Legacy contaminants of emerging concern: lead (Pb), Flint (MI), and human health

ENVIRONMENTAL CLAIMS JOURNAL https://doi.org/10.1080/10406026.2019.1661947 1 2 Legacy Contaminants of Emerging Concern Lead (Pb), 3 4 Flint (MI), and Human Health 5 6 Robert A. Michaels 7 RAM TRAC Corporation 8 9 ABSTRACT KEYWORDS 10 As a heavy metal industrially mined for millenia, lead (Pb) is a lead; Pb; drinking water; 11 legacy contaminant. It is also a contaminant of emerging con- children’s health; legacy contaminants; contaminants cern because of its persistence, toxicity, and recent discovery 12 of emerging concern; of its resurgence in drinking water serving homes and schools, human health risk 13 recently and most notoriously in Flint, Michigan. Concern assessment; environmental 14 about lead, however, has reemerged beyond Flint, exemplify- justice; science policy; ing adoption of bad science policy despite availability of rele- social policy 15 vant good science. Much is known about lead toxicity, and 16 profiled here. Whereas adults chronically exposed to lead may experience peripheral neuropathy, infants and children are 17 more susceptible. They constitute sensitive subpopulations 18 because their blood-brain barriers are immature, making them susceptible to central nervous system effects, most notably 19 reduced IQ, when lead penetrates to developing brains. 20 Failure to protect disadvantaged populations in Flint and 21 beyond despite availability of proven science and inexpensive technology also exemplifies instances of environmental injust22 ice. Emerging concern about lead thus illustrates failure of 23 social as well as science policy. A critical lesson to be learned is that vigilance must be maintained, as knowledge about 24 lead exposure and toxic effects provided by science does not 25 automatically result in consistent and evenhanded legal and 26 regulatory protection provided by government. 27 28 29 30 Introduction 31 Use of lead (Pb, Latin, plumbum) in water pipes as far back as ancient 32 Rome gave rise to the term ‘plumbing’, and to ‘plumbism’ in heavily 33 exposed people such as plumbers. Lead use in ancient Roman aqueducts, 34 continuing to present-day plumbing, has exposed humans via ingestion of 35 drinking water. Modern use of lead in manufacture of paint has resulted in 36 human exposure via ingestion of paint chips, especially in children with 37 pica, the habit of ingesting non-food items. Infants and children constitute 38 sensitive subpopulations because their blood-brain barriers are immature, 39 40 41 CONTACT Robert A. Michaels ram@ramtrac.com; www.ramtrac.com RAM TRAC Corporation, 3100 Rosendale Road, Schenectady, NY 12309, USA. 42 Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/becj. 43 (cid:1) 2019 Taylor & Francis Group, LLC

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making them susceptible to neurological effects, most notably reduced IQ, when lead penetrates to developing brains. The problem of lead exposure, including exposure of children, also has been exacerbated by the centurylong use of lead as a gasoline additive, giving rise to airborne exposure from automotive exhaust emissions, and to multiple routes of exposure to

residues of lead and its compounds, even after lead was banned as a gasoline additive in the 1970s (for example: Day et al. 1975, Duggan and Williams 1977, Lepow et al. 1974, 1975; Mahaffey 1977). Lead continues to be a component of ammunition and sinkers used in recreational hunting and fishing respectively, together giving rise to ongoing ecosystem exposure and to human exposure from ingestion of game birds and fish. As a heavy metal industrially mined for millenia, lead is a legacy contaminant. It is also a contaminant of emerging concern because of its persistence, toxicity, and recent discovery of its resurgence in drinking water serving homes and schools, recently and most notoriously in Flint, Michigan (Erickson 2018). Concern about lead, however, actually is a

widespread problem [Pell, and Schneyer (2016); and see, for example, Beller (2019) regarding New Orleans, Louisiana; Hallum (2019) regarding New York City, and Corasaniti, Gilgannon, and Schwartz (2018) regarding Newark, New Jersey]. Testing of water fountains in New York City parks, for example, revealed widespread lead contamination, of sufficient magnitude (exceeding the 15-ppb Federal safe drinking water standard) to require shutting down numerous fountains (Queens was the most affected of New York City’s five boroughs) pending remediation (Hallum 2019). Contaminants of ‘emerging concern’ constitute a subset of legacy contaminants, distinguished by the recency of awareness of their presence and/or sig- (cid:1) nificance in the environment (Sauve and Desrosiers 2014). An alternative definition inappropriately would include substances that are not yet in commerce, as they ‘emerge’ as candidates for possible commercial use. This moving-target definition suggests that emerging candidates for commercial use also are contaminants of emerging concern. They might turn out to be if their entry into commerce materializes, but they should not be by definition, as their commercial use should be regulated proactively, consistent with their properties and environmental dynamics. Some substances placed in commerce before regulation under modern national and international environmental statutes have been disseminated globally, and some of these exhibit essentially infinite persistence in the

environment. Most of the latter are heavy metals, most notably including lead, and also including (the metalloid) arsenic (As), until recent decades widely used in pesticides (‘arsenicals’). Several of the persistent substances

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are organic, including DDT, PAHs, PCBs, PFCs1, and chlorinated dibenzop-dioxins (‘dioxins’). Many of the metals and organics also tend to bioconcentrate, meaning that they may attain concentrations in organisms that are higher, possibly orders of magnitude higher, than the concentrations in environmental media from which they originated.

U. S. Environmental Protection Agency (US EPA) regulation of lead must be viewed holistically, including in the special context of lead toxicity to children, and the Agency’s longstanding special mandate regarding children’s health, embodied by EPA’s Children’s Health Risk Initiative (see, for example, US EPA 2001). In 1997 the Office of Children’s Health Protection was instituted within EPA. Its mission was and remains “to make children’s health protection a fundamental goal of public health and environmental protection … [by] ensuring strong standards that protect children’s health … ” Indeed, EPA recently has initiated a grant program for clean diesel school buses, and cre-

ated a federal lead action plan, but inexplicably has eliminated funding for children’s health research centers (Hiar and Wittenberg 2019). Lead appropriately has been the focus of much regulatory agency attention, domestically (for example US EPA 1988a, b; 1989a) and internationally (for example, UN WHO 1977). Domestically, the Agency for Toxic Substances and Disease Registry (ATSDR), within the U. S. Public Health Service, Centers for Disease Control, has performed some of the most detailed analysis of lead toxicology, releasing two extensive toxicological profiles in 1993 and 2007 and, in May 2019, a draft toxicological profile for

public comment (ATSDR 2019). ATSDR also released its Toxicological Profiles on CD-ROM (ATSDR 1997).

Methods

This assessment is based upon critical examination of available literature relating to lead and its compounds, including environmental dynamics and processes potentially giving rise to human exposure. The analysis is mostly qualitative. Methods applied are generally those of scientific peer review and toxicological health risk assessment, most essentially including critical evaluation of published findings, including both recent and historical findings. Critical evaluation of recent literature holistically, in the context of earlier literature, facilitates reexamination of earlier conclusions, and inte-

gration with more recent findings toward updating them, and/or drawing new conclusions.

1 DDT: 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane, PAHs: polycyclic aromatic hydrocarbons, PCBs: polychlorinated biphenyls, and PFCs: perfluroalkyl compounds.

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Findings

Lead (Pb) in flint (MI): emerging concern about a legacy contaminant To maintain drinking water potability, corrosion of chloride from aging lead pipes must be controlled to within acceptable limits. One way of accomplishing this is via the process of ‘scaling’: treating water with negative phosphate ions, which react with positive lead ions leached from the

pipes, forming an insoluble crust (‘scale’) of lead phosphate [Pb (PO ) ] 3 4 2 that seals the pipes and prevents further leaching (Service 2019). Laboratory tests suggest that this process, which may take months to years, can be greatly accelerated by threading a wire through the lead pipes, and running an electric current through the wire, producing the required protective scale within hours. Water supplied by the City of Detroit to the City of Flint was appropriately treated (McNutt 2016). However, this protection of the drinking water supply changed when, faced with a $15-million budget deficit, Flint decided to switch its drinking water supply, requiring temporary (two-year) reliance on water from the Flint River pending construction of a pipeline to Lake Huron. Levels of the negative chloride ion in Flint River water were some eight times higher than in Detroit water which, if uncontrolled, would promote leaching of lead into the water. Indeed, the chloride could have been controlled at a cost of about $100,000, that is, for about $1 per resident. According to McNutt (2016), “What is inexcusable in the Flint case is the apparent failure by the Michigan Department of Environmental Quality to weigh the costs of corrosion control against the harm to public health, despite informing … EPA of their intent to control corrosion.” Lead in Flint’s drink-

ing water rose to unacceptably high, toxic levels. In response, “Governor [Rick] Snyder of Michigan sought $28 million to fix the problem that his office created” (McNutt 2016). Also inexcusable is environmental injustice evident in Flint. “Certain communities are disproportionately burdened by environmental contamination and health risks. Like Flint, those places tend to be locations where poor people and people of color are concentrated” (Erickson 2018, emphasis added). Residents of Flint were denied meaningful input to decisions affecting their community and quality of life. Concerns about pollution and health were minimized. Residents were treated disrespectfully

(Erickson 2018).

