摘要:

AbstractThe target enzyme in organophosphorous‐induced delayed neuropathy (OPIDN) has been designated neuropathy target esterase or neurotoxic esterase (NTE). NTE activity can be measured in blood lymphocytes and platelets, which could be of use as biomonitors in man at risk for the development of OPIDN. Separation of lymphocytes and platelets from whole blood, recovery, purity, storage and expression of data were examined. A substantial amount of the NTE activity of a human lymphocyte preparation made using Ficoll/Pacque was due to contamination by platelets; further purification was achieved by sucrose‐gradient centrifugation. In an easily prepared sample of human platelets less than 10% of NTE was associated with contaminating white cells. We were unable to preserve NTE activity of platelets or lymphocytes at −80°C either ‘dry’ or with added buffer and glycerol. In 68 male subjects, NTE activity in platelets averaged 8.36±1.54 nmol min−1mg protein−1and NTE activity in lymphocytes, obtained from blood after removal of platelets, 13.34±2.42 nmol min−1mg protein−1. A good correlation was found between platelet and lymphocyte NTE activity. NTE activity in platelets may be a preferable method for measuring exposure to axonopathic organophosphorous compounds because of the ease and purity of separation. No correlation with other neuropathic risk factors such as age, smoking and alco

ISSN:0260-437X    

DOI:10.1002/jat.2550060102

出版商:John Wiley&Sons, Ltd.    

年代:1986

数据来源: WILEY

摘要:

AbstractA group of 30 coal‐tar workers was treated with 1 g of ascorbic acid (AA) orally five times a week for 3 months. The effect of this treatment was assessed on serum IgG, IgM, IgA, α1‐antitrypsin, prealburmin, orosomucoid, transferrin, α2‐macroglobulin, C‐reactive protein, ceruloplasmin, the latex fixation test and cancer serum index (CSI). After 3 months treatment the concentration of AA in the blood increased from 9.52 to 60.75 μmol 1−1(i.e. from 0.15 to 1.07 mg 100 ml−1), prealbumin increased from 0.37±0.08 g 1−1to 0.48±0.08 g 1−1(P<0.01), CSI decreased from 2.28±0.88 to 1.76±0.50 (P<0.01) and α2‐macroglobulin decreased from 3.40±0.95 to 2.06±0.39 g 1−1(P<0.01). These findings, together with reports that AA is a strong stimulator of xenobiotic biotransformatin in the liver, support the use of AA as a prophylactic agent

ISSN:0260-437X    

DOI:10.1002/jat.2550060103

出版商:John Wiley&Sons, Ltd.    

年代:1986

数据来源: WILEY

摘要:

AbstractMale Swiss‐Webster mice were exposed to napthalene, 1‐methyl‐, 2‐methyl‐, 1‐nitro‐ and 2‐nitronaphthalene by intraperitoneal injection of peanut oil solutions over a dose range of 0.5–3.0 mmol kg−1body weight. Treated mice were killed at times from 6 hours to 14 days post‐treatment. Tissues were analyzed for cytotoxic effects by optical and electron microscopy, and for cell proliferation by autoradiography followingin vitrolabeling of lung slices with3H‐thymidine. The naphthalene derivatives varied widely in their cytotoxic effects. The most toxic was 1‐nitronaphthalene with no mice surviving doses greater than 1 mmol kg−1. Naphthalene and 2‐methylnaphthalene were about equally toxic, followed by 2‐nitro‐ and 1‐methylnaphthalene, in decresing order of toxicity. In all cases the first evidence of cytotoxic effects was seen in the Clara cells of the bronchiolar epithelium, and at the highest doses, toxic effects were found in the adjacent ciliated cells. Changes could be detected at the ultrastructural level at all doses, and within 6 hours after treatment. Only slight effects were seen in other cell types. Increased cell proliferation following chemical treatment was seen only in the bronchiolar epithelium, among cells tentatively identified as Clara cells or their precursors. Cytotoxic effects of naphthalene and its 1‐ and 2‐methyl derivatives were confined to the lung, with minimal evidence of toxicity in the liver and kidney. The mononitronaphthalenes both produce small areas of centrizonal necrosis in the liver, but no discernible effects in the kidney. The experiments demonstrate the effect of small structural differences on the cytotoxicity of this group of environmental pollutants and also illustrate the sensitivity of the

ISSN:0260-437X    

DOI:10.1002/jat.2550060104

出版商:John Wiley&Sons, Ltd.    

