg/dL or higher must be removed from work involving lead exposure. An employee may resume work associated with lead exposure only after two BLLs are lower than 40 μg/dL. Thus, maintaining BLLs lower than 40 μg/dL was judged by OSHA to protect workers from adverse health effects. The OSHA standard also includes a recommendation that BLLs of workers who are planning a pregnancy be under 30 μg/dL.
A large body of literature on health effects of lead exposure and factors that influence lead toxicity has been published since the 1978 OSHA standard was established. Most recently, the US National Toxicology Program (NTP) released a monograph on the health effects of low-level lead exposure, defined by the NTP as BLLs of under 10 μg/dL and in some cases under 5 μg/dL. The
US Environmental Protection Agency (EPA) has also released an external review draft of its Integrated Science Assessment for Lead in support of its review of the National Ambient Air Quality Criteria for lead. The NTP and EPA reviews provide compelling evidence of a variety of health effects associated with BLLs of 10-40 μg/dL and of some health effects at lower levels.
In light of knowledge about the hazards posed by occupational lead exposure, the Department of Defense (DOD) asked the National Research Council to evaluate potential health risks from recurrent lead exposure of firing-range personnel. Specifically, DOD asked the National Research Council to determine whether current exposure standards for lead on DOD firing ranges protect its workers adequately. To address its charge, the committee focused on determining whether there is evidence of adverse health effects in people who have BLLs of 40 μg/dL or lower because that is the implicit level in the OSHA standard to protect workers from adverse health effects; indeed, the standard allows workers to have a BLL up to 40 μg/dL for a 40-year working lifetime. The committee also considered measures of cumulative lead dose. These can include the measurement of lead stored in bone or the calculation of a cumulative blood lead index (CBLI). At a BLL of 40 μg/dL, a CBLI of 1,600 μg-years/dL (the product of a BLL of 40 μg/dL and a 40-year working lifetime) could be achieved. The index is roughly equivalent to a bone (tibia) lead concentration of 40-80 μg/g (2.5-5% of the CBLI). Thus, the committee also sought evidence that would relate these cumulative measures of lead dose to adverse health effects.
The committee obtained data from the US military services to determine current lead exposure on DOD firing ranges. Data collected for the last 5 years show that the OSHA PEL for lead of 50 μg/m3 was frequently exceeded on Army, Navy, and Air Force firing ranges, in some cases by several orders of magnitude. BLL data on firing-range personnel were not available from either the Army1 or the Navy because the available measurements were not linked to job classifications, but the Air Force reported that BLLs of its firing-range personnel were all under 40 μg/dL.
A review of the epidemiologic and toxicologic data allowed the committee to conclude that there is overwhelming evidence that the OSHA standard provides inadequate protection for DOD firing-range personnel and for any other worker populations covered by the general industry standard. Specifically, the premise that maintaining BLLs under 40 μg/dL for a working lifetime will protect workers adequately is not valid; by inference, the OSHA PEL and action level are also inadequate for protecting firing-range workers. The committee found sufficient evidence to infer causal relationships between BLLs under 40 μg/dL and adverse neurologic, hematopoietic, renal, reproductive, and cardio-vascular
1After the committee completed its evaluation and released the prepublication draft of this report, the Army submitted data on BLLs for Department of the Army civilian personnel working at shoot houses. The Army’s submission can be obtained by contacting the National Research Council’s Public Access Records Office at (202) 334-3543 or firstname.lastname@example.org.
effects. The committee also found compelling evidence of developmental effects in offspring exposed to lead in utero and during breastfeeding, and this raises additional concerns about exposures of women of childbearing age.
BLLs are generally considered to represent recent exposure to lead (on the basis of the lifespan of the erythrocyte and BLL’s representing the integrated dose over the prior 4 months or so). Because lead in blood is in equilibrium with lead stored in bone, where lead can reside for decades, some BLLs can also reflect past higher or cumulative exposures. Therefore, BLLs measured later in life can reflect both current and past cumulative exposure, so interpretation is difficult. For example, studies that used data from the National Health and Nutrition Examination Survey to relate BLLs to risk of chronic kidney disease have reported a striking rise in risk of the disease in the highest quintile of BLL compared with the lowest quintile even though the mean BLL in the highest quintile is only 3-4 μg/dL. Those in the highest quintile may have had higher BLLs earlier in life that resulted in a greater cumulative lifetime exposure to lead than may be inferred from the current BLL, which is in equilibrium with possibly higher bone stores. In that case, cumulative exposure is more likely to be associated with the observed chronic effect on renal function, so the BLL of 3-4 μg/dL might not represent a “threshold level”.