Physical and chemical properties of lead and compounds

Lead (Pb) is a metal of atomic number 82 and weight 207.19 daltons, assigned CASRN No. 7439-92-1. Elemental (metallic) lead, such as that

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(cid:2) Table 1. Physical-chemical properties of lead and its compounds.

element or chemical density compound formula (g/cm3) elemental form lead Pb 11.3520 divalent compounds Pb metaarsenate Pb(AsO3)2 6.4215 Pb orthoarsenate Pb(AsO4)2 7.80 Pb pyroarsenate Pb2As2O7 6.8515 Pb bromate Pb(BrO3)2.H2O 5.53 Pb bromide PbBr2 6.66 Pb carbonate PbCO3 6.6 Pb chlorate Pb(ClO3)2 3.89 Pb chlorate, hydrate Pb(ClO3)2.H2O 4.037 Pb perchlorate Pb(ClO4)2.3H2O 2.6 Pb chloride PbCl2 5.85 Pb oxide PbO 9.53 Pb sulfate PbSO4 6.2 Pb sulfide PbS 7.5 tetravalent compounds Pb dioxide PbO2 9.375 Pb tetrachloride PbCl4 3.180 organic compounds Pb acetate Pb(C2H3O2)2 3.254-20 Pb, tetramethyl Pb(CH3)4 – Pb, tetra ethyl Pb(C2H5)4 – (cid:2) Adapted from: Weast, R. C. Handbook of Chemistry and Phys Company, i. p., 1968. Superscripted numbers are applicable temperatures. used in projectiles including bullets and s zero valence. Lead may, however, assum (þ4) oxidation state when forming com chemistry of lead is dominated by the þ 1989a). Lead also forms organo-lead com tetraethyl lead. Useful physical-chemical and organic compounds are set forth in T Environmental effects As an element, lead can be degraded onl physical, chemical, or biological ones. C be transformed from one to another (an concomitant changes of oxidation state (v transformations, when mediated by micro erally will result in formation of relatively as those forms listed as being soluble in inability of biota to degrade it, lead reaso accumulate dramatically within the biotic as its excretion by microorganisms absor by substance insolubility.

Melting boiling water point point solubility ((cid:3) C) ((cid:3) C) (g/100 mL) 327.5 1,744 insoluble – – decomposes 1,042 – very sl. sol. 802 – insoluble decomp180 – 1.3820 373 916 0.45540 decomp315 – 0.0001120 decomp230 – very soluble decomp110 – 151.318 decomp100 – 499.725 501 950 0.9920 888 – 0.001720 1,170 – 0.0042525 1,114 – 0.0124420 decomp290 – insoluble (cid:4)15 expl105 decomposes 0 280 – 44.320 – – 0.0015 – – 0.0000820 sics, 49th edition. Cleveland, Ohio; Chemical Rubber shot and in fishing sinkers, exhibits me the divalent (þ2) or tetravalent mpounds, although the inorganic þ2 oxidation state (US EPA 1984, mpounds, such as tetramethyl and l properties of lead and its ionic Table 1 (Weast 1968).

ly by nuclear processes, but not by Compounds of lead, however, may nd often back again), possibly with valence). Over the long term, such obiota of soils and sediments, geny more soluble forms of lead, such n Table 1. Accordingly, despite the onably may be assumed not to bio-

c portion of ecosystems, inasmuch rbing it is unlikely to be precluded

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Baseline levels. Natural levels of lead in soils have been reported to range from 2 to 200 ppm-w (parts per million, by weight), whereas average levels have been reported to be 10-15 ppm-w (Klaassen, Amdur, and Doull 1986). Fresh waters typically harbor lead residues in the range of 1-10 mg/L (ppb-w). Although seawater has been reported to contain approximately 5 mg/M3 (ppb-

w; Dietrich 1963), marine surface waters have been reported to harbor levels of only 0.20 mg/kg (ppb-w) in the Mediterranean and 0.35 mg/kg in the Pacific (Klaassen, Amdur, and Doull 1986). Finally, the National drinking water regulation for lead, set by the U. S. EPA, is 15 mg/L (ppb-w) as an action level, and zero as the public health goal; ATSDR 2019). The average daily adult dietary intake of lead was reported to be about 150 mg/day (Klaassen, Amdur, and Doull 1986).

Soil and sediment microorganisms. Microorganisms naturally occurring in soils and sediments evidently are highly sensitive to toxic effects of lead (US EPA 1986). As a result, resistant species tend to emerge, with concomitant changes in species composition and relative abundance. Levels of lead exceed-

ing 750 mg/g (ppm-w) in soil may inhibit decomposition processes, and levels exceeding 1,000 mg/g may inhibit nitrification. This is the process by which soil ammonia is converted to nitrates that enrich soil fertility, especially by bacteria of the genera Nitrosomonas and Nitrobacter. In sediments, microbiota may methylate inorganic lead compounds, enhancing toxicity, although the importance of this process was reported to be undetermined (US EPA 1986), and possibly minor as methylated lead compounds have been only unusually detected in sediments. Regarding this process, therefore, EPA concluded that “[t]he evidence for the biomethylation of lead is circumstantial at best and clearly not conclusive” (US EPA 1986, page 8-2).

Plants. The principal effect of lead on plants evidently is growth inhibition, which may be mediated by any of several proximal physiological causes (US EPA 1986). These include ATPase inactivation, as well as inhibition of photosynthesis, respiration, the growth hormone indole acetic acid (IAA), and cell division, among others. Tolerance to the toxic effects of lead may develop among plants. Tolerance to lead toxicity occurs in especially those organisms that may bind lead to the cell surface or otherwise exclude it during nutrient uptake processes; effectively pump out absorbed lead; or protect potentially sensitive cellular structures, for example, by oxidizing the lead to a less toxic form, by synthesizing a polymer to chelate (trap and

sequester) it, or by precipitating the lead in an insoluble form. Tolerance to lead toxicity has been observed in plants exposed to lead levels greatly exceeding environmental lead concentrations, except the unusually high concentrations occurring near smelters and roadsides.

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Uptake of lead by plants was reported to be biphasic (Heaton, Frame, and Hardy 1986). In one study, for example, a 4-hour initial, rapid phase of uptake of lead by cultured water hyacinth, Eichhornia crassipes, occurred, followed by a slower, nearly linear phase exceeding 24 hours. Formation of lead complexes with such agents as acetate, glycine, and EDTA (ethylenedi-

amine-tetraacetate) added to the growth medium inhibited root uptake. The uptake rate appeared to be diffusion-limited, inasmuch as it was increased by stirring (Heaton, Frame, and Hardy 1986). In terrestrial plants, lead may be taken up not only by plant roots, but by translocation across leaf surfaces (US EPA 1986). Although most of the lead present in or on a plant may occur on the surfaces of leaves, stems, or tree trunks, the internal concentration of lead has been reported to be at most only 20 percent of the external concentration, and foliar uptake was believed to account for less than one percent of root uptake.

Invertebrates. Levels of lead detected in insects evidently reflect levels in

their habitats and diets (US EPA 1986), suggesting that significant bioaccumulation will not occur in these organisms. Lead was found to pass through the gut of the centipede Lithobius variegatus, although inhibition of growth–presumably caused by uptake–was observed in the detritus-feeding soil insect Onychiurus armatus when fed a fungal diet containing up to 3,100 mg/g (ppm-w) of lead. Aquatic insects and crustaceans appear to be resistant to relatively high lead concentrations in water, although the mature amphipod (crustacean) Gammarus pseudoilimnaeus exhibited an adverse response to lead at as little as 32 mg/L (ppb-w). In earthworms, measurable bioaccumulation occurred among worms exposed to high concentrations of lead. The worm Lumbricus rubellus

exposed to lead in soil at 1,800 mg/g accumulated levels of 3,600 mg/g, corresponding to a bioconcentration factor (BCF) of 2, whereas the worm Dendrobaene rubida accumulated 7,600 mg/g, corresponding to a BCF of 4. Likewise, in sludge-treated soils, earthworms accumulated about 2.3 times the lead concentration of the sludge (BCF (cid:5)2.3). Among grazing and burrowing gastropods (such as snails), lead levels were correlated with levels in the water rather than in the diets of Physa integra, Pseudosuccinea columella, and Helisoma trivolvis (US EPA 1986). In the burrowing gastropod Campeloma decisum, however, lead levels apparently were uncorrelated with any monitored environmental param-

eter. The freshwater snail Lymnaea palutris exhibited elevated mortality when exposed to lead at levels as low as 19 mg/L (ppb-w) in stream water.

Aquatic vertebrates. The most commonly observed sublethal adverse effects of chronic lead exposure upon aquatic vertebrates were reported to be

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hematological and neurological responses (US EPA 1986). Hematological effects have included destruction of mature red blood cells and inhibition of the hemoglobin-synthetic enzyme ALA-D. At low levels of exposure, however, fish may compensate for these effects by increasing their rates of red blood cell formation (erythropoiesis), although higher exposure levels

may cause anemia. Neurological effects have included neuromuscular distortion, muscle tremors, and anorexia. Spinal curvature eventually also may appear, for example, as observed in developing eggs of the killifish Fundulus heteroclitus following exposure to lead at a level of 10 mg/mL (ppm-w) during the first seven days following fertilization. The most reliable–although not necessarily the earliest–clinical signs of low-level lead toxicity to rainbow trout (Salmo gairdneri) were found to consist of spinal curvature and black fin. These effects, which appeared following exposure to 120 mg/L (ppb-w), preceded appearance of other signs of toxicity, such as effects on red blood cells; liver function; and

histopathological indicators in the liver, spleen, kidneys, gills, brain, spinal chord, and gastrointestinal tract. Rainbow trout were considered to be adequately protected by maintaining lead levels in water at 25 mg/L or below, inasmuch as spinal cord curvature did not occur.

Pharmacokinetics

Pharmacokinetics and pharmacodynamics (next section) are, respectively (and very generally), the effects of the body on substances, and the effects of substances on the body. Pharmacokinetics includes intake (absorption), distribution, metabolism, and excretion (subsections below). Principal routes of exposure to substances generally include inhalation, ingestion (oral exposure), and dermal contact. Routes are subdivided into pathways,

for example, food versus drinking water for oral exposure. Thus, body burdens depend upon the intensity and duration of exposure, the efficiency of absorption via all routes and pathways, the targets of substance distribution and possible storage, the efficiency and nature of metabolic breakdown and substance transformation, and the efficiency and time course of excretion. Most generally, therefore, body burdens of substances depend upon the net result of processes of increase and processes of decrease, as well as the nature of storage and possible accumulation. Storage may include organs that metabolize and/or sequester substances out of harm’s way. Substances may be stored in fat, for example, where they may be relatively inactive

metabolically; this may change in the event of fat metabolism, however, for example as a result of metabolic challenges such as starvation or migration in which fat stores may be metabolized and fat-sequestered substances mobilized. These concepts are addressed in subsections below.

