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There is a clear lack of information on the toxicological risk of dietary intake of cadmium-metallothionein (CdMt). The present study aimed at establishing dose-dependent cadmium (Cd) disposition and to investigate differences in renal toxicity after long-term dietary exposure to CdMt or cadmium chloride (CdCl in rats. Male Wistar rats were fed diets containing 0.3, 3, 30, or 90 mg Cd/kg either as CdMt or as CdCl for 10 months. In rats fed 30 and 90 mg/kg Cd as CdCl the Cd concentrations in intestine, liver, and kidneys were all higher than in rats fed the same doses in the form of CdMt. The kidney/liver Cd concentration ratio was higher with CdMt than with CdCl. At the lower Cd concentrations (0.3 and 3 mg/kg), no differences in Cd accumulation between CdMt and CdCl groups were observed and the kidney/liver Cd ratio was also similar. When based on the amount of CdMt per milligram Cd in the tissue, rats fed CdMt and those fed CdCl had a similar relative CdMt concentration in liver and kidney. First signs of renal injury, indicated by an increase of urinary lactate dehydrogenase (LDH) activity, were seen 4 months after exposure to 90 mg/kg Cd as CdCl. After 8 and 10 months the renal effect of 90 mg/kg Cd as CdCl became more pronounced and urinary enzyme activities of LDH, -acetyl--D-glucosaminidase and alkaline phosphatase were all elevated. The only clinical effect of CdMt at the dose level of 90 mg/kg was a slight increase in urinary γ-glutamyl transpeptidase activity at 8 and 10 months. Histopathological changes (e.g., glomerulonephrosis and basophilic tubules) were observed after 10 months of exposure in rats fed 30 and 90 mg/kg Cd as CdCl. Rats fed 90 mg/kg as CdMt also showed slight histomorphological changes, but the effect was less pronounced than that of CdCl and was mainly restricted to the tubules. In conclusion, no difference was observed in renal disposition between CdMt and CdCl after long-term exposure to low (≤3 mg/kg) dietary doses. Nephrotoxicity was mainly related to the total renal Cd concentration and, in contrast to Cd administered intravenously, not to a difference in sensitivity between CdMt and CdCl Therefore, the health risk of dietary intake of Cd at low doses does not seem to differ between CdMt and CdCl. [ABSTRACT FROM PUBLISHER]

A method was developed to isolate lipophilic compounds efficiently from small aliquots of blood plasma and test these for total dioxin-like toxic potency using recombinant rat (H4IIE) and mouse (Hepa1c1c7) hepatoma cell lines, containing the firefly (Photinus pyralis) luciferase gene under trans-activational control of the aryl hydrocarbon receptor (AhR). For this experiment, blood plasma was used originating from eider ducks (Somateria mollissima) that had been dosed with 3,3',4,4'-tetrachlorobiphenyl (PCB-77) or with the technical PCB-mixture Clophen A50. For each sample the CALUX (chemical -activated luciferase expression) response of both the fat-containing organic extract andthe fat-free, cleaned extract were compared with data from chemical analyses of these samples. The CALUX responses for the extracts were converted into so-called CALUX TEQs (TCDD equivalents), using a 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) standard curve. The CALUX TEQs in both fatty and cleaned extracts correlated significantly with PCB-77 or PCB-153 levels (depending on the dosage group) determined in blood plasma using gas chromatography-mass spectrometry (GC-MS). For PCB-77 a toxic equivalency factor (TEF) of 1.5 X 10 -3 was calculated based on these correlations. In addition, PCB-118 and PCB-156 levels in abdominal fat (assessed with GC with electron capture detection) and hepatic ethoxyresorufin O-deethylase activities correlated well with the CALUX TEQs in both fatty and cleaned blood plasma extracts, suggesting the TEQ levels in blood offer a good measure for internal dose. Plasma cholesterol and triglyceride levels were determined as a measure of lipid content, in 10-mu l aliquots of blood plasma using enzymatic spcctrophotometric determination. In conclusion, wehave demonstrated that the CALUX assay is a rapid, sensitive assay for assessing the toxic potency of (mixtures of) AhR-active compounds in small aliquots of blood plasma. The limit of detection for the CALUX [ABSTRACT FROM AUTHOR]

During several seasons in 1995 common whelks (Buccinum undatum), mussels (Mytilus edulis) and sediment were analysed for organotin compounds. For butyltin compounds, the order of concentrations in whole body homogenate of common whelks was DBT>MBT>TBT. TBT was usually just above the detection limit except for the samples of the neural ganglia(nerve center) taken in September. Here, only TBT could be detected,while the TBT/TPC ratio was >l. This could be important since the induction of imposex concerns the involvement of neuropeptides and/or steroid hormones. TPT concentrations in whole body homogenates of common whelks were 4-100 times higher than those of TBT. TPT clearly showed much higher levels than its metabolites DPT and MPT. No structuraldifferences in organotin contamination were found between the sexes,different stages of imposex, or adult and juvenile common whelks. Inmussels, TBT>DBT>MBT, but phenyltin ratios were comparable to those in the common whelk. Phenyltin whole body concentrations, however, were 5-10 fold below those of B. undatum. Biomagnification of butyltin compounds is not expected, whereas comparison of phenyltin ratios between the two species suggests biomagnification. In total sediment samples organotins were usually below their detection limit. The percentage of adult and juvenile female B. undatum showing imposex was > 95%throughout the year. [ABSTRACT FROM AUTHOR]

Oral doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were administered twice within 7 d (total concentration 0.01, 0.1, 1, 10, or 100mu g TCDD/kg body weight) to flounder (Platichthys flesus). After 10d of exposure, flounder were sacrificed, and the effects of TCDD exposure on hepatic microsomal total cytochrome P450 content, 7-ethoxyresorufin-0-deethylase (EROD) activity, and glutathione-S-transferase activity were examined. In addition, plasma and hepatic retinoid and plasma thyroid hormone levels were analyzed. Overall a good correlation existed between the dose and liver concentrations of TCDD. However,only 0.75% of the total dose of TCDD was retained in the flounder liver. The TCDD caused a dose-related, statistically significant induction of the hepatic microsomal total cytochrome P450 content (4.4-fold; p < 0.001) and associated EROD activity (27-fold; p < 0.001), without obvious changes in body weight, liver weight, and condition factor. Total glutathione-S-transferase activity was not induced in livers of flounder exposed to TCDD. No TCDD-induced changes in liver retinoid, plasma retinol, and plasma thyroid hormone parameters were observed. These results indicate that the flounder is an aryl hydrocarbon (Ah) receptor-responsive species with respect to CYP1A induction but not with respect to other mammalian Ah receptor-associated responses. [ABSTRACT FROM AUTHOR]