摘要:

AbstractA laboratory experiment was conducted to compare the toxicological response and metabolism of inorganic fluoride by three species of wild mammals and laboratory white mice (Mus musculusL.). The experimental populations of the wild species—the short‐tailed field vole (Microtus agrestisL.), the bank vole (Clethrionomys glareolusL.) and the wood mouse (Apodemus sylvaticusL.)—were laboratory reared from wild stock, and all test animals were exposed to 0, 40 or 80 μg F ml−1in their drinking water for up to 84 days. The 40 and 80 μg F ml−1treatments induced premature mortalities inM. agrestisandC. glareolusonly. Differential intakes, absorption and retention of fluoride were evident betweenM. musculusandM. agrestis, the two species subject to cage studies of fluoride metabolism budgets. Interspecific variation in accumulation of fluoride with time was also evident between all four species as regards the femur, molars and incisors. Severe dental lesions were apparent in species surviving the 80 μg ml−1treatment for 84 days. Overall, however, there were few clear differences in inherent species sensitivity to fluoride, the interspecific variation in metabolism and accumulation rates being attributable mainly to varia

ISSN:0260-437X    

DOI:10.1002/jat.2550150602

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractSulfur mustard (HD) is a potent vesicating agent of military importance, with known radiomimetic properties. The euthymic hairless guinea pig (EHGP) (Cavia porcellus) is emerging as the animal model of choice for cutaneous HD study. With elucidation of the systemic effects, we may better utilize this animal for all HD toxicity work. To this end, studies were conducted to determine the definitive median lethal dose (MLD) of subcutaneously applied sulfur mustard (HD) in the EHGP, and to correlate the induced hematological changes. Eight groups of two animals each were dosed at 0.3 log intervals from an extrapolated expected dose, deriving a tentative mean around which five groups of six animals each were dosed at 0.1 log intervals, resulting in a definitive MLD of 48.17 mg kg−1. Sulfur mustard was then administered to seven groups of six animals each at a dose of 30 mg kg−1and hematology performed. Significant leukocyte count suppression was found to occur on days 4, 5 and 6, following a leukocyte elevation on day 1 after exposure. Serum potassium levels were found to be elevated all 7 days after HD exposure. Establishing the MLD for subcutaneously applied HD and the pattern of induced leukocyte suppression allows for more definitive evaluation of successful toxicity counter‐mea

ISSN:0260-437X    

DOI:10.1002/jat.2550150603

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractToxicological evaluation of two recently reported treatment protocols for cyanide—SN (sodium nitrite) + DMAP (4‐dimethylaminophenol) and SN + HA (hydroxylamine)—was carried out in male rats. Both treatments produced transient hyperammonaemia and decreased mean arterial pressure. Heart rate decreased and respiratory rate increased, but these changes reached the level of significance only after SN + HA. Histopathological lesions in lung, liver (SN+HA) and kidney (SN+DMAP) were predominantly in the vicinity of blood vessels.The results indicate toxic effects in both treatment groups at a dose known to induce methaemoglobin concentration to the level of antidotal efficiency in cyanide intoxic

ISSN:0260-437X    

DOI:10.1002/jat.2550150604

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractThe present study was conducted as part of a larger project to determine the toxicity of dermally applied coal coprocessing products. Groups of male and female rats were administered, dermally, heavy gas oil II (HGOII) at 8.7, 20.8, 50.0 and 120 mg kg−1body wt. day−1for 91 days. A coal liquefaction product was given as positive control at 120 mg kg−1body wt. day−1. Saline was used on control animals. At termination, the blood and bone marrow were taken from the animals and subjected to hematological examination. Dose‐dependent hematological effects were seen in peripheral blood in HGOII‐treated animals and consisted of significantly reduced hemoglobin, hematocrit, red cell count and platelet count. Mean corpuscular volume was increased, along with mean corpuscular hemoglobin, at the highest dose level. Red cell protoporphyrin, total iron and total iron binding capacity were also significantly elevated at this dose level. Morphological analysis of blood showed increases in polychromatic red cells, schizocytes, Howell‐Jolly bodies, injured cells, hypersegmented neutrophils and shift platelets primarily at the highest dose level. In addition, there was notable anisocytosis, microcytosis and macrocytosis. Quantitative bone marrow evaluation revealed a significant reduction in the myeloid/erythroid ratio for the three highest treatment levels of HGOII. These data indicate that the effect of HGOII on the hemopoietic system is a treatment‐related, partially compensated, hemolytic anemia. The apparent reduction in myelopoiesis may be compensated for by a concurrent increase i

ISSN:0260-437X    

DOI:10.1002/jat.2550150605

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractInterferons have been used to treat chronic hepatitis owing to their antiviral properties. However, now interferons are recognized to inhibit collagen production. Because fibrosis has been associated with liver damage and disfunction, the effects of interferon‐α2bon biliary obstruction‐induced cirrhosis were investigated. Obstructive jaundice was induced in male Wistar rats (ca. 200 g) by double ligation and division of the common bile duct. Control rats were sham operated. Interferon‐α2b(IFN‐α; 100 000 IU per rat) was administered subcutaneously daily after surgery. The animals were sacrificed after 4 weeks of bile duct ligation (BDL) or sham operation. Bilirubins and serum enzyme activities of alkaline phosphatase and γ‐glutamil transpeptidase (determined as markers of liver damage) increased several‐fold after BDL. Erythrocyte and hepatocyte plasma membrane Na+/K+‐ and Ca2+‐ATPase activities decreased significantly in the BDL group. Administration of IFN‐α to BDL rats resulted in a partial normalization of serum markers of liver damage. The normal activity of both ATPases on erythrocyte and hepatocyte plasma membranes was completely preserved by IFN‐α. It is concluded that interferons possess interesting hepatoprotective effects not related to their antiviral properties but probably associated with th