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Absorption

Inhalation Inorganic lead. A fraction of inhaled lead is deposited in the respiratory tract (ATSDR 1997). Whereas large particles tend to be deposited high in the respiratory tract, aerosols and other fine particulates may penetrate deeper, into the lower respiratory tract, including lung alveoli (air sacs). The deposition rate of particulate airborne lead and lead compounds depends upon particle size and ventilation rate (US EPA 1986a). In one study, subjects inhaled particulate lead compounds through a standard respiratory mouthpiece. Inhaled compounds were lead chloride with mass median aerodynamic diameter (MMAD) of 0.26 mm, and lead hydroxide

with MMAD 0.24 mm. After five minutes, 23 percent and 26 percent, respectively, of the aerosol was deposited in the lungs and respiratory tract (Morrow et al. 1980). A fraction of deposited lead and lead compounds is then absorbed. Once deposited in the lower respiratory tract, particulate elemental lead is absorbed nearly completely. All chemical forms of lead likewise appear to be absorbed (US EPA 1986a; Morrow et al. 1980).

Organic lead. In one study (Heard et al. 1979), four male subjects breathed tetra-alkyl lead compounds via mouthpiece, taking 10 to 40 breaths, each breath of approximately 1-liter volume. Initial deposition in the respiratory

tract amounted to 37 percent and 51 percent of inhaled tetraethyl and tetramethyl lead, respectively. A significant fraction of each compound was subsequently lost via exhalation. Approximately 60-80 percent of deposited tetra-alkyl lead was absorbed via the lungs. Likewise a case study of a 22year-old male exposed to tetramethyl lead reported evident absorption as indicated by elevated urinary lead levels persisting for four days after exposure (Gething 1975).

Ingestion The efficiencies with which lead and its compounds are absorbed following ingestion have been reported to be approximately 15.0 percent in adults and 50 percent in children (Donald, Cutler, and Moore 1987; Ewers, Stiller-Winkler, and Idel 1982; Faith, Luster, and Kimmel 1979). According to ATSDR (1997): “Although there were limited data, oral absorption of lead appears to be low in humans, except in children.” The extent and rate

of gastrointestinal absorption were reported affected by fasting, and by the solubility of a particular lead salt in gastric acid. In one study (Rabinowitz et al. 1976), males were fed diets supplemented with 0.0008 to 0.003 mg/(kg day) of lead-204 (204Pb)-labeled lead nitrate for up to 124 days.

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Gastrointestinal absorption was reported to be 6.5 to 10.9 percent of the tracer. Gastrointestinal absorption of lead and compounds, however, has been reported to be as high as 45 percent in adults under fasting conditions, and as low as six percent when administered with food (Chamberlain et al. 1979). In another study, intestinal absorption of lead chloride was reported to be three percent with meals, but increased to 60 percent when

the subjects were fasted (Heard and Chamberlain 1982). Intestinal absorption also was shown to be variable among individuals (Heusler-Bitschy et al. 1988), with intestinal absorption reported to range from 10 percent to 80 percent in eight fasted volunteers, each receiving a single exposure of 0.007 or 0.02 mg/(kg day) of lead in their drinking water. Oral intake of lead can result from consuming lead-containing food and beverages, and from swallowing lead deposited in the upper respiratory tract after inhalation exposure (Kehoe 1987). In addition, ingestion of lead in children may occur through normal mouthing activity and pica, which is the habit of ingesting material not fit for food, such as soil, clay, ashes, paint chips, or plaster (US EPA 1986a). In one study, a high degree of life-time exposure to lead

(childhood and adulthood combined) was inferred from indirect evidence, specifically from high lead levels in tissues revealed in autopsies (Barry 1975). The primary site of lead absorption in children was reported to be the gastrointestinal tract (Hammond 1982). Children’s absorption of dietary lead was reported to be approximately 50 percent, compared with 15 percent gastrointestinal absorption reported in adults (Chamberlain et al. 1979). In infants, gastrointestinal absorption efficiency was shown to depend upon daily intake (Ziegler et al. 1978). Infants ranging from two weeks to two years of age, who were exposed to lead in milk and commercially prepared strained food for 72 hours, exhibited absorption efficiency of 26.2 percent when daily intake was below 0.005 mg/kg, but 41.5 percent

when daily intake exceeded 0.005 mg/kg. According to ATSDR (1997), “however, the authors indicated that at lower lead levels there was difficulty in controlling lead intake.”

Dermal Following dermal contact, an absorption efficiency of inorganic lead of 0.3 percent has been reported (US EPA 1984, 1986). Organic, such as tet-

raalkyl, lead compounds are rapidly and extensively absorbed through the skin of rabbits and rats (ATSDR 2019).

Distribution

The principal tissues and organs to which lead and its compounds are distributed have been reported to include blood, bones, kidneys, and nervous

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system (Klaassen, Amdur, and Doull 1986). Lead levels reported in autopsies revealed similar distribution of lead in adults and children, except that a larger fraction of the body burden in adults was reported to reside in bone (Mari et al. 2014). Toxicological effects of lead frequently are reported in terms of blood

lead levels, which then must be related to exposure doses. ATSDR (1997, page 31) concluded the following: “Experimental studies relating blood lead levels to dietary lead intake for adults produced slope estimates of an [approximately] 0.02 mg/dL increase in blood lead per microgram of lead per day total intake … … . When blood lead kinetics were considered, the slope increased to 0.04 mg/dL per microgram per day. Estimates from population studies extrapolated to typical dietary intakes yielded a slope of 0.05 mg/dL per microgram per day. For infants, the EPA … . calculated a dietary slope of 0.16 mg/dL per microgram per day … .”

Metabolism Lead may exist in neutral, divalent, and tetravalent forms, but inorganic

lead chemistry is dominated by the divalent form (US EPA 1984). Tetravalent lead is exemplified by lead dioxide (PbO ) and lead tetrachlor2 ide (PbCl ). Organolead compounds, such as tetramethyl and tetraethyl 4 lead, would be expected to be of little if any significance as products of combustion, such as from coal-fired electricity generator emissions. Lead metabolism begins with binding to hemoglobin and red blood cell membranes (Klaassen, Amdur, and Doull 1986). In a longer time frame, lead is deposited with calcium in the bone lattice . Blood lead levels therefore indicate recent exposure to lead, whereas the more stable bone levels (half-life about 20 years) may indicate chronic exposure, possibly but not necessarily continuing to the present. Lead in soft tissues preferentially binds to cellular nuclei and mitochondria (US EPA 1984). Excretion

The principal excretion route of ingested lead, including inhaled lead particulates that are later swallowed, is in the feces (US EPA 1984). Blood lead that is not retained is excreted via the urine and bile. Hair and milk also constitute excretion pathways for lead. Relative importance of the various excretion pathways has been reported to depend upon factors such as species, intake route, age, and dose (US EPA 1984). According to ATSDR

(2109): “Independent of the route of exposure, absorbed lead is excreted primarily in urine and feces; sweat, saliva, hair and nails, breast milk, and seminal fluids are minor routes of excretion … ”

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Lead elimination is non-linear, involving slow- and fast-turnover pools described in pharmacokinetic models (Klaassen, Amdur, and Doull 1986). The half-life of lead in the largest and slowest pool, skeletal tissue, has been reported to be in excess of 20 years. The half-life of lead in the soft tissue pool is very much shorter, in the range of 19 days (Donald, Cutler, and

Moore 1987). The 19-day pool has been reported to account for some 50-60 percent of the absorbed fraction of lead in adults (ATSDR 1997). Thus, using these values, an overall half-time of lead would be nine years [calculation: (20 y (cid:6) 365 d/y (cid:6) 0.45) þ (19 d (cid:6) 0.55) ¼ 3,295.45 d; (cid:7) 365 d/y ¼ 9.03 y].

Pharmacodynamics Acute toxicity Lead is a cumulative poison and, as such, it is not principally associated with acute toxic effects, which are effects resulting from single exposures, or exposures over a single day. Nonetheless, acute toxic reactions do occasionally occur. Acute toxicity of lead is manifested in a variety of functional

deficits, usually preceded by appearance of swollen cells, cell nuclear inclusion bodies, and altered mitochondria (Klaassen, Amdur, and Doull 1986). Clinical effects include neurological, hematological, and renal deficits. Neurological effects may be focused upon the central nervous system, including lead encephalopathy (brain disease) and neuropathy (nerve disease). Symptoms of encephalopathy usually are evoked in children, and include ataxia (incoordination of voluntary muscles), stupor, coma, convulsions, severe cerebral edema (swelling), increase in cerebrospinal fluid pressure, proliferation and swelling of capillary and arteriole endothelial cells, glial cell proliferation, neuronal degeneration and, in fatal cases, appearance

of areas exhibiting focal cortical necrosis. Preclinical or presymptomatic effects of low-level lead intoxication include disturbance of neuronal and possibly synaptic nerve impulse transmission, which are manifested by altered brain wave patterns recorded in electroencephalograms (EEGs). Such effects may be associated with lead levels in the range of 30-50 mg/dL (micrograms per deciliter) in blood (Klaassen, Amdur, and Doull 1986). Neuropathies induced by lead tend to be peripheral in adults and central in children because children’s immature blood-brain barriers may be only incompletely effective at preventing the passage of lead into the brain (Klaassen, Amdur, and Doull 1986). Peripheral neuropathy, that is, nerve

disease involving only nerves outside of the brain–especially nerves of the extremities, is more characteristic of adults, who more effectively exclude lead from potential cerebral targets of its toxic action. Classical symptoms of peripheral neuropathy exhibited by individuals experiencing excessive

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exposure, such as house painters using leaded paints, include footdrop and wristdrop, which have been associated with this occupation since as early as 1904. The onset of dysfunction of motor nerves, which includes reduced velocity of nerve impulse conduction, may occur at lead levels in the range of 50-70 mg/dL in blood (Klaassen, Amdur, and Doull 1986).

