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 The findings have not been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by the NTP on March 2009 (see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.
Immunotoxicity of Gallium Arsenide (CAS No. 1303-00-0) in Female B6C3F1 Mice
NTP Report Number IMM90013
Gallium arsenide is used extensively in the semiconductor industry for the manufacture of various electronic components including light-emitting diodes. In light of studies suggesting that arsenic compounds are immunotoxic, the potential effects of gallium arsenide on the immune system of mice were studied following intratracheal exposure.
Gallium arsenide (Lot #M100386/B04) was obtained from Alpha Products (Danvers, MA.) and was determined by HPLC to be greater than 98% pure. The material was ground in a mortar and pestle and administered to female B6C3F1 mice as a suspension of particles in saline containing 0.05% Tween 80; mean particle size of 1.5 mm. Prior to exposure, mice were anesthetized by an intravenous injection of hexobarbital (80 mg/kg). Mice received a single intratracheal instillation of the material at dose levels of 50, 100 or 200 mg/kg in a volume of 0.1ml. Control groups received vehicle or 10 mg/kg sodium arsenite (Sigma Chemical Corp.) also by the intratracheal route. Animals were sacrificed 15 days after the exposures for immune testing. For each of the parameters examined, usually 8 mice were examined per treatment and vehicle group except the sodium arsenite control group which consisted of 4 mice per group.
There were no treatment-related effects on mortality. In most cases there were no effects on body weight although in one replicate experiment a decrease in weight was observed in the high dose group and body weight gain was decreased over the 2 week post-exposure. Spleen weights were increased in all gallium arsenide treated groups while thymus weights were decreased at the high dose (Table 1). A dose-response increase in lung weights occurred following treatment but none of the individual values were significant. The lungs were characterized by darkened areas consisting of lymphocyte and macrophage infiltration. There was a tendency (not significant) for a treatment-related decrease in peripheral leukocyte counts (Table 1) which was associated with a significant decrease in peripheral lymphocyte counts in the 200 mg/kg treatment group (not shown).
The immune and bone marrow studies are also summarized in Table 1. Gallium arsenide suppressed the following immune parameters dose- dependently: the IgM and IgG (not shown) antibody response to sheep erythrocytes, the delayed hypersensitivity response to KLH, the mixed leukocyte response (MLR), and, to a lesser extent, splenic B lymphocyte numbers. There were no effects on mitogenesis or T lymphocyte numbers. Although there was a treatment-related increase in the natural killer cell response, the values from the control group were below historical control values. Bone marrow changes were not observed except for an increase in CFU-C1s when based upon total cellularity (data not shown).
Table 2 summarizes the host resistance studies in mice exposed to gallium arsenide. Exposure to gallium arsenide increased the resistance to Listeria monocytogenes and to a lesser extent, PYB6 tumor cell growth, while decreasing resistance to pulmonary burden of B16F10 melonoma. There were no consistent treatment-related effects on resistance to Streptococcus pneumoniae.
Under these experimental conditions, gallium arsenide produced multiple immunotoxic effects. The effects could result from a direct action of the chemical on lymphoid cells or indirectly via local pulmonary damage. The later may account for the variability observed in the host resistance models.
Table 1: Summary of Gallium Arsenide Immune Studies
|Parameter||Dose (mg/kg)||sodium arsenite|
|Body Weight (g)||22.0||21.6||21.7||20.9||21.9|
|Spleen:Body wt. (%)||0.33||0.38#||0.41#||0.50#||0.37#|
|Thymus:Body wt. (%)||0.28||0.22||0.28||0.20*||0.28|
|Lung: Body Wt (%)||1.95||2.23||2.48||2.69||2.27|
|Peripheral Leukocyte Count(10E3/mm3)||4.0||3.2||2.9||2.8||3.7|
|Spleen cell no. (x 10E7)||16.8||14.7||13.2#||12.0#||15.1|
|Delayed Hypersensitivity Response (SI)||4.0||3.1||2.3||1.1#||2.6|
|NK Cell Activity (% cytotoxicity)||7.4||14.5#||16.3#||14.9#||11.6*|
|IgM PFC/106 cells||2013||1432*||1227#||694#||1529*|
|IgM PFC/spleen (x 10E3)||340||206#||162#||84#||228#|
(cpm x 10E3):
|Mixed Leukocyte Resp.||28||11#||11#||10#||29|
|Bone Marrow Cells/Femur (x10E6)||9.7||10.6||11.4||11.7||12.3|
|DNA Synthesis (cpm x 10E3)||58||60||58||61||73|
|CFU-C1/105 Nucleated Cells^||99||107||116||111||95|
|CFU-C2/105 Nucleated Cells^||59||55||59||52||59|
^ CFU-C1 and C2 are defined in Appendix A.
* different from vehicle control at P less than 0.05
# different from vehicle control at P less than 0.01
Table 2. Summary of Gallium Arsenide Host Resistance Studies
|Host Resistance Test|| Dose mg/kg|
(No. Per Group)
|S pneumoniae % Morbidity||(12)||(12)||(12)||(12)||(11)|
|Low Infective Challenge||17||0||25||17||0|
|High Infectivity Challenge||82||58||67||75||91|
|PYB6 Tumor- % pos.||(12)||(12)||(12)||(12)||(12)|
|21 days post transplant||33||58||17||17||8|
|CPM (x 10E3)/Lung||3,9||5,1||8.0#||22.0#||4.0|
Report Date: May 1987