The toxicology of gallium oxide in comparison with gallium arsenide and indium oxide.

Gallium arsenide (GaAs) and indium oxide (InO) are used in electronic industries at high and increasing tonnages since decades. Gallium oxide (GaO) is an emerging wide-bandgap transparent conductive oxide with as yet little industrial use. Since GaAs has received critical attention due to the arsenic ion, it seemed reasonable to compare its toxicology with the respective endpoints of GaO and InO toxicology in order to find out if and to what extent arsenic contributes.

The toxicology of indium oxide.

Indium oxide (InO) is a technologically important semiconductor essentially used, doped with tin oxide, to form indium tin oxide (ITO). It is poorly soluble in all so far tested physiologic media. After repeated inhalation, InO particles accumulate in the lungs.

Particle-induced Pulmonary Alveolar Proteinosis and Subsequent Inflammation and Fibrosis: A Toxicologic and Pathologic Review.

This review analyzes the published data on cases of pulmonary alveolar proteinosis (PAP) in workers inhaling crystalline aluminum, indium, silicon, and titanium particles and possible sequelae, that is, inflammation and fibrosis, and compares these findings with those from animal experiments. In inhalation studies in rodents using crystalline indium and gallium compounds, pronounced PAP followed by inflammation and fibrosis down to very low concentration ranges have been reported. Crystalline aluminum, silicon, and titanium compounds also induced comparable pulmonary changes in animals, though at higher exposure levels.

The toxicology of indium tin oxide.

Indium tin oxide (ITO) is a technologically important semiconductor. An increasing number of cases of severe lung effects (characterized by pulmonary alveolar proteinosis and/or interstitial fibrosis) in ITO-exposed workers warrants a review of the toxicological hazards. Short- and long-term inhalation studies in rats and mice revealed persistent alveolar proteinosis, inflammation and fibrosis in the lungs down to concentrations as low as 0.

Evaluation of the carcinogenicity of gallium arsenide.

Gallium arsenide (GaAs) is an important semiconductor material. In 2-year inhalation studies, GaAs increased the incidence of lung tumors in female rats, but not in male rats or male and female mice. Alveolar proteinosis followed by chronic active inflammation was the predominant non-neoplastic pulmonary findings.

Hypoxaemia affects male reproduction: a case study of how to differentiate between primary and secondary hypoxic testicular toxicity due to chemical exposure.

Classification for fertility is based on two conditions, namely on evidence of an adverse effect on sexual function and fertility and that the effect is not secondary to other toxic effects. To decide on an adverse effect is a relatively simple day-to-day decision in toxicology but whether this effect is secondary often leads to serious controversy. As the seminiferous epithelium operates on the verge of hypoxia, oxygen deficit can lead to secondary impairment of testicular function.

Evaluation of the male reproductive toxicity of gallium arsenide.

Gallium arsenide is an important semiconductor material marketed in the shape of wafers and thus is not hazardous to the end user. Exposure to GaAs particles may, however, occur during manufacture and processing. Potential hazards require evaluation.

Genotoxic activities of aniline and its metabolites and their relationship to the carcinogenicity of aniline in the spleen of rats.

Aniline (in the form of its hydrochloride) has been shown to induce a rather rare spectrum of tumors in the spleen of Fischer 344 rats. The dose levels necessary for this carcinogenic activity were in a range where also massive effects on the blood and non-neoplastic splenotoxicity as a consequence of methemoglobinemia were to be observed. This review aimed at clarifying if aniline itself or one of its metabolites has a genotoxic potential which would explain the occurrence of the spleen tumors in rats as a result of a primary genetic activity.

High-dose clastogenic activity of aniline in the rat bone marrow and its relationship to the carcinogenicity in the spleen of rats.

To clarify the question of clastogenicity of aniline in rats two studies were performed: a bone marrow micronucleus test and a bone marrow metaphase test. In the micronucleus test aniline (as aniline hydrochloride) was administered to groups of seven male PVG rats at single oral doses of 0, 300, 400, or 500 mg/kg body weight. Bone marrow was obtained 24 and 48 h after oral treatment.

O-phenylphenol and its sodium and potassium salts: a toxicological assessment.

Ortho-phenylphenol (OPP) and its sodium (SOPP) and potassium (POPP) salts are used as fungicides and disinfectants. Due to the widespread use of especially OPP and SOPP, the potential for consumer exposure and some "critical" findings the toxicological database is quite extensive and complex. In experimental animals toxicity after single oral and dermal administration of these compounds is low.

Investigations on the mutagenicity of 1,4-dichlorobenzene and its main metabolite 2,5-dichlorophenol in vivo and in vitro.

The genotoxic potential of 1,4-dichlorobenzene (1,4-DCB) has been extensively evaluated in vitro and in vivo. The majority of the studies demonstrated the absence of a genotoxic potential for 1, 4-DCB. At variance are a bone marrow micronucleus test (MNT) after intraperitoneal (i.

Trends in mortality, body weights and tumor incidences of Wistar rats over 20 years.

Historical data of more than 8,000 Wistar rats (designation: WISW SPF Cpb) used as controls in seventy 2-year studies terminated between 1975 and 1994 were analyzed for time trends in food consumption, terminal body weight, mortality, and tumor incidences. In males there was a significant (p < 0.01) time trend towards higher terminal body weight and a tendency (p > 0.

Time course of chronic oral cadmium nephrotoxicity in Wistar rats: excretion of urinary enzymes.

