摘要:

A number of studies have reported on the inhibitory effects of organophosphorus pesticides (OPs) on the enzyme cholinesterase (ChE) among agricultural workers. With the increasing use of OPs, surveys of blood ChE activity on exposed workers may help to identify workers at greatest risk and to provide insight into the use history—e.g., mixing, loading, application, and harvesting—that might lead to a hazardous situation. Although it does appear that measurements of ChE acitivity are valuable in worker surveillance programs, it is difficult to interpret findings from various studies since they are dependent on the method of assay and the emphasis is usually placed on statistical tests (i.e., p values) that depend on the number of subjects studied. In the present paper a method is presented to compare ChE values reported in several studies utilizing various methods and units of measurement, and to assess the impact of OP exposure as a percentage of subjects with ChE values depressed below normal limits.

ISSN:0098-4108    

DOI:10.1080/15287398609530843

出版商:Taylor & Francis Group    

年代:1986

数据来源: Taylor

摘要:

The actions of different insecticides known to affect binding of ligands to y‐amino‐butyric acid (GABA) receptors were studied on the function of GABAAreceptors in rat brain as assayed by GABA‐induced36Cl‐influx into membrane microsacs. This flux was inhibited by the competitive antagonist bicuculline and the noncompetitive antagonist t‐butylbicyclophosphorothionate, and the GABA effect was potentiated by the tranquilizer flunitrazepam and the depressant pentobarbital, as expected for effects on a GABAAreceptor. The GABA‐induced36Cl‐flux was inhibited by several cyclo‐dienes and y‐hexachlorocyclohexane (γ‐BHC) with the following order of decreasing potency: endosu/fan I > endrin > endosulfan II > dieldrin > heptachlor epoxide > y‐BHC > heptachlor. The noninsecticidal β‐BHC had no effect, while the IC 50 values for y‐BHC and endrin were 7 and 0.2 μM, respectively. The four pyrethroids tested also inhibited the GABA‐induced36Cl‐flux with the following decreasing potencies: 1R,cis,αS‐cypermethrin > 1R, trans,αS‐cypermethrin > fluvalinate > allethrin. Aver‐mectin B1awas the only insecticide tested that, in the absence of GABA, stimulated36Cl‐flux in a dose‐dependent manner, and this flux was inhibited by bicuculline. The stereospecific inhibition of the GABA‐induced36Cl‐influx by the cyclodienes and γ‐BHC supports previously published data on their binding to mammalian brain ABAAreceptor and suggests that these insecticides inhibit this receptor's function. It is also suggested that type II pyrethroids are potent inhibitors of the same receptor. However, avermectin B1aappears to act as a partial agonist of CABAAreceptors.

ISSN:0098-4108    

DOI:10.1080/15287398609530844

出版商:Taylor & Francis Group    

年代:1986

数据来源: Taylor

摘要:

Long‐lasting organic damage has been reported following in utero exposure to certain environmental or therapeutic agents. The sensitivity of the developing immune system to chemical insult during organogenesis or histogenesis was evaluated in mice employing the known immunosuppressive agent cyclophosphamide (CY). Experiments were conducted employing one of the following treatment regimens: (1) 7 μg/g • d intravenously on d 9–12 or 14–17 of gestation; (2) 5 μg/g intravenously on 12 of gestation; (3) 1, 2.5, or 5 μg/g • d intraperitoneally on d 12 of gestation; or (4) 5, 10, or 20 μg/g intraperitoneally on d 17 of gestation. There were no surviving pups born to mothers administered CY by schedule 2; otherwise, numbers of surviving offspring were not affected by drug treatment, and no gross terata were observed. Employing this variety of exposure protocols, consistent enhancement or suppression of cell‐mediated or humoral immune function was not observed in offspring of treated dams. Reduced body weight in 5‐ and 8‐wk‐old progeny was noted after exposure to 20 μg/g on gestational d 17. Increased in vitro B‐lymphocyte blastogenic response to lipopolysaccharide occurred in 5‐wk‐old animals, and production of antibody to sheep erythrocytes was increased in 8‐wk‐old offspring exposed to CY at 20 μg/g on d 17 of gestation. The T‐lymphocyte parameters were relatively unaffected by in utero exposure to CY, suggesting either that cell‐mediated immune function was not affected by treatment or that homeostasis was restored prior to immunologic evaluation of offspring.

ISSN:0098-4108    

DOI:10.1080/15287398609530845

出版商:Taylor & Francis Group    

年代:1986

数据来源: Taylor

摘要:

Protection against the lethal effects of ethanol at 4.5 g/kg administered acutely was maximal when zinc was administered 60 min prior to ethanol. The timing of ethanol administration corresponded with elevated plasma levels of absorbed zinc. Protection was inversely related to the dose of zinc employed, as 0.5 μ.mol provided greater protection than 1.0 μmol, which provided greater protection than 2.0 μmol. Protection against ethanol lethality was greater if zinc was administered 60 min prior to each injection of ethanol. Acute zinc pretreatment did not alter the activity of liver alcohol dehydrogenase (ADH), nor did it alter the blood clearance of ethanol. Chronic zinc administration as ZnCl2, 100 μg/ml in the drinking water for 30 d, produced a 25% decrease in hepatic ADH activity, which was accompanied by a similar decrease in the intravascular clearance of ethanol.

