sodium-bromate and Body-Weight

Bromate is a drinking water disinfection by-product formed during the ozonation of source water containing bromide. Sodium bromate is also used as an analytical reagent, in the oxidation of sulfur and vat dyes, and for cleaning boilers. As a mixture with sodium bromide, it is used for dissolving gold from its ores. The cosmetic industry uses sodium bromate and potassium bromate as neutralizers or oxidizers in hair wave preparations. Sodium bromate was nominated for toxicity and carcinogenicity studies in transgenic mouse models by the United States Environmental Protection Agency and the National Institute of Environmental Health Sciences. Male and female Tg.AC hemizygous mice received sodium bromate by dermal application for 26 or 39 weeks and by exposure in drinking water for 27 or 43 weeks. Male and female p53 haploinsufficient mice were exposed to sodium bromate (at least 99% pure) in drinking water for 27 or 43 weeks. Genetic toxicology studies were conducted in mouse peripheral blood erythrocytes. 26- and 39-WEEK DERMAL STUDIES IN Tg.AC HEMIZYGOUS MICE: Groups of 15 male and 15 female Tg.AC hemizygous mice received dermal applications of 0, 64, 128, or 256 mg sodium bromate/kg body weight in ethanol/water, 5 days per week for 26 weeks. Additional groups of 10 male and 10 female Tg.AC hemizygous mice were dermally administered the same doses for 39 weeks. Survival of dosed groups was similar to that of vehicle control groups at 26 and 39 weeks. Mean body weights of 256 mg/kg males were less than those of the vehicle control group in both studies. Mean body weights of all dosed groups of females were less than those of the vehicle controls at 39 weeks. Minimal decreases in hematocrit and hemoglobin concentration values occurred in 128 mg/kg females and 256 mg/kg males and females at 26 weeks. A minimal decrease in erythrocyte count also occurred in 256 mg/kg males. These decreases in erythron were accompanied by a minimal decrease in mean cell hemoglobin and mean cell hemoglobin concentration values, primarily in the females. Reticulocyte counts were significantly increased in 128 mg/kg females and 256 mg/kg males and females. There were no increased incidences of neoplasms in male or female Tg.AC hemizygous mice exposed to sodium bromate dermally. Relative kidney weights were significantly increased in 256 mg/kg males at 26 weeks and in all dosed groups of males at 39 weeks. Absolute testis weights in 256 mg/kg males and absolute kidney weights in 25. Sodium bromate exposure resulted in significantly increased frequencies of micronucleated erythrocytes in male and female Tg.AC hemizygous and p53 haploinsufficient mice administered the chemical in drinking water for 27 weeks or by dermal application for 26 weeks. Tg.AC hemizygous mice were treated by both routes; p53 haploinsufficient mice were exposed only through drinking water. In all three micronucleus tests, a clear dose response was observed in male and female mice. Significant increases in the percentage of polychromatic erythrocytes among total erythrocytes were observed in male and female Tg.AC hemizygous mice exposed via drinking water and in male Tg.AC hemizygous mice dosed dermally with sodium bromate. The percentage of polychromatic erythrocytes was not significantly altered in male or female p53 mice.. Under the conditions of these drinking water studies, there was no evidence of carcinogenic activity of sodium bromate in male or female p53 haploinsufficient mice exposed to 80, 400, or 800 mg/L for 27 or 43 weeks. No treatment-related neoplasms were seen in male or female Tg.AC hemizygous mice exposed dermally to 64, 128, or 256 mg sodium bromate/kg body weight for 26 or 39 weeks. No treatment-related neoplasms were seen in male or female Tg.AC hemizygous mice exposed by drinking water to 80, 400, or 800 mg sodium bromate/L for 27 or 43 weeks. In drinking water and dermal studies in Tg.AC hemizygous mice there were increased incidences of nonneoplastic lesions in the thyroid gland and kidney.

Topics: Administration, Cutaneous; Animals; Body Weight; Bromates; Carcinogenicity Tests; Female; Genes, ras; Kidney; Male; Mice; Mice, Transgenic; Sodium Compounds; Thyroid Gland; Tumor Suppressor Protein p53; Water Pollutants, Chemical; Water Supply

Bromate is one of the water disinfection by-products (DBPs) produced during the process of ozonation. The purpose of this study was to evaluate the immunotoxic potential of sodium bromate (SB) in female B6C3F1 mice. SB was administered in the drinking water for 28 days at doses of 80-800 mg/l. There was no difference in drinking water consumption between the animals exposed to SB and the tap water controls. Exposure to SB did not produce any signs of overt toxicity. Furthermore, no significant differences were observed in body weight, body weight gain, or the weights of thymus, liver, kidneys or lungs. No gross pathological lesions were observed in SB-treated animals. However, animals exposed to SB had a significant increase in absolute (28%) and relative (26%) spleen weights. The erythrocyte count, hemoglobin, hematocrit, mean corpuscular volume (MCV), platelet count, total leukocyte count, and counts of differential leukocytes were unaffected by SB. A dose-related increase in reticulocytes was observed following exposure to SB with the greatest increase (78%) observed at the highest dose level. Overall, there were no changes in the absolute number of total T cells, CD4+CD8- T cells, CD4-CD8+ T cells, natural killer (NK) cells and macrophages. Exposure to SB did not affect the percentage of B cells, although a slight increase in absolute number of B cells at the dose of 600 mg/l was observed. There was no alteration in IgM antibody-forming cell (AFC) response, mixed leukocyte reaction (MLR) and NK cell activity after exposure to SB. When the activity of peritoneal macrophages, unstimulated or stimulated with IFN-gamma and LPS, was evaluated using the cytotoxic/cytostatic assay of B16F10 tumor cells, the suppressive effect of macrophages on the proliferation of B16F10 tumor cells was decreased after exposure to SB. In conclusion, SB, when administered in the drinking water at doses from 80 mg/l to 800 mg/l, produced minimal toxicological and immunotoxic effects in female B6C3F1 mice.

Topics: Animals; Blood Cell Count; Body Weight; Bromates; Disinfection; Female; Hematocrit; Kidney; Leukocyte Count; Liver; Lymphocyte Culture Test, Mixed; Mice; No-Observed-Adverse-Effect Level; Organ Size; Ozone; Sodium Compounds; Spleen; Thymus Gland; Water