Twelve male and female Wistar rats each received cadmium (as CdCl2) in their diet at concentrations of 0, 10, 50, and 250 ppm for 72 weeks. After 1, 4, 8, 13, 18, 26, 32, 45, 57, and 68 weeks a total of 8 enzymes from different cellular compartments of the nephron were measured. At the end of the study period, the kidneys were examined histopathologically.

Urinary antigens as markers of papillary toxicity. II: Application of monoclonal antibodies for the determination of papillary antigens in rat urine.

We have previously reported the preparation of monoclonal antibodies specific for antigens localized in the rat renal papilla. Three of the monoclonal antibodies reacting with antigens localized in papillary and cortical collecting duct epithelia were selected for the development of enzyme-linked immunosorbent assay (ELISA)-type assays. The papillary antigens ('PapA') determined in these tests were designated PapAl (applying the monoclonal antibody PapX 5C10), PapA2 (applying the monoclonal antibody PapX 12F6), and PapA3 (applying the monoclonal antibody PapXI 3C7).

Direct lysosomal uptake of alpha 2-microglobulin contributes to chemically induced nephropathy.

Background: An abnormal accumulation of alpha 2-microglobulin (alpha 2 mu) in kidney lysosomes of male rats has been described in the nephropathy resulting from exposure to a variety of chemicals. The increment in lysosomal levels of alpha 2 mu cannot be explained by a decrease in its proteolytic susceptibility. Because a portion of alpha 2 mu resides in the cytosol of kidney cells, we decided to analyze whether this cytosolic form also contributes to the abnormal lysosomal accumulation of alpha 2 mu after exposure to chemicals.

Time course of enzyme induction in liver and kidneys and absorption, distribution and elimination of 1,4-dichlorobenzene in rats.

Time course of enzyme induction was measured in Fischer344 rats treated daily at 150 and 600 mg 1,4-dichlorobenzene (1.4-DCB)/kg p.o.

Short- and intermediate-term carcinogenicity testing--a review. Part 2: available experimental models.

Numerous experimental protocols for short- and intermediate-term carcinogenicity assays have been available for many years. This paper surveys various of these test systems in rodents, fish species, non-vertebrates and avian embryos in ovo. The mouse skin tumour assay and the rat liver foci assay were used to introduce the basic concepts of short- and intermediate-term carcinogenicity testing in the previous part of the review.

Short- and intermediate-term carcinogenicity testing--a review. Part 1: the prototypes mouse skin tumour assay and rat liver focus assay.

Carcinogenicity testing is by far the most expensive and time-consuming study type of toxicology. For many years, the lifetime exposure with the maximum tolerated dose in two rodent species has been the gold standard of carcinogenicity testing of pharmaceuticals. Major change was introduced by the Fourth International Conference on Harmonization in July 1997; a chronic rodent bioassay in one species and a short-term carcinogenicity assay are regarded as sufficient for registration.

D-glucose combined chronic toxicity and carcinogenicity studies in Sprague-Dawley rats and Syrian golden hamsters.

After an initial period of 16 weeks with increasing concentrations, D-glucose was administered at 30% in the diet to 50 male and 50 female Sprague-Dawley rats from the 17th to the 112th study week. Additional 10 male and 10 female animals were treated for 14 months and then sacrificed for interim examination. Groups of 60 male and 60 female Syrian golden hamsters received D-glucose in the form of 20% solution in tap water for a period of 80 weeks.

Subacute oral toxicity of tetraethylene glycol and ethylene glycol administered to Wistar rats.

A subacute toxicity study with administration of tetraethylene glycol in dosages of 0-220-660-2000 mg/kg body weight to male and female Wistar rats via gavage was conducted in order to characterize a possible toxic action of this compound. The structurally related compound ethylene glycol is known to cause kidney toxicity. Therefore, special attention was paid to investigating possible toxic effects of tetraethylene glycol on this organ.

Calcium channel blockers and the risk of cancer: a preclinical assessment.

The preclinical evidence for a potential influence of calcium channel blockers (CCBs) on carcinogenesis is discussed in the light of a broad database from rodent carcinogenicity studies as well as literature data. In all bioassays performed in rats and mice on the dihydropyridine CCBs--nifedipine, nimodipine, nisoldipine, and nitrendipine--no evidence was found for a carcinogenic potential of these compounds. Calcium is an essential intracellular signal for cell proliferation and apoptosis.

Serotonin (5-HT1A-receptor) agonist-induced collecting duct vacuolation and renal papillary necrosis in the rat.

General anxiety in humans is treated with azaspirodecanedions, which act through a reduction of serotonin transmission. Ipsapirone also represents a serotonin (5-HT1A) receptor agonist and was under development as an anxiolytic drug. Histopathologic evaluation of animal experiments revealed cellular swelling and/or vacuolation of renal papillary and medullary collecting duct (MCD) epithelium in rats but not in dogs or mice.

Trimethylphosphate: a 30-month chronic toxicity/carcinogenicity study in Wistar rats with administration in drinking water.

Trimethylphosphate (TMPO) was administered to 50 male and 50 female Wistar rats through their drinking water at doses of 0, 1, 10, or 100 mg/kg body weight up to 30 months. The dosage of 100 mg/kg was reduced to 50 mg/kg in week 54 for reasons of tolerance, and the animals were euthanized in week 100. Additional 10 animals per dose and sex were treated for 12 months and then euthanized for interim analysis.