Fundamental and Applied Toxicology Journal Impact Factor & Information

Publisher: Society of Toxicology (U.S.)

Journal description

This journal is no longer published by Academic Press

Current impact factor: 0.00

Impact Factor Rankings

2015 Impact Factor Available summer 2015
1999 Impact Factor 2.205
1998 Impact Factor 2.167
1997 Impact Factor 1.89

Impact factor over time

Impact factor
Year

Additional details

5-year impact 0.00
Cited half-life 0.00
Immediacy index 0.00
Eigenfactor 0.00
Article influence 0.00
Website Fundamental and Applied Toxicology website
Other titles Fundamental and applied toxicology (Online), Fundamental and applied toxicology
ISSN 0272-0590
OCLC 36980446
Material type Document, Periodical, Internet resource
Document type Internet Resource, Computer File, Journal / Magazine / Newspaper

Publications in this journal

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    ABSTRACT: Methyl tert -butyl ether (MTBE) is a widely used gasoline oxygenate. Two other ethers, ethyl tert -butyl ether (ETBE) and tert -amyl methyl ether (TAME), are also used in reformulated gasoline. Inhalation is a major route for human exposure to MTBE and other gasoline ethers. The possible adverse effects of MTBE in humans are a public concern and some of the reported symptoms attributed to MTBE exposure appear to be related to olfactory sensation. In the present study, we have demonstrated that the olfactory mucosa of the male Sprague-Dawley rat possesses the highest microsomal activities, among the tissues examined, in metabolizing MTBE, ETBE, and TAME. The metabolic activity of the olfactory mucosa was 46-fold higher than that of the liver in metabolizing MTBE, and 37- and 25-fold higher, respectively, in metabolizing ETBE and TAME. No detectable activities were found in the microsomes prepared from the lungs, kidneys, and olfactory bulbs of the brain. The observations that the metabolic activity was localized exclusively in the microsomal fraction, depended on the presence of NADPH, and was inhibitable by carbon monoxide are consistent with our recent report on MTBE metabolism in human and mouse livers (Hong et al., 1997) and further confirm that cytochrome P450 enzymes play a critical role in the metabolism of MTBE, ETBE, and TAME. The apparent K m and V max values for the metabolism of MTBE, ETBE, and TAME in rat olfactory microsomes were very similar, ranging from 87 to 125 μM and 9.8 to 11.7 nmol/min/mg protein, respectively. Addition of TAMIE (0.1 to 0.5 mM) into the incubation mixture caused a concentration-dependent inhibition of the metabolism of MTBE and ETBE. Coumarin (50 μM) inhibited the metabolism of these ethers by approximately 87%. Further comparative studies with human nasal tissues on the metabolism of these ethers are needed in order to assess the human relevance of our present findings.
    Fundamental and Applied Toxicology 01/1998; DOI:10.1093/toxsci/40.2.205
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    ABSTRACT: This symposium focused on the research which documents benefit and toxicity in beta-carotene supplementation. Reflecting on past and current studies, the panel of experts discussed: (1) the potential harm of a high intake of beta-carotene on selected populations, (2) biochemical antioxidant/prooxidant mechanisms of beta-carotene at the cellular level, (3) potential benefits of other carotenoids and antioxidants, and (4) future directions for research in beta-carotene and other antioxidants.
    Fundamental and Applied Toxicology 01/1998; 40(2):163-74. DOI:10.1093/toxsci/40.2.163
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    ABSTRACT: Primary hepatocyte cultures prepared from male beagle dog liver were used to determine susceptibility of the canine liver to tetracycline-induced steatosis. The effects of the drug on mitochondrial lipid metabolism and intracellular triglyceride accumulation were monitored at the same time that steatosis was detected by light microscopy and quantitated using lipid-specific stains. Exposure of primary canine hepatocyte cultures to tetracycline for 24-48 h resulted in concentration-dependent, significant increases in the Oil Red O-stained lipid inclusions. Microscopic examination of the total stained areas suggested that increases over control levels were due primarily to the increase in the size of the lipid inclusions rather than in the number. Biochemical analyses for triglyceride content and histological staining with Nile red, another neutral lipid-specific dye, confirmed a specific increase in intracellular triglyceride following a 24-h exposure to noncytotoxic levels of tetracycline beta-oxidation studies based on the oxidation of [14C]palmitic acid or [14C]palmitoyl carnitine demonstrated a concentration-dependent inhibition of mitochondrial but not peroxisomal beta-oxidation in hepatocytes after a 24-h exposure to tetracycline. In vitro incubation of tetracycline with mitochondria isolated from dog liver showed similar concentration-dependent inhibition. This study clearly indicates that the canine hepatocyte is susceptible to tetracycline-induced steatosis. Triglyceride accumulation was concomitant with the inhibition of mitochondrial lipid metabolism, indicating that this is a primary mechanism leading to steatosis in dog hepatocytes following tetracycline exposure.