年代:1986

数据来源: WILEY

摘要:

AbstractThe effect of exercise on particle deposition in rats was investigated. Twenty male rats were trained to run on a treadmill and were exposed to gallium‐67 oxide (67Ga2O3) particles (0.1 μm activity median diffusion diameter) for 30 min while running at 30m min−1. Twenty resting controls were exposed in the same system while confined in wire mesh cages. Ten exercising and 10 resting rats were killed 2 h and 12 days after exposure. Tissue radioactivity levels of67Ga2O3were measured and normalized for differences in exposure concentration and body weight. Significantly (P<0.05) more67Ga was deposited in the nasal passages (20vs5 nCi) and in the trachea and mainstem bronchi (0.5vs0.03 nCi) of exercising rats than in resting rats. There were no significant differences between the exercising and resting rats in amounts of67Ga in the lung lobes at 2 h after exposure. Using assumed minute volumes, exercising rats had a significantly (P<0.05) lower lung deposition effeciency, expressed as percentage of estimated inhaled material, than did resting rats (3vs10%). The results suggest that exercising rats inhale more ultrafine particles, but deposit a smaller fraction of them in their lungs. The result is a similar lung burden of 0.1 μm particles in resting and exercising an

ISSN:0260-437X    

DOI:10.1002/jat.2550060105

出版商:John Wiley&Sons, Ltd.    

年代:1986

数据来源: WILEY

摘要:

AbstractThe respiration of naive F344 rats confined in nose‐only inhalation exposure tubes was measured to obtain data for normal adult rats of different ages and to evaluate the tubes for exposures lasting several hours. Exposure tubes were modified for use as volume‐displacement plethysmographs. Respiration of 10 male and 10 female rats at 3, 6, 12 and 24 months of age was measured in the tubes during simulated exposures of up to 6 h duration. Measurements included respiratory frequency, tidal volume, minute volume and body surface temperature. The mean respiratory frequencies of 3, 6, 12 and 24 month old rats during the first hour of exposure were 172, 152, 123 and 136 breaths min−1, respectively. Minute volumes were 1.40, 089, 0.67 and 0.82 ml g−1body weight, respectively. Both frequency and minute volume g−1body weight were significantly greater for the youngest group, declined with age to 12 months and then increased at 24 months. Minute volumes g−1body weight were similar for males and females. Minute volume and respiratory frequency of 3 and 12 month old rats declined progressively between 1 and 6 h of confinement in the tubes. Surface temperature did not increase after the first hour. The age and sex‐specific data provide a basis for predicting respiration of naive tube‐confined rats during inhalation exposures to non‐irr

ISSN:0260-437X    

DOI:10.1002/jat.2550060106

出版商:John Wiley&Sons, Ltd.    

年代:1986

数据来源: WILEY

摘要:

AbstractAmetantrone acetate (anthracenedione diacetate, NSC 287513) is an experimental antineoplastic agent with activity against a comprehensive panel of solid transplantable tumors in mice. The studies reported here were aimed at establishing the toxicologic profile of this drug. Studies in mice and dogs were carried out to establish tolerable levels. In mice, LD10, LD50and LD90values were respectively, 26, 35 and 47 mg kg−128 days following single intravenous injection and 22, 67 and 206 mg kg−114 days after single intraperitoneal injection. Hemorrhage and necrosis of the small intestine occurred in intercurrent deaths. A 5‐day, consecutive intraperitoneal dosing study yielded 28 day, LD10, LD50and LD90values of 18, 21 and 26 mg kg−1, respectively, in mice. Bone marrow hypoplasia, lymphoid depletion and focal cardiac changes were observed in animals which died during the 28‐day postdose observation period. In dogs, single intravenous injections repeated twice at intervals of 3–8 weeks resulted in leukopenia and thrombocytopenia at a dose of 2.71 mg kg−1and decreased myeloid : erythroid ratios at a dose of 0.68 mg kg−1. Five consecutive daily intravenous injections in dogs of 0.7 mg kg−1induced significant clinical and laboratory signs of toxicity but 0.35 mg kg−1day−1was tolerated. In dogs, bone marrow, lymphoid tissue and gastrointestinal tract in both sexes and gonads in the males were target organs for toxicity. Clinical signs and clinical laboratory abnormalities abated in surviving mice and dogs. The spectrum of tissue changes induced by ametantrone was qualitatively similar to that elicited with other

ISSN:0260-437X    

DOI:10.1002/jat.2550060107

出版商:John Wiley&Sons, Ltd.    

