摘要:

AbstractThe N‐phenylsuccinimides are being evaluated as experimental agricultural fungicides. The purpose of this study was to examine the relationship between the electron withdrawing or electron donating properties of phenyl ring substituents on meta‐substituted N‐phenylsuccinimide (NPS) derivatives and the nephrotoxic potential of the corresponding fungicides. Male Fischer 344 rats were administered a single intraperitoneal injection of a succinimide (0.4 or 1.0 mmol/kg) or vehicle (sesame oil, 2.5 ml/kg), and renal function monitored at 24 and 48 hr. Non‐halogen‐substituted NPS derivatives produced little evidence of nephrotoxicity at the doses used in this study. Among the meta‐halogen derivatives of NPS, N‐(3‐chlorophenyl)succinimide (NCPS) was the most nephrotoxic. NCPS‐induced nephrotoxicity was characterized by diuresis, proteinuria, hematuria, elevated blood urea nitrogen (BUN) concentration, decreased organic ion accumulation and proximal tubular necrosis. However, all renal effects produced by NCPS were mild to moderate. These results suggest that the electron withdrawing or donating property of a functional group is not a good predictor of the nephrotoxic potential for the corresponding fungicide. In addition, lipophilicity did not correlate with nephrotoxic potential for the meta‐substituted NPS derivatives eval

ISSN:0260-437X    

DOI:10.1002/jat.2550070302

出版商:John Wiley&Sons, Ltd.    

年代:1987

数据来源: WILEY

摘要:

AbstractAlcide Allay® gel, a highly effective germicidal compound, was evaluated for teratogenic potential in rabbits. Pregnant rabbits were administered 2 g/kg Allay® get (containing either of two concentrations of sodium chlorite as active ingredient) or placebo topically on days 6–18 of gestation. Moderate to severe erythema was recorded in the high‐dose gel group on day 11 (Draize score = 3.5). By day 18, the skin of all rabbits in the high dose treatment group appeared normal. Decreased maternal body weight gain was observed in the low dose and placebo gel groups. Fetal weights and lengths were significantly reduced in all gel groups. There was some incidence of skeletal anomalies in all gel treated groups, however, these incidences were not statistically different from the control group. The commonly occurring skeletal defects were incomplete ossification of skull bones, small or missing sternebrae, and extra ribs. The incidence of visceral abnormalities in all gel groups was not statistically different from control animals. Visceral anomalies included heart displacement, fusion or serration of the liver, and kidney displacement. Alcide Allay® gel at 2 g/kg was non‐teratogenic to rabbit

ISSN:0260-437X    

DOI:10.1002/jat.2550070303

出版商:John Wiley&Sons, Ltd.    

年代:1987

数据来源: WILEY

摘要:

AbstractFemale Swiss mice were exposed to lead in the drinking water at concentrations ranging from 0 to 1000 ppm for 105 or 280 day periods of time. The effect of lead on urethan‐induced pulmonary adenoma formation was evaluated in the 105 day study. Urethan‐induced sleeping times observed following ip injection of urethan (1.5 mg/g) after 3 weeks of lead exposure were not altered by lead indicating that lead did not affect the rate of urethan elimination. Pulmonary adenoma formation was evaluated 84 days later. Lead exposure did not affect the number of tumors produced, nor did it alter the mean tumor diameter in the lead treatment groups. This suggests that the immunosuppressive activity of lead does not enhance urethan‐induced adenoma formation. In the 280 day study, the incidence of spontaneous murine lymphocytic leukemia was evaluated. Leukemia was observed in all treatment groups. Mortality was greater in the lead‐exposed mice. Mice exposed to 50 or 1000 ppm lead had 41.6% and 58.3% more deaths associated with the virus. The median survival time was also reduced in the lead‐exposed mice. It appears that the immunosuppressive effects of lead allow for increased expression of the murine lymphocytic leuke

ISSN:0260-437X    

DOI:10.1002/jat.2550070304

出版商:John Wiley&Sons, Ltd.    

年代:1987

数据来源: WILEY

摘要:

AbstractCovalent binding of reactive metabolites of14CCI4were found 1 or 3 h after treatment with the solvent in the lipid and protein fractions of highly purified liver mitochondrial of rats. Most of the label was found in the phospholipid (PL) fraction, much less in cholesterol esters (ChE), and only minor quantities in other lipids. The reactive metabolites of14CCI4activated by isolated mitochondria interact mostly with ChE and far less with PL and other fractions. Bothin vivoandin vitrocovalent binding to PL is decreasing in the following order: phosphatidylethanolamine>diphosphatidylglycerol>phosphatidylcholine>sphingomyelin>lysophosphatidyl choline. No evidence of lipid peroxidation was found in liver mitochondrial lipids in the first 6 h and only a slight tendency of decrease in arachidonic acid concentration at 24 h. The incorporation of [14C] leucine in mitochondrial, microsomal or cytosolic proteins decreased as early as 1 h after treatment. These results, in agreement with previous reports suggest the existence of multiple sites in liver cells for the activation of CCI4. The transport of altered phospholipids and proteins and the inhibition of protein synthesis might contribute to the propagation of damage from the endoplasmic reticulum to other organelles.

