摘要:

AbstractA soil sample originating from an area of suspected chemical warfare activity was subjected to chemical analysis and bioassay. Sarin and several related compounds were confirmed in the soil by capillary column gas chromatography–mass spectrometry (GC–MS); however, the binding of these compounds to the soil hindered quantitation. The chemical results were then compared to those obtained by bioassay in primary cultures of chick embryo forebrain neurons. By comparing the sample's anticholinesterase activity against those of purified standards in chick embryo neuron cultures, a reasonable agreement was found between the chemical and bioassay semi‐quantitative estimates of sarin content in the soil extract. Furthermore, thein vitrosystem appears to offer a sensitive technique for the estimation of sarin remaining bound to the soil following solvent extraction as well as for an assessment of the potential toxicity of the contaminated soilin

ISSN:0260-437X    

DOI:10.1002/jat.2550120103

出版商:John Wiley&Sons, Ltd.    

年代:1992

数据来源: WILEY

摘要:

AbstractDoxazosin, an α‐adrenergic blocking agent, has a plasma half‐life in male rats of 1–2 h after i.v. administration. Plasma concentrations of doxazosin were measured in male rats receiving the drug mixed in the diet at dose levels from 5 to 40 mg kg−1. Samples taken at 4‐h intervals during the light (0700–1900) and dark phases revealed peak concentrations at 0400 which were only about three times higher than the trough concentrations observed ca. 12 h later. The 24‐h area under the curve (AUC) values increased disproportionately with dose and with age from 2 months up to 8 months of age; thereafter they were fairly stable to 24 months of age. This age‐related effect may have been due to a reduction in clearance and/or a change in the feeding pattern of the rats. Young rats consumed ca. 84% and old rats only 45% of their daily feed during the nocturnal (active) phase. Given the known diurnal rhythms in absorption, protein binding and enzyme metabolising activity, such a change in feeding pattern with age may have wider toxicokine

ISSN:0260-437X    

DOI:10.1002/jat.2550120104

出版商:John Wiley&Sons, Ltd.    

年代:1992

数据来源: WILEY

摘要:

AbstractHexachlorobenzene (HCB) is a known reproductive toxin. However, the full spectrum of its reproductive toxicity is unknown. Consequently, the effect of HCB on serum oestradiol (E2) and progesterone (P4) concentrations during the follicular (days 1–9), periovulatory (days 10–14) and luteal (days 15 to beginning of next menses) phases was investigated in the spontaneously cycling cynomolgus monkey. Adult female cynomolgus monkeys (n= 16) were randomly assigned to one of four treatment groups and orally dosed with gelatin capsules containing HCB (0.0, 0.1, 1.0 and 10.0 mg kg−1body wt. day−1) mixed with glucose. A 10‐week acclimitization phase was followed by 13 weeks of dosing. HCB induced a dose‐dependent suppression of serum P4concentrations during the luteal phase. However, circulating levels of P4were unaffected during the follicular and periovulatory phases of the menstrual cycle. Serum E2concentrations, body weight, menstrual cycle length and duration of menses were not affected by HCB treatment. The range of menstrual cycle length and duration range of menses, however, were broader in the highest dose group. We conclude that HCB interfers with mechanisms regulating ovarian steroidogenesis and suppresses P4levels during the luteal phase in the cynomo

ISSN:0260-437X    

DOI:10.1002/jat.2550120105

出版商:John Wiley&Sons, Ltd.    

年代:1992

数据来源: WILEY

摘要:

AbstractThis study investigated if the attenuation in cephaloridine toxicity associated with streptozotocin (STZ)‐induced diabetes can be attributed to a direct cellular effect. Comparative studies examined the direct toxicity of cephaloridine 14 days after (35 mg kg−1, i.p.) STZ or vehicle injection of male Fischer 344 (F344) rats.In vitrocephaloridine toxicity was assessed by measuring lipid peroxidation, renal gluconeogenesis and organic ion accumulation in renal cortical slices. Thein vitrotoxicity of cephaloridine was reduced in the diabetic group since lipid peroxidation was not increased following a 120‐min exposure to cephaloridine. This was in contrast to a concentration‐ and time‐dependent increase in lipid peroxidation in renal tissue derived from normoglycemic animals pre‐incubated with 0–5 mM cephaloridine. Renal gluconeogenesis was inhibited in a concentration‐dependent manner in the normoglycemic group following a 15–90‐min exposure to 0–5 mM cephaloridine. Pyruvate‐stimulated gluconeogenesis was diminished in the diabetic group only after a 90‐min preincubation. Renal cortical slice accumulation ofp‐aminohippurate (PAH) and tetraethylammonium (TEA) was decreased in the normoglycemic group. Accumulation of TEA, but not PAH, was decreased (P<0.05) in the diabetic group. These results indicate thatin vitrocephaloridine toxicity was attenua

ISSN:0260-437X    

DOI:10.1002/jat.2550120106

出版商:John Wiley&Sons, Ltd.    

