PRINCIPLES OF TOXICOLOGY - Biology East Borneo

108 HEMATOTOXICITY: CHEMICALLY INDUCED TOXICITY OF THE BLOOD4.16 MISCELLANEOUS TOXICITIES EXPRESSED IN THE BLOODLead poisoning may affect normal red blood cell parameters. For one, lead interferes with hemesynthesis in the liver, which can lead to anemias. This interference results in the accumulation ofprotoporphyrin, a heme precursor that is measurable in the form of zinc protoporphyrin in the blood.The term basophilic stippling is often associated with RBCs that are prematurely destroyed in responseto lead-induced anemia. Basophilic stippling is characterized by various-sized purple granules that aremicroscopically observed within the RBC. The purple granules are comprised of pyrimidine compoundsthat accumulate because lead inhibits erythrocyte pyrimidine-5-nucleotidase, the enzymeresponsible for the normal degradation of these pyrimidine nucleotides. The apparent blood leadthreshold affecting porphyrin biochemistry is around 25–30 µg/dL and the threshold for affectinghemoglobin is around 50 µg/dL. Treatment of lead poisoning generally involves chelation therapy withdrugs such as penicillamine, EDTA, Dimercarpol, or BAL (British anti-lewisite).A number of chemicals affect the formation and action of clotting factors. Many of these chemicalsinhibit clot formation and are extremely useful as anticoagulants in individuals with atheroscleroticcardiovascular and cerebrovascular disease. Thus, the anticoagulants aid in the prevention of heartattacks and strokes. For example, the drug warfarin effectively reduces circulating clotting factorswithin a few hours to days following treatment. Warfarin’s mechanism of action involves theantagonism of vitamin K, which is involved in the carboxylation of clotting factor proteins. Anticoagulantssuch as warfarin are also used as pesticides. Several additional rodenticides include difenacoum,chlorphacinone, and brodifacoum. Unless ingested, these anticoagulants are relatively safe sincethey are nonvolatile and cannot be absorbed through the skin. Poisoning by the anticoagulants usuallyoccurs in infants and suicide cases. In the clinical setting, physicians monitor the patient’s clottingtimes to control for the desired therapeutic effect and to avoid excessive anticoagulation, which couldresult in a fatal hemorrhage. Vitamin K is the recommended antidote for treating individuals poisonedby anticoagulants.4.17 SUMMARYHematotoxicity involves a wide range of effects ultimately affecting oxygen delivery, maintenance ofa viable immune or clotting system, and cancer. It is fortunate that hematotoxicity is a relativelyuncommon occurrence. Overall, the real concern regarding bone marrow injury is related to benzeneexposure in occupational settings. Benzene exposure in the workplace has dramatically declined sincethe days of the Pliofilm workers and before, and currently, there is little evidence to suggest that existingoccupational settings pose a risk of AML. The threshold for benzene-induced AML has been reportedto range of 0.1–50 ppm, although the actual concentration which poses a serious threat is still heavilydebated. On the other hand, benzene exposure resulting from ingestion of ppb concentrations inambient air or drinking water does not pose a risk of AML or any other hematopoietic tumors. Ingeneral, hematotoxicity is an occupational concern since the exposures and doses of chemicals requiredto cause a toxic response cannot be achieved from the low levels found in the environment (i.e., ppbair concentrations). The exceptions, of course, are carbon monoxide poisonings, which frequentlyoccur in home settings, or toxicities from medications, such as chemotherapeutic agents used to treatcancer.REFERENCES AND SUGGESTED READINGEllenhorn’s Medical Toxicology Diagnosis and Treatment of Human Poisoning. Matthew J. Ellenhorn editor, 2ndedition. Williams & Wilkins, Baltimore, (1997).Fishbeck, W. A., J. C. Townsend, and M. G. Swank, “Effects of chronic occupational exposure to measuredconcentrations of benzene.” J. Occup Med. 20(8): 539–542 (1978).