ISSN:0260-437X    

DOI:10.1002/jat.2550070305

出版商:John Wiley&Sons, Ltd.    

年代:1987

数据来源: WILEY

摘要:

AbstractThree groups, each of 18 lambs were grazed during autumn in paddocks which had been divided longitudinally by temporary fencing to give twofold differences in grazing intensity between the groups. During the period when spore numbers were elevated the high grazing pressure (HGP) group lost some body weight (−34 g/day). The low grazing pressure (LGP) group gained +90 g/day and the intermediate grazing pressure (IGP) group gained weight slightly (+14 g/day). There were two spore rises during the experimental grazing period, a minor and a major rise. Peak pasture spore counts were 88 000, 130 000 and 282 000 spores/g grass for the LGP, IGP and HGP groups respectively. These were reflected in the peak rumen content counts which were 6640, 17 050 and 24 470 spores/g and the faecal peak counts which were 141 400, 330 800 and 568 200 spores/g for the LGP, IGP and HGP groups respectively. Liver injury scores were 0.9, 2.6 and 1.7 and peak mean serum GGT levels were 139, 312 and 220 U/I for the LGP, IGP and HGP groups respectively. The greater liver injury in the IGP groups was considered due to the greater total consumption of spores caused by the combination of pasture spore concentration and dry matter intak

ISSN:0260-437X    

DOI:10.1002/jat.2550070306

出版商:John Wiley&Sons, Ltd.    

年代:1987

数据来源: WILEY

摘要:

AbstractTo examine the effect of the exposure pattern on the inhalation toxicity of carbon tetrachloride (CCI4) two 4‐week inhalation studies with this compound were carried out in male rats at basic exposure concentrations of 63 and 80 ppm and basic exposure periods of 6 hours per day, 5 days per week. The two main variables studied were interruption of the daily 6‐hour exposures by 1.5 hours (2 × 3‐hour exposures with a non‐exposure interval of 1.5 hour), and peak loads of 5–7 times the basic concentration with or without 1.5‐hour interruption of the daily 6‐hour exposures. Adverse effects of CCI4included abnormal activities of several enzymes in serum and liver, decreased quantity of microsomal proteins in the liver, increased relative liver weight, and hydropic and fatty degeneration of hepatocytes. As compared with uninterrupted, interrupted exposures increased more the activities of glutamic oxalacetic and glutamic pyruvic transaminase in serum; peak exposures only slightly affected these enzyme activities. Uninterrupted exposures caused less severe fat accumulation in and hydropic degeneration of liver cells than interrupted exposures with or without peak loads. In addition, uninterrupted exposure to 63 ppm CCI4with peak loads resulted in more severe hydropic liver degeneration than uninterrupted exposure to the same concentration without peak loads. It was concluded that interruption of the daily 6‐hour exposures by 1.5 hour did not result in less severe but rather in slightly more severe hepatotoxicity, and peak loads superimposed on a fixed concentration only slightly aggravated the toxic effects of

ISSN:0260-437X    

DOI:10.1002/jat.2550070307

出版商:John Wiley&Sons, Ltd.    

年代:1987

数据来源: WILEY

摘要:

AbstractThe effects of taurine, its initial precursorL‐cysteine, and the major metabolite taurocholic acid on two ethanol‐mediated responses in rodents were studied. Administration of a single dose of taurocholic acid reduced voluntary intake of a 5% ethanol solution by the rat. In the mouse, taurine had no effect on alcohol drinking or on the central depressant action of ethanol, as measured by the duration of ET‐produced loss of the righting reflex. Likewise, taurocholic acid andL‐cysteine did not significantly influence the duration of ethanol‐narcosis time from control mice. Also studied were the effects of acute and short‐term (7 or 10 days) administration of these compounds on hepatic ethanol and acetaldehyde metabolizing enzymes. Short‐term administration of an equimolar concentration of taurine enhanced endogenous NADP‐linked rat liver aldehyde dehydrogenase (L‐ALDH) as contrasted with inhibition of the same enzyme byL‐cysteine. Short‐term (7 days) treatment withL‐cysteine induced rat liver NAD‐linked ALDH, but acute (single dose) treatment did not. Taurocholic acid short‐term administration caused an induction and an inhibition of endogenous mouse liver alcohol dehydrogenase (L‐ADH) andL‐ALDH, respectively. The results suggest that taurine does not directly interact with ethanol. However, its major metabolite, taurocholic acid, may cause rapid metabolic conversion of ethanol to acetaldehyde by induction ofL‐ADH, which is then slowly metabolized due to a concomitant inhibition ofL‐ALDH. This may cause a build‐up of acetaldehyde and thereby produce adverse reactions similar to those resulting from the

ISSN:0260-437X    

DOI:10.1002/jat.2550070308

出版商:John Wiley&Sons, Ltd.    

