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1. |
BEHAVIOR OF HEAVY METALS IN HUMAN URINE AND BLOOD FOLLOWING CALCIUM DISODIUM ETHYLENEDIAMINE TETRAACETATE INJECTION: OBSERVATIONS IN METAL WORKERS |
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Journal of Toxicology and Environmental Health, Part A,
Volume 54,
Issue 3,
1998,
Page 167-178
Fumihiro Sata Shunichi Araki Katsuyuki Murata Hiroshi Aono,
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摘要:
To evaluate the effects of calcium disodium ethylenediamine tetraacetate (CaEDTA) on the behavior of 8 heavy metals in human urine and blood, CaEDTA was administered for 1 h by intravenous injection to 18 male metal foundry workers, whose blood lead concentrations (PbB) were between 16 and 59 (mean 34) mug/ dl. Significant increases were found in urinary excretion of manganese, chromium, lead, zinc, and copper after the start of CaEDTA injection. Urinary chromium excretion reached a maximal level within 1 h after the start of injection, while urinary manganese, lead, and zinc excretion reached their highest concentrations between 1 and 2 h. Urinary copper excretion reached the highest level between 2 and 4 h. The rapid increases in urinary excretion of five metals were different from the ''circadian rhythms," which are the normal, daily variations in renal glomerular filtration, reabsorption, and excretory mechanisms. Plasma lead concentrations were highest 1.5 h after the start of the 1-h injection, while plasma zinc concentration became lowest 5 h after the start of CaEDTA injection. Data suggest that manganese and chromium absorbed in human tissues might be mobilized by CaEDTA.
ISSN:1528-7394
DOI:10.1080/009841098158881
出版商:Informa UK Ltd
年代:1998
数据来源: Taylor
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2. |
URINARY EXCRETION OF ARSENIC METABOLITES AFTER LONG-TERM ORAL ADMINISTRATION OF VARIOUS ARSENIC COMPOUNDS TO RATS |
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Journal of Toxicology and Environmental Health, Part A,
Volume 54,
Issue 3,
1998,
Page 179-192
Kaoru Yoshida Yoshinori Inoue Koichi Kuroda Hua Chen Hideki Wanibuchi Shoji Fukushima Ginji Endo,
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摘要:
The metabolism of arsenic compounds in rats was studied by comparing urinary metabolites of arsenic compounds administered for 1 wk or 7 mo. Male F344/DuCrj rats were given 100 mg As/L as monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), trimethylarsine oxide (TMAO), or arsenobetaine (AsBe), or 10 mg As/L as arsenite \[As(III)] via drinking water for 7 mo. Urine was collected by forced urination after 1 wk or 7 mo. Arsenic metabolites in urine were analyzed by ion chromatography with inductively coupled plasma mass spectrometry. In the case of As(III) ingestion, a small portion of all arsenic excreted in urine (about 6% ) was excreted in inorganic form, while most arsenic was excreted as methylated arsenic metabolites. Following MMA treatments for 1 wk or 7 mo, the predominant products excreted were unchanged MMA and DMA accompanied by small amounts of TMAO and tetramethylarsonium (TeMA). In the case of DMA treatment the urinary compounds found were mainly the parent DMA and TMAO with minute amounts of TeMA. TMAO was methylated to TeMA to a slight extent after 1 wk and 7 mo of administration, although most TMAO was excreted in the form of unchanged TMAO. AsBe was predominantly eliminated in urine without any transformation. Two unidentified metabolites were detected in urine after 7 mo of arsenic species exposure; the amounts of these metabolites increased in the order DMA > MMA > TMAO with only small quantities of these detected in the As(III)-treated group. These results suggest that these unidentified metabolites are formed during a demethylation process, and not during methylation. Our findings indicate that long-term exposure to As(III), MMA, or DMA decreases the proportion of TMAO elimination in urine and increases that of DMA, M-1, and M-2, and that further methylation to TMAO to TeMA does occur to a slight extent following long-term exposure to arsenical compounds in rats.