The principal hematologic effect of acute lead intoxication is anemia (Klaassen, Amdur, and Doull 1986). Lead-induced anemia is characterized by presence of microcytic and hypochromic (reduced hemoglobin and coloration) red blood cells, as well as increased numbers of reticulocytes exhibiting basophilic stippling. Anemia results from the fragility and shortened life span of red blood cells exposed to lead, as well as disruption of heme synthesis. Heme synthesis disruption appears to be mediated by inhibition of the enzyme delta-aminolevulinic acid dehydratase (ALA-D; Astrin et al. 1987, Klaassen, Amdur, and Doull 1986). The principal renal effect of acute lead intoxication is renal tubular dysfunction which may progress to chronic interstitial nephropathy (kidney

disease) with prolonged (chronic) exposure (Klaassen, Amdur, and Doull 1986). Renal tubular dysfunction usually occurs in children and is usually reversible. Effects are most pronounced in the cells of the kidney’s proximal tubule, and changes in kidney function are usually confined to the renal tubules.

Mutagenicity Lead has been found to exert genotoxic effects at the level of nucleic acids (RNA and DNA) and chromosomes (US EPA 1984). Lead sulfate at 20 mM concentration interfered with normal in vitro DNA synthesis and replication. Lead compounds have been shown to inhibit RNA synthesis from

DNA templates originating from calf thymus and T phage (virus). Lead 4 also was shown to decrease the fidelity of DNA replication by viral DNA polymerase, that is, incorrect (non-homologous) nucleotide bases were incorporated into the DNA strand during synthesis. The ability of metal ions to decrease fidelity of DNA replication is correlated with mutagenic (and carcinogenic) potential (US EPA 1984). Chromosome aberrations in microbial, plant (root tip), and animal cells, as well as in whole organisms, including humans, have been observed to be induced by exposure to lead compounds (Klaassen, Amdur, and Doull 1986; US EPA 1984). Chromosome aberrations have been demonstrated to occur in laboratory-cultured animal and human lymphocytes (US EPA 1984). For example, 72-hour exposure of cultured human lymphocytes to 100 mM lead acetate induced chromosome aberrations. Likewise, experiments with intact animals administered lead compounds have revealed

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causation of chromosome aberrations. For example, cynomulgus monkeys treated with lead acetate at 6 mg/d, 6 d/wk, for 16 months exhibited sister chromatid exchanges, despiralization (untwisting of chromosomes), translocations, ring chromosomes, and polycentric chromosomes. The effects were influenced by the amount of calcium in the diet, such that low calcium

increased the effects (US EPA 1984). Finally, increased incidences of chromosome aberrations have been observed among occupationally exposed individuals exhibiting lead levels above 60 mg/dL in blood (Klaassen, Amdur, and Doull 1986).

Carcinogenicity

The carcinogenic potential and potency of lead are unknown, although some suggestive results of animal and epidemiological studies have been reported (Klaassen, Amdur, and Doull 1986, US EPA 1984). Industries in which occupational lead exposures were considered to be high include the lead smelting and battery manufacturing industries, whose employees have been studied epidemiologically. Both standard mortality ratios (SMRs) and observed/expected ratios (O/Es) of cancer incidence were elevated among smelter industry employees relative to control populations, and cancers of

the respiratory and digestive systems appeared to be elevated among employees of both industries. The incidence of urinary system cancers among smelter employees was also elevated. Nevertheless, flaws in the investigations of these populations, such as failure to ascertain smoking and possibly alcohol consumption, and the methods of selecting subjects, have given rise to controversy over how to interpret the results. Other studies also have been conducted revealing, for example, suggestive (statistically insignificant) elevations of renal cancer incidence among lead smelter employees. The renal cancers resembled cancers induced in animal models

(US EPA 1984). Numerous carcinogenicity bioassays have been conducted using rodents (US EPA 1984). At least 18 studies have been conducted in which tetraethyl lead, lead powder, or lead acetate, subacetate, naphthenate, nitrate, phosphate, oxide, or chromate was administered to mice, rats, or hamsters. Most, but not all, positive results were associated with lead levels producing very high mortality and morbidity among test animals. Kidney tumors, however, were produced in some rodent studies at relatively low levels, such as 0.1 percent lead acetate in the diet. Evidence of a dose-response

relationship also has been developed. Lead powder administered orally also was associated with lymphomas and leukemias and, following intramuscular injection, with occurrence of one fibrosarcoma among 50 animals.

LEGACY CONTAMINANTS 15

One study of lead carcinogenicity was a long-term (two-year) feeding study of rats administered lead acetate at levels of 0, 10, 50, 100, 500, 1,000, and 2,000 parts per million. Four beagle dogs also were exposed. No tumors were produced in the dogs. Statistically significant elevations of renal tumor incidence in rats were observed, but only at highly toxic doses

(above 500 ppm), producing unacceptably high mortality rates (US EPA 1984). The study, though inconclusive, suggests that lead may be a weak renal carcinogen, as possibly indicated by elevations of renal tumor incidence at the lower doses, even though statistically insignificant. The United Nations International Agency for Research on Cancer, in the World Health Organization, has deemed certain forms of lead to be carcinogenic, despite the equivocal nature of available data (UN IARC 1980, 1982). Lead acetate, lead subacetate, and lead phosphate have been classified as IARC Group 3 carcinogens. This means that IARC has found inad-

equate evidence of human carcinogenic potential; sufficient evidence of potency in animals; but inadequate supporting evidence of genotoxicity in short-term bioassays. Substances known to be carcinogenic to animals typically are assumed to be carcinogenic to humans, even in the absence of sufficient direct evidence of human carcinogenicity. Likewise, the U. S. EPA has classified lead as a Group B2 probable human carcinogen (US EPA 1985), but qualified this classification with the statement that lead’s carcinogenic potency is low, as indicated by the fact

that doses above the human lethal dose were required to induce tumors in animals. Moreover, no relationship between cancer causation and exposure to lead was revealed in several major epidemiological studies involving occupationally exposed populations. Thus, lead is generally evaluated in health risk assessments (HRAs) as an assumed non-carcinogen.

Teratogenicity

Transfer of lead across the placenta with little if any reduction in concentration has been documented (Klaassen, Amdur, and Doull 1986), although the statement did not specify whether placental transfer had been demonstrated with respect to inorganic lead, organic lead, or both. Although fetotoxic effects in the human conceptus attending severe maternal lead exposure have been observed, teratogenic effects were not (US EPA 1984). Animal studies, mostly involving rodents, however, have revealed teratogenic effects, but only via the injection route, probably at maternally toxic doses. A need for further

study is indicated by the small number of available reports in this area. Notwithstanding apparent absence of morphological effects, epidemiological studies have revealed association between prenatal exposure to lead, as

16 R. A. MICHAELS

indicated by blood lead levels of >10 mg/dL, and delayed mental development during the first year of life (Bellinger et al. 1984, 1986, 1987).

Reproductive effects

Lead is known to exert adverse effects upon the reproductive performance of adults. It has been shown to exert gametotoxic effects upon both sperm and egg cells (Klaassen, Amdur, and Doull 1986). Severe lead intoxication has produced sterility, spontaneous abortion, and neonatal mortality and morbidity. Animal experiments on mice and rats have revealed that lead administered in drinking water at 25 ppm may result in adverse reproduct-

ive outcomes (US EPA 1986). In rats, these effects included delay in birth of the first litter, runting, excessive mortality, decreased male/female ratio, reduced pregnancy incidence, and decreased litter size. Effects were similar but more severe in mice, requiring termination of the three-generation study after two generations because of diminished sample size. In humans, maternal blood lead levels associated with miscarriages and stillbirths are probably in excess of 30 mg/dL, although lower levels have been associated with pre-term delivery (Dietrich et al. 1986; McMichael et al. 1986, US EPA 1986). Specifically, maternal blood lead levels of as low

as 10–15 mg/dL have been associated with delivery before week 37 of gestation, which normally lasts 40 weeks. In men, occupational exposures giving rise to blood lead levels of 40 - 50 mg/dL have been associated with alterations in spermatogenesis and testicular function (Lancrajan et al. 1975). Nilsson, Ljung, and Wide (1991) studied impregnated mice in which implantation was experimentally delayed. The mice were administered 75 mg/g of lead chloride (56 mg/g of lead) intravenously. Treated mice exhibited prolonged opening of the uterine lumen, which was closed in controls. The authors concluded that lead had caused an increase in uterine secre-

tion. Moreover, the presence of lead was demonstrated in precipitates on the uterine epithelium, suggesting the possibility that lead might exert a direct effect upon the functioning of the uterine epithelium, and might be secreted into the uterine lumen and there affect blastocysts (mass of cells, in humans formed about five days after fertilization of the egg, giving rise to the embryo). Lead was associated with alteration of reproductive parameters in female rats orally administered 5 or 100 mg/d of organic lead (lead acetate) for 30 days Hilderbrand et al. (1973). Female rats exhibited irregular estrous

cycles. At the higher dose, female rats exhibited ovarian follicular cysts and reduced numbers of corpora lutea. Male rats similarly treated exhibited testicular damage at the higher dose. The two doses resulted in blood lead

LEGACY CONTAMINANTS 17

levels of 30 and 53 mg/dL respectively in females, and 19 and 30 mg/dL respectively in males.

Other chronic effects “Lead is a poison that affects virtually every system in the body”

(ATSDR 1998).

Hematological Hematopoietic effects include interference with metabolism of vitamin D,

erythrocyte (red blood cell) physiology and production (erythropoiesis), including effects upon hemoglobin synthesis, red blood cell survival and morphology, and erythropoietic nucleotide metabolism (US EPA 1984). In addition, effects upon heme synthesis have been reported (US EPA 1984, ATSDR 1997). Cardiovascular effects of lead have been reported to occur at high exposure levels, and may include hypertension secondary to renal effects (US EPA 1984). Exposure to relatively low lead levels for a prolonged period reduced concentration of high-energy phosphates, such as ATP, in rat hearts, and may have caused reduction in phosphorylation of myosin light chain 2

(LC-2) in cardiac muscle, and subsequent cardiac contractility. Animal bioassays have suggested lead association with atherosclerosis.