ISSN:0260-437X    

DOI:10.1002/jat.2550150606

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractGroups of ten male and female weanling Sprague‐Dawley rats were fed diet containing 0, 5, 50, 500 or 5000 ppm of a medium‐chain chlorinated paraffin (C14‐17, 52% chlorination) for a period of 13 weeks. Increased relative liver weight was observed at 500 and 5000 ppm in females and at 5000 ppm in males. Relative kidney weight was increased at 5000 ppm in both sexes. Serum cholesterol was increased in the females in a dose‐related manner starting at 50 ppm. At 5000 ppm, animals of both sexes had elevated hepatic UDP‐glucuronosyltransferase activity while only females showed increased aminopyrineN‐demethylase activity. Increased urinaryN‐acetylglucosaminidase activity occurred at 5000 ppm in females. Increased urinary ascorbic acid excretion monitored at week 12 and a decreased hepatic vitamin A level were detected in females receiving the 500 ppm diet and male and female rats at 5000 ppm. Mild, adaptive histopathological changes were detected in the liver of rats of both sexes at 500 and 5000 ppm, and in the thyroid of males and females starting at 500 and 50 ppm, respectively. Minimal changes were observed in the kidney proximal tubules of male rats fed the 5000 ppm diet and in the inner medulla tubules of female rats fed the 500 and 5000 ppm diets. These data indicate that the medium‐chain chlorinated paraffin produces biochemical and histological changes at dietary levels of ± 50 ppm in females and ±

ISSN:0260-437X    

DOI:10.1002/jat.2550150607

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractA modified version of the local lymph node assay (LLNA) is presented, using bromodeoxyuridine to label proliferating lymphocytes. Cell counting is done on mid‐sagittal sections of individual nodes under light microscopy. Two irritants (sodium lauryl sulfate and salicylic acid), four allergens of various sensitizing potential (potassium dichromate, 4‐chloroaniline, neomycin sulfate and nickel sulfate) and one chemical of unknown sensitizing potential (ethyl 3‐aminobenzoate) were tested either in the short protocol using three daily topical applications and/or in the long protocol with a pre‐exposure step under an occluded patch. A weak T cell proliferation was noted with both irritants in the short protocol, but not in the long protocol. Potassium dichromate induced a strong proliferative response in the short protocol. A lesser sensitizing potential was detected for 4‐chloroaniline, ethyl 3‐aminobenzoate and neomycin sulfate but only in the long protocol. Nickel sulfate was negative in both protocols. The long protocol was the most valuable for weak or moderate sensitizers. Histological examination of nodes ruled out intercurrent processes.The present procedure offers several advantages. The use of a non‐isotopic marker enables this test to be run in a routine safety assessment department and allows the preparation of permanent slides. An increased specificity is obtained by restricting cell counting to the paracortex. Moreover, the collection of individual data permits statistical analysis of the results. This method is sensitive and reproducible and may be viewed as a useful adjunc

ISSN:0260-437X    

DOI:10.1002/jat.2550150608

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractThe utility of an increase in the level of interleukin lα (IL‐1α) as an indicator of cytotoxicity from exposure to bis‐(2‐chloroethyl)sulfide (BCES) was evaluated in submerged monolayer cultures of human cutaneous keratinocytes. Four‐day‐old cultures were exposed to 1–100 (μM BCES at 37°C for 30 min. The amounts of IL‐1α in the medium at and in cells 72 h after exposure were measured immunologically with an enzyme‐linked immunosorbent assay using monoclonal antibody to human IL‐1α. The antibody was conjugated with peroxidase for visualization. Cell viability was measured concomitantly using the trypan blue exclusion technique. The degree of interstrand cross‐linking as a measure of damage in the cellular DNA was determined by measuring the fluorescence resulting from the intercalation of ethidium bromide into double‐stranded molecules that remained in heat‐denatured DNA isolated from cells that had been exposed to BCES. A high correlation was observed between the dose‐responsive increase in the level of IL‐1α in the medium and in the cells, and the dose‐responsive decrease that took place in the fraction of viable cells in exposed cultures. The dose‐responsive increase in the interstrand cross‐linking found in the DNA of cells immediately after exposure to BCES also correlated with the increase in IL‐1α 72 h after exposure. These data suggest that the appearance of IL‐1α can be used to quantify the cytotoxicity resulting from BCES‐mediated damage to cellular DNA and that the degree of cross‐linking in the DNA immediately after exposure to BCES is predictive of the level

ISSN:0260-437X    

DOI:10.1002/jat.2550150609

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

ISSN:0260-437X    

DOI:10.1002/jat.2550150610

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

ISSN:0260-437X    

DOI:10.1002/jat.2550150611

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY