Myelotoxic effect

The model by Medinsky et al. (1995) considered the dosimetry of benzene and its metabolites in bone marrow in order to help explain their hematotoxic and myelotoxic effects. It is well known that none of the metabolites alone produces the effects seen with benzene exposure. Although it is not yet a fully developed PBPK model, this study lays the groundwork for further model development. 

Toluene exposure does not result in the hematopoietic effects caused by benzene. The myelotoxic effects previously attributed to toluene are judged by more recent investigations to be the result of concurrent exposure to benzene present as a contaminant in toluene solutions. Most of the toluene absorbed from inhalation is metabolized to benzoic acid, conjugated with glycine in the liver to form hippuric acid, and excreted in the urine. The average amount of hippuric acid excreted in the urine by persons not exposed to toluene is approximately 0.7-1.0 g/1 of urine. ... 

CHLORAMBUCIL AZATHIOPRINE t risk of myelosuppression and immunosuppression. Deaths have occurred following profound myelosuppression and severe sepsis Additive myelotoxic effects Azathioprine is metabolized to 6-mercatopurine in vivo, which results in additive myelosuppression, immunosuppression and hepatotoxicity Avoid co-administration... 

Ciclosporin is an immunosuppressant drug that primarily inhibits T cell activation, therefore down-regulating the T cell responses that mediate graft rejection. Myelotoxic effects are therefore not expected. Ciclosporin has also been used in a wide range of chronic inflammatory or autoimmune diseases. 

Although rare, acute hemolytic anemia can occur. This may reflect an immune reaction or may be due to glucose-6-phosphate dehydrogenase deficiency. Agranulocytosis occurs in -0.1% of patients who receive sulfadiazine and also can occur with other sulfonamides. Although neutropenia may persist for weeks or months after sulfonamide is withdrawn, most patients recover spontaneously with supportive care. Pancytopenia with complete suppression of bone-marrow activity is extremely rare. It probably results from a direct myelotoxic effect and may be fatal. Reversible suppression of the bone marrow is quite common in patients with limited bone marrow reserve (e.g., patients with AIDS or those receiving myelosuppressive chemotherapy). 

Agranulocytosis occurs in 0.1 % of cases after sulfadiazine and also occurs after other sulfonamides. The myelotoxic effect is demonstrated as impaired development of the myeloblasts. Granulocytopenia is not related to the applied dosage and as a rule appears after 10 days treatment. Slight passing thrombocytopenia is frequent, but serious thrombocytopenia and aplastic anemia are rare. Isolated peripheral eosinophilia can be observed, disappearing rapidly after cessation of sulfonamides. It can also appear in combination with other signs of hypersensitivity (Thirkettle et al. 1963 Johnson and Korst 1961). 

Some studies showed decreases of thrombocyte counts in car painters and paint industry workers, other studies, however, recorded no changes.Studies concerning effects of paints on the white cell and thrombocyte counts were inconsistent. A decrease of white cells was described in several studies" and a lymphocytosis was noted by Angerer and Wulf Elofsson et al., however, recorded no changes in white cell counts. Additionally, myelotoxic effects of solvents were shown, especially for benzene. 

Hemopoietic system benzene metabolites (e.g., benzoquinone, hydroquinone) marrow depression, myelotoxic effects... 

Benzene has the ability to damage the bone marrow and to cause anemia and leukemia. This hematopoietic toxicity shown by benzene is unique as the myelotoxic effect disappears when one or more alkyl groups are attached to the benzene structure. Toluene and xylene are examples of the aromatic solvents which do not show the hematopoietic toxicity. The OS HA regulation 29 CFR 1910.1028 allows a Permissible Exposure Limit (PEL) of 1.0 ppm benzene in the work area for an 8 hr day and 40 hr work week. The current documents of both the OSHA and ACGIH organizations consider benzene as a suspected human carcinogen. 

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