Inhalation

In one study, men voluntarily exposed to lead at air levels of 3.2 or 10.9 mg/M3 for 23 h/d for 3-4 months exhibited elevated blood lead levels (ATSDR 1997). Among men in the low-dose group, levels rose 30 percent, from 20 mg/dL to 26 mg/dL. This elevation was correlated with a 15-percent decrease in the activity of the enzyme delta-aminolevulinic acid dehydrase (d-ALA-D), which is essential for heme synthesis. Impairment of heme synthesis, which would impair red blood cell production, also may result in reduced activity of cytochrome P-450 and related enzymes that are essential for metabolism of toxic substances, primarily in the liver. The exposure

dose that is equivalent to the lower air level reported to impair heme synthesis is 1.0 x 10 (cid:4)3 mg/(kg d) [calculation: 3.2 mg/M3 (cid:6) 22.8 M3/d (cid:6) 23/ 24 (cid:7) 70 kg ¼ 1.0 mg/(kg d)].

Ingestion Lead has been reported to affect heme biosynthesis adversely (ATSDR 1997). The mechanism by which this occurred was via affecting the activities of several enzymes in the heme biosynthetic pathway. Two

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experimental studies of the effects of oral exposure to lead on heme synthesis in humans were available (Stuik 1974, Cools et al. 1976). In the Stuik 1974 study, two groups of five women, and one group of five men, ingested lead acetate at 0.02 mg lead/(kg day) daily for 21 days. They exhibited decreases in erythrocyte ALAD by day three. The decreases peaked by day 14, and then remained constant through day 21. An increase

in erythropoiesis (red blood cell production) occurred in the women, but not in the men, starting two weeks after onset of ingestion. Blood lead levels were approximately 15 mg/dL before exposure, and increased to approximately 40 mg/dL during exposure. Increased erythropoiesis was observed in five men at a higher dosage, 0.03 mg lead/(kg day) (which produced a mean blood lead level of 46 mg/dL), starting after 2 weeks of ingestion (Stuik 1974). Similar results were reported by Cools et al. (1976), who studied 11 men ingesting lead acetate at an initial dosage of 0.03 mg lead/(kg day). This intake rate was decreased to 0.02 mg lead/(kg day) or less, as necessary to maintain a blood lead level of 40 mg/dL. The mean pre-exposure blood lead level was 17.2 mg/dL.

Renal Renal effects also have been assessed in the Acute Toxicity subsection but, in addition, if exposure resulting in reversible renal tubular dysfunction is prolonged (chronic), the condition may progress to irreversible chronic interstitial nephropathy and glomerular sclerosis (Klaassen, Amdur, and Doull 1986). Ingesting drinking water containing lead was associated with

renal insufficiency in people (ATSDR 1997, Campbell et al. 1977). Ingestion of drinking water containing lead for an average of 21.5 years was correlated with blood lead levels in a study of 283 residents. Elevated blood lead concentrations were associated with renal insufficiency, reflected as raised serum urea concentrations and hyperuricemia (elevated uric acid level in blood). No renal biopsies were performed. Renal toxicity of ingested lead has been reported in several species, including rats, rabbits, dogs, and monkeys. Histopathological changes in the kidneys of lead-treated animals were similar to changes reported in humans … , though glomerular lesions were not reported in the animal studies (ATSDR 1997). Reduced glomerular filtration rates and aminoaciduria (excess amino acid levels in urine) were reported in some ani-

mal studies. Fowler et al. (1980) exposed rats to lead acetate in drinking water through the dams during gestation and lactation, and then directly until age nine months. Results in summary (lead concentration in water, blood lead levels, effects in proximal tubule cells) were as follows:

LEGACY CONTAMINANTS 19

0 ppm 5 mg/dL no lesions

0.5 ppm 4.5 mg/dL no lesions

5 ppm 11 mg/dL cytomegaly

50 ppm 26 mg/dL cytomegaly, intranuclear inclusion bodies, and swollen mitochondria;

250 ppm 67 mg/dL cytomegaly, intranuclear inclusion bodies,

swollen mitochondria, and hemosiderin.

No lesions were seen in glomeruli (clusters of capillaries at ends of kidney tubules, for waste removal from blood via urine), and no evidence of interstitial reaction or of tumor formation was reported. Vyskocil et al. (1989), studying effects of intermediate-duration exposure to lead in drinking water on renal function of male Wistar rats, reported similar results. Three daily intake levels were administered. Results in summary (daily lead intake, effects) indicated that exposure to lead acetate at 892 mg/(kg d) caused proximal tubular dysfunction. Results were as follows:

446 mg/(kg d) no effect n renl function or on kidneys;

892 mg/(kg d) increased urinary excretion of b2-M, morphological changes, primarily in the epithelial cells of the proximal tubules, including intranuclear inclusion bodies and enlarged nuclei; hyperplasia and flattening of the proximal tubular epithelium; 1783 mg/(kg d) increased urinary excretion of b2-M, glucose, total proteins, lysozyme, and lactate dehydrogenase (LDH) levels; morphological changes, primarily in the epithelial cells of the proximal tubules, including intranuclear inclusion bodies and enlarged nuclei; hyperplasia and flattening of the proximal tubular epithelium. In contrast, Koller, Kerkvliet, and Exon (1985) reported histopathological

changes in the kidneys of rats administered lead acetate in their drinking water for 76 weeks at lower doses than those in Vyskocil et al. (1989). These changes were observed at a dose of 37 mg/(kg day). They included necrotic and dilated cortical tubules, tubular protein casts, areas exhibiting large nuclei and fibrous connective tissue, and large intranuclear inclusion bodies in the enlarged epithelial cells of the kidney cortex near the corticalmedullary junction.

Dermal ATSDR (2019) found no epidemiology studies of adverse dermal effects associated with chronic exposure to lead.

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Respiratory ATSDR (1997) reported an absence of human studies of respiratory effects of inhalation exposure to inorganic lead. Animal studies, however, revealed respiratory effects. In one study (Hillam and Ozkan 1986), mice inhaling lead nitrate in air at 1.6 mg/M3 exhibited slightly, but significantly, elevated lung weights. Their lungs appeared hemorrhagic at necropsy, probably due to lead aerosol irritation causing pulmonary edema during 28 days of

exposure. Neither increased lung weight nor hemorrhage was observed in lungs of mice similarly exposed for 14 days. Thus, effects observed in mice exposed for 28 days were dependent upon exposure duration.

Neurological The hypothesis has been advanced that a threshold for neurotoxic effects of lead might not exist. For example, in one study revealing impairment of

cognitive abilities based upon tests administered to children aged 6-9 years in Edinburgh (Fulton et al. 1987), the authors noted that “[t]here was a dose-response relationship between blood-lead and test scores, with no evidence of a threshold” (page 1,221). Similarly, McMichael, et al. (1988) investigated the effects of lead exposure on the abilities of four-year-olds living near a lead smelter in Port Pirie, Australia. The authors indicated that “[d]ebate continues over whether there is a threshold, or ’safe’ level of exposure to lead,” and concluded that “[w]ithin the range of exposure studied, no threshold dose for an effect of lead was evident” in the Port Pirie population (page 468). One test of the non-threshold hypothesis involved measuring nerve conduction velocities in 5- to 9-year-old children, and relating conduction vel-

ocity to blood lead levels (Schwartz et al. 1988). The dose-response curve indicated that increasing blood lead levels were associated with slower nerve impulse conduction. Regression analysis yielded evidence of a threshold in the dose-response curve, regardless of the shape of the dose-response curve that was assumed in the regression analysis (including ‘hockey stick’ curve, logistic curve, or quadratic curve). Nervous system effects have been described in the Acute Toxicity subsection, and are similar when exposure is chronic. Neurotoxic effects exerted by lead and lead compounds have been demonstrated on astrocytes and neuronal cells cultured in vitro (Holtzman et al. 1987), as well as in vivo in animals such as mice (Donald, Cutler, and Moore 1987), rats (Cory-Slechta

and Thompson 1979, Cory-Slechta et al. 1983) and monkeys (Gilbert and Rice 1987, Rice and Gilbert 1985). Clarkson (1987) reviewed hypotheses regarding the mechanism(s) by which lead (and other metals) exert neurotoxic effects. Clarkson indicated that, as a potent inhibitor of heme synthesis, lead may reduce the activity of essential heme-containing enzymes and

LEGACY CONTAMINANTS 21

thereby compromise energy metabolism, presumably including energy metabolism of nervous system components. Lead also may interfere with such neurotransmitters as gamma-amino-isobutyric acid. Finally, lead may interfere with membrane transport and calcium ion binding. Lead levels associated with neurological deficits have been reported extensively (ATSDR 1997, 2019). Lead effects on the optic nerve may medi-

ate toxic effects on the visual system. In one study, chronic (long-term) exposure of seven cynomolgus monkeys to lead from birth produced cytoarchitectural changes (Reuhl et al. 1989). Three of the monkeys were administered lead acetate dissolved in glycerin orally at a dose of 2 mg lead/(kg day), starting at 89, 91, and 145 days of age, respectively. Four other monkeys received lead acetate in glycerin at daily doses of 0.025 mg lead/(kg day) starting at birth. All seven monkeys were killed at age six. The high-dose group had a blood lead level of 90 mg/dL before weaning, and 50 mg/dL after weaning. In contrast, the low-dose group had a blood lead level of approximately 9 mg/dL.

