Fundamental and applied toxicology : official journal of the Society of Toxicology最新文献

{"title":"Evaluation of effect profiles: Functional Observational Battery outcomes.","authors":"S. Baird, Paul J. Catalano, Louise M. Ryan, John S. Evans","doi":"10.1093/toxsci/40.1.37","DOIUrl":"https://doi.org/10.1093/toxsci/40.1.37","url":null,"abstract":"The Functional Observational Battery (FOB) is a neurotoxicity screening assay composed of 25-30 descriptive, scalar, binary, and continuous endpoints. These outcomes have been grouped into six biologically logical domains as a means to interpret the neuroactive properties of tested chemicals (V. C. Moser, 1992, J. Am. Coll. Toxicol. 10(6), 661-669). However, no data-based exploration of these functional domains has been done. We investigated the degree to which experimental data correspond to the domain groupings by examining severity scores from 10 chemicals tested using a standardized protocol for acute exposure (V. C. Moser et al., 1995, J. Toxicol. Environ. Health 45, 173-210) and identifying endpoint groupings (factors) that best describe the interrelationships in the data, allowing a statistical assessment of whether the FOB endpoints break into domains. We also used a standard measure of bivariate association to confirm the results of the factor analysis. Our results show that while there are clear relationships among variables that compose some domains, there is often substantial correlation among endpoints in different domains. In addition, we investigated a related issue concerning the relative power of the chosen endpoint groupings for identifying significant domain effects. Results from a randomization analysis of the 10 chemicals suggest that the neurophysiologic domain structuring may provide some degree of statistical efficiency for identifying effects.","PeriodicalId":12658,"journal":{"name":"Fundamental and applied toxicology : official journal of the Society of Toxicology","volume":"40 1","pages":"37-51"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85116503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sequence of toxic events in arsine-induced hemolysis in vitro: implications for the mechanism of toxicity in human erythrocytes.","authors":"Shannon L. Winski, David S. Barber, L. Rael, Dean E. Carter","doi":"10.1093/toxsci/38.2.123","DOIUrl":"https://doi.org/10.1093/toxsci/38.2.123","url":null,"abstract":"Arsine, the hydride of arsenic (AsH3), is the most acutely toxic form of arsenic, causing rapid and severe hemolysis upon exposure. The mechanism of action is not known, and there are few detailed investigations of the toxicity in a controlled system. To examine arsine hemolysis and understand the importance of various toxic responses, human erythrocytes were incubated with arsine in vitro, and markers of toxicity were determined as a function of time. The earliest indicators of damage were changes in sodium and potassium levels. Within 5 min incubation with 1 mm arsine, the cells lost volume control, manifested by leakage of potassium, influx of sodium, and increases in hematocrit. Arsine did not, however, significantly alter ATP levels nor inhibit ATPases. These changes were followed by profound disturbances in membrane ultrastructure (examined by light and electron microscopy). By 10 min, significant numbers of damaged cells formed, and their numbers increased over time. These events preceded hemolysis, which was not significant until 30 min. It has been proposed that arsine interacts with hemoglobin to form toxic hemoglobin oxidation products, and this was also investigated as a potential cause of hemolysis. Essentially on contact with arsine, methemoglobin was formed but only reached 2-3% of the total cellular hemoglobin and remained unchanged for up to 90 min. There was no evidence that further oxidation products (hemin and Heinz bodies) were formed in this system. Based on these observations, hemolysis appears to be dependent on membrane disruption by a mechanism other than hemoglobin oxidation.","PeriodicalId":12658,"journal":{"name":"Fundamental and applied toxicology : official journal of the Society of Toxicology","volume":"38 1","pages":"123-8"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76821619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of testis exposure levels in the insensitivity of prepubertal rats to carbendazim-induced testicular toxicity.","authors":"Junghee Lim, Marion G. Miller","doi":"10.1093/toxsci/37.2.158","DOIUrl":"https://doi.org/10.1093/toxsci/37.2.158","url":null,"abstract":"Our recent studies have indicated that benomyl (BNL)-induced testicular toxicity is mediated by its major metabolite carbendazim (CBZ). The present study has used CBZ to investigate hypotheses that could explain prepubertal insensitivity to BNL. When CBZ (164 mg/kg intraperitoneally) was administered to postpubertal and prepubertal rats, it caused little testicular damage in prepubertal rats, but in adult rats, sloughing of the seminiferous epithelium resulted. When the inhibitory effect of CBZ on prepubertal testicular microtubule assembly was compared with that on postpubertal assembly, the IC50 values were very similar. Pharmacokinetic studies revealed that blood levels of CBZ were comparable in the two age groups; however, higher levels of CBZ were found in the adult testes (210.52 nmol/g wet