    Fundamental and Applied Toxicology 01/1998; 40(2):256-63. DOI:10.1093/toxsci/40.2.256
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    ABSTRACT: Our laboratory has developed a method of intratracheal inhalation whereby rats can be exposed to high aerosol concentrations, resulting in high lung particle burdens in a short time period with deposition occurring directly in the lower respiratory tract, thus avoiding many drawbacks of larger nose-only or whole body inhalation systems. In this report, we compare the response of rats exposed by intratracheal inhalation to "fine" (approximately 250 nm) and "ultrafine" (approximately 21 nm) titanium dioxide particles with rats exposed to similar doses by intratracheal instillation. Animals receiving particles through inhalation showed a decreased pulmonary response, measured by bronchoalveolar lavage parameters, in both severity and persistence, when compared with those receiving particles through instillation. These results demonstrate a difference in pulmonary response to an inhaled vs an instilled dose, which may be due to differences in dose rate, particle distribution, or altered clearance between the two methods.
    Fundamental and Applied Toxicology 01/1998; 40(2):220-7. DOI:10.1006/faat.1997.2390
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    ABSTRACT: Tributyl phosphate (TBP) produces tumors of the bladder urothelium in rats at high doses (700 and 3000 ppm), with greater effects in males than in females. TBP does not produce tumors in mice and it is nongenotoxic. The dose response of TBP effects on urine and urothelium was evaluated in male Sprague-Dawley rats at 0, 200, 700, and 3000 ppm of the diet, 10 rats per group, for 10 weeks. Another group received 3000 ppm TBP plus 12,300 ppm NH4Cl to evaluate the effect of urinary acidification. An additional group of 10 rats received 12,300 ppm NH4Cl. A high-dose recovery group (10 weeks 3000 ppm TBP, then 10 weeks control diet) was included to evaluate reversibility. Urine chemistries for control and TBP-treated animals were similar except for a slight decrease in osmolality and creatinine at the highest dose. Scanning electron microscopic examination of the urine of TBP-treated rats showed no increased or abnormal crystalluria, urinary precipitate, or calculi. The urothelial effects were seen at the two highest doses, but were most severe at 3000 ppm TBP, with ulceration and hemorrhage into the bladder lumen and consequent diffuse papillary and nodular hyperplasia. Dietary NH4Cl acidified the urine but did not prevent the urothelial toxicity and regeneration. The bladder epithelial changes were reversible, but the ulcer repair process was accompanied by submucosal fibrosis. TBP at high doses appears to produce urothelial cytotoxicity with marked regenerative hyperplasia which is reversible upon withdrawal of treatment. The cytotoxicity is likely due to the direct effect of TBP or its metabolites rather than an indirect consequence of urinary changes.
    Fundamental and Applied Toxicology 01/1998; 40(2):247-55. DOI:10.1093/toxsci/40.2.247
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    ABSTRACT: The proposed Neurotoxicity Risk Assessment Guidelines (U.S. EPA, 1995c Fed Reg. 60(192), 52032–52056) of the U.S. Environmental Protection Agency (EPA) were the subject of a workshop at the 1997 Meeting of the Society of Toxicology. The workshop considered the role of guidelines in the risk assessment process, the primary features, scientific basis, and implications of the guidelines for EPA program offices, as well as for industrial neurotoxicologists from the perspectives of both pesticides and toxic substances regulation. The U.S. National Academy of Sciences (NAS, 1983, Risk Assessment in the Federal Government: Managing the Process) established a framework for distinguishing risk management from risk assessment, the latter being the result of integrating hazard identification, hazard characterization, and exposure assessment data. The guidelines are intended to establish operating principles that will be used when examining data in a risk assessment context. The proposed neurotoxicity risk assessment guidelines provide a conceptual framework for