摘要:

Trichothecene mycotoxins are a group of structurally similar fungal metabolites that are capable of producing a wide range of toxic effects. Deoxynivalenol (DON, vomitoxin), a trichothecene, is prevalent worldwide in crops used for food and feed production, including in Canada and the United States. Although DON is one of the least acutely toxic trichothecenes, it should be treated as an important food safety issue because it is a very common contaminant of grain. This review focuses on the ability of DON to induce toxicologic and immunotoxic effects in a variety of cell systems and animal species. At the cellular level, the main toxic effect is inhibition of protein synthesis via binding to the ribosome. In animals, moderate to low ingestion of toxin can cause a number of as yet poorly defined effects associated with reduced performance and immune function. The main overt effect at low dietary concentrations appears to be a reduction in food consumption (anorexia), while higher doses induce vomiting (emesis). DON is known to alter brain neurochemicals. The serotoninergic system appears to play a role in mediation of the feeding behavior and emetic response. Animals fed low to moderate doses are able to recover from initial weight losses, while higher doses induce more long-term changes in feeding behavior. At low dosages of DON, hematological, clinical, and immunological changes are also transitory and decrease as compensatory/adaptation mechanisms are established. Swine are more sensitive to DON than mice, poultry, and ruminants, in part because of differences in metabolism of DON, with males being more sensitive than females. The capacity of DON to alter normal immune function has been of particular interest. There is extensive evidence that DON can be immunosuppressive or immunostimulatory, depending upon the dose and duration of exposure. While immunosuppression can be explained by the inhibition of translation, immunostimulation can be related to interference with normal regulatory mechanisms. In vivo, DON suppresses normal immune response to pathogens and simultaneously induces autoimmune-like effects which are similar to human immunoglobulin A (IgA) nephropathy. Other effects include superinduction of cytokine production by T helper cells (in vitro) and activation of macrophages and T cells to produce a proinflammatory cytokine wave that is analogous to that found in lipopolysaccharide-induced shock (in vivo). To what extent the elevation of cytokines contributes to metabolic effects such as decreased feed intake remains to be established. Although these effects have been largely characterized in the mouse, several investigations with DON suggest that immunotoxic effects are also likely in domestic animals. Further toxicology studies and an assessment of the potential of DON to be an etiologic agent in human disease are warranted.

ISSN:0098-4108    

DOI:10.1080/009841096161447

出版商:Informa UK Ltd    

年代:1996

数据来源: Taylor

摘要:

Of the three-quarters of a million service personnel involved in the Persian Gulf War, approximately 30,000 have complained of neurological symptoms of unknown etiology. One contributing factor to the emergence of such symptoms may be the simultaneous exposure to multiple agents used to protect the health of service personnel, in particular, the anti-nerve agent pyridostigmine bromide (PB; 3-dimethylaminocarbonyloxy- N -methylpyridinium bromide), the insect repellent DEET ( N,N -diethyl- m -toluamide), and the insecticide permethrin (3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarboxylic acid (3-phenoxyphenyl)methyl ester). This study investigated neurotoxicity produced in hens by individual or simultaneous exposure to these agents (5 d/ wk for 2 months to 5 mg/ kg/ d PB in water, po; 500 mg/kg/d DEET, neat, sc; and 500 mg/kg/d permethrin in corn oil, sc). At these dosages, exposure to single compounds resulted in minimal toxicity. Combinations of two agents produced greater neurotoxicity than that caused by individual agents. Neurotoxicity was further enhanced following concurrent administration of all three agents. We hypothesize that competition for liver and plasma esterases by these compounds leads to their decreased breakdown and increased transport of the parent compound to nervous tissues. Thus, carbamylation of peripheral esterases by PB reduces the hydrolysis of DEET and permethrin and increases their availability to the nervous system. In effect, PB "pumps" more DEET and permethrin into the central nervous system. Consistent with this hypothesis, hens exposed to the combination of the three agents exhibited neuropathological lesions with several characteristics similar to those previously reported in studies of nearlethal doses of DEET and permethrin. If this hypothesis is correct, then blood and liver esterases play an important "buffering" role in protecting against neurotoxicity in the population at large. It also suggests that individuals with low plasma esterase activity may be predisposed to neurologic deficits produced by exposure to certain chemical mixtures.

ISSN:0098-4108    

DOI:10.1080/009841096161456

出版商:Informa UK Ltd    

年代:1996

数据来源: Taylor

摘要:

With the aim of identifying a surrogate marker for the neurotoxic effects of methylmercury using a peripheral blood sample, the sensitivity of microtubules in circulating blood cells to depolymerization by methylmercury was compared. Methylmercuric chloride was added to samples of human venous blood or to isolated platelets and lymphocytes (human or rabbit) suspended in RPMI medium plus 10% fetal calf serum. After 1 h, microtubular networks were visualized by immunolabeling with antibody specific for tubulin. The percentage of platelets without visible, intact microtubules and the percentage of viable, unactivated lymphocytes without microtubules visibly radiating from the centriolar region through the cytoplasm were counted. A concentration-dependent loss of microtubules was observed in both cell types. Loss of microtubules was more easily quantitated and was observed at significantly lower concentrations in platelets compared to lymphocytes. The IC50 (concentration of methylmercuric chloride resulting in dissolution of microtubules in 50% of the cells) was 3.1 mu M in platelets and 7.4 mu M in lymphocytes in samples exposed in culture medium without erythrocytes. When methylmercury was added to whole blood for 1 h, the IC50 increased to 182 mu M in platelets and > 700 mu M in lymphocytes, consistent with the known sequestration of methylmercury in erythrocytes. With longer durations of exposure, much lower concentrations of methylmercury were effective in both cell types. When rabbit lymphocytes and platelets were exposed to methylmercury under culture conditions, IC50s in platelets/lymphocytes were 2.5 mu M / 4.8 mu M after 1 h of exposure, 0.77 mu M /1.12 mu M after 20 h, and 0.51 mu M /0.63 mu M after 70 h. The results of this study suggest that platelets may be more suitable than lymphocytes as a cell type in which to monitor in vivo effects of methylmercury on microtubules.

