摘要:

Survival rates, changes in body weight, gait/ataxia scores, and neuropathological lesions were compared between adult Long‐Evans rats and adult White Leghorn hens given equivalent dosages of the peripheral neurotoxicants acrylamide and 2,5‐hexanedione (12, 25, and 50 mg/kg acrylamide 3 times per week; or 75, 105, 150, 225, or 350 mg 2,5‐hexanedione/kg/d, with hens receiving the lowest 3 dosages of 2,5‐hexanedione and rats receiving the highest 3 dosages of this test compound). All rats survived the 3‐wk acrylamide study period, although those given 50 mg/kg did not gain weight and showed alterations in gait. Hens given 50 mg/kg acrylamide were moribund by 2 wk and were sacrificed before the end of the 3‐wk study period. By this time they had lost 29 ± 3% of their body weight, but none showed significant renal or hepatic lesions on necropsy. Hens given all doses of acrylamide showed dose‐related ataxia, weakness, and depression. Gait changes were seen in rats given the high dose of acrylamide for the 3‐wk test period. Neuropathological studies revealed that both rats and hens given acrylamide had distal myelinated fibers with dose‐related neurofilament‐rich axonal swelling and Wallerian‐like degeneration, better developed in the rodents. In addition, high‐dose acrylamide rats had recent necrosis of cerebellar Purkinje cells. Deaths occurred in all groups of hens given 2,5‐hexanedione (75, 105, or 150 mg/kg) before sacrifice at 3 wk, but all rats given 2,5‐hexanedione (150, 225, 350 mg/kg) survived a 4‐wk study period, even though gait changes were evident in the 225 and 350 mg/kg dosage groups by 3 wk. Neither hens nor rats dosed with 2,5‐hexanedione for 3 wk had significant neuropathic lesions, although the bens showed dose‐related ataxia, weakness, and depression. Early neurofilamentous intraaxonal masses in distal levels of selected myelinated tracts were seen in rats given the high dose of 2,5‐hexanedione for an additional week. These studies suggest that hens are sensitive to acrylamide and 2,5‐hexanedione toxicities, and that the rat is more likely than the hen to develop neuropathological lesions.

ISSN:0098-4108    

DOI:10.1080/15287399309531762

出版商:Taylor & Francis Group    

年代:1993

数据来源: Taylor

摘要:

The effects of acrylamide on fast axonal transport have been measured primarily using the indirect methods of isotope or enzyme accumulation. We report the first direct evaluation of the effects of subchronic acrylamide dosing (150, 300, or 500 mg/kg total dose, i.e., 50 mg/kg, 2x/wk, for 1.5, 3, 5 wk, respectively) on the fast axonal transport motility machinery itself using video‐enhanced differential interference contrast optics with digital image processing and computer analysis. Four principle observations were made: (1) Rapid antero‐grade transport was not affected at any dosage level within 1 wk after cessation of dosing. (2) A high cumulative dosage (500 mg/kg total) of acrylamide or bisacrylamide produced approximately 7–18% decrease in the rate of retrograde transport in both myelinated and unmyelinated axons. (3) Lower dosages of acrylamide (150 or 300 mg/kg total) produced an increase in retrograde transport rates in myelinated axons only. (4) During the “recovery” phase for the 500 mg/kg acrylamide animals (i.e., 3 or 5 wk after the last dosage of acrylamide) the rate of anterograde transport in the myelinated axons was decreased at 3 wk but not at 5 wk, and the rate of retrograde transport in the myelinated axons returned to control levels while the retrograde transport in the unmyelinated axons continued at abnormally slow speeds. The application of this new technique to evaluate the neurotoxic effects of acrylamide provides evidence of dynamic changes in the axonal transport motility machinery itself and differential effects on myelinated versus unmyelinated fibers.

ISSN:0098-4108    

DOI:10.1080/15287399309531763

出版商:Taylor & Francis Group    

年代:1993

数据来源: Taylor

摘要:

Acrylamide (2‐propenamide) monomer produces central‐peripheral distal axonopathy in humans and some animal species. Its neurotoxicity is characterized by abnormal sensation, decreased motor strength, and ataxia. Acrylamide forms adducts with glutathione, proteins, and DNA. Recent studies demonstrated that acrylamide is metabolized to its epoxide, glycidamide (2,3‐epoxy‐1‐propanamide). We studied the neurotoxicity potential of glycidamide in male Sprague‐Dawley rats. Animals (groups of 6) were injected ip daily with either aqueous acrylamide or glycidamide at an acrylamide‐equivalent dose of 50 mg/kg (0.70 mmol/kg). Both treatments resulted initially in the rats circling, which was followed by the onset of ataxia at 7–9 d and hindlimb paralysis at 12–14 d. Treated animals showed muscle wasting. At termination, acrylamide‐ and glycidamide‐treated rats weighed 105% and 86% of initial weight, respectively, compared to 145% for controls. Animals were anesthetized and perfused with 10% neutral phosphate‐buffered formalin 12 or 14 d after beginning of treatment. Both treatment groups exhibited similar neuropathologic changes in the central and peripheral nervous systems. More severe lesions were produced by glycidamide. A marked increase in the number of affected Purkinje cells in the cerebellum, which exhibited changes ranging from pyknosis to cell death, were present. The brainstem exhibited axonal degeneration with chromatolytic necrosis in midbrain medial and lateral reticular nuclei. The spinal cord was characterized by spongy form changes with vacuoles of different sizes in various levels. These results suggest that glycidamide is an active neurotoxic metabolite of acrylamide.