deciding whether or not a chemically induced effect can be considered to be evidence of neurotoxicity. Topics in the proposed guidelines include structural and functional effects, dose-response and duration considerations, and relationships between effects. Among the issues that must be considered are the multiplicity of chemical effects, the levels of biological organization in the nervous system, and the tests, measurements, and protocols used. Judgment of the adversity of an effect depends heavily on the amount and types of data available. The attribution of a chemically induced effect to an action on the nervous system depends on several factors such as the quality of the study, the nature of the outcome, dose-response and time-response relationships, and the possible involvement of nonneural factors. The guidelines will also serve as a reference for those conducting neurotoxicity testing, as well as establish a consistent approach to neurotoxicity risk assessment by regulators. Extending this approach through international harmonization would be advantageous to the development of products for a worldwide market. Thus, both risk assessors and regulated industries have a large stake in the guidelines to provide a framework that will lead to accurate risk assessment decisions.
    Fundamental and Applied Toxicology 01/1998; DOI:10.1093/toxsci/40.2.175
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    ABSTRACT: Nitroaromatic musks, including musk ketone (MK; 2,6-dimethyl-3,5-dinitro-4-t-butylacetophenone), are chemicals used as perfume ingredients in household products, cosmetics, and toiletries. Musk xylene (MX; 1,3,5-trinitro-2-t-butylxylene), another nitromusk, is not genotoxic but has been reported to produce mouse liver tumors in a chronic bioassay. In addition, MX has been shown to both induce and inhibit mouse liver cytochrome P450 2B (CYP2B) isozymes. The ability of MX to inhibit CYP2B enzyme activity is attributable to inactivation of the enzyme by a specific amine metabolite. MK is structurally similar to MX, but lacks the nitro substitution that is reduced to the inactivating amine metabolite. Therefore, we hypothesized that MK would induce, but not inhibit, CYP2B isozymes. To test this hypothesis, and to evaluate the effects of MK on mouse liver cytochrome P450 enzymes, two sets of experiments were performed. To evaluate the ability of MK to induce cytochromes P450, mice were dosed daily by oral gavage at dosages ranging from 5 to 500 mg/ kg MK for 7 days. This treatment resulted in a pleiotropic response in mouse liver, including increased liver weight, increased total microsomal protein, and centrilobular hepatocellular hypertrophy. At the highest dose tested, MK caused a 28-fold increase in CYP2B enzyme activity and a small (approximately 2-fold) increase in both cytochromes P450 1A and 3A (CYP1A and CYP3A) enzyme activities over control levels. Protein and mRNA analyses confirmed the relative levels of induction for CYP2B, CYP1A, and CYP3A. In addition, the no-observable-effect level (NOEL) for CYP2B induction by MK was 20 mg/kg. To evaluate the ability of MK to inhibit phenobarbital-induced CYP2B activity, mice were given 500 ppm phenobarbital (PB) in the drinking water for 5 days to induce CYP2B isozymes, followed by a single equimolar (0.67 mmol/kg) oral gavage dose of either MK (198 mg/kg) or MX (200 mg/kg), and microsomes were prepared 18 h later. While MX inhibited more than 90% of the PB-induced CYP2B activity in the microsomes, MK caused only a small (about 20%) reduction in PB-induced CYP2B enzyme activity. These results indicate that, like MX. MK is a PB-type inducer of mouse liver CYP2B isozymes, but unlike MX, MK does not effectively inhibit PB-induced CYP2B enzyme activity.
    Fundamental and Applied Toxicology 01/1998; 40(2):264-71. DOI:10.1093/toxsci/40.2.264
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    ABSTRACT: Triglyceride-containing lipid emulsions have been designed as caloric sources that can be administered intravenously to patients that cannot meet their nutritional needs by conventional parenteral therapies. In their study, we evaluate the developmental toxicity of a 20% lipid emulsion that contains a 3:1 ratio of medium chain triglyceride (MCT) to one long chain containing lipid emulsion (LCT). This emulsion was administered by intravenous infusion to rats and rabbits at dosages of 1 and 4.28 g lipid/kg body weight (g lipid/kg) at dose volumes of 5 and 21.4 mL/kg, respectively, once daily during organogenesis to assess the potential developmental toxicity of the test article. The control group received 0.9% saline at a dose volume of 21.4 mL/kg. Animals were observed for clinical signs of toxicity and adverse effects on body weights and feed consumption. On