年代:1992

数据来源: WILEY

摘要:

AbstractThe subacute effects of pyridostigmine bromide were investigated on the contractile properties of rat extensor digitorum longus (EDL) and diaphragm muscles. The cholinesterase inhibitor was delivered via subcutaneously implanted osmotic minipumps (Alzet®) at 9 μg h−1(low dose) or 60 μg h−1(high dose). Animals receiving high‐dose pyridostigmine pumps exhibited marked alterations in muscle properties within the first day of exposure that persisted for the remaining 13 days. With 0.1 Hz stimulation, EDL twitch tensions of treated animals were elevated relative to control. Repetitive stimulation at frequencies>1 Hz led a use‐dependent depression in the amplitude of successive twitches during the train. Recovery from pyridostigmine was essentially complete by 1 day of withdrawal. Rats implanted with low‐dose pyridostigmine pumps showed little or no alteration ofin vivotwitch tensions during the entire 14 days of treatment.Diaphragm and EDL muscles excised from pyridostigmine‐treated rats and testedin vitroshowed no significant alterations in twitch and tetanic tensions and displayed the same sensitivity as muscles of control animals to subsequent pyridostigmine exposures. In the presence of atropine, subacutely administered pyridostigmine protected rats from two LD50doses of the irreversible cholinesterase inhibitor, soman. In the absence of atropine, the LD50of soman was not altered by subacute pyridostig

ISSN:0260-437X    

DOI:10.1002/jat.2550120107

出版商:John Wiley&Sons, Ltd.    

年代:1992

数据来源: WILEY

摘要:

AbstractD‐Penicillamine (DPA) causes axial skeletal defects in rats and fetal lethality when given as 0.83% and 1.6% of the diet, but its mechanism of action on the axial skeleton is unknown. We have been using submerged fetal CD‐1 mouse limb‐bud organ cultures to evaluate the mechanisms of teratogenesis in the developing murine limb. Before attempting to evaluate thein vitroeffects of DPA, a dose response morphological teratology study was undertaken using CD‐1 mice to determine the effects of DPA on the mouse and determine the potential of using the mouse limb‐bud assay to investigate the terata produced by DPA. Groups (n= 8) of nulliparous pregnant mice (vaginal plug = day 0 of gestation) were dosed, via oral gavage, with 0, 250, 500, 1000 and 2000 mg kg−1DPA for the first 12 days of gestation. Body weights and food consumption were measured daily. On day 18, fetuses were removed by Caesarian section. Two‐thirds of the fetal skeletons were stained with alcian blue and alizarin red and then cleared and examined for defects. Soft‐tissue defects were examined in the remaining one‐third using a modification of the Wilson freehand technique. Maternal body weight gains were not different before day 12 of the experiment, but differed in the interval of day 13–18 (P= 0.004). No group differences were noted in male/female ratios, site of implantation, implantation numbers and number of fetuses. Decreased survivability was seen in the 2000 mg kg−1group. No treatment‐related defects were seen. As the main purpose of this experiment was to determine a dose at which limb defects occurred, the results indicate that the CD‐1 mouse does not appear to be a good model for DPA

ISSN:0260-437X    

DOI:10.1002/jat.2550120108

出版商:John Wiley&Sons, Ltd.    

年代:1992

数据来源: WILEY

摘要:

AbstractIn a few epidemiological studies on oil refinery workers, a slight excess of melanoma incidence has been reported. To see if this might be linked to exposure to polycyclic aromatic hydrocarbons (PAHs) contained in refinery streams, a review of animal data on the relationship between PAH exposure, UV light and melanoma induction has been carried out and compared with human data.This revealed that the highly carcinogenic PAH 7,12‐dimethylbenz[a]anthracene (DMBA) was capable of inducing melanomas in hamsters, mice and guinea pigs, but only under certain experimental conditions. Evidence suggested that other carcinogenic PAHs were unable to induce melanomas. As high dose levels of DMBA were generally required to produce melanomas, it was not considered that the amounts present in refinery streams would be sufficient to account for an increase in melanoma incidence in exposed workers.This conclusion was substantiated by the failure of petroleum‐derived complex hydrocarbon mixtures to produce melanomas in animals or man and by drawing attention to the absence of any association between melanoma incidence and the incidence of other skin cancers in man. If PAHs were responsible for an increase in melanoma incidence, an increase in other skin tumours would also be expected.It was concluded that animal data, taken in conjunction with other information, do not suggest that PAH exposure is likely to be the cause of any elevation in melanoma incidence in refinery workers. More detailed epidemiological findings would be required to establish whether any excess incidence of melanomas was due to sunlight, other risk factors or chance occurren

ISSN:0260-437X    

DOI:10.1002/jat.2550120109

出版商:John Wiley&Sons, Ltd.    