ISSN:0098-4108    

DOI:10.1080/15287398609530846

出版商:Taylor & Francis Group    

年代:1986

数据来源: Taylor

摘要:

Sex differences in mercury distribution and excretion after single administration of methylmercury chloride (MMC, 5 mg/kg) were studied in mice. A sex difference in urinary mercury excretion was found in sexually mature mice (age of 7 wk) of C57BL/ 6N and BALB/cA strains. Males showed higher mercury levels in urine than females, though no significant difference was found in fecal mercury levels 24 h post exposure to MMC. The higher urinary excretion rates in males accounted for significant lowering of mercury levels in the brain, liver, and blood, but not in the kidney, which showed higher values. At 5 min, however, these sex difference was found only in the kidney, showing higher levels in males. Changes in mercury distribution with time were studied in C57BL/6N mice. The brain mercury increased in both sexes up to 3 d, and decreased only in males on d 5. Liver and blood mercury decreased with time in both sexes, and these were constantly higher in females than in males. Renal mercury in males decreased to similar levels to females on d 3. The sex differences at various ages were studied with C57BL/6N mice 24 h after dosing. Two‐week‐old mice, the youngest in this study, did not show significant sex difference in the mercury distribution and excretion, and their urinary mercury levels were much lower as compared to the older mice. Then, urinary mercury excretion in both sexes increased at 4 wk of age and then decreased at 45 wk of age. At 4, 7, 10, and 45 wk of age, males showed higher urinary mercury levels than females. These studies demonstrated sex and age differences in the mercury distribution and urinary excretion after methylmercury administration in mice. From these findings, it has been suggested that urinary mercury excretion may be related to sex hormones, especially androgens.

ISSN:0098-4108    

DOI:10.1080/15287398609530847

出版商:Taylor & Francis Group    

年代:1986

数据来源: Taylor

摘要:

Lead nephropathy, characterized functionally by depression of effective renal plasma flow (ERPF), glomerular filtration rate (CFR), and maximum glucose reabsorption rate, is associated with prolonged occupational exposure to lead. Production of comparable lead‐related renal functional deficits in rats has been difficult to achieve. We have examined in rats some of the factors that might be expected to influence the development of lead‐induced renal functional damage, using CFR (as inulin clearance), ERPF (as para‐aminohippurate clearance), and maximum glucose reabsorption rate as indices of renal functional competence. Although lead produces a significant weight loss, this can be accounted for by reduced food intake and is not associated with reduction in renal function. Even exposure to large amounts of lead in conjunction with other factors, such as controlled diet (NIH‐07 and AIN‐76) and early age of initial exposure, that might have been expected to increase the rats’ susceptibility has not resulted in the development of renal functional deficits. It is unlikely that the rat can be successfully exploited as an animal model of human lead nephropathy with accompanying functional deficits.

ISSN:0098-4108    

DOI:10.1080/15287398609530848

出版商:Taylor & Francis Group    

年代:1986

数据来源: Taylor

摘要:

Groups of 30 male and 30 female Fischer‐344 rats were fed dietary concentrations of 0. 30, 100, 300, 3000, or 10,000 ppm decarboxyfenvalerate (DC‐FEN) for up to 13 wk. An interim kill of 10 rats/sex · group was performed at 7 wk. Following 7 or 13 wk of dietary treatment, groups of rats were necropsied, which included evaluation of he‐mocellular, hemochemical, and uretic parameters, selected absolute and relative organ weights, and macroscopic and microscopic observations. DC‐FEN did not affect mortality. Body weight was decreased in male rats fed 10,000 ppm DC‐FEN. Statistically and toxicologically significant differences in clinicopathologic parameters were observed at either the highest or two highest exposure levels. Some statistically significant differences were noted in some hemocellular and/or hemochemical parameters at either 100 or 300 ppm. These subtle changes were either not dose‐related, inconsistent, or not of sufficient difference to be determined to have biological significance. Absolute and relative liver weights of male and female rats fed ≥300 ppm DC‐FEN were all higher than control values except for absolute weights in female rats (300 ppm) at the interim kill. Consistent significant increases in absolute or relative kidney weights were observed in male and female rats fed 3000 or 10,000 ppm DC‐FEN. Other statistically significant differences in absolute and/or relative organ weights were seen primarily where the higher doses had caused decreased carcass weight. Macroscopic treatment‐related liver enlargement (hepatomegaly) was observed in male and female rats fed 3000 or 10,000 ppm DC‐FEN. Only one female rat fed 300 ppm DC‐FEN had hepatomegaly at the terminal kill. Significant treatment‐related microscopic effects were limited to glomerulonephrosis in male and female rats fed 10,000 ppm and hepatocellular hypertrophy and other associated liver changes in male and female rats fed 3000 or 10,000 ppm DC‐FEN. Liver effects at doses <3000 ppm were indicative of a physiologic adaptive response and were not toxicologically significant. Therefore, the biologically significant no‐effect level was 300 ppm.

