National Toxicology Program

National Toxicology Program
https://ntp.niehs.nih.gov/go/TER89143-01abs

Abstract for TER89143 and TER90043 on Gallium Arsenide

ABSTRACT

Inhalation Developmental Toxicology Studies: Gallium Arsenide (CAS No. 1303-00-0) in Rats and Mice

Report Date: December 1990

The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program. The findings may not have been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by NTP in March 2009. For more information, see the Explanation of Levels of Evidence for Developmental Toxicity. The findings and conclusions for this study should not be construed to represent the views of NTP or the U.S. Government.


Abstract

Gallium arsenide is a crystalline compound used extensively in the semiconductor industry. Workers preparing solar cells and gallium arsenide ingots and wafers are potentially at risk from the inhalation of gallium arsenide dust. The potential for gallium arsenide to cause developmental toxicity was assessed in Sprague-Dawley (CD) rats and CD-1 (Swiss) mice exposed to 0, 10, 37, or 75 mg/m3 gallium arsenide, 6 h/day, 7 days/week. Each of the four treatment groups consisted of 10 virgin females (for comparison), and ~ 30 positively mated rats or ~ 24 positively mated mice. Mice were exposed on 4-17 days of gestation, and rats on 4-19 dg. The day of plug or sperm detection was designated as 0 dg. Body weights were obtained throughout the study period, and uterine and fetal body weights were obtained at sacrifice (rats, 20 dg; mice, 18 dg). Implants were enumerated and their status recorded. Live fetuses were sexed and examined for gross, visceral, skeletal, and soft-tissue craniofacial defects. Gallium and arsenic concentrations were determined in the maternal blood and uterine contents of the rats (3/group) at 7, 14, and 20 dg.

Pregnant and virgin rats exhibited signs of pulmonary toxicity (dyspnea and grey, mottled lungs); however, there were no effects on maternal body weight. Developmental toxicity in the form of concentration-related growth retardation, evidenced as reduced fetal body weight and an increased incidence of skeletal variations became statistically significant at 37 mg/m3. There was no evidence of embryotoxicity or frank teratogenicity. The maternal no observed adverse effect level for inhaled gallium arsenide in rats is at least 10-mg/m3. The NOAEL for developmental toxicity is 10 mg/m3 if determined solely on the basis of adverse effects achieving statistical significance; however, nonsignificant indications of developmental toxicity were present at this exposure concentration.

Determination of gallium and arsenic concentrations in maternal rat blood and in the conceptus showed that arsenic concentration in the blood achieved high levels (170 mg/g at 75 mg/m3 on 20 dg), increased with exposure concentration, and over the course of exposures. Arsenic concentrations in the developing fetus were elevated above controls in a concentration-related fashion (2.2 mg/g at 75 mg/m3 on 20 dg), but were far exceeded by maternal blood concentrations. The excess arsenic in the maternal blood was probably tightly bound to hemoglobin in the erythrocytes, and thus was not available for placental transfer. Gallium concentrations were much lower than arsenic levels in both the maternal blood and in the conceptus, but gallium concentration was greater in the fetus than in the dam (approximately 1.3 vs. 0.5 mg/g at 75 mg/m3 on 20 dg, respectively).

Swiss (CD-1) mice were much more sensitive to the effects of gallium arsenide than were the rats. The two highest exposure concentrations were maternally lethal to some animals; body weights and body weight gains were reduced in survivors of both of these groups. mice in the 37 and 75 mg/m3 groups exhibited signs of pulmonary toxicity; minimal pulmonary toxicity was observed in the 10-mg/m3 mg/m3 group. A NOAEL for maternal toxicity in mice was not achieved in this study. Developmental toxicity was evident in all three exposed groups, and became statistically significant at the 37-mg/m3 exposure concentration. There were signs of embryolethality, fetal growth retardation, significant increases in the incidence of fetal variations (primarily sternebral defects), and a slight, but not statistically significant, increase in the incidence of fetal malformations. A NOAEL for developmental toxicity was not achieved in this study.


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