During the experiment, a dietary study also was conducted, elevating the monkeys blood lead levels for approximately 100 days. The monkeys were killed 36 months after completion of the dietary study. The high-dose monkeys were found to have maintained steady state blood lead levels of 50 mg/dL for three years. The optic nerve, lateral geniculate body of the brain (involved in temporal or spatial visual function), and visual areas Vl and V2 from the occipital cortex were sampled for morphological analysis. Area V2 represents secondary visual cortex. Along with area V1, area V2 contributes numerous projections to higher visual centers, and involves input from progressively larger visual projection fields. Changes in neither the optic nerve nor the lateral geniculate body were

observed in either group of monkeys under light or electron microscopy. Quantitative analysis revealed lower neuronal volume density in high-dose monkeys in areas Vl and V2, but not in the lateral geniculate nucleus. Morphometric analysis revealed inhibition of initial branching of neurons in both medial and lateral samples of areas V1 and V2 in the high dosemonkeys (Reuhl et al. 1989). The results suggest that long-term lead exposure may affect neurons in the primary visual cortex, but the morphological findings are of unknown clinical and toxicological signficance because the sample size was small and the low-dose and high-dose groups had different exposure regimens. Rats with blood lead levels <30 mg/dL exhibited deficits in performance

in learning tasks. For example, Bushnell and Levin (1983) reported significant learning deficits in rats exposed to lead in drinking water starting at postnatal day 21 (postweaning), as indicated by behavioral observations. Rats exposed to a dose of 1.6 mg lead/(kg day) for 35 days, producing a

22 R. A. MICHAELS

mean lead level of 0.05 mg/g in the brain one day after termination of exposure, exhibited decreased spontaneous alternation in a radial arm maze. Exposure of neonatal male Wistar rats to lead acetate in water was reported to produce deficits in complex maze learning (Cory-Slechta and

Thompson 1979, Dietrich 1963, Massaro and Massaro 1987). Maze training began on day 31 post-partum, with testing on days 41-45 (Cory-Slechta and Thompson 1979, Dietrich 1963); or on day 143 with testing on days 153-157 (Massaro and Massaro 1987). After training, rats were tested for latent learning, via comparison of performance of trained vs. untrained rats. Trained rats in the control group, unexposed to lead acetate, made fewer errors navigating the maze than lead-exposed rats.

Hepatic Hepatic effects of lead among occupationally exposed individuals appears to be associated with a variety of biochemical changes indicative of liver function, such as SGOT (serum glutamic-oxaloacetic transaminase) and cytochrome P450 enzymes. In an intermediate-duration study, lead acetate at a dose rate of 0.01 mg lead/(kg day) was administered to rats via drinking water (Krasovskii et al. 1979). Treated rats exhibited increased liver weight, decreased RNA and glycogen, pyknosis (degeneration) of Kupffer

cell nuclei, and decreased activity of enzymes, for example, lactate dehydrogenase.

Immunological Several studies implicate lead as an immunotoxin (see, for example, ATSDR 1997; Blakley, Sisodia, and Mukkur 1980; Ewers, Stiller-Winkler,

and Idel 1982; Faith, Luster, and Kimmel 1979; Kimber et al. 1986; Kowolenko, Tracy, and Lawrence 1991; Luster, Faith, and Kimmel 1978; € Reigart and Graber 1976, Schlipkoter and Frieler 1979, and US EPA 1984). Immunologic effects of lead include increased susceptibility to endotoxins and infectious agents in animal models. The macrophage may be the target cell type, resulting in effects upon the humoral immune system, including immunosuppression at low lead levels. Effects upon humans were reported as yet undetermined (US EPA 1984). Reviewing the available literature as of 1988, ATSDR (1997) concluded that immunological effects reported in rats exhibiting blood lead levels of 29 mg/ dL (Faith, Luster, and Kimmel 1979; Luster, Faith, and Kimmel 1978) suggest the possibility of such effects also occurring in humans. ATSDR, however, concluded then that available data pertaining to humans revealed no indication of adverse immunological effects in children exhibiting blood

LEGACY CONTAMINANTS 23

lead levels of (cid:8)40 mg/dL (Reigart and Graber 1976) or in occupationally exposed adults exhibiting blood lead levels of 25-53 mg/dL (with a mean level of 38.4 mg/dL; Kimber et al. 1986). Based upon the relationships between blood lead levels and dietary intake, set forth in the Distribution subsection, the above blood levels might correspond to exposures of (cid:8)33.8 mg/(kg d) for children (7.4-kg infants)

and 8.3-15.1 mg/(kg d) [mean 11.0 mg/(kg d)] for (70-kg) adults. A study of the effects of lead acetate on resistance of mice to infection by the bacterium Listeria monocytogenes revealed increased infection rates following oral exposure of mice to 0.4 or 10 millimolar solutions two weeks prior to inoculation with the pathogen (Kowolenko, Tracy, and Lawrence 1991). After two weeks of exposure under these regimens, blood lead had reached approximately 18 or 100 mg/dL, respectively. These blood levels might correspond to human oral exposure levels of 5.1 or 28.6 mg/(kg d) for adults or to 15.2 or 84.5 mg/(kg d) for infants.

Visual system effects Visual system effects of lead may include effects on the central nervous system (discussed earlier) as well as retinal effects, such as effects on rod cells mediating non-color vision (Tessier-Levigne, Mobbs, and Attwell 1985).

Gastrointestinal effects Gastrointestinal effects include abdominal or epigastric pain, abnormal bowel movements, and nausea.

Endocrine effects Endocrine effects associated with high levels of lead include effects on the functioning of thyroid, adrenal, pituitary, and reproductive glands.

Blood levels associated with toxic effects Symptoms of lead intoxication have been associated with blood lead levels above 25 - 30 mg/dL in children and 30 - 40 mg/dL in adults (US CDC 1985; US EPA 1986). Lower blood lead levels have been associated with subtle effects. In particular, levels of 10 - 15 mg/dL have been associated with effects upon heme synthesis, vitamin D and pyrimidine metabolism, blood pressure, and neurological functioning. In one study, for example,

cognitive development up to age three appeared to have been affected adversely among babies whose mothers’ umbilical cord blood lead levels were between 10 and 25 mg/dL, based upon tests of infant development administered at six-month intervals during the second year of life (Bellinger et al. 1987). Neurological functioning of children may be more

24 R. A. MICHAELS

severely impaired than that of adults because of the incomplete formation of the immature blood-brain barrier, which permits lead in blood to enter the brain and cause neuropathic effects in the central nervous system. In contrast, the mature human adult blood-brain barrier is more capable of excluding lead; thus, adults tend to experience peripheral rather than central neuropathy following chronic lead intoxication (Klaassen, Amdur, and

Doull 1986). The U. S. EPA, commenting on developments since publication of the Agency’s 1986 Air Quality Criteria Document, stated: “Various lines of evidence still relate neurobehavioral effects to blood levels of ‘10-15 mg/dL, and possibly lower’, as was previously concluded in the 1986 Addendum … Further analysis from the Boston study, which has provided the most direct information bearing on dose-response relationships for neurobehavioral effects, not only supported the 10-15 mg/dL level of concern, but indicated that MDI [mental development index] deficits can be detected in relation to cord blood lead levels of 6-7 mg/L in lower SES [socioeconomic status] children” (US EPA 1990, page 53). Airborne lead has been associated with elevations of blood lead as follows (US EPA 1986):

“The experimental studies at lower air lead levels (3.2 mg/M3 or less) and lower blood levels (typically 30 mg/dL or less) have linear blood lead inhalation relationships with slopes B of 0-3.6 for most subjects. A typical value of 1.64 þ/- 0.22 [mg/dL per mg/M3 i in air] may be assumed for adults” (US EPA 1986, volume 1, page 1-101). Threshold for lead toxicity

Substances causing cancer (carcinogens) often are assumed to act as if a single molecule has the potential to cause cancer. In contrast, non-cancer effects are nearly universally assumed associated with a threshold, below which the exposure cannot produce the observed effects. Lead, however, is an exception. U. S. EPA evaluation of lead toxicology has revealed inability to discern a threshold for lead toxicity to people (IRIS 2019): “By comparison to most other environmental toxicants, the degree of uncertainty about the health effects of lead is quite low. It appears that some of these effects, particularly changes in the levels of certain blood enzymes and in aspects of children’s neurobehavioral development, may occur at blood lead levels so low as to be essentially without a threshold.”

Sensitive subpopulations

Several subpopulations, such as auto shop employees, may be at elevated risk due to their already-high exposure to lead. However, individuals in these subpopulations may not be physiologically more susceptible than members of the general population. The distinction between elevated

LEGACY CONTAMINANTS 25

exposure risk vs. elevated susceptibility is important to maintain, given the goal of regulatory guidelines and standards to protect populations by controlling potential exposure in accordance with the physiological susceptibilities and tolerances of even the most sensitive subpopulations. Several subpopulations appear to be physiologically at elevated risk, including fetuses, preschool age children, hypertensive individuals (Beevers 1976,

Harlan 1985), white males between 40-59 years of age, due to their high incidence of hypertension (US EPA 1986b), and black males (who are more frequently hypertensive than white males). Fetuses are at risk inasmuch as lead readily crosses the placenta during pregnancy. Maternal exposure to lead during pregnancy can result in fetal exposure, as can pre-pregnancy exposure, inasmuch as lead may be released from bones over a protracted period of time following the termination of external exposure. Perinatal exposure is of concern because of effects of lead on prenatal and postnatal early cognitive development (Bellinger, et al. 1987), among related effects (Lin-Fu 1973, Lin-Fu 1973b).