ISSN:0098-4108    

DOI:10.1080/15287399309531764

出版商:Taylor & Francis Group    

年代:1993

数据来源: Taylor

摘要:

Diethyldithiocarbamate (DDC) was used to treat the neuroblastoma cell line Neuro‐2a. Cell injury caused by DDC affects the calcium‐binding protein calmodulin (CaM) and alters copper homeostasis in these cells. Neuro‐2a cells were treated with 1 × 10−5M DDC for 1 h and were harvested at various time points over a 24‐h period. Light microscopy of control cells showed CaM deposited around the cell periphery and along the neuritic processes. Treated cells showed the same distribution until 3 h after treatment. Electron microscopy showed CaM deposited around the cell periphery and within the cytoplasm and nucleus of control cells. Treated cells showed a time‐dependent localization of CaM in relation to cellular disorganization. Staining of electrophoretic transfers by ProtoGold showed that CaM was present in all control samples and treated samples through 6 h. Atomic absorption spectrophotometry showed no difference in calcium levels between control and treated samples, but copper levels were significantly elevated. This study indicated that degenerative changes induced by DDC altered calmodulin levels. These changes may have been caused by elevated copper content within the cells and subsequent cell injury.

ISSN:0098-4108    

DOI:10.1080/15287399309531765

出版商:Taylor & Francis Group    

年代:1993

数据来源: Taylor

摘要:

Residents adjoining a die‐casting plant bad excessive headaches, numbness of hands and feet, dizziness, blurred vision, staggering, sweating, abnormal heart rhythm, and depression, which led to measurements of neurobehavioral performance, affective status, and the frequency of symptoms. They had all been exposed via well water and proximity to the plant to volatile organic chemicals (VOC) and to polychlorinated biphenyls (PCBs). The 117 exposed women and men and 46 unexposed referents were studied together for simple and choice visual reaction time, body sway speed, blink reflex latency, color discrimination, Culture Fair (a nonverbal nonarithmetic intelligence test), recall of stories, figures, and numbers, cognitive and psychomotor control (slotted pegboard and trail making A and B), long‐term memory, profile of mood states (POMS), and scores and frequencies of 34 symptoms. Choice reaction time, sway speed, and blink latency were impaired in both sexes of the exposed group and trail making B was impaired in exposed women. The POMS scores and frequencies of 30 of 34 symptoms were elevated in both sexes, compared to referents. Recall, long‐term memory, psychomotor speed, and other cognitive function tests were reduced in exposed subjects and in the referents as compared to national referents. Neurophysiological impairment, and cognitive and psychomotor dysfunction and affective disorders, especially depression and excessive frequency of symptoms, were associated with the use of wells contaminated with VOCs, TCE and PCBs.

ISSN:0098-4108    

DOI:10.1080/15287399309531766

出版商:Taylor & Francis Group    

年代:1993

数据来源: Taylor

摘要:

Separate inhalation‐chamber studies were conducted to assess acute/subacute food intake (g), water intake (ml), and body weight (g) effects of four whole‐body phosphoric‐acids‐aerosol exposures in black‐tailed prairie dogs (Cynowys ludovicianus,); subacute effects of two exposures were studied in rock doves (Columba livia). A 95% red phosphorus/5% butyl rubber (RP/BR) mixture was burned to produce the aerosol. Each study involved (1) 3 RP/BR target concentration groups (0.0, 1.0, and 4.0 mg/L), (2) 24 prairie dogs or doves (8/group), with gender included as a factor in each study, and (3) a successive 3‐phase paradigm (2 d preexposure; 4 and 2 d of ∼80 min/d exposures to RP/BR for prairie dogs and rock doves, respectively; and 6 d postexposure). Results showed that in‐chamber atmospheres were uniform and acceptable for all exposures. No prairie dogs died, but 1 male rock dove died on d 3 postexposure to 4.0 mg/L aerosol. Concentration and gender main effects were significant for the acute (2 h out‐of‐chamber) food intake, water intake, and weight change of prairie dogs, with aerosol‐exposed and male rodents showing decrements. Cender and day main effects were also significant for the subacute (23 h/d) variables in prairie dogs; females weighed less than males, and reduced food/water/weight was evident for all animals during the 4 exposure days and first 3 postexposure days. For rock doves, subacute gender and day main effects, plus concentration x day and concentration × gender × day interactions, characterized the data. A transitive relationship was evident among RP/BR aerosol conditions (0.0 < 1.0 <4.0 mg/L) and mean decreased food intakes on the exposure days (d2 < d1). Enhanced postexposure water replenishment by female versus male doves exposed to 4.0 mg/L RP/BR aerosol was a main finding. Results are explained based upon a temporal model of phosphoric acid caused ulcers/edema. Effects are compared to prior evidence for albino rats, prairie dogs and rock doves; these are also discussed relative to certain human health and ecotoxicological literature.

