Some of the rare earth elements such as Sc are believed to be non-toxic and, at present, are widely utilized for the replacement of toxic heavy metals in technological applications, but they are not entirely free of toxicity, with hidden potential health risks. In this animal experiment, we report the urinary scandium (Sc) excretion rate and nephrotoxiciy in male Wistar rats. For this purpose, the rats were given a single dose of a solution of scandium chloride by intraperitoneal injection. The Sc excretion (U-Sc) was determined in 24-h urine samples by inductively coupled plasma-argon emission spectrometry along with the Sc nephrotoxicity, urine volume (UV), creatinine (Crt), beta-2-microglobulin (beta2-MG) and N-acetyl-beta-D-glucosaminidase (NAG). A dose-dependent Sc excretion of 0.0063% (r = 0.97) via 24-h urine was confirmed. The administration of Sc induced a significant decrease of UV and Crt and a significant increase of NAG and beta2-MG. These results suggest that U-Sc can be a useful tool for monitoring Sc exposure. The formation of Sc colloidal conjugates that deposit in glomeruli may be the cause of a reduction of the glomerular filtration rate. We propose that the analytical method and results described in this study will be of great importance for future toxicological studies on Sc exposure.

As fluoride has a very short half-life in the body and the major route for fluoride excretion is via the kidney, human exposure is best measured in urine, where the concentration is expected to be highest. The urinary fluoride concentrations of 167 healthy Japanese adults were determined by means of a fluoride ion selective electrode. When the results were corrected for a specific gravity rho = 1.024 g cm-3, the histogram of urinary fluoride concentrations highly skewed toward low values with sharp peakedness (skewness = 1.56, kurtosis = 3.08). The normality of the log-transformed histogram (skewness = 0.12, kurtosis = 0.07) and the straight line on log-probability paper clearly showed a key feature of lognormal distribution of urinary fluoride. A geometric mean (GM) of 613.8 microg/l and 95% confidential interval (CI) of 241.0-1633.1 microg/l were established as reference values for urinary fluoride. The results presented in this study will be useful as guidelines for the biological monitoring of fluoride in normal subjects and individuals at risk of occupational or environmental fluoride exposure.

In our previous study, we reported that even a sublethal dose of hydrofluoric acid (HFA) could cause acute toxic effects 60 min after intravenous injection. This study was designed to investigate the time-and dosedependent changes associated with these disorders. The serum fluoride (F) kinetics are also considered in the discussion of the relationship between the concentrations of serum F and the disorders. Methods: Rats were injected with HFA (1.6 or 9.6 mg/kg body weight) for the dose-response relationship study. For each dose, the rats were assigned to one of seven groups. Blood samples of the 0-min group were obtained from the carotid artery prior to injection as a control. The other six groups were labeled according to sampling times (5, 10, 30, 60, 120 and 300-min) in the time-dependent study. Results: The 1.6 mg/kg dose decreased the ionized calcium (Ca 2+ ) level significantly after 30 min, and it also decreased the total calcium (Ca) level after 300 min. The 9.6 mg/kg dose rapidly worsened renal dysfunction after 60 min. It increased the serum potassium level after 60 and 120 min and it decreased Ca and Ca 2+ levels until 300 min. Although there was respiratory compensation, the base excess and HCO 3 -level and had not completely recovered by 300 min. Conclusions: Even low exposure to HFA caused renal dysfunction, and electrolyte abnormalities and metabolic acidosis lasted for several hours in rats. Therefore, persons involved in HFA accidental exposure should be closely monitored over time, even if the exposure is less than the sublethal dose. (J Occup Health 2009; 51: 287-293)

Sodium monofluoroacetate (SMFA; also known as compound 1080) is a highly toxic chemical; therefore, accidental exposure and intentional misuse are of great concern. SMFA intoxication is reportedly caused by the inhibition of aconitase. However, the pathogenesis underlying SMFA intoxication is not clear. This study was conducted to elucidate the acute effects of SMFA on glucose, amino-acid, and fatty-acid metabolism and to assess glucose supplementation as a possible alleviator or aggravator in SMFA intoxication. Rats were assigned to three groups: SMFA+saline, SMFA+glucose, and control (i.e., no SMFA), and blood samples were analyzed at 3 hours after SMFA or saline (control) administration. Additional rats were used for the monitoring of blood-glucose and lactate concentrations for 10 hour- and 14-day survival rates. SMFA increased the serum-citrate, serum-pyruvate, and blood-lactate concentrations. However, despite significant increases in these parameters when SMFA was administered with glucose, the effects on pH values were small and the survival rate was not changed. SMFA also increased the serum concentrations of free fatty acids, branched-chain amino acids, ammonia, urea, and calcium. The presence of glucose enhanced or suppressed these metabolic changes. Amphibolic intermediates in the tricarboxylic acid cycle might be supplied through the catabolism of proteins in SMFA intoxication. We conclude that other factors, in addition to the accumulation of lactate, citrate, and pyruvate, may affect survival rates, and that SMFA induces imbalances in glucose, amino-acid, and, fatty-acid metabolism. All these changes are inter-related and may contribute to SMFA intoxication.

Abnormalities in Cadmium FluorideKinetics in Serum, Bile, and Urine after Single Intravenous Administration of Toxic Doses to Rats: Tomotaro DOTE, et al. Department of Hygiene and Public Health, Osaka Medical College-Cadmium fluoride (CdF 2 , CdF for short) is the most lethal and hepatotoxic of all Cd-containing compounds. The toxic effects of CdF appear to depend on its detoxification and elimination. This study was designed to determine the early dynamics of the absorption, systemic distribution, and metabolism of CdF. The kinetics of cadmium and fluoride were investigated in the blood, bile, and urine of rats as a model of accidental occupational exposure to CdF. The serum concentration-time profiles measured after intravenous CdF (1.34, 2.67 or 4.01 mg/ per kg body weight) administration were analyzed by compartmental modeling using the WinNonlin program. Bile and urine were collected for 300 min after the administration. The kinetic profiles indicate that the clearance of Cd was diminished in the 2.67 and 4.01 mg/kg groups, leading to a persistently high serum Cd level. The mean total biliary excretions of Cd in the 2.67 and 4.01 mg/kg groups were significantly higher than that in the 1.34 mg/kg group. The abnormal kinetics of Cd was attributable to severe hepatic injury that diminished the capacity for Cd accumulation. The elimination of serum F was delayed in the 4.01 mg/kg group. The mean urinary F excretion amount was not significantly higher in the 4.01 mg/kg group than in the 2.67 mg/kg group. The abnormal kinetics of F was attributable to nephrotoxicity that diminished its elimination from the kidney. (J Occup Health 2008; 50: 339-347)