年代:1992

数据来源: WILEY

摘要:

AbstractWe conducted experiments to determine the effects of chloroquine (CQ) on the oestrus cycle and ovulation in 4‐day cyclic rats. There were two treatment groups. Group I animals had chloroquine phosphate (40 mg kg−1body wt.) administered intraperitoneally (i.p.) starting from dioestrus day 1, once a day, 5 days a week for 4 weeks. Oestrus smear was monitored by daily saline vaginal lavage. Control rats received an equal volume of physiological saline. All animals were sacrificed at the end of the 4th week of treatment.Group II animals also received chloroquine phosphate (40 mg kg−1body wt.) administered in a single dose at either 0900 h or 1800 h pro‐oestrus, and on the morning of oestrus the rats were killed. Trunk blood was collected in each group at the time of sacrifice, centrifuged and the serum stored for subsequent radioimmunoassay of luteinizing hormone (LH), follicle stimulating hormone (FSH) and oestrogen. The fallopian tube was dissected out and a search made for the ova.Results showed that administration of chloroquine altered the oestrus cycle (i.e. the rats showed a persistent dioestrus smear), lowered serum oestrogen and luteinizing hormone levels while serum FSH was unaltered, prevented the expected ovulation when injected at 0900 h pro‐oestrus and did not affect ovulation in rats injected at 1800 h pro‐oestrus. This study supports the notion that chloroquine has an adverse effect on hypothalamo‐pituitary ov

ISSN:0260-437X    

DOI:10.1002/jat.2550120110

出版商:John Wiley&Sons, Ltd.    

年代:1992

数据来源: WILEY

摘要:

AbstractThe Frog Embryo Teratogenesis Assay—Xenopus(FETAX) was used to assess the teratogenic potential of four solvents. Embryos of the South African clawed frog,Xenopus laevis, were exposed for 96 h to ethanol, dimethyl sulfoxide (DMSO), formamide or glycerol formal. Exposure groups were maintained using a static renewal system in which the exposure media were changed at 24‐h intervals. Survival was monitored at 24‐h intervals. Length, as an indicator of growth effects, and developmental malformations were determined at the end of the assay (96 h). Using this information, the 96‐h LC50, the 96‐h EC50(Malformation), and the no observable effect levels (NOELs) for mortality, malformation and length were determined for each solvent. The teratogenic index [TI = 96‐h LC50/96‐h EC50(Malformation)] also was calculated for each of the solvents. DMSO apeared to be the least toxic or teratogenic solvent examined, with a pooled LC50of 1.92%, a pooled EC50(Malformation) of 1.57% and TI values of 1.20 and 1.24 in replicate trials. Formamide appeared to be the most toxic solvent, with a pooled LC50of 1.04%. Data trends suggested that ethanol was the most teratogenic solvent tested, with a pooled EC50(Malformation) of 1.04% and TI values of 1.42 and 1.50. The results obtained in the present work for ethanol and DMSO were compared to previously published FETAX results for these two solvents. The present results are in close agreement with these results from other laboratories, thus providing further evidence supporting the interlaboratory reproducibility of

ISSN:0260-437X    

DOI:10.1002/jat.2550120111

出版商:John Wiley&Sons, Ltd.    

年代:1992

数据来源: WILEY

摘要:

AbstractThe objective of the present study was to determine if periods of exposure would modify the developmental toxicity of butyl benzyl phthalate (BBP). Pregnant Wistar rats were given BBP at a dose of 2.0% in the diet on days 0–20, days 0–7, days 7–16 or days 16–20 of pregnancy. Food consumption and body weight gain were decreased in the pregnant rats given BBP. All dams given BBP on days 0–20 exhibited complete resorption of all the implanted embryos. Post‐implantation loss in the pregnant rats given BBP on days 0–7 or 7–16 was higher than that in the control and pair‐fed pregnant rats. No increase in post‐implantation loss was found in the pregnant rats given BBP on days 16–20. Pre‐implantation loss in the BBP‐treated groups was comparable to the control and pair‐fed groups. Striking teratogenicity was detected in fetuses of the dams given BBP on days 7–16. Cleft palate and fusion of the sternebrae were predominantly observed. About 95% of the fetuses in this group had cleft palate. The incidence of malformations in this group was significantly and markedly higher than that in th

ISSN:0260-437X    

DOI:10.1002/jat.2550120112

出版商:John Wiley&Sons, Ltd.    

年代:1992

数据来源: WILEY