ISSN:0098-4108    

DOI:10.1080/15287398609530849

出版商:Taylor & Francis Group    

年代:1986

数据来源: Taylor

摘要:

Early transient incapacitation (ETI) is the complete cessation of performance during the first 30 min after radiation exposure, and performance decrement (PD) is a reduction in performance at the same time. Supralethal doses of radiation have been shown to produce a marked decrease in regional cerebral blood flow in primates concurrent with systemic hypotension and a dramatic release of mast‐eel! histamine. In an attempt to elucidate mechanisms underlying the radiation‐induced ETI/PD phenomena and the postradiation decrease in cerebral blood flow, primates were given the mast‐cell stabilizers disodium cromoglycate (DSCC) or BRL 22321 (Beecham Pharmaceuticals, Research Division) before exposure to 100 Cy whole‐body gamma radiation. Hypothalamic and cortical blood flows were measured by hydrogen clearance, before and after radiation exposure. Systemic blood pressures were determined simultaneously. The data indicated that DSCC was successful in diminishing postradiation decrease in cerebral blood flow. Irradiated animals pretreated with DSCC, showed only a 10% decrease in hypothalamic blood flow 60 min postradiation, while untreated, irradiated animals showed a 57% decrease. The cortical blood flow of DSCC treated, irradiated animals showed a triphasic response, with a decrease of 38% at 10 min postradiation, then a rise to 1% below baseline at 20 min, followed by a fall to 42% below baseline by 50 min postradiation. In contrast, the untreated, irradiated animals showed a steady decrease in cortical blood flow to 79% below baseline by 50 min postradiation. There was no significant difference in blood‐pressure response between the treated and untreated, irradiated animals. Systemic blood pressure showed a 60% decrease at 10 min postradiation, falling to a 71% decrease by 60 min. The effects of BRL 22321 in altering postradiation blood flow in the cerebral cortex and hypothalamus were intermediate between the irradiated controls and those pretreated with DSCC, but were not considered to be significant at the concentration employed. The overall results of this study indicate that the postradiation decrease in regional cerebral blood flow may be partially alleviated by treatment with a mast‐cell stabilizer.

ISSN:0098-4108    

DOI:10.1080/15287398609530850

出版商:Taylor & Francis Group    

年代:1986

数据来源: Taylor

摘要:

Behavioral responses to atropine in rats exposed to the potent anticholinesterase agents Soman and Sarin were studied. Atropine itself produced limb‐shakes and certain stereotyped activities, in a dose‐dependent manner. The neurotoxicity elicited by Soman and Sarin was antagonized by atropine, while at the same time the responses induced by the latter were attenuated. In contrast, where rats were challenged with atropine 6–72 h after giving single doses of Soman or Sarin, the limb‐shake myoclonus was markedly enhanced. The atropine‐induced stereotypies were not, however, significantly affected, except for an increase seen at 24 h after Sarin treatment. Repeated treatment with Soman for 3 wk also led to similar supersensiti‐vity of atropine‐induced responses. The peripheral muscarinic receptor antagonist, methylatropine, produced no such hyperactivity on its own or at any time after anticholinesterase exposure. The rapid occurrence of hypersensitivity to antimuscarinic compounds following exposure to these anticholinesterases, therefore, suggests the need for observation of subjects who are poisoned with such agents and treated with antimuscarinics, for adverse reactions such as myoclonus during the critically sensitive period, especially if repeated antimuscarinic therapy is carried out.

ISSN:0098-4108    

DOI:10.1080/15287398609530851

出版商:Taylor & Francis Group    

年代:1986

数据来源: Taylor

摘要:

The arabinose‐resistant and Ames assay systems of Salmonella typhimurium were used to evaluate the mutagenic potential of azo dyes and their aromatic amine reduction products. Azo dyes, namely direct black 38, direct blue 75, and direct red 2, were mutagenic in the arabinose‐resistant and Ames assays with both hamster and rat liver S9 activation. Both assays gave relatively higher mutagenic responses with hamster S9. Reduction products of these dyes, namely benzidine, o‐dianisidine, and o‐tolidine, were mutagenic in the Ames assay. Benzidine was weakly mutagenic and o‐dianisidine and o‐tolidine were nonmutagenic in the arabinose‐resistant assay. These results indicate that both arabinose‐resistant tester SV50 and Ames tester TA98 were sensitive in detecting mutagenicity of azo dyes. The use of the standard plate protocol with Ames tester TA98 is more efficient than the modified azo dye protocol in detecting mutagenicity of aromatic amine reduction products. Additional modifications in either the standard plate or modified azo dye protocols may improve detection of mutagenicity of these compounds in the arabinose‐resistant assay system.

ISSN:0098-4108    

DOI:10.1080/15287398609530852

出版商:Taylor & Francis Group    

年代:1986

数据来源: Taylor