ISSN:0098-4108    

DOI:10.1080/15287399309531767

出版商:Taylor & Francis Group    

年代:1993

数据来源: Taylor

摘要:

A7BeCl2solution containing 0.5 μg Be per mouse was injected subcutaneously, intraperitoneally, intramuscularly, intrathoracically, and intravenously, and distribution was observed for periods up to 1 wk.7Be was excreted more rapidly following intravenous injection than by the other routes of injection.

ISSN:0098-4108    

DOI:10.1080/15287399309531768

出版商:Taylor & Francis Group    

年代:1993

数据来源: Taylor

摘要:

The incidence of a set of neoplasms arising “spontaneously” in Fischer 344 (F344) rats was determined in control and carcinogen‐treated animals. Data were obtained from approximately 9000 rats (4000 males and 5000 females) used to study the carcinogenicity of a variety of alkylating compounds, including N‐nitroso compounds, azoxyalkanes, and triazenes. In these experiments treated rats and controls were allowed to die naturally and were necropsied, and the tissues were examined histopathologically. The spontaneous neoplasms of interest were mononuclear cell leukemia and neoplasms of the anterior pituitary, adrenal medulla, pancreas, thyroid gland, mammary gland, and testis. These tumors were generally absent from control animals that (rarely) died before 70 wk of age. Although many carcinogen‐treated rats died early with treatment‐related tumors, a substantial number (1700 males and 2300 females) survived as long as controls. The incidence of spontaneous neoplasms was determined among controls and chemically treated rats at 10‐wk intervals from 0 to 140 wk. The incidence of spontaneous tumors was not higher and was frequently statistically lower among treated rats than the corresponding incidence in controls, with the exception of leukemia in female rats. The same result was obtained with the subset of carcinogens not requiring metabolic activation (mostly alkyl‐nitrosoureas). These data indicate that in this rat tumor model system, the alkylating carcinogens, while capable collectively of tumor induction at more than 20 sites, did not accelerate the development of any of the six spontaneously arising solid tumors. This suggests that these spontaneous tumors might arise by a mechanism that is unresponsive to the actions of the alkylating carcinogens.

ISSN:0098-4108    

DOI:10.1080/15287399309531769

出版商:Taylor & Francis Group    

年代:1993

数据来源: Taylor

摘要:

The influence of genotypes of the major histocompatibility complex (MHC) on susceptibility to acute and delayed effects of an organophosphorus ester was measured in adult White Leghorn chickens from lines differing in response to sheep red blood cell (SRBC) antigen. Chickens from lines selected for high (HA) or low (LA) antibody response to SRBC and homozygous for B13B13or B21B21genotypes at the MHC were administered a single subcutaneous injection of diisopropyl phosphorofluoridate (DFP) at dosages of 0, 0.25, 0.50, or 1.0 mg/kg body weight using com oil as the carrier. Criteria for toxicologi‐cal responses included clinical, biochemical, and pathological measures. Clinical signs of acute cholinergic poisoning and delayed neuropathy were dose related. Brain and blood cholinesterase and carboxylesterase activities were more sensitive to inhibition by DFP than were liver cholinesterase and carboxylesterase activities. Cholinergic signs 3 h after administration of DFP were more pronounced in line HA than in line LA chickens. Pathological evidence of delayed neuropathy 2 wk after DFP administration was also more evident in HA than LA chickens. Although less pronounced than that for lines, differences in neurotoxic manifestations following DFP administration were greater for chickens of B21B21than B13B13genotypes. Activity of A‐esterases, which hydrolyze organophosphorus esters without being inhibited by them, was lower in plasma of fine HA than line LA chickens. Differences among the genotypes in activity of other esterases were not found in chickens not receiving DFP. These results indicated that responses of chickens to the neurotoxicant DFP were influenced by the background genome of the chickens.

ISSN:0098-4108    

DOI:10.1080/15287399309531770

出版商:Taylor & Francis Group    

年代:1993

数据来源: Taylor

ISSN:0098-4108    

DOI:10.1080/15287399309531761

出版商:Taylor & Francis Group    

年代:1993

数据来源: Taylor