Go Mitsui

Strong Acute Toxicity, Severe Hepatic Damage, Renal Injury and Abnormal Serum Electrolytes after Intravenous Administration of Cadmium Fluoride in Rats

Strong Acute Toxicity, Severe Hepatic Damage, Renal Injury and Abnormal Serum Electrolytes after Intravenous Administration of Cadmium Fluoride in Rats: Kazuya Adachi, et al. Department of Hygiene and Public Health, Osaka Medical College—Cadmium fluoride (CdF) is commonly used as an insulator for ulta high speed mass telecommunications equipment, and there is a considerable risk that industrial workers will inhale CdF particles. Despite the possibility that acute exposure can cause harmful systemic effects, there are no studies to date that address the health consequences of acute CdF exposure. This study therefore aimed to determine the acute lethal dose of CdF and its effects on various target organs, including the liver and kidney. We also determined the effect of CdF on serum electrolytes and acid‐base balance. The effective lethal dose was determined and dose‐response study was conducted after intravenous administration of CdF in rats. The 24 h LD50 of CdF was determined to be 3.29 mg/kg. The dose‐response study used doses of 1.34, 2.67, 4.01 mg/kg CdF. Saline or sodium fluoride solution were used for controles. Severe hepatocellular injury was induced at doses greater than 2.67 mg/kg, as demonstrated by AST and ALT activities greater than 1,500 IU/l in rats injected with a dose of 4.01 mg/kg. Acute renal failure was induced at doses greater than 2.67 mg/kg. Decreased serum Ca, increased serum K and metabolic acidosis were induced at a dose of 4.01 mg/kg. Decreased serum Ca was caused by exposure to ionized F. CdF has the strongest lethal and hepatic toxicity among all Cd containing compounds.

Determination of reference concentrations of strontium in urine by inductively coupled plasma atomic emission spectrometry.

ObjectiveThe aim of this study was to establish reference concentrations of urinary strontium by inductively coupled plasma atomic emission spectrometry (ICP-AES).MethodsFor the determination of strontium, urine samples were collected from healthy Japanese (n=146; 115 males, 31 females; mean age, 33±9 years; age range, 18 to 58 years). The urine samples stored at or below −20°C were thawed with incubation at 40°C for 30 min and sediments were dissolved by vigorous shakings. Then, the samples were centrifuged at 3000 g for 5 min, and the supernatant was directly aspired into a P-5200-3600/1200 ICP-AES system from Hitachi Ltd., Tokyo, Japan.ResultsA steeper increase in the S/N ratio and a good effective linearity of the calibration line was obtained at 407.771 nm in the range of 0–300 μg/L strontium standard solution. Urine samples having the same background signal as that of 18 MΩ cm ultrapure blank water, a good correspondence of the single peak pattern of the spectra, accuracy and precision of spike recovery were also confirmed. Urinary strontium concentrations showed a log-normal distribution and a geometric mean concentration of 143.9 μg/L, with 5–95% confidential interval of 40.9–505.8 μg/L.ConclusionThe results of this study will be useful as guidelines for the biological monitoring of strontium in normal subjects and in individuals therapeutically or environmentally exposed to strontium.

Urinary yttrium excretion and effects of yttrium chloride on renal function in rats

Evaluation of yttrium exposure in biological samples has not been fully examined. To evaluate yttrium nephrotoxicity, yttrium chloride was orally administered to male Wistar rats and the urine volume (UV) and N-acetyl-β-d-glucosaminidase (NAG) and creatinine excretion (Crt) were measured in 24-h urine samples. The urinary yttrium concentration and excretion rate were determined by inductively coupled plasma-argon emission spectrometry (ICP-AES). Large significant decreases of UV (>30%) and Crt (>10%) were observed at yttrium doses of 58.3–116.7 mg per rat, but no significant NAG changes was observed. This response pattern shows that a high yttrium dosage alters glomerular function rather than the proximal convoluted tubules. A urinary yttrium excretion rate of 0.216% and good dose-dependent urinary excretion (r=0.77) were confirmed. These results suggest that urinary yttrium is a suitable indicator of occupational and environmental exposure to this element, an increasingly important health issue because recent technological advances present significant potential risks of exposure to rare earth elements. We propose that the ICP-AES analytical method and animal experimental model described in this study will be a valuable tool for future research on the toxicology of rare earth elements.

