TOXICOLOGY
AND APPLIED PHARMACOLOGY
116,66-70 (19%)
Metabolism of Subcutaneous Administered lndium Arsenide in the Hamster’ HIROSHI YAMAUCHI,*,~,~
KEIKO TAKAHASHI,~
YUKIO YAMAMURA,?
AND BRUCE A. FOWLER*
*1 “he University Program in Toxicology, University ofMaryland School of Medicine, Baltimore, Maryland 21201; and TDepartment of Public Health, St. Marianna University School of Medicine, Kawasaki, Japan
ReceivedNovember 15, 1991; acceptedApril 20. 1992 compounds in target tissues have been extensively studied (WHO, 1981; Squibb and Fowler, 1983) but there are no published reports concerning InAs metabolism or toxicity. Previous experimental studies with GaAs have shown that this III-V semiconductor dissolves in vivo (Webb et al., 1984; Yamauchi et al., 1986; Rosner and Carter, 1987) and may create possible toxicity problems as a result of either arsenic (Webb et al., 1984) or gallium (Goering et al., 1988). Intratracheal instillation studies by Webb et al. (1984) showed that exposure to GaAs resulted in systemic arsenic intoxication as measured by characteristic arsenic porphyrinuria pattern (Woods et al., 1979). Goering et al. (1988), demonstrated biochemical effects associated with both moieties. Similar basic metabolic and toxicity studies have not previously been published for InAs. The present study was designed to compare the metabolism and excretion patterns of indium and arsenic following SCadministration of InAs. These studies were undertaken to provide basic scientific information on the metabolism of InAs using a route of administration that would not produce the chemical pneumonitis previous observed with GaAs (Rosner and Carter, 1987; Goering et al., 1988).
Metabolism of Subcutaneous Administered Indium Arsenide in the Hamster. YAMAUCHI, H., TAKAHASHI, K., YAMAMURA, Y., ANDFOWLER,B. A. (1992). Toxicol. Appl. Pharmacol. 116, 66-70.
Indium arsenide (InAs) is partially dissociated in vivo to form inorganic arsenic and indium and excreted into the urine and feces. InAs dissolves slowly over time with deposits at the site of injection. Results of this study demonstrated that the principal metabolite of arsenic in the urine of hamsters was dimethylated arsenic (DMA). Inorganic arsenic and DMA accumulated in the fur, hut the concentrations of indium were very low in this matrix. Urine and feces were the principal routes of elimination from the body. Analysis of tissues for arsenic demonstrated as concentrations in the parts per billion range. Results of these studies indicate that InAs is dissociated in vivo with release of both the indium and arsenic moieties to target tissues. o 1992 Academic Press, Inc.
In recent years, indium arsenide (InAs) has attracted extensive attention as a new material for the manufacture of semiconductors. InAs and gallium arsenide (GaAs) are major representatives of the III-V semiconductor class of materials (Dupuis, 1984), with GaAs as the currently more widely used compound. These compounds share similar physical properties and both GaAs- and InAs-based semiconductors have faster electronic speeds than silicon-based semiconductors (Dupuis, 1984). They are hence expected to have wide applications for electronic devices in the future. In contrast with GaAs, the in vi175 metabolism and toxicity of InAs have received relatively little attention. The exposure of workers to InAs may create health problems due to possible toxicity from either the indium (Hart and Adamson, 197 1; Fowler, 1986) or arsenic components (Squibb and Fowler, 1983). The possible effects of arsenic
MATERIALS Chemicals
InAs (purity more 99.99%) was obtained from Sumitomo Electric Industries (Osaka, Japan). The InAs was ground into a powder by an agate mortar and produced particles with a measured mean volume diameter of 4.8 hrn. Metabolism Studies Metuboiism of1nAs. Adult male Syrian golden hamsters (Charles River. Kingston, NY) weighing 120-l 50 g (a group of five hamsters) were maintained in an environmentally controlled facility maintained on a 12-hr light/ dark cycle. Urine and feceswere collected for 24-hr periods by placing the animals in individual metabolic cages (Nalge Company, Rochester, NY). The InAs sample was suspended in distilled water (pH 7.0), and the suspension was drawn into a syringe (21-gauge needle) while gently stirring with a magnetic mixer. The mixture was prepared fresh immediately before each administration and administered quickly. The hamsters were given a single sc injection of InAs at a dose of 100 mg/kg body wt. Hamsters were
’ This work was supported by NIH Research Grant ROl-ESO-4979-02. ’ To whom correspondence should be addressed at The University Program in Toxicology, University of Maryland School of Medicine, Howard Hall, Room 544, 660 West Redwood St., Baltimore, MD 2 1201.
0041-008X/92 $5.00 Copyright 0 I992 by Academic Press, Inc. All rights of reproduction in any form reserved.
AND METHODS
66
METABOLISM
OF INDIUM
ARSENIDE
67
TABLE 1 Urinary and Fecal Excretion Rate of Arsenic and Indium up to 30 Days after a Single SC Administration of 100 mg/kg Body Wt of InAs to the Hamster % of dose“ Arsenic Days after administration
Indium
Urine
O-l l-2 2-3 3-4 4-5 14-15 29-30
0.043 0.041 0.047 0.037 0.039 0.028 0.024
rt: 0.013 2 0.009 f 0.019 f 0.018 Z!L0.026 + 0.005 2 0.008
Feces 0.008 0.004 0.005 0.005 0.004
+ * f + k
Urine
0.005 0.003 0.003 0.003 0.002
0.009 0.020 0.024 0.015 0.025
-co.00 1
AND APPLIED PHARMACOLOGY
116,66-70 (19%)
Metabolism of Subcutaneous Administered lndium Arsenide in the Hamster’ HIROSHI YAMAUCHI,*,~,~
KEIKO TAKAHASHI,~
YUKIO YAMAMURA,?
