PRINCIPLES OF TOXICOLOGY

340 PROPERTIES AND EFFECTS OF METALS
The current daily oral RfD for chromium (+3) is 1.0 mg/kg. The current daily oral RfD for chromium
(+6) is 5 × 10 –3 mg/kg. Chromium (+6) is classified as a Class A (confirmed human carcinogen) by
the inhalation route of exposure only. Chromium (+3) is not classified as a carcinogen by any route of
exposure.
Lead
Lead is a naturally occurring bluish-gray metal found in the earth’s crust. Lead can combine with other
chemicals to form what are known as lead salts. These compounds are water-soluble, while elemental
lead is not. Lead is used in the production of batteries, ammunition, metal products, as well as scientific
and medical equipment. Most of the lead mobilized in the environment is the result of human activities.
Exposure to inorganic lead and inorganic lead compounds or to organic lead compounds can occur
in environmental or occupational circumstances. Inorganic lead exposure is most applicable to general
and occupational exposure. Human body burdens of lead result from inhalation and oral exposure to
inorganic lead. In humans, oral absorption of ingested lead occurs primarily in the gastrointestinal
tract; 50 percent of the oral dose is absorbed by children and 15 percent is absorbed by adults. Typically,
the lead body burden of an average adult human has been reported to range between 100 and 300 mg.
Exposure to lead can affect a number of organs and/or systems in humans and animals. The research
on lead contains dose–response data for humans primarily from studies of occupationally exposed
groups, as well as the general population. Inhalation contributes a greater proportion of the dose for
occupationally exposed groups, and the oral route contributes a greater proportion of the dose for the
general population. The effects of lead are the same regardless of the route of entry into the body and
are well correlated with blood lead level.
Lead in soil and dust are important sources of exposure in children. The Centers for Disease Control
(CDC) in 1985 stated that concentrations of lead in soil or dust at 500–1000 mg/kg are associated with
blood levels in children that exceed background levels. Death from lead poisoning occurred in children
with blood lead levels >125 µg/dL, including several deaths in children who exhibited severe
encephalopathy. The duration of exposure associated with this effect was on the order of a few weeks
or more, and, in some cases, it may have been an acute toxic response. For industrial sites, where access
to soil may be limited or restricted, it was recommended that the upper end of the range that was
identified in the Office of Solid Waste and Emergency Response (OSWER) Directive 9355.4-02 for
lead be used in establishing protective concentrations for lead in soil at industrial sites (range of
500–1000 mg/kg). However, subsequent studies in areas of high lead soil concentrations in mining
areas have not confirmed those recommendations.
Relatively low exposure levels of lead may cause adverse neurological effects in fetuses and young
children. Very low blood lead levels (e.g., 10–20 µg/dL) have been associated with effects on learning
ability. The CDC initially defined lead toxicity in a child as a blood lead level in the range of 25–35
µg/dL, coupled with an erythrocyte protoporphyrin level of >35 µg/dL. The threshold has since been
lowered to 10 µg/dL by that agency. A blood lead level of 50 µg/dL has been determined to be an
approximate threshold for the expression of lead toxicity in exposed adult workers, and the occupational
recommended conservative benchmark typically is 30 µg/dL. Neurobehavioral effects have also
been documented in animal studies as well as human studies.
Lead affects the hematopoietic system by altering the activity of three enzymes involved in heme
biosynthesis. The impairment of heme synthesis has a number of subsequent effects, including
decreased hemoglobin levels and anemia. These effects have been observed in lead workers and in
children with prolonged lead exposure. A decrease in cytochrome P450 content of hepatic microsomes
has been noted in animal studies.
Lead may cause kidney damage as a result of acute or chronic exposure. Reversible proximal tubular
damage can result from acute lead exposure. Heavy, chronic exposure can result in nephritis, interstitial
fibrosis, and tubular atrophy.
Colic—characterized by abdominal pain, constipation, cramps, nausea, vomiting, anorexia, and
weight loss—is a symptom of lead poisoning in occupationally exposed cases and in children.