Urinary and serum titanium : Assessment as an indicator of exposure to ammonium citratoperoxotitanate (IV) and its influence on renal function

Ammonium citratoperoxotitanate IV (TAS-FINE) is a water-soluble titanium complex used to synthesize a photocatalytic titanium(IV) oxide film. This study was aimed to investigate the LD50, dose-response, time-course response, and renal toxicity of TAS-FINE using an animal model. Serum titanium (S-Ti) and its 24-h urinary excretion (U-Ti) were determined by inductively coupled plasma-argon emission spectrometry (ICP-AES) after a single oral TAS-FINE administration to male Wistar rats. The LD50 of TAS-FINE was 7.97 g/kg body weight in 24 h, and its half-life was 3.78±1.28 d for S-Ti and 2.19±0.09 d for U-Ti. Although TAS-FINE was not easily absorbed in the gastrointestinal tract, it was distributed into the bloodstream in a dose-dependent manner. Within 24 h, 0.189% of administrated Ti was excreted via urine. It was speculated that TAS-FINE formed conjugates with serum constituents that resulted in nephrotoxicity resulting from an allergic reaction. The observed indices in this study were revealed to be good indicators for TAS-FINE exposure. The analytical method and animal model described in this study will help to further elucidate details about human exposure to TAS-FINE, which in recent times has become an occupational and environmental toxicant of concern.

Harmful effects and acute lethal toxicity of intravenous administration of low concentrations of hydrofluoric acid in rats.

The acute toxicity of hydrofluoric acid (HFA) was investigated in a 24-h lethal dose study of intravenous infusion in rats. The lethal dose lowest (LDLo) and LD50 were 13.1 and 17.4mg/kg, respectively. Harmful systemic effects were also studied 1 h after acute sublethal exposure to HFA. The maximum dose was set at 9.6mg/kg (LD 5). Rats were injected with HFA (1.6, 3.2, 6.4 or 9.6mg/kg), saline, sodium fluoride (NaF) or HCl solution. NaF and HCl solution concentrations corresponded to the F— and H+ concentrations of 9.6mg/kg HFA. Blood urea nitrogen (BUN) and Cr were significantly increased in response to HFA concentrations greater than 3.2mg/kg. Acute glomerular dysfunction also occurred at HFA concentrations greater than 3.2mg/kg. HCO 3 — and base excess (BE) were significantly decreased in the 6.4 and 9.6mg/kg groups. Ca2+ was significantly decreased, and K + was increased in the 9.6mg/kg group. BUN was significantly increased in the NaF and HFA groups and was increased in the HFA group compared with that in the NaF group. Cr was significantly increased in the HFA group only. HCO3 — and BE were significantly decreased in the NaF and HFA groups and were increased in the HFA group compared with values in the NaF group. Ca2+ was significantly decreased in the NaF and HFA groups, and K+ was significantly increased in the NaF and HFA groups. F— exposure directly affected serum electrolytes. Mortality was thought to be due to cardiac arrhythmia resulting from hypocalcemia and hyperkalemia. Metabolic acidosis and renal failure were more severe in response to HFA exposure than in response to NaF exposure because of more free F—, which has strong cytotoxicity, in the HFA group than in the NaF group. Lethal effects of HFA are promoted by exposure routes such as inhalation that cause rapid absorption into the body. Even low exposure to HFA can cause acute renal dysfunction, electrolyte abnormalities and metabolic acidosis. These complications result in a poor prognosis. Toxicology and Industrial Health 2007; 23: 5—12.

Toxicokinetics and Metabolism Deteriorated by Acute Nephrotoxicity after a Single Intravenous Injection of Hydrofluoric Acid in Rats

Toxicokinetics and Metabolism Deteriorated by Acute Nephrotoxicity after a Single Intravenous Injection of Hydrofluoric Acid in Rats: Go Mitsui, et al. Department of Hygiene and Public Health I · II, Osaka Medical College