wt) in comparison with young testes (67.77 nmol/g wet wt). These data suggest that delivery to and/or retention of CBZ in the testis may play a role in the age-dependent differences in susceptibility to CBZ toxicity. When CBZ was administered intratesticularly to reach levels sufficient to cause damage, the young animals did show an increased incidence of vacuolization and detachment of the seminiferous epithelium; however, in contrast to the older animals, sloughing of the seminiferous epithelium was not observed in the prepubertal animals. Overall, the low levels of CBZ measured in the testes of prepubertal animals offer a partial explanation for the insensitivity of young animals to CBZ-induced testicular toxicity following intraperitoneal administration. A differential responsiveness between the two age groups is also likely, however, since prepubertal animals lack elongated spermatids and it is sloughing of this cell type that characterizes CBZ-induced testicular toxicity in the adult.","PeriodicalId":12658,"journal":{"name":"Fundamental and applied toxicology : official journal of the Society of Toxicology","volume":"55 1","pages":"158-67"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82740573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tetracycline-induced steatosis in primary canine hepatocyte cultures.","authors":"D. Amacher, B. Martin","doi":"10.1093/toxsci/40.2.256","DOIUrl":"https://doi.org/10.1093/toxsci/40.2.256","url":null,"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.","PeriodicalId":12658,"journal":{"name":"Fundamental and applied toxicology : official journal of the Society of Toxicology","volume":"19 1","pages":"256-63"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72875308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Promotion of altered hepatic foci by 2,3',4,4',5-pentachlorobiphenyl in Sprague-Dawley female rats.","authors":"M. Haag-Grönlund, L. Wärngård, S. Flodström, G. Scheu, T. Kronevi, U. Ahlborg, R. Fransson-Steen","doi":"10.1093/TOXSCI/35.1.120","DOIUrl":"https://doi.org/10.1093/TOXSCI/35.1.120","url":null,"abstract":"The tumor promotion potential of 2,3',4,4',5-pentachlorobiphenyl (PCB-118) was studied in a two-stage initiation/promotion bioassay in female Sprague-Dawley rats. The animals were initiated by intraperitoneal administration of N-nitrosodiethylamine after partial hepatectomy. After 5 weeks of recovery, the promotion period commenced by once-weekly subcutaneous administrations of PCB-118 at six dose levels (10, 40, 160, 640, 2500, and 10,000 microg/kg body weight/week) for 20 weeks. In addition, three of these dose levels (40, 640, and 10,000 microg/kg body weight/week) were administered for 52 weeks. Evaluation of hepatic foci positive for glutathione S-transferase P demonstrated that the mono-ortho chlorine substituted congener PCB-118 significantly increased the number of foci/cm3 of liver in the two highest dose groups after 20 weeks, but did not significantly increase the percentage of the liver occupied by foci. After 52 weeks of treatment, both the percentage and the number of foci/cm3 were significantly increased in the highest dose group. A toxic equivalency factor based on foci development during 20 weeks of treatment would be less than 0.00002. Altered relative liver and thymus weights were observed after treatment with both substances as well as an induction of methyl cholanthrene- and phenobarbital-inducible isoenzymes of cytochrome P450 monooxygenase. These results show that PCB-118 has a potency to enhance foci growth in rat liver, although the potency is low compared to that of structurally related compounds.","PeriodicalId":12658,"journal":{"name":"Fundamental and applied toxicology : official journal of the Society of Toxicology","volume":"16 1","pages":"120-30"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86549347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of methimazole, an FMO substrate and competitive inhibitor, on the neurotoxicity of 3,3'-iminodipropionitrile in male rats.","authors":"C. Nace, M. Genter, L. Sayre, K. Crofton","doi":"10.1093/toxsci/37.2.131","DOIUrl":"https://doi.org/10.1093/toxsci/37.2.131","url":null,"abstract":"This study was designed to examine the role of flavin-containing monooxygenase (FMO) on the auditory and vestibular neurotoxicity of 3,3'-iminodipropionitrile (IDPN) using the FMO substrate and competitive inhibitor methimazole (MMI). Specifically, the purpose was to block the FMO-mediated conversion of IDPN to the putative neurotoxic metabolite N-hydroxy3,3'-iminodipropionitrile (HOIDPN). In three separate experiments, adult male Long-Evans hooded rats were administered (ip) saline (vehicle), MMI, IDPN, or HOIDPN individually, or a combination of IDPN and MMI or HOIDPN and MMI. Animals were observed daily for signs of the ECC syndrome (excitation with choreiform and circling movements) for 10 days. One to 2 weeks after exposure, a battery of behavioral tests was used to examine vestibular and auditory function. MMI completely blocked the neurotoxicity associated with a 600 mg/kg dose of IDPN and partially blocked the effects of a 1000 mg/kg dose of IDPN. In contrast, MMI failed to block, and instead increased, the neurotoxicity associated with HOIDPN. These data suggest that FMO-mediated metabolism of IDPN is necessary for the generation of