While a complete blood count provides information regarding possible treatment-related effects reflected in the peripheral blood, morphological evaluation of bone marrow cytology and paraffin sections provides information about bone marrow tissue architecture that otherwise would be missed by examination of peripheral blood alone. In decalcified, paraffin-embedded, hematoxylin and eosin (H&E)-stained sections of bone marrow, the more mature stages of the erythroid and myeloid cells, adipocytes, mast cells, and megakaryocytes can be identified, but lymphoid cells as well as immature progenitor cells can not be reliably identified. The quality of the marrow sections is governed by numerous variables related to specimen collection and processing and must be considered. In addition to discussing normal structure, function, and histology of bone marrow, methods for preparation and evaluation of bone marrow are presented.

Melatonin (MEL) is a widely used, over-the-counter sleep aid, and it has putative contraceptive, antioxidant, antiaging, and anticancer effects. The developmental toxicity potential for repeated oral doses of MEL had not previously been evaluated. In the present studies, time-mated, Sprague-Dawley-derived (CD) rats were administered MEL or vehicle by gavage on gestation days (gd) 6-19. MEL-treated groups received 1-, 10-, 100-, 150-, or 200-mg/kg body weight/day in the screening study (15 rats/group), and 50, 100, or 200 mg/kg/day in the definitive study (25 rats/group). In both studies, maternal food/water consumption, body weight, and clinical signs were monitored at regular intervals throughout gestation. At termination (gd 20, both studies), maternal liver and gravid uterine weights, number of ovarian corpora lutea, conceptus survival, fetal sex, and fetal body weight were evaluated. Fetal morphological examination included external structures (both studies) as well as visceral and skeletal structures (definitive study). In the screening study, maternal serum levels of 17beta-estradiol, progesterone, prolactin, and luteinizing hormone were determined by radioimmunoassay, and mammary tissue was fixed, stained, and evaluated for percent glandular area within the fat pad. No maternal morbidity/mortality was found in either study. In the screening study, aversion to treatment (> or =100 mg/kg/day) and reduced maternal weight gain (> or =150 mg/kg/day) were noted, but reproductive/endocrine parameters and fetal development were not affected. In the definitive study, aversion to treatment was noted at > or =50 mg/kg/day, and mild sedation, reduced maternal food intake, and reduced body weight gain were found during initial treatment with 200 mg/kg/day. MEL had no effect on prenatal survival, fetal body weight, or incidences of fetal malformations/variations. Thus, in the definitive study, the maternal toxicity NOAEL and LOAEL were 100 and 200 mg/kg/day, respectively, and the developmental toxicity NOAEL was > or =200 mg/kg/day.

BackgroundHexavalent chromium [Cr(VI)] is a human carcinogen after inhalation exposure. Humans also ingest Cr(VI) from contaminated drinking water and soil; however, limited data exist on the oral toxicity and carcinogenicity of Cr(VI).ObjectiveWe characterized the chronic oral toxicity and carcinogenicity of Cr(VI) in rodents.MethodsThe National Toxicology Program (NTP) conducted 2-year drinking water studies of Cr(VI) (as sodium dichromate dihydrate) in male and female F344/N rats and B6C3F1 mice.ResultsCr(VI) exposure resulted in increased incidences of rare neoplasms of the squamous epithelium that lines the oral cavity (oral mucosa and tongue) in male and female rats, and of the epithelium lining the small intestine in male and female mice. Cr(VI) exposure did not affect survival but resulted in reduced mean body weights and water consumption, due at least in part to poor palatability of the dosed water. Cr(VI) exposure resulted in transient microcytic hypochromic anemia in rats and microcytosis in mice. Nonneoplastic lesions included diffuse epithelial hyperplasia in the duodenum and jejunum of mice and histiocytic cell infiltration in the duodenum, liver, and mesenteric and pancreatic lymph nodes of rats and mice.ConclusionsCr(VI) was carcinogenic after administration in drinking water to male and female rats and mice.