The potential testicular toxicity of potassium dichromate (hexavalent) was evaluated in BALB/c mice. Potassium dichromate (hexavalent) was administered at dose levels of 0, 15, 50, 100, and 400 ppm in the diet for nine weeks followed by a nine week recovery (potassium dichromate free) period. Interim necropsies occurred after 3, 6, and 9 weeks of administration and a terminal necropsy occurred following Week 17. Endpoints included body weights, feed and water consumption, organ weights, microscopic evaluation of the liver, kidney, and ovaries, hematology, histology of the testis and epididymis for Sertoli nuclei and preleptotene spermatocyte counts in Stage X or XI tubules, and chromatin analysis.
There was a slight decrease in mean body weights in the 400 ppm males (5-9%) and females (4%) and the 100 ppm females (2-4%) during the dosing periods. Feed consumption was generally increased in all treated groups especially the 400 ppm males and females. During the recovery period, feed consumption was comparable across groups. The achieved dose levels were approximately 4 mg/kg/day in the 15 ppm group, 13 mg/kg/day in the 50 ppm group, 28 mg/kg/day in the 100 ppm group, and 115 mg/kg/day in the 400 ppm group. There were no treatment-related effects noted for clinical signs, necropsy findings, microscopic evaluation, or hematology findings except for decreased mean corpuscular volume (MCV) and possibly mean corpuscular hemoglobin (MCH) in the 400 ppm males and females which may suggest a possible bone marrow/erythroid response. This effect returned to normal by Week 17 in the 400 ppm female mice but increased in the 400 ppm male mice. Cytoplasmic vacuolization in hepatocytes was noted in the 50, 100, and 400 ppm males and females. Testicular cell counts for Sertoli nuclei and preleptotene spermatocyte counts in Stage X and XI tubules did not reveal any differences between the treated groups and control.
Results of this study indicate that potassium dichromate treatment did produce slight general toxicity in the 50, 100, and 400 ppm dose level. A maximum tolerated dose (MTD) was achieved, based on decreased body weights, MCV and MCH values, and cytoplasmic vacuolization of hepatocytes in the 400 ppm males and females. The no-observable-adverse-effect-level (NOAEL) was determined to be 15 ppm.
NTIS # PB97-125363