PRINCIPLES OF TOXICOLOGY

Zinc is required for normal growth and development, reproduction, and immune function. Zinc
deficiency can have numerous adverse effects on the normal function of all of these systems. The
Recommended Dietary Allowance (RDA) for zinc ranges from 5 mg/day for infants to 19 mg/day for
lactating women.
Metal fume fever has been observed in humans exposed to high concentrations of zinc oxide fumes.
These exposures have been acute, intermediate, and chronic. Metal fume fever is thought to be an
immune response characterized by flulike symptoms and impaired lung function.
Zinc salts of strong mineral acids are astringent, are corrosive to the skin, and are irritating to the
gastrointestinal tract. When ingested, they may act as emetics. In these cases, fever, nausea, vomiting,
stomach cramps, and diarrhea occurred within 3–13 h following ingestion. The dose associated with
such effects is greater than 10 times the RDA. Aside from their irritant action, inorganic zinc
compounds are relatively nontoxic by oral exposure. Zinc ion, however, is ordinarily too poorly
absorbed to induce acute systemic intoxication.
The USEPA has established a daily oral reference dose (RfD) of 3 × 10 –1 mg/kg for zinc; however,
no inhalation RfD has been established. Zinc is classified in group D, defined as not classifiable with
regard to human carcinogenicity (USEPA, 1998).
14.7 SUMMARY
This chapter has briefly discussed the fundamental concepts of metal toxicity. Because of the large
number of metals, their ubiquitous nature, and their chemical and physical diversity, the field of metal
toxicology is one of the broadest areas of health effects research.
Metals vary greatly in their physical and chemical properties, and therefore, in their potential for
absorption and toxicity. Some metals are considered essential for good health, but these same metals,
at sufficient concentrations, can be toxic.
Inhalation and ingestion are the most common routes of metal exposure. Dermal effects may be
severe, but typically are limited to the site of application. Some metals can remain in the body for
significant periods of time, stored in specific tissues and slowly released over time. Urine and feces
are the primary routes of excretion for most ingested metals. Biomarkers of exposure to some metals
can thus be detected in these excretory products, as well as in stored forms in hair and fingernails.
Following sufficient acute or chronic exposure to certain metals, a variety of toxic effects can be
observed in humans and animals. A review of the toxicology of some selected metals is presented in
Section 14.6 of this chapter.
The following bibliography provides some additional sources of information for the toxicity and
general characteristics of metals.
REFERENCES AND SUGGESTED READING
14.7 SUMMARY 343
ACGIH (American Conference of Governmental Industrial Hygienists), Documentation of Threshold Limit Values
and Biological Exposure Indices, 6th ed., 1991–1998.
ATSDR (Agency for Toxic Substances and Disease Registry), Toxicological Profiles, Atlanta, GA, 1993–1999.
Chang, L. W., L. Magos, and T. Suzuki, eds., Toxicology of Metals, CRC Press, Boca Raton, FL, 1996.
Clayton, G. D., and F. E. Clayton, eds., Patty’s Industrial Hygiene and Toxicology, Vol. II, Toxicology, 4th ed.,
Wiley, New York, 1994.
Ellenhorn, M. J., Medical Toxicology: Diagnosis and Treatment of Human Poisoning, 2nd ed., Williams & Wilkins,
Baltimore, 1997.
IARC (International Agency for Research on Cancer), Monographs 1972–present, World Health Organization.
Lyon, France.
Klaassen, C. D., ed)., Casarett and Doull’s Toxicology: The Basic Science of Poisons, 5th ed., 1996.