年代:1986

数据来源: WILEY

摘要:

AbstractThe intestinal absorption of aluminum (Al) was studied in anin situperfusion system of rat small intestine in combination with systemic and portal blood sampling. The jejunum‐ileum was perfused with media containing 4.63, 9.25 and 18.50 mmol l−1Al chloride at pH 4.0 and 7.0. Both mucosal retention and release of Al into the blood increased at increasing perfusate concentrations. Mucosal retention was not affected by pH but at lower pH more Al was released into the blood. The amount of Al which appeared in the blood was linearly related to the mucosal retention. The Al release into the blood was much less (μmol l−1) than the mucosal retention (mmol l−1). It is concluded that the intestinal absorption of Al is pH‐ and concentration

ISSN:0260-437X    

DOI:10.1002/jat.2550060108

出版商:John Wiley&Sons, Ltd.    

年代:1986

数据来源: WILEY

摘要:

AbstractA stainless‐steel skin‐depot is discussed that may be used during short‐term studies to measure directly percutaneous absorption of radiolabeled, volatile chemicals through the skin of unanesthetized, unrestrained hairless mice. The skin‐depot is glued to the backs of the mice using cynaocrylate glue. The top portion of the depot contains activated charcoal (or other sorbent) to capture for analysis the portion of the test chemical which normally evaporates from the treatment site. This allows the use of metabolism cages for the capture of expired breath, as well as urine and feces. Thus, dermal absorption of the test chemical can be summed directly from the radioactivity found in excreta (urine and feces), the animal carcass (including the skin treatment site) and expired

ISSN:0260-437X    

DOI:10.1002/jat.2550060109

出版商:John Wiley&Sons, Ltd.    

年代:1986

数据来源: WILEY

摘要:

AbstractThe effects of prednisolone was investigated on the foetoxicity of cadmium. CFLP female mice were given a single i.p. dose of 2.5 mg cadmium (Cd) per kg body weight on day 5 or 9 of gestation. This treatment significantly decreased both the number of live foetuses and foetal weights on day 18 of gestation. Prednisolone (0.1 mg kg−1) given daily from the day of cadmium treatment death, prevented the effects of cadmium on foetal weights in both groups, and on the number of live foetuses when cadmium was given on day 9 of gestation. When Cd was given on day 13 of gestation similar treatment with prednisolone did not influence either litter size or the weights of 1‐day old p

ISSN:0260-437X    

DOI:10.1002/jat.2550060110

出版商:John Wiley&Sons, Ltd.    

年代:1986

数据来源: WILEY

摘要:

AbstractThe effect of methyl mercuric chloride on the activity of phospholipid synthesis of rat lymph node lymphocytes was compared with that of sulfhydryl inhibitors. Measurement of the radioactivity of [14C]oleic acid and [14C]acetate incorporated into lecithin of cells during short‐term incubation showed that all the inhibitors tested similarly reduced the incorporation. However, methyl mercuric chloride (MMC) was the strongest inhibitor, being effective at 4 μM, and causing more than 80% decrease at 20 μM. Inhibition by the sulfhydryl inhibitors, at less than 40 μM, ranked as follows:N‐ethylmaleimide>α‐chloroacetophenone>hydroquinone>iodoacetamide. MMC also obstructed the enhancement by phytohemagglutinin of [14C]oleic acid incorporation into lecithin. MMC was effective at 2 μM, while the other agents had little or no effect at this concentration. Further investigation suggested that inhibition of phospholipid synthesis did no depend on reduced incorporation of oleic acid into the cellular membrane but on decreased turnover of the fatty acid into phospholipids after the incorporation. The viability of lymphocytes incubated with the agents was measured by trypan blue dye‐exclusion test. More than 90% of the cells treated with MMC at a concentration as low as 20–40 μMdied, but the SH inhibitors, including NEM which greatly inhibited the phospholipid synthesis, produced few cell deaths at these concentrations. These observations show that the SH inhibitors affect enzymes in phospholipid synthesis, whereas MMC not only inhibits the enzymes

ISSN:0260-437X    

DOI:10.1002/jat.2550060111

出版商:John Wiley&Sons, Ltd.    

年代:1986

数据来源: WILEY