ISSN:1528-7394
DOI:10.1080/009841098158890
出版商:Informa UK Ltd
年代:1998
数据来源: Taylor
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3. |
EFFECTS OF ACUTE INHALATION EXPOSURE TO 1,1,1-TRICHLOROETHANE ON THE HYPOTHALAMO-PITUITARY-ADRENAL AXIS IN MALE SPRAGUE-DAWLEY RATS |
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Journal of Toxicology and Environmental Health, Part A,
Volume 54,
Issue 3,
1998,
Page 193-208
Varsha M. Pise Thomas G. Reigle Srinivasa Muralidhara Cham E. Dallas,
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摘要:
1,1,1-Trichloroethane (TRI) is a commonly used industrial solvent with a considerable potential for inhalation abuse. Previous studies in our laboratory and elsewhere have shown that this agent exerts a suppressant effect on operant responding, as well as a number of additional neurobehavioral effects that are similar to those of central nervous system (CNS) depressant drugs. In an effort to provide information relevant to potential mechanisms involved in the behavioral effects and abuse potential of TRI, the present study evaluated the acute effects of this agent on the activity of the hypothalamo-pituitaryadrenal (HPA) axis. Male Sprague-Dawley rats were exposed to 3500 or 5000 ppm TRI by inhalation for 10 or 30 min. Following exposure, plasma levels of adrenocorticotropic hormone (ACTH) and corticosterone and levels of ACTH and corticotropin-releasing factor (CRF) in three brain regions-hypothalamus, hippocampus, and frontal cortexwere determined by selective radioimmunoassays. Levels of TRI in the three brain regions as well as blood were measured by headspace gas chromatography to determine the target tissue concentrations responsible for neuroendocrine changes. Uptake of TRI in blood and all brain regions was very rapid, with stable concentrations apparently achieved within 10 min and maintained for 30 min. During this time course, a significant decrease in plasma corticosterone was produced at 30 min but no significant change in plasma ACTH was observed with 3500 ppm TRI. However, after exposure to 5000 ppm, both plasma ACTH and plasma corticosterone were significantly reduced at 10 and 30 min. ACTH levels in the three brain regions were not significantly changed by TRI, while hypothalamic CRF was significantly increased during exposure to 3500 ppm. However, hypothalamic concentrations of CRF declined following 30 min at 3500 ppm and were not significantly changed by 5000 ppm. This complexity of effects on the regulation of HPA axis activity likely precluded the establishment of consistent relationships between changes in hormonal levels and blood or regional brain concentrations of the inhalant. However, these actions of TRI were strikingly similar to those previously reported for the benzodiazepines.
ISSN:1528-7394
DOI:10.1080/009841098158908
出版商:Informa UK Ltd
年代:1998
数据来源: Taylor
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4. |
METABOLISM OF CHLORAL HYDRATE IN MICE AND RATS AFTER SINGLE AND MULTIPLE DOSES |
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Journal of Toxicology and Environmental Health, Part A,
Volume 54,
Issue 3,
1998,
Page 209-226
Frederick A. Beland Thomas C. Schmitt Nancy F. Fullerton John F. Young,
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摘要:
Chloral hydrate is a hepatocarcinogen in mice but not rats. To examine this speciesrelated difference, male and female B6C3F1 mice and Fischer (F344) rats were treated by gavage with 1 or 12 doses of chloral hydrate, and concentrations of the drug and its metabolites were determined in plasma at 0.25, 1, 3, 6, and 24 h and 2, 4, 8, and 16 d after the last treatment. Maximum levels of chloral hydrate were observed at the initial sampling time of 0.25 h. By 1 h, levels dropped substantially, and by 3 h, chloral hydrate could not be detected. Trichloroacetic acid was the major metabolite found in the plasma, with peak levels being observed 1-6 h after dosing. The concentrations then slowly decreased such that by 2 d this metabolite could no longer be detected. Trichloroethanol was assayed as both the free alcohol and its glucuronide. Maximum levels of trichoroethanol occurred at 0.25 h, and by 1-3 h approached the limits of detection. A pharmacokinetic model was constructed to describe the metabolic data. The plasma halflife values of chloral hydrate were similar in both species. In mice, the rate of elimination of trichloroacetic acid was significantly increased after multiple doses; this difference was not observed with rats. The half-life of trichloroethanol and its glucuronide was significantly greater in rats as compared to mice. None of the metabolic parameters appears to account for the hepatocarcinogenicity of chloral hydrate seen in mice but not rats.
