The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program (NTP). The findings have not been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by the NTP on March 2009 (see http://ntp.niehs.nih.gov/ntp/htdocs/levels/09-3566%20NTP-ITOX-R1.pdf). The findings and conclusions for this study should not be construed to represent the views of the NTP or the US Government.
Dose Range-Finding Study for the Immunotoxicity Evaluation of Sodium Arsenite (CAS No. 7784-46-5) in Female B6C3F1 Mice
NTP Study Number: IMM94004
Sodium arsenite (AS) is used in the manufacture of arsenical soap for use on skin, for treating vines against certain scale diseases and as an insecticide, especially for termites. The primary interest in these studies relates to the immunotoxicology studies of gallium arsenide (GaAs). GaAs was shown to have a selective action on the immune system and arsenic was implicated as the immunotoxic component. These studies were conducted in part to confirm that arsenic was immunotoxic. Several studies have been reported indicating the immunotoxic potential of arsenic. These have recently been reviewed by Burns et al..
Sodium arsenite was nominated to the NTP for toxicological evaluation and was selected for immunotoxicity studies by the chemical manager. The purpose of the range-finding study was to determine the doses of sodium arsenite to be used in an immuntoxicology protocol.
The range-finding studies were conducted in female B6C3F1mice. The animals were administered sodium arsenite as a pellet implanted subcutaneously. The sodium-meta arsenite was purchased from Sigma Chemical Company and pelletized by Innovative Research of America. The pellets were prepared using 1, 3 and 6 mg/pellet as recommended by the producer to obtain the desired blood levels of 100, 300 and 600 ng/ml. These doses proved highly toxic and the pellets were then prepared at 0.01, 0.03 and 0.06 mg/pellet. Two studies were carried out in completing the range-finding protocol. The pellets were implanted on day 1 and the assay evaluations were performed on day 15. Dose levels of 0.01, 0.03 and 0.06 mg/pellet were used; however, the high dose of 0.06 mg/pellet resulted in the death of the mice.
Executive Summary Table 1 (ES-1) shows a summary of the standard toxicology studies for sodium arsenite. The results of the sodium arsenite range-finding studies demonstrate that, in the female B6C3F1 mouse, exposure to sodium arsenite, administered by a subcutaneous implanted pellet for a 14-day exposure at doses of 0.06 or greater, produced overt toxicity and death of the animals. Exposure to lower doses of sodium arsenite (0.01 and 0.03 mg/pellet) did not result in significant changes in body weight, change in body weight gain, erythrocyte number, hemoglobin, hematocrit, mean corpuscular hemoglobin concentration, reticulocytes or leukocyte number. A slight, but significant decrease was seen in the mean corpuscular volume and mean corpuscular hemoglobin. Exposure to lower doses of sodium arsenite (0.01 and 0.03 mg/pellet) did not result in significant changes in liver, spleen, thymus or kidney weight when the data were expressed as absolute weight (mg) or as percent body weight. A significant decrease was seen in the lung absolute weight (22.6%) but not in the percent body weight.
Executive Summary Table 2 (ES-2)
shows a summary of the immunology studies for sodium arsenite.
Exposure to lower doses of sodium arsenite (0.01 and 0.03 mg/pellet)
did not produce significant changes in the antibody-forming cell
response to the T-dependent antigen, sheep erythrocytes, expressed
as IgM AFC/10, while the IgM AFC/spleen did show a significant
increase at 0.03 mg/pellet (49.2%). In the surface marker absolute
values, no effects were observed in the number of B cells, T cells
or CD8+ cells,
but a significant decrease in the CD4+ cells (12.3%)
was seen. Exposure to lower doses of sodium arsenite (0.01 and
0.03 mg/pellet) did not result in significant changes in the mixed
leukocyte response (MLR) or natural killer (NK) cell activity.
Based on the overall negative toxicological and immunological
results of this range-finding study, the test article, sodium
arsenite, will not be pursued as an expanded protocol.
SUMMARY TABLE FOR TOXICOLOGY STUDIES
|Body Weight||No Effect|
|Body Weight Gain||No Effect|
SUMMARY TABLE FOR IMMUNOLOGY STUDIES
|IgM AFC to sRBC|
|Mixed Leukocyte Response||No Effect|
|Natural Killer Cell Activity||No Effect|
Report Date: February 1994