摘要:

Abstract1. Most pyrethroids can be divided into two classes on the basis of differences in the signs of toxicity (T- orCS-syndromes). Since these syndromes also correspond to particular aspects of their chemical structure and since the order of appearance of the signs of poisoning is the same in each class, it is concluded that these syndromes originate from a single primary action of the pyrethroid.2. Pyrethroids cause morphological changes in peripheral nerves of rats when given in high doses. The production of these minor lesions are correlated with a dose of the pyrethroid that causes death in some of the treated rats. Lower doses do not cause these effects. Therefore, the morphological changes are produced as a secondary consequence of the primary action of pyrethroids and are not due to a different form of toxicity.3. Pyrethroids have been shown to cause functional changes (behavioral) in rats shown as a deficit in performance on an inclined plane. Increases in peripheral nerves ofβ-glucuronidase andβ-galactosidase have also been demonstrated. These increases are a late finding and are considered to be associated with repair processes. As with the morphological changes these enzyme changes are correlated with doses that cause death in some of the animals. There is no firm evidence that the behavioral changes are correlated with either the morphological or biochemcial changes.4. Available information indicates that all the above changes described in 2 and 3 are reversible or repairable.5. Many pyrethroids cause an effect in humans termed parasthesia. It seems probable from structure-activity relationships that parathesia, as for their systemic toxicity, is brought about by an action of pyrethroids on sodium channels of the sensory nerves.6. Studies have been carried out on human volunteers and a guinea pig model has been developed. Subjective human experience and some experimental work indicates that the effects are reversible and result in no permanent change.7. There is no conclusive evidence that pyrethroids have neurotoxic actions other than those originating from their primary action on sodium channels, through a dissociable interaction with macromolecular component(s).8. Further research is recommended to extend knowledge of pyrethroids as a class rather than for individual compounds.9. All available evidence indicates that, at doses of pyrethroids likely to be encountered in working practice, when serious poisoning does not occur, neurotoxicity due to the pyrