Bone marrow, toxicology

TOXICOLOGY OF THE BLOOD AND BONE MARROW Richard D. Irons, editor, 192 pp., 1985... 

Rats and mice are generally used for in vivo studies, with the mouse being employed for bone marrow micronucleus analysis and the rat for metaphase analysis, but both can be used for either. Mice are cheaper and easier to handle than rats, and only a qualitative difference in response has been found between the species (Albanese et al., 1987). Chinese hamsters are also widely used for metaphase analysis because of their low diploid chromosome number of 22. However, there are few other historical toxicological data for this species. 

OECD (1983). OECD Guidelines for the Testing of Chemicals. No. 475. Genetic toxicology in vivo mammalian bone marrow cytogenetic test chromosomal analysis. Adopted 4 April 1984. 

Subrahmanyam VV, Doane-Setzer P, Steinmetz KL, et al. 1990a. Phenol-induced stimulation of hydroquinone bioactivation in mouse bone marrow in vivo Possible implications in benzene myelotoxicity. Toxicology 62 107-116. 

The toxicological profile for vindesine includes effects observed with both vinblastine and vincristine. Among the effects observed with vindesine are bone marrow depression, alopecia, and peripheral neurotoxicity. 

Immunotoxicity. No information was found regarding immunotoxicity in humans from inhalation, oral, or dermal exposures to fuel oils. Only two animal studies were identified that tested immunological effects, both using mice. These studies identified cellular effects in the bone marrow, lymph nodes, and/or thymus and decreases in the relative weights of the lymph nodes and thymus from acute dermal exposures to kerosene (Upreti et al. 1989) and chronic dermal exposures to JP-5 and marine diesel fuel (NTP/NIH 1986). However, the toxicological significance of these effects on the immune system cannot be determined from these data. Additional data are needed to identify the toxic potential of fuel oils on the immune system by all routes of exposure and in different animal systems. 

Studies on the toxicology of some of these purine analogues in rodents and dogs at sublethal doses showed that rapidly dividing tissues, especially the intestinal mucosa and bone marrow, are most sensitive to these compounds... 

Toxicology. Acute benzene exposure causes central nervous system depression chronic exposure causes bone marrow depression leading to aplastic anemia and is also associated with an increased incidence of leukemia. 

Toxicology. In animal studies, target organs of diethanolamine (DEA) toxicity have included bone marrow, kidney, testis, skin, and central nervous system. 

Until recent times, the only toxicological hazards attributable to nitrous oxide were those common to asphyxiants, with death or permanent brain injury occurring only under conditions of hypoxia. A number of untoward and toxic effects have now been associated with exposure. One of the earliest findings was that patients given 50% nitrous oxide and 50% oxygen for prolonged periods, to induce continuous sedation, developed bone marrow depression and granuloqn openia. The bone marrow usually returned to normal within a matter of days once the nitrous oxide was removed, but several deaths from aplastic anemia have been recorded. ... 

Cytotoxicity Evaluated for confounding interpretation of in vitro efficacy assays, for predicting potential for human toxicity especially in liver but also if warranted by other safety assessments in bone marrow, kidney, neurons, immu-nocytes and so on. Also used for developing understanding of biochemical mechanisms of toxicity. HCA has been repeatedly demonstrated to be an effective tool in predictive toxicology. May also be used for certain translational safety biomarkers of toxicity [37]... 

Criswell, K.A., Sulkanen, A.P., Hochbaum, A.F. and Bleavins, M.R. (2000) Effects of phenylhydrazine or phlebotomy on peripheral blood, bone marrow and erythropoietin in wistar rats. Journal of Applied Toxicology, 20, 25—34. 

Micronucleus formation, male B6C3Fi mouse bone-marrow cells in vivo 100 ip X 3 National Toxicology Program (1993)... 

Mieronueleus formation, male and female B6C3F i mouse bone-marrow eells in vivo + 150 ipxl National Toxicology Program (1996)... 

The heme iron in the peroxidase is oxidized by the peroxide from III+ to V4- in compound I. The compound I is reduced by two sequential one-electron transfer processes giving rise to the original enzyme. A substrate-free radical is in turn generated. This may have toxicological implications. Thus the myeloperoxidase in the bone marrow may catalyze the metabolic activation of phenol or other metabolites of benzene. This may underlie the toxicity of benzene to the bone marrow, which causes aplastic anemia (see below and chap. 6). The myeloperoxidase found in neutrophils and monocytes may be involved in the metabolism and activation of a number of drugs such as isoniazid, clozapine, procainamide, and hydralazine (see below). In in vitro systems, the products of the activation were found to be cytotoxic in vitro. 

SVA. Sister chromatid exchange, B6C3F, mouse bone marrow — 1700 ip X1 US National Toxicology... 

MVM, Mieronueleus test, BbCSFj mouse bone marrow in vivo - 1250 ipx3 US National Toxicology... 

CBA, Chromosomal aberrations. B6C3Fi mouse bone marrow - 1700 ipx 1 US National Toxicology... 

Snoeij NJ, van lersel AA, Penninks AH, et al. 1986b. Triorganotin-induced cytotoxicity to rat thymus, bone marrow and red blood cells as determined by several in vitro assays. Toxicology 39 71-83. 

What are the chronic toxicological effects of benzene What kinds of blood abnormalities are caused by benzene exposure How does benzene toxicity affect white cell count How does it affect bone marrow ... 

T.S.S. Dikshith, Cytogenetic effects of pesticides in the bone marrow system of male rats, (unpublished data 1982, Scientific report ITRC, Lucknow, India 1981-1984), in Toxicology of Pesticides in Animals, Ed., T.S.S. Dikshith, CRC Press, Boca Raton, FL, 194, 1999 (Update) PB/99/166662. 

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