ISSN:1528-7394
DOI:10.1080/009841098158917
出版商:Informa UK Ltd
年代:1998
数据来源: Taylor
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5. |
MODULATION OF 7,12-DIMETHYLBENZ\[a]ANTHRACENE DISPOSITION AND HEPATOCARCINOGENESIS BY DIELDRIN AND CHLORDECONE IN RAINBOW TROUT |
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Journal of Toxicology and Environmental Health, Part A,
Volume 54,
Issue 3,
1998,
Page 227-242
Regina M. Donohoe Quan Zhang Lisbeth K. Siddens Hillary M. Carpenter Jerry D. Hendricks Lawrence R. Curtis,
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摘要:
The present study examined whether modified xenobiotic transport, resulting from chlordecone (CD) or dieldrin pretreatment, would alter polycyclic aromatic hydrocarbon (PAH) or organochlorine (OC) target organ doses and subsequent tumor organospecificity or incidence rates in rainbow trout. Additionally, the potential for exposure to dieldrin or CD, following PAH exposure, to enhance tumor incidence was assessed. Evaluation of CD pretreatment effects on \[14C]CD disposition in trout was conducted following two ip (0-15 mg/kg) and two dietary (0-0.4 mg/kg/d) pretreatment regimes. To assess the influence of OC pretreatment on cancer induced by the PAH 7,12-dimethylbenz\[a]anthracene (DMBA), juvenile trout were fed control, CD (0.1, 0.4 mg/kg/d), or dieldrin (0.1, 0.3 mg/kg/d) diets for 9 wk, received a waterborne \[3H]DMBA exposure (1 mg/L, 20 h), and resumed control, CD, or dieldrin diets for 33 wk. \[3H]DMBA disposition and hepatic \[3H]DMBA binding were examined immediately and 24 h after exposure. Hepatic and stomach tumor incidences were determined 33 wk after DMBA exposure. CD pretreatment did not influence \[14C]CD or \[3H]DMBA hepatic concentrations, hepatic \[3H]DMBA DNA binding, or hepatic/stomach tumor incidence. It did, however, elevate bile \[14C]CD and \[3H]DMBA concentrations. Postinititation exposure to CD weakly enhanced DMBA-induced hepatic tumor incidence at the low but not the high CD dose. Dieldrin pretreatment did not influence stomach \[3H]DMBA equivalents or stomach tumor incidence but did cause an elevation in biliary and hepatic concentrations of \[3H]DMBA equivalents. \[3H]DMBA binding to liver DNA was significantly increased and hepatic tumor incidence was elevated by dieldrin pretreatment. Dieldrin treatment following DMBA initiation did not enhance hepatic or stomach tumor incidence. Ecoepidemiology studies, to date, have reported correlations between the co-occurrence of PAHs and OCs and elevated tumor incidence in feral fish, but cause-and-effect relationships have been difficult to establish. The results of the present study confirm that OCs, such as dieldrin and CD, play a role in modifying PAH-induced carcinogenesis in fish.
ISSN:1528-7394
DOI:10.1080/009841098158926
出版商:Informa UK Ltd
年代:1998
数据来源: Taylor
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