ISSN:0098-4108    

DOI:10.1080/009841096161465

出版商:Informa UK Ltd    

年代:1996

数据来源: Taylor

摘要:

The relative abilities of a series of acyclic polyamine chelating agents containing only nitrogen donors (N-donors) to induce the urinary excretion of cadmium has been examined in the rat. The compounds examined include triethylenetetramine dihydrochloride (TRIEN), tris(2-aminoethyl)amine trihydrochloride (TREN), tetraethylenepentamine pentahydrochloride (TETRAEN), and pentaethylenehexamine hexahydrochloride (PENTAEN). Sodium N-methyl-D-glucamine-N-carbodithioate (NaG) was used as a positive control compound. The polyamines induced a significant increase in the urinary excretion of cadmium in rats that had been loaded with cadmium at least 4 d prior to the polyamine treatments. A comparison of these with similar data on macrocylic nitrogen donor systems, which form much more stable complexes with cadmium but are also ineffective in enhancing the excretion of cadmium from such aged deposits, suggests that the factors responsible for the relative inefficiency of these compounds may involve either a difficulty in penetrating cellular membranes or a slow rate of reaction with biologically bound cadmium. The occurrence of oliguria and anuria following the administration of the several of the polyamines indicates that their use is accompanied by significant renal damage in cadmium-exposed rats.

ISSN:0098-4108    

DOI:10.1080/009841096161474

出版商:Informa UK Ltd    

年代:1996

数据来源: Taylor

摘要:

Terbium (Tb) is a rare earth metal that finds use in several emerging technologies. However, little is known about the biological effects of Tb. Thus, in this study the pulmonary toxicity of systemic Tb in mice was investigated. Mice were treated intravenously with a single dose of 20 or 200 mumol Tb/kg, as TbCl3, and killed at 3, 6, 12, 24, 48, or 72 h later. Administration of Tb at a dose of 200 mumol/kg increased pulmonary weight, lipid peroxidation, and protein content but decreased pulmonary glutathione content. Pulmonary-glutamyl transpeptidase (-GTP) activity was increased after Tb administration at a dose of 200 mumol/ kg. Pulmonary alkaline phosphatase (ALP) activity was also increased after Tb administration at a dose of 200 mumol/kg. Investigation of the defense system against oxidative damage in the lung showed that superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities were all decreased after Tb administration at the higher dose. The concentrations of Tb, Ca, and P in lung was increased by the dose of 200 mumol/kg. These results suggest that pulmonary lipid peroxidation may be an early and sensitive consequence of Tb exposure and that SOD, CAT, and GSH-Px might be considered as potential modulators of Tb-induced lipid peroxidation. The mechanisms involved in Tb-induced pulmonary lipid peroxidation deserve further study.

ISSN:0098-4108    

DOI:10.1080/009841096161483

出版商:Informa UK Ltd    

年代:1996

数据来源: Taylor

摘要:

The effect of soil loading on the dermal uptake of soil-borne contaminants was examined using an in vitro evaporation/penetration apparatus and abdominal skin from human cadavers. Dermal uptake of two 14C-labeled pesticides, lindane and 2,4-dichlorophenoxyacetic acid (2,4-D), was assessed at nominal soil loadings of 1, 5, and 10 mg/cm2. Sub-150-mum fractions of two soils with differing organic carbon contents were employed. Mean 24-h dermal absorption values ranged from 0.45 to 2.35% for lindane and from 0.18 to 1.64% for 2,4-D, depending upon soil load and type. Mean mass fluxes ranged from 8.8 to 32 pg/cm2/h for lindane and from 1.9 to 6.4 pg/ cm2/h for 2,4-D. Results were aggregated as ratios of flux or percent absorption at 1 and 10 mg/cm2 to corresponding values obtained at 5 mg/ cm2. Fluxes at 5 and 10 mg/cm2 did not differ significantly, but flux at 1 mg/cm2 was about one-half the value observed at the higher loadings. The most plausible explanation for this decrease in mass flux is incomplete (submonolayer) coverage of the skin. Evidence in the form of electron micrographs is presented in support of this conclusion. Relative percent absorption increased significantly with decreases in soil load from 10 to 5 and from 5 to 1 mg/cm2. This effect was inversely proportional to loading reduction in the former case, but was less than proportional due to the impact of contact area reduction (and, in the case of lindane, volatilization losses) in the latter. Percent dermal absorption data obtained in the laboratory require adjustment for differences in loading and coverage before application to assessment of exposure to contaminants in soils. Description of dermal absorption from soil in a manner comparable to that used to describe absorption from a liquid or vapor (i.e., using a driving force and a mass transfer coefficient) would reduce confusion on this point and is recommended.

ISSN:0098-4108    

DOI:10.1080/009841096161492

出版商:Informa UK Ltd    

年代:1996

数据来源: Taylor