PRINCIPLES OF TOXICOLOGY

4 Hematotoxicity: Chemically Induced
Toxicity of the Blood
HEMATOTOXICITY: CHEMICALLY INDUCED TOXICITY OF THE BLOOD
ROBERT A. BUDINSKY JR.
This chapter describes toxicities affecting blood. The following subjects are covered:
• The origin, formation, and differentiation of blood cells
• Clinical tests used to evaluate hematotoxicity
• Oxygen transport by erythrocytes (red blood cells or RBCs) and interference with oxygen
transport by drugs and chemicals
• Chemicals that affect the formation of red blood cells, platelets, and white blood cells (bone
marrow suppression)
• Leukemias and lymphomas (cancers of the white blood cells)
• Neurological and cardiovascular toxicities caused by interference with oxygen utilization
(e.g., cyanide, hydrogen disulfide)
• Medical treatment of hematotoxicity
This chapter describes common occupational and environmental chemicals and drugs that affect blood
formation and function. Only the recognized chemically induced blood toxicities are included in this
chapter, although there are many examples of anecdotal reports linking a large number of chemicals
and drugs with hematotoxicity.
4.1 HEMATOTOXICITY: BASIC CONCEPTS AND BACKGROUND
Hematotoxicity essentially involves two basic homeostatic functions: (1) RBC-mediated oxygen
transport and (2) the production of red and white blood cells and platelets. Perhaps the earliest
experiences with hematotoxicity involved the consumption of fava beans and the development of
favism among people in the Mediterranean region. Favism is the development of acute hemolytic
anemia in individuals with a deficiency in the red blood cell enzyme glucose-6-phosphate dehydrogenase
following the ingestion of fava beans. It is also likely that methemoglobinemia, a blood
condition characterized by cyanosis, was observed when individuals consumed well water containing
large amounts of nitrates and nitrates.
Chemically induced hematotoxicity has been reported in the medical literature for over a century.
For example, the 1919 publication by Dr. Alice Hamilton, entitled Industrial Poisoning by Compounds
of the Aromatic Series, described a number of blood toxicities that were commonly encountered in
occupational settings such as benzene-induced bone marrow suppression, aniline and nitrobenzeneinduced
methemoglobinemia, and hydrogen sulfide–induced effects. The major hematotoxicities
encountered in the workplace involve benzene (bone marrow suppression and acute myelogenous
leukemia), carbon monoxide (impairment of oxygen transport), aniline/nitrobenzene analogs
Principles of Toxicology: Environmental and Industrial Applications, Second Edition, Edited by Phillip L. Williams,
Robert C. James, and Stephen M. Roberts.
ISBN 0-471-29321-0 © 2000 John Wiley & Sons, Inc.
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