Dose Range-Finding on the Immunotoxicity of Indium Arsenide in Female B6C3F1 Mice (CAS No. 1303-11-3)
The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program. The findings have not been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by NTP in March 2009. The findings and conclusions for this study should not be construed to represent the views of the NTP or the U.S. Government.
Indium arsenide is used as a semiconductor in the electronics industry as is gallium arsenide. The primary interest in these studies relates to the immunotoxicology studies of GaAs. GaAs was shown to have a selective action on the immune system and arsenic was implicated as the immunotoxic component.
Indium arsenide was nominated to the NTP for toxicological evaluation and was selected for immunotoxicity studies by the chemical manager. Thus, the purpose of this range-finding study was to determine the doses of IA to be used in the protocol to determine the potential effects of IA on the immune system.
The range-finding studies were conducted in female B6C3F1 mice. The animals were administered IA on day 1 by a single intratracheal instillation of 200 mg/kg. IA was prepared as a solution in sterile physiological saline with 0.05% Tween 80. A time course consisted of five different exposure times between 1 day and 15 days. The T-dependent antibody response to sRBC was measured on days 1, 4, 8, 11, and 14 after the single exposure. The mixed leukocyte response was evaluated on days 1, 3, 6, 11, and 14 after the single exposure. Organ weights were also obtained from the second study.
The results of the indium arsenide range-finding studies demonstrate that, in the female B6C3F1 mouse, exposure of 200 mg/kg by intratracheal instillation produced a slight decrease in body weight at all time periods with significant decreases up to 11%. A significant decrease of up to 24% in liver weight was seen on days 1, 3, and 6 after exposure. A significant decrease in spleen weight was seen on days 1 and 3 after exposure up to 23%. A significant increase in the lung weight was seen on days 6, 11, and 14 after exposure up to 90%. A significant decrease in the thymus weight was seen on days 1, 3, 6 and 11 after exposure up to 44%. A slight decrease in kidney weight was seen on days 1, 3, 6, and 11 after exposure up to 12%. Exposure to 200 mg/kg on days 1, 3, 6, 11, and 14 after intratracheal instillation did not result in significant changes in erythrocyte number, hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, hemoglobin concentration or leukocyte number. A slight, but significant increase (7%) was seen in the hematocrit on day 1 after exposure and a significant decrease (37%) in the reticulocyte count 3 days after exposure. Results from the leukocyte cell differential showed decreases in the percent lymphocytes at 1, 3, and 6 days after exposure by 15%, 11%, and 15%, respectively. The percentage of neutrophils was increased at 1, 3, and 6 days after exposure by 80%, 53%, and 80%, respectively. The absolute values of the neutrophils were also increased at 1 and 6 days after exposure by 102% and 93%, respectively. All of the leukocyte cell differential effects returned to vehicle control values after 11 days of exposure to the single administration of 200 mg/kg indium arsenide.
A summary of the immunology studies demonstrated that treatment with indium arsenide did not produce significant changes in the antibody-forming cell response to the T-dependent antigen, sheep erythrocytes, expressed either as IgM AFC/106 or IgM AFC/spleen. In the mixed leukocyte response, a decrease was observed only after 11 days of exposure to 200 mg/kg (40%) with a return to non-significance after 14 days of exposure. Based on the overall negative immunological results of this range-finding study, the test article, indium arsenide, was not pursued as an expanded protocol.