年代:1987

数据来源: WILEY

摘要:

AbstractThe effects on embryonic cardiac function of caffeine administration (two non‐cardioteratogenic and two cardioteratogenic doses) to Hamburger–Hamilton stage 19 (3–3 1/2 days of incubation) chick embryos were investigated. Using microcinephotoanalysis, we have determined that caffeine (1.0–4.7 mg/egg), within the initial three hours after treatment, produced a dose‐dependent decrease in end diastolic volume, stroke volume, cardiac output, and ejection fraction. These effects were sustained for a longer period of time following dosing at a cardioteratogenic level (3.5–4.7 mg/egg). Caffeine (1.0–4.7 mg/egg) also increased cardiac rate with a maximum increase of 30% seen 60 minutes after treatment with doses of 2.7 mg and 3.5 mg. However, the increase in cardiac rate was not related to dose. At 20 hours after treatment, caffeine increased stroke volume, ejection fraction and cardiac output relative to the controls. End‐diastolic volume and cardiac rate were not changed. These results are evidence for a biphasic effect of cardioteratogenic dosing with caffeine during the first 20 hours after treatment—initially a sustained decrease in cardiac output, suggesting decreased flow through the embryonic heart, followed by an increase in ejection fraction, suggesting increased

ISSN:0260-437X    

DOI:10.1002/jat.2550070309

出版商:John Wiley&Sons, Ltd.    

年代:1987

数据来源: WILEY

摘要:

AbstractGuinea pigs were exposed to 400 ppm or 5500 ppm of isopropyl alcohol (IPA) for 24 successive hours, and then middle ear mucosal samples in both proximal and distal sites to the eustachian tube were obtained for functional and morphological examinations. The ciliary activity was examined according to the photoelectric method of Ohashi and Nakai. The morphology of the middle ear lining was examined by transmission electron microscopy. The results showed that IPA at the allowable level of 400 ppm has an acute effect on the mucociliary system of the middle ear mucosa. Recovery from damage occurs within two weeks. At higher levels of exposure to IPA (more than 10 times the allowable level) moderate deterioration of the ciliary activity and severe damage of epithelial cells were observed and recovery within two weeks was not seen. It is concluded that IPA at the allowable level of 400 ppm does not cause significant middle ear disorders, but workers exposed to higher levels of IPA should be given careful otolaryngological examinations and follow‐up observation

ISSN:0260-437X    

DOI:10.1002/jat.2550070310

出版商:John Wiley&Sons, Ltd.    

年代:1987

数据来源: WILEY

摘要:

AbstractThe influence ofin vivoadministration of detergents on the hepatic microsomal cytochrome P‐450 system was studied in rat. Male Wistar rats were administered detergents, Emulgen 913 (50 mg or 100 mg kg−1of body weight (B.W.)), or sodium dodecylsulfate (SDS, 25 mg or 50 mg kg−1of B.W.) intraperitoneally once a day for 3 days. Cytochrome P‐450 content in liver microsomes was significantly decreased to 85% and 73% of control by the administration of 50 mg or 100 mg Emulgen, respectively, but the microsomal protein concentration was not changed by these administrations. The content of cytochrome P‐450 was also reduced to 76% and 70% of control by the administration of 25 mg or 50 mg SDS/kg of B.W., respectively. The total hydroxylation activity (the sum of ω‐ and (ω ‐ 1)‐hydroxylase activity) of laurate almost paralleled the decrease in cytochrome P‐450 in detergent‐treated rats. However, the ω/ω‐1‐hydroxylation ratio was not changed. These results suggest that the administration of these detergents lowered the level of cytochrome P‐450 species catalyzing ω‐ and (ω ‐ 1)‐hydroxylation of laurate to a similar extent. On the other hand, aminopyrineN‐ andp‐nitroanisoleO‐demethylation activities in Emulgen 913‐treated rats was decreased while those in SDS‐treated rats did not change, though the content of cytochrome P‐450 was decreased by both administrations. Thus, it was demonstrated that the livers of rats respo

ISSN:0260-437X    

DOI:10.1002/jat.2550070311

出版商:John Wiley&Sons, Ltd.    

年代:1987

数据来源: WILEY