a metabolite responsible for the vestibular and auditory neurotoxicities.","PeriodicalId":12658,"journal":{"name":"Fundamental and applied toxicology : official journal of the Society of Toxicology","volume":"62 1","pages":"131-40"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78951457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aquatic pollution-induced immunotoxicity in wildlife species.","authors":"R. Luebke, P. Hodson, M. Faisal, P. Ross, K. Grasman, J. Zelikoff","doi":"10.1093/toxsci/37.1.1","DOIUrl":"https://doi.org/10.1093/toxsci/37.1.1","url":null,"abstract":"The potential for chemicals to adversely affect human immunologic health has traditionally been evaluated in rodents, under laboratory conditions. These laboratory studies have generated valuable hazard identification and immunotoxicologic mechanism data; however, genetically diverse populations exposed in the wild may better reflect both human exposure conditions and may provide insight into potential immunotoxic effects in humans. In addition, comparative studies of species occupying reference and impacted sites provide important information on the effects of environmental pollution on the immunologic health of wildlife populations. In this symposium overview, Peter Hodson describes physiological changes in fish collected above or below the outflows of paper mills discharging effluent from the bleaching process (BKME). Effects attributable to BKME were identified, as were physiological changes attributable to other environmental factors. In this context, he discussed the problems of identifying true cause and effect relationships in field studies. Mohamed Faisal described changes in immune function of fish collected from areas with high levels of polyaromatic hydrocarbon contamination. His studies identified a contaminant-related decreases in the ability of anterior kidney leukocytes to bind to and kill tumor cell line targets, as well as changes in lymphocyte proliferation in response to mitogens. Altered proliferative responses of fish from the contaminated site were partially reversed by maintaining fish in water from the reference site. Peter Ross described studies in which harbor seals were fed herring obtained from relatively clean (Atlantic Ocean) and contaminated (Baltic Sea) waters. Decreased natural killer cell activity and lymphoproliferative responses to T and B cell mitogens, as well as depressed antibody and delayed hypersensitivity responses to injected antigens, were identified in seals fed contaminated herring. In laboratory studies, it was determined that rats fed freeze-dried Baltic Sea herring had higher virus titers after challenge with rat cytomegalovirus (RCMV) than rats fed Atlantic Ocean herring; perinatal exposure of rats to oil extracted from Baltic herring also reduced the response to challenge with RCMV. Keith Grassman reported an association between exposure to polyhalogenated aryl hydrocarbons and decreased T cell immunity in the offspring of fish-eating birds (herring gulls and Capsian terns) at highly contaminated sites in the Great Lakes. The greatest suppression of skin test responses to phytohemagglutinin injection (an indicator of T cell immunity) was consistently found at sites with the highest contaminant concentrations. Judith Zelikoff addressed the applicability of immunotoxicity studies developed in laboratory-reared fish for detecting altered immune function in wild populations. She presented data from studies done in her laboratory with environmentally relevant concentrations of metals as examples. Al","PeriodicalId":12658,"journal":{"name":"Fundamental and applied toxicology : official journal of the Society of Toxicology","volume":"74 1","pages":"1-15"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82875489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic polymorphisms in human drug metabolic enzymes.","authors":"M. S. Miller, D. McCarver, D. Bell, D. Eaton, J. Goldstein","doi":"10.1093/toxsci/40.1.1","DOIUrl":"https://doi.org/10.1093/toxsci/40.1.1","url":null,"abstract":"Results obtained from both epidemiologic studies and experimental animal model systems have shown a wide range of phenotypic variation in the ability of individuals to metabolize drugs and environmental chemicals. Several studies have noted correlations between specific metabolic phenotypes and the incidence of disease, suggesting that certain allelic forms of drug metabolic enzymes can render the individual either more sensitive or resistant to the toxic or therapeutic effects of exogenous drugs and chemicals. While some of this variation can be attributed to different environmental exposures, it has become clear that genetic factors also play an important role in determining the response of the individual organism to exogenous agents. Recent advances in molecular biological techniques have begun to allow scientists to correlate observed phenotypic differences with the actual differences in genetic sequence at the gene level. This has allowed a correlation between gene structure and function, thus providing a mechanistic basis to explain the interaction between genetic background and individual response to environmental exposures. Results presented at this symposium discussed how genetic polymorphisms for both Phase I and Phase II metabolic enzymes in the human population modulate