Young children are at elevated risk because they experience relatively high exposure due to frequent hand-to-mouth contact (Lin-Fu 1973, Lin-Fu 1973b), and higher intake due to relatively efficient gastrointestinal absorption. Children also exhibit a relatively high incidence of dietary deficiencies in nutrients such as iron, protein, and calcium; such deficiencies have been associated with potentiation of the toxic effects of lead. Children exhibit less lead sequestration in bone than adults, leaving a higher fraction of their total body burden of lead in bioavailable form. Finally, children have a less completely developed blood-brain barrier, which renders them susceptible to central nervous system neuropathies, whereas in comparison adult susceptibility generally tends toward peripheral neuropathies (ATSDR 1997, Clarkson 1987;

Klaassen, Amdur, and Doull 1986; Schwartz et al. 1988). Lead exposure has been associated with deficits in various aspects of children’s physical, neurological, psychological, and intellectual development (see, for example, Bellinger et al. 1987; Huseman, Moriarty, and Angle 1987; McMichael et al. 1988). Children with sickle cell disease may be especially sensitive to peripheral nervous system effects of lead exposures (Rice and Gilbert 1985). Middle-aged men are at elevated risk because blood lead (down to 7 mg/ dL) has been correlated with increased blood pressure (Beevers 1976, US EPA 1986b). White males between 40-59 years of age tend to exhibit relatively high blood pressures. The incidence of hypertension is greater among black males than white males (Harlan 1985), however, suggesting that black

males also constitute a sensitive subpopulation. Indeed, all hypertensive individuals might be at elevated risk (Beevers 1976, Harlan 1985). Finally, individuals who possess the ALAD or ALAD allele, which 1-2 2-2 are variants of the delta-aminolevulinic acid dehydratase gene, may

26 R. A. MICHAELS

constitute a sensitive subpopulation (Astrin et al. 1987). Sufficiently great lead exposure in such individuals may reduce the rates at which they synthesize essential macromolecules, such as heme, cytochromes, and cobalamins (including cobalamin, which is vitamin B ). Indeed, in New York 12 City, individuals heterozygous or homozygous for the less-common ALAD2 allele were reported to exhibit an increased incidence of blood lead levels (cid:8)30 mg/dL.

Chemical interactions

The toxicological effects of lead can be affected by interaction with essential elements and nutrients (ATSDR 1997, 2019). This interaction is especially significant in children, who may exhibit wide fluctuations in nutrient status. Most of the data pertaining to this issue involve the nutrients calcium, iron, phosphorus and vitamin D. The preponderance of evidence suggests that diets poor in these nutrients contribute to increased lead absorption and severity of ensuing effects (ATSDR 1997, 2019).

Cadmium and lead administered together to rats may exert synergistic effects (Anca 1982, Fahim and Khare 1980, Fulton 1987). Lead appears to exert an additive effect upon in vitro enzyme inhibition and lethality in the presence of mercury (Singh and Sivalingam 1982) and upon neurological and hepatotoxic effects with ethanol (Flora and Tandon 1987).

Dose-response parameter estimation Cancer Epidemiological associations have been reported between lead in blood vs. cancer risk (ATSDR 2019). At blood lead levels <10 ug/dL, risk was elevated for all cancers and for lung cancer. At blood lead levels exceeding 10

ug/dL, risks were elevated for all cancers, respiratory tract cancer, stomach cancer, intestinal cancer, laryngeal cancer, and glioma (ATSDR 2019). Reliable dose-response parameter estimates to quantify the cancer potency of lead are, however, unavailable (ATSDR 2019; IRIS 2004, 2019; UN IARC 2006, US NTP 2016), notwithstanding that EPA classified lead as a probable human carcinogen based upon sufficient animal evidence (IRIS 2004, 2019). EPA’s Carcinogen Assessment Group (CAG) recommended that, due to a lack of understanding and perhaps unique nature of lead pharmacokinetics, a numerical estimate of the cancer potency of lead

should not be used (IRIS 1997, 2004, 2019). Likewise, the U. S. National Toxicology Program in 2016 classified lead and its compounds as reasonably anticipated to be human carcinogens (US NTP 2016), but did not establish cancer potency (slope) factors.

LEGACY CONTAMINANTS 27

Non-cancer effects Inhalation. The U. S. EPA has promulgated no reference dose (RfD) or reference concentration (RfC) for chronic inhalation of lead and lead compounds (US EPA 1989b, IRIS 2019), notwithstanding the richness of toxicological data availabe. This decision most essentially was based upon the concern that possibly no safe level of lead intake exists:

“EPA considered providing an RfD for inorganic lead in 1985, and concluded that it was inappropriate to develop an RfD, as documented online in the following statement in 1988: A great deal of information on the health effects of lead has been obtained through decades of medical observation and scientific research. This information has been assessed in the development of air and water quality criteria by the Agency’s Office of Health and Environmental Assessment (OHEA) in support of regulatory decision-making by the Office of Air Quality Planning and Standards (OAQPS) and by the Office of Drinking Water (ODW). By comparison to most other environmental toxicants, the degree of uncertainty about the health effects of lead is quite low. It appears that some of these effects, particularly changes in the levels of certain blood enzymes and in aspects of children’s neurobehavioral development, may occur at blood lead levels so low as to be essentially without a threshold. The Agency’s RfD Work Group discussed inorganic lead (and lead compounds) at two meetings (07/08/1985 and 07/22/1985) and considered it inappropriate to develop an RfD for inorganic lead.” Airborne lead is regulated under the Clean Air Act, however, via a National Ambient Air Quality Standard (NAAQS). The NAAQS initially was promulgated in 1976, with a value of 1.5 ug/M3, as a three-month average (US EPA 2016). Subsequent review of this standard in 2008 resulted in significant strengthening, to a new (and current) NAAQS of 0.15 ug/M3 (US EPA 2016, 2019). In the absence of an official U. S. EPA RfD, an RfD of 4.29 (cid:6) 10 (cid:4)5 mg/(kg day) for inhalation of lead may be computed using the NAAQS of 0.15 mg/M3, a reference breathing rate of 20 M3/day, and a reference body weight of 70 kg [HSDB 2016 1997, 2019; calculation: 0.15 mg/M3 (cid:6) 10 (cid:4)3 mg/mg x 20 M3/d (cid:7) 70 kg ¼ 4.29 (cid:6) 10 (cid:4)5 mg/ (kg d)]. The ability to relate an airborne lead standard (NAAQS) to an equivalent inhalation RfD as above does not render the resulting inhalation RfD appropriate. Concerns about such RfD derivation were explicated clearly and succinctly (US EPA 2019):

“Current knowledge of lead pharmacokinetics indicates that risk values derived by standard procedures would not truly indicate the potential risk, because of the difficulty in accounting for pre-existing body burdens of lead. Lead bioaccumulates in the body, primarily in the skeleton. Lead body burdens vary significantly with age, health status, nutritional state, maternal body burden during gestation and lactation, etc. For this reason, and because of the continued apparent lack of threshold (Centers for Disease Control, [CDC, 2004 … url link invalid, but see below]), it is still inappropriate to develop reference values for lead.”

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According to CDC’s ATSDR (2019, page 4): “Exposure thresholds for effects on specific organ systems have not been identified (i. e., no safe level has been identified).” ATSDR toxicological profiles generally derive ‘minimal risk levels’ (MRLs) but, consitent with the above, ATSDR did not do so with respect to lead:

“ … epidemiological studies have evaluated the health effects of Pb in all organ systems. For the most studied endpoints (neurological, renal, cardiovascular, hematological, immunological, reproductive, and developmental, effects occur at the lowest PbBs [blood lead levels] studied (<5 ug/dL). Because the lowest PbBs are associated with serious adverse effects (e. g., declining cognitive function in children), MRLs for Pb have not been derived.”

Ingestion. The analysis provided above regarding chronic inhalation exposure to lead applies also to chronic ingestion (oral) exposure. No chronic oral risk reference dose (RfDo) was derived by EPA, and no MRL for oral exposure was derived by ATSDR (2019). No equivalent value will be derived here.

Discussion Control of exposure to lead is accomplished via environmental and occupational statutes and regulations. Underpinning such controls must be a consistent and technically justified regulatory philosophy, which might

encompass social, economic, and toxicological factors. Economic factors might include whether, and under what if any circumstances, health benefits must be balanced against anticipated compliance costs required to achieve them. Economic issues will be excluded from the scope of the present analysis. Toxicological issues that might guide control of exposure to lead in environmental and occupational settings are numerous. Only two will be discussed here. These are –1. how to define an adverse health effect that is subject to regulatory action, and –2. whether such adverse health effects caused by lead are mediated via threshold or non-threshold mechanisms.

Toxicological issues Definition of ‘adverse health effect’ Explication of adverse health effects arising from exposure to lead, or

exposure to any stressor, critically depends upon the definition of the phrase ‘adverse health effect’ that is applied. This issue is especially significant with respect to determining the lowest exposure level(s) that might elicit a particular health effect. The issue was addressed in two very different statements issued in 1985 and 1999 respectively by the American

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Thoracic Society (1985, 2000) with respect to inhalation exposure. Explication of this issue, however, is likewise applicable to other (noninhalation) routes and pathways of exposure. In the 1985 statement, ATS restricted the concept of effect adversity to clinical effects, excluding pre-clinical effects:

“[I]t is important to consider differences between statistical significance and medical or biological significance … Not all [statistically significant] changes (e. g., physiologic) are necessarily adverse … [For example, according to the US EPA] the eye, nose, and throat irritation associated with … urban ’smog’ or photochemical oxidant air pollution is not medically important and is, therefore, not considered an ’adverse health effect’ in relation to the Clean Air Act. This irritation certainly is annoying or bothersome, which puts it in the category of an effect on human welfare. However, irritation that triggers an asthmatic attack is an adverse health effect. The EPA has portrayed this pollution burden (figure 1) by indicating the proportion of the population that might be affected … . [and] an area of responses that might be considered adverse. This spectrum of biologic responses would be evoked more strongly as the concentrations of pollutants are increased” (American Thoracic Society 1985, page 666). The figure on page 667 of American Thoracic Society (1985) illustrates a long standing U. S. EPA policy, that adverse health effects may include mortality, morbidity, and pathophysiologic changes; but must exclude physiologic changes of uncertain significance and pollutant burdens. In July 1999, however, the 1985 ATS statement was updated with respect to many detailed issues (American Thoracic Society 2000). The most significant, in the present context, is the potential inclusion of preclinical effects in the definition of adverse health effects:

Figure 1. A generic dose-response curve in toxicological health risk assessment.