Despite those shortcomings of the BLL, the committee decided to present the range of BLLs that have been associated with various acute and chronic health outcomes:
• Adverse renal effects are manifested by increases in serum creatinine at BLLs of 8-12 μg/dL, decreases in creatinine clearance and glomerular filtration rate at BLLs of 20-30 μg/dL, and effects on renal endocrine functioning at BLLs of 30-40 μg/dL. The latter might be responsible, in part, for the increases in blood pressure observed with high BLLs.
• Adverse cardiovascular effects of concern include increased blood pressure at BLLs under 10 μg/dL and increased cardiovascular-disease mortality at BLLs of 8 μg/dL or higher. A relationship between BLLs under 40 μg/dL and cardiovascular mortality and some subclinical cardiovascular outcomes has also been observed in older and other susceptible subpopulations.
• Adverse nervous system effects include dose-related changes in cognitive and psychomotor performance at a BLL of about 18 μg/dL and such neurophysiologic changes as hearing loss at BLLs under 10 μg/dL, changes in balance at BLLs of about 14 μg/dL, changes in visual function at BLLs of 17-20 μg/dL, slowed auditory evoked potentials at BLLs of 26-30 μg/dL, changes in autonomic function at BLLs over 20 μg/dL, and changes in peripheral sensory nerve function at BLLs around 30 μg/dL.
• Adverse hematologic effects include impaired formation and impaired survival of erythrocytes at BLLs of about 20-30 μg/dL.
• Adverse developmental effects were found in infants and children at maternal BLLs under 10 μg/dL, and reduced fetal growth and low birth weight
• The International Agency for Research on Cancer, the NTP, and EPA have identified lead as likely to be carcinogenic to humans largely on the basis of nonhuman experimental evidence. The committee found no reason to disagree with those conclusions but notes that the available human studies were insufficient to support a conclusion about an association of BLLs with cancer in humans.
Given the committee’s findings about the inadequacy of the OSHA lead standard, DOD should review its guidelines and practices for protecting workers from lead exposure on firing ranges. One consideration should be a lowering of acceptable BLLs to more stringent levels that reduce the risk of adverse health effects. Professional organizations have called for more protective guidelines. For example, the American College of Occupational and Environmental Medicine has recommended medical removal of workers who have BLLs over 20 μg/dL, and the Council of State and Territorial Epidemiologists has suggested that the case definition of an elevated BLL in adults be changed from 25 μg/dL to 10 μg/dL. The Association of Occupational and Environmental Clinics has recommended more stringent guidelines for medical management of lead-exposed workers, which have been incorporated into DOD’s guidance for occupational medical examinations and surveillance. All those organizations recommend that BLLs be kept under 5 μg/dL in pregnant women to reduce the risk of spontaneous abortion. The Centers for Disease Control and Prevention has developed guidelines that recommend followup activities and interventions beginning at a BLL of 5 μg/dL in pregnant women.
Because little BLL data on DOD range workers were available, it was not possible to determine potential health risks to this specific population. However, data on airborne concentrations of lead on DOD firing ranges indicate that the current OSHA PEL is exceeded in the performance of some job duties, in some cases by several orders of magnitude, and this may lead to increased BLLs. Thus, DOD should consider analyzing BLLs of a representative sample of range workers in all the services and comparing them with BLLs linked to adverse health outcomes to understand potential health risks and to guide risk-management decisions at its ranges. Protecting workers from exposure to lead involves an integrated approach that combines protective air and BLL guidelines, environmental and biologic monitoring to ensure that the guidelines are met, environmental controls to minimize exposure to lead, and appropriately designed medical surveillance. Consideration should be given to performing risk analyses of available control options to determine the best way to minimize exposure to lead. Such analyses could include assessment of exposure to lead (and other contaminants) at ranges where lead-free or jacketed ammunition is primarily used, assessment of risks related to range design and ventilation controls, and evaluation of the contribution of surface contamination to oral lead exposure.