the response to environmental toxicants.","PeriodicalId":12658,"journal":{"name":"Fundamental and applied toxicology : official journal of the Society of Toxicology","volume":"25 1","pages":"1-14"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87558229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Subacute toxicity of a mixture of nine chemicals in rats: detecting interactive effects with a fractionated two-level factorial design.","authors":"J. Groten, ERIC D. Schoen, Peter J. van Bladeren, C. F. Kuper, J. VAN ZORGE, Victor J. Feron","doi":"10.1093/toxsci/36.1.15","DOIUrl":"https://doi.org/10.1093/toxsci/36.1.15","url":null,"abstract":"The present study was intended (1) to find out whether simultaneous administration of nine chemicals at a concentration equal to the \"no-observed-adverse-effect level\" (NOAEL) for each of them would result in a NOAEL for the combination and (2) to test the usefulness of fractionated factorial models to detect possible interactions between chemicals in the mixture. A 4-week oral/inhalatory study in male Wistar rats was performed in which the toxicity (clinical chemistry, hematology, biochemistry, and pathology) of combinations of the nine compounds was examined. The study comprised 20 groups, 4 groups in the main part (n = 8) and 16 groups in the satellite part (n = 5). In the main study, the rats were simultaneously exposed to mixtures of all nine chemicals [dichloromethane, formaldehyde, aspirin, di(2-ethylhexyl)phthalate, cadmium chloride, stannous chloride, butyl hydroxyanisol, loperamide, and spermine] at concentrations equal to the \"minimum-observed-adverse-effect level\" (MOAEL), NOAEL, or 1/3NOAEL. In the satellite study the rats were simultaneously exposed to combinations of maximally five compounds at their MOAEL. These combinations jointly comprise a two-level factorial design with nine factors (=9 chemicals) in 16 experimental groups (1/32 fraction of a complete study). In the main part many effects on hematology and clinical chemistry were encountered at the MOAEL. In addition, rats of the MOAEL group showed hyperplasia of the transitional epithelium and/or squamous metaplasia of the respiratory epithelium in the nose. Only very few adverse effects were encountered in the NOAEL group. For most of the end points chosen, the factorial analysis revealed main effects of the individual compounds and interactions (cases of nonadditivity) between the compounds. Despite all restrictions and pitfalls that are associated with the use of fractionated factorial designs, the present study shows the usefulness of this type of factorial design to study the joint adverse effects of defined chemical mixtures at effect levels. It was concluded that simultaneous exposure to these nine chemicals does not constitute an evidently increased hazard compared to exposure to each of the chemicals separately, provided the exposure level of each chemical in the mixture is at most similar to or lower than its own NOAEL.","PeriodicalId":12658,"journal":{"name":"Fundamental and applied toxicology : official journal of the Society of Toxicology","volume":"63 1","pages":"15-29"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85397718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of the effects of cinnamyl anthranilate on hepatic peroxisome proliferation and cell replication in the rat and mouse.","authors":"B. Lake, R. J. Price, M. Cunninghame, D. G. Walters","doi":"10.1093/toxsci/39.1.60","DOIUrl":"https://doi.org/10.1093/toxsci/39.1.60","url":null,"abstract":"The effects of cinnamyl anthranilate (CA) have been compared in female B6C3F1 mice and female F344 rats fed diets containing 0-3.0% CA for periods of 1, 4, and 13 weeks. In the mouse, treatment with CA at all time points produced a marked dose-dependent increase in relative liver weight and hepatic peroxisome proliferation as demonstrated by the induction of peroxisomal (cyanide-insensitive palmitoyl-CoA oxidation) and microsomal (lauric acid 12-hydroxylase) fatty acid oxidizing enzyme activities. CA produced only small increases in relative liver weight and palmitoyl-CoA oxidation in the rat and did not induce lauric acid 12-hydroxylase activity. Replicative DNA synthesis was studied by implanting osmotic pumps containing 5-bromo-2'-deoxyuridine during Study Weeks 0-1, 3-4, and 12-13. After 1 week of CA treatment, labeling index values were increased in rat and to a greater extent in mouse hepatocytes. While CA treatment for 4 and 13 weeks did not increase hepatocyte-labeling index values in the rat, a sustained stimulation of replicative DNA synthesis was observed at some dietary levels in the mouse. These results demonstrate a marked species difference between the hepatic effects of CA in female B6C3F1 mice and female F344 rats. While CA is a potent peroxisome proliferator in the mouse, it is only a very weak agent in the rat. The formation of liver tumors in long-term studies, at high doses of CA, appears to be attributable to a sustained stimulation of both peroxisome proliferation and cell replication in mouse hepatocytes.","PeriodicalId":12658,"journal":{"name":"Fundamental and applied toxicology : official journal of the Society of Toxicology","volume":"4 1","pages":"60-6"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82066950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}