AND BRUCE A. FOWLER*
*1 “he University Program in Toxicology, University ofMaryland School of Medicine, Baltimore, Maryland 21201; and TDepartment of Public Health, St. Marianna University School of Medicine, Kawasaki, Japan
ReceivedNovember 15, 1991; acceptedApril 20. 1992 compounds in target tissues have been extensively studied (WHO, 1981; Squibb and Fowler, 1983) but there are no published reports concerning InAs metabolism or toxicity. Previous experimental studies with GaAs have shown that this III-V semiconductor dissolves in vivo (Webb et al., 1984; Yamauchi et al., 1986; Rosner and Carter, 1987) and may create possible toxicity problems as a result of either arsenic (Webb et al., 1984) or gallium (Goering et al., 1988). Intratracheal instillation studies by Webb et al. (1984) showed that exposure to GaAs resulted in systemic arsenic intoxication as measured by characteristic arsenic porphyrinuria pattern (Woods et al., 1979). Goering et al. (1988), demonstrated biochemical effects associated with both moieties. Similar basic metabolic and toxicity studies have not previously been published for InAs. The present study was designed to compare the metabolism and excretion patterns of indium and arsenic following SCadministration of InAs. These studies were undertaken to provide basic scientific information on the metabolism of InAs using a route of administration that would not produce the chemical pneumonitis previous observed with GaAs (Rosner and Carter, 1987; Goering et al., 1988).
Metabolism of Subcutaneous Administered Indium Arsenide in the Hamster. YAMAUCHI, H., TAKAHASHI, K., YAMAMURA, Y., ANDFOWLER,B. A. (1992). Toxicol. Appl. Pharmacol. 116, 66-70.
Indium arsenide (InAs) is partially dissociated in vivo to form inorganic arsenic and indium and excreted into the urine and feces. InAs dissolves slowly over time with deposits at the site of injection. Results of this study demonstrated that the principal metabolite of arsenic in the urine of hamsters was dimethylated arsenic (DMA). Inorganic arsenic and DMA accumulated in the fur, hut the concentrations of indium were very low in this matrix. Urine and feces were the principal routes of elimination from the body. Analysis of tissues for arsenic demonstrated as concentrations in the parts per billion range. Results of these studies indicate that InAs is dissociated in vivo with release of both the indium and arsenic moieties to target tissues. o 1992 Academic Press, Inc.
In recent years, indium arsenide (InAs) has attracted extensive attention as a new material for the manufacture of semiconductors. InAs and gallium arsenide (GaAs) are major representatives of the III-V semiconductor class of materials (Dupuis, 1984), with GaAs as the currently more widely used compound. These compounds share similar physical properties and both GaAs- and InAs-based semiconductors have faster electronic speeds than silicon-based semiconductors (Dupuis, 1984). They are hence expected to have wide applications for electronic devices in the future. In contrast with GaAs, the in vi175 metabolism and toxicity of InAs have received relatively little attention. The exposure of workers to InAs may create health problems due to possible toxicity from either the indium (Hart and Adamson, 197 1; Fowler, 1986) or arsenic components (Squibb and Fowler, 1983). The possible effects of arsenic
MATERIALS Chemicals
InAs (purity more 99.99%) was obtained from Sumitomo Electric Industries (Osaka, Japan). The InAs was ground into a powder by an agate mortar and produced particles with a measured mean volume diameter of 4.8 hrn. Metabolism Studies Metuboiism of1nAs. Adult male Syrian golden hamsters (Charles River. Kingston, NY) weighing 120-l 50 g (a group of five hamsters) were maintained in an environmentally controlled facility maintained on a 12-hr light/ dark cycle. Urine and feceswere collected for 24-hr periods by placing the animals in individual metabolic cages (Nalge Company, Rochester, NY). The InAs sample was suspended in distilled water (pH 7.0), and the suspension was drawn into a syringe (21-gauge needle) while gently stirring with a magnetic mixer. The mixture was prepared fresh immediately before each administration and administered quickly. The hamsters were given a single sc injection of InAs at a dose of 100 mg/kg body wt. Hamsters were
’ This work was supported by NIH Research Grant ROl-ESO-4979-02. ’ To whom correspondence should be addressed at The University Program in Toxicology, University of Maryland School of Medicine, Howard Hall, Room 544, 660 West Redwood St., Baltimore, MD 2 1201.
0041-008X/92 $5.00 Copyright 0 I992 by Academic Press, Inc. All rights of reproduction in any form reserved.
AND METHODS
66
METABOLISM
OF INDIUM
ARSENIDE
67
TABLE 1 Urinary and Fecal Excretion Rate of Arsenic and Indium up to 30 Days after a Single SC Administration of 100 mg/kg Body Wt of InAs to the Hamster % of dose“ Arsenic Days after administration
Indium
Urine
O-l l-2 2-3 3-4 4-5 14-15 29-30
0.043 0.041 0.047 0.037 0.039 0.028 0.024
rt: 0.013 2 0.009 f 0.019 f 0.018 Z!L0.026 + 0.005 2 0.008
Feces 0.008 0.004 0.005 0.005 0.004
+ * f + k
Urine
0.005 0.003 0.003 0.003 0.002
0.009 0.020 0.024 0.015 0.025
-co.00 1