Day 20 (rats) or Day 29 (rabbits), females were necropsied and examined for maternal and embryo/fetal toxicity. Fetuses were removed, weighed, and examined for external, soft tissue, and skeletal abnormalities. Dosages of 4.28 g lipid/kg resulted in lower feed consumption for rats and rabbits, an expected finding based on the high-caloric nature of the test article. Potentially test article-related gross necropsy findings, including enlarged lymph nodes and spleen, small thymus, and enlarged renal pelvis, for rats given 4.28 g lipid/kg were present at a low incidence. There were no adverse effects on fetal parameters for rats even in the presence of some maternal toxicity. However, embryo and fetal toxicity (i.e., resorptions) and skeletal abnormalities were present for rabbits given 4.28 g lipid/kg. Under the conditions of this study, the no-observable-effect level for developmental toxicity was greater than or equal to 4.28 g lipid/kg for rats and greater than or equal to 1 g lipid/kg but less than 4.28 g lipid/kg for rabbits.
    Fundamental and Applied Toxicology 01/1998; 40(2):185-90. DOI:10.1093/toxsci/40.2.185
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    ABSTRACT: Tributyl phosphate (TBP) was tested for reproductive toxicity in rats. Thirty weanlings/sex (F0) were exposed to TBP in the diet ad libitum at 0, 200, 700, or 3000 ppm for 10 weeks and then randomly mated within groups for 3 weeks with continued exposure. F0 parents and 10 F1 weanlings/sex/dose were necropsied, and adult reproductive organs, urinary bladders (both sexes), kidneys (males), and livers (females) were evaluated histologically. Thirty F1 weanlings/sex/dose continued exposure for 11 weeks and were bred as described above. F1 parents and F2 weanlings, 10/sex/dose, were then necropsied as described above. Adult toxicity was observed in both sexes and generations at 700 and 3000 ppm; observations included reduced body weights, weight gain and feed consumption, urinary bladder epithelial hyperplasia (both sexes), renal pelvis epithelial hyperplasia only at 3000 ppm (male kidneys), and centrilobular hypertrophy (female livers). At 200 ppm, transient reductions in body weight were observed in F0 and F1 females, with urinary bladder epithelial hyperplasia in F0 males and females and in F1 males. There was no evidence of reproductive toxicity, of reproductive organ pathology, or of effects on gestation or lactation at any dose tested. Postnatal toxicity was evidenced by consistent reductions in F1 and F2 pup body weights at 3000 ppm and by occasional weight reductions in F2 litters at 700 ppm, and was associated with maternal toxicity observed at these doses and times. Under the conditions of this study, a NOAEL was not determined for adult toxicity; the NOAEL for reproductive toxicity was at least 3000 ppm and the NOAEL for postnatal toxicity was approximately 200 ppm.
    Fundamental and Applied Toxicology 12/1997; 40(1):90-100. DOI:10.1006/faat.1997.2373
  • Fundamental and Applied Toxicology 12/1997; 40(2):185-190. DOI:10.1006/faat.1997.2378
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    ABSTRACT: The 3-demethylation of caffeine can be used as an index of cytochrome P450 CYP1A2 activityin vivo.We compared the plasma levels of caffeine and the 3-demethylated metabolite, 1,7-dimethylxanthine, in six common inbred strains (A/J, P/J, BALB/cJ, C3H/HeJ, AKR/J, and SWR/J) and one inbred strain (APN) derived in our laboratory from outbred Swiss–Webster mice on the basis of its relative susceptibility to acetaminophen-induced hepatotoxicity. We found significant variations between a number of the common strains, all of which produced significantly higher caffeine 3-demethylation indices than our APN strain. In three of the six common strains, there was a significant difference between males and females, with the females having consistently lower 1,7-xanthine/caffeine ratios. HepaticCyp1a2expression was compared between APN and C3H/HeJ males. Microsomal methoxyresorufin O-demethylation, acetanilide 4-hydroxylation, and CYP1A2 immunoreactive protein levels were significantly higher in C3H/HeJ relative to APN mice, as were hepatic CYP1A2 mRNA levels. These results indicate the importance of strain and gender to the outcome of pharmacological or toxicological studies involving CYP1A2-mediated metabolism, as well as the suitability of the plasma 1,7-dimethylxanthine/caffeine ratio as a marker of CYP1A2 activity in the mouse. The striking differences observed between the APN and C3H/HeJ mice suggest that these strains may be suitable for a genetic analysis of the regulation of the basal expression of CYP1A2, a key enzyme in procarcinogen activation.
    Fundamental and Applied Toxicology 12/1997; 40(2):228-237. DOI:10.1006/faat.1997.2394