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“Population health versus individual risk. Assuming that the relationship between the risk factor and the disease is causal, the committee considered that such a shift in the risk factor distribution, and hence the risk profile of the exposed population, should be considered adverse, even in the absence of the immediate occurrence of frank illness” (American Thoracic Society 2000, page 672). The threshold issue A threshold mechanism of toxicity exhibits an exposure below which the

adverse effect cannot be caused by the agent in question. A non-threshold mechanism exhibits no threshold or, equally accurately, it exhibits a threshold of just one molecule. A non-threshold model, therefore, also is termed a ‘one-hit’ model, referring to a single molecule ’hitting’ a susceptible target gene, tissue, or organ; thereby causing the adverse health effect in question. Application of the one-hit model is exclusively, or almost exclusively, limited to cancer causation. The susceptible target is a gene, or a site on a gene, at which a ‘hit’ may cause mutation in a DNA strand, gene, or chromosome, resulting in cellular release from contact inhibition (growth

stoppage upon physically contacting a neighboring cell), and uncontrolled growth (producing a tumor, which may be solid or non-solid). In practice, one-hit cancer is unlikely to materialize. Generally, many if not most stressors act via threshold mechanisms. Among non-threshold stressors, many molecules may be needed to ‘hit’ a DNA molecule, even just once, as the preponderance of molecules will hit other targets, relatively harmlessly. The most commonly cited ‘one-hit’ carcinogen is ionizing radiation, that is, radiation that is sufficiently energetic to break chemical bonds in DNA molecules. If a single molecule actually contacts a DNA molecule, it might not break

the necessary chemical bond to cause mutation and cancer. If it did break a bond in DNA, then DNA repair mechansims are likely to be triggered, by which a mutated DNA molecule might be restored. If restoration failed, the newly formed cancer cell then would likely be recognized by the immune surveillance system, and its ‘foreign’ antigens attacked by host antibodies. Under immune attack, such a cancer cell also might (or might not) commit the cell version of suicide, termed ‘apoptosis’2. Ultimately, the theoretical ‘one-hit’ model is likely to materialize as a ‘multi-hit’ process of cancer causation, requiring many ‘hits’ and much time, and engendering a

great deal of uncertainty. In health risk assessment, the risk that a stressor will cause an adverse health effect is commonly visualized (and quantified) via the dose-response

2 Apoptosis: “a type of cell death in which a series of molecular steps in a cell lead to its death. This is one method the body uses to get rid of unneeded or abnormal cells. The process of apoptosis may be blocked in cancer cells. Also called programmed cell death.” National Cancer Institute, NCI Dictionary of Cancer Terms, https://www. cancer.gov/publications/dictionaries/cancer-terms/def/apoptosis, access date 9 August 2019.

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curve (Fig. 1). The shape of the dose-response curve might or might not include a threshold. As a single molecular ‘hit’ typically is far below any observable experimental exposure dose, the risk must be visualized (and quantified) via extrapolation from observable exposure doses to the ‘twilight zone’ of unobservable exposures. The one-hit model, in such

extrapolations, typically will produce the highest cancer risk, and therefore is the most conservative. It is not, however, likely also to be the most accurate. Lead may be the only substance for which non-threshold mechanisms have been postulated for non-cancer effects. In theory, a non-threshold mechanism can exist for non-cancer effects. For example, a single molecule of lead (or another stressor) might break a chemical bond in the DNA of a germ cell (sperm or egg). Such damage might produce a mutation that adversely affects a newborn organism, rather than a mutation in a somatic

(body) cell that might adversely affect an adult (or an immature) individual by causing a malignancy. Regulatory agencies have refrained from promulgating benchmark exposure doses for lead and lead compounds, below which non-cancer effects cannot occur. Such concerns were described earlier. Specifically, examination of the toxicology database suggests that no observation of a safe dose has been made. That is, a no-effect level, or a no-adverse-effect level, has not been discerned, and its absence denies regulators the needed benchmark to which safety and uncertainy factors might be applied to protect

sensitive subpopulations. Failure to discern a no-effect level is different from inferring a nonthreshold mechanism of toxicological action in producing adverse heatlh effects. Such a threshold is likely to exist for lead, as for other stressors, but the experimental dose range so far has not been sufficiently low to discern the threshold, though it might exist (indeed, is likely to exist). The problem, ultimately, more probably relates to the resolution provided by toxicological and epidemiological data than to the possible action of lead via a non-threshold mechanism.

Social issues Social issues that might guide control of exposure to lead in environmental and occupational settings are numerous. Only one social issue will be discussed here: the need to apply scientific knowledge evenhandedly to protect public health without prejudice. That is, good science policy must be based

upon good science, and good social policy must be based upon good social policy. In Flint, Michigan and elsewhere, science and social policy both failed.

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This broad issue of social policy encompasses the narrower ‘environmental justice’ issue, which specifically relates to equitable treatment of communities. Environmental justice most essentially refers to equitable use of authority. Failure of environmental justice may (or maybe ‘must’) encompass failure of both science and social policy, to the disadvantage of some communities. According to the U. S. EPA (2019):

Environmental justice is the fair treatment and meaningful involvement of all people regardless of race, color, national origin or income with respect to the development, implementation and enforcement of environmental laws, regulations and policies. In this usage, environmental justice denotes the general premise that communities must be treated equitably with respect to environmentally sensitive issues, such as siting of risk-posing facilities or adoption of riskposing policies. In this usage, too, the term ‘communities’ may refer to geo-

graphically or to ethnically distinct entities, such that environmental justice precludes targeting disadvantaged communities for the benefit of other (usually wealthier) communities: “Certain communities are disproportionately burdened by environmental contamination and health risks. Like Flint, those places tend to be locations where poor people and people of color are concentrated” (Erickson 2018). With respect to the status of lead as a legacy contaminant of emerging concern, the experience of Flint, Michigan is instructive. It is instructive only in part because it exemplifies the potential for concern about a legacy contaminant to reemerge. An important additional feature of this unfortunate experience is the failure of government to apply scientific knowledge about lead evenhandedly to protect public health without prejudice. The experience of Flint, Michigan represents an egregious failure of science policy and of social

policy. According to University of Michigan professor Paul Mohai: “Given the magnitude of the disaster in Flint, the role that public officials’ decisions played that led to the poisoning of the city’s water, their slow pace at acknowledging and responding to the problem, and the fact that Flint is a city of almost 100,000 people indeed makes this the most egregious example of environmental injustice and racism in my over three decades of studying this issue” (Erickson 2018). The problem of lead exposure is far more widespread than Flint, with “nearly 3,000 areas with recently recorded lead poisoning rates at least double those in Flint during the peak of that city’s contamination crisis” [Pell, and Schneyer (2016); and also see Beller (2019) regarding New Orleans, Louisiana; Hallum (2019) regarding New York City, and Corasaniti,

Gilgannon, and Schwartz (2018) regarding Newark, New Jersey]. The Office of the New York State Comptroller recently audited the NYS Lead Poisoning Prevention Program administered by the NYS Department of Health (NYS Comptroller 2019). The audit found that some children with elevated blood lead levels did not receive required services. Indeed, five of

LEGACY CONTAMINANTS 33

eight local health departments visited by auditors had cases in which follow-up services were not provided and/or not documented, amounting to 43 of 400 case files that were reviewed. This 11-percent noncompliance fraction must be extrapolated to the full case load of 80,946 children with elevated blood lead levels. A critical lesson to be learned, therefore, is that

vigilance must be maintained, as knowledge about lead exposure and toxic effects provided by science does not automatically result in consistent and evenhanded legal and regulatory protection provided by government.

Conclusion As a heavy metal industrially mined for millenia, lead (Pb) is a legacy contaminant. It is also a contaminant of emerging concern because of its persistence, toxicity, and recent discovery of its resurgence in drinking water

serving homes and schools, recently and most notoriously in Flint, Michigan. Concern about lead, however, has reemerged beyond Flint, exemplifying adoption of bad science policy despite availability of relevant good science. Much is known about lead toxicity. Whereas adults chronically exposed to lead may experience peripheral neuropathy, infants and children are more susceptible. They constitute sensitive subpopulations because their blood-brain barriers are immature, making them susceptible to central nervous system effects, most notably reduced IQ, when lead penetrates to developing brains. Failure to protect disadvantaged populations

in Flint and beyond despite availability of proven science and inexpensive technology also exemplifies instances of environmental injustice. Emerging concern about lead thus illustrates failure of social policy in addition to failure of science policy. A critical lesson to be learned is that vigilance must be maintained, as knowledge about lead exposure and toxic effects provided by science does not automatically result in consistent and evenhanded legal and regulatory protection provided by government.

About the author Robert A. Michaels, PhD, CEP (ram@ramtrac.com) is President of Schenectady-based RAM TRAC Corporation, and a toxicologist specializing in assessment and management of risks to public health potentially posed by environmental contaminants. He has served numerous corporate clients, the U.S. Congressional Office of Technology Assessment, and public interest organizations such as the Natural Resources Defense Council (NRDC). Dr. Michaels chaired the State of Maine Scientific Advisory Panel, and for 20 years chaired the Certification Review Board of the Academy of Board Certified Environmental Professionals (ABCEP). He has been Secretary of the NFPA Committee on Classification and Properties of Hazardous Chemicals, Board Member of the National Association of Environmental Professionals, and Member of the Editorial Advisory Boards of Springer-Verlag and Cambridge University Press science journals. He earned his doctorate at SUNY at Stony

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Brook in 1979, and in 2004 was awarded ABCEP’s Kramer Medal recognizing his professional contributions.

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Michaels, RA. Legacy contaminants of emerging concern: lead (Pb), Flint (MI), and human health. Routledge, Taylor & Francis Group, Environmental Claims Journal, 32(1):6-45, doi: 10.1080/10406026.2019.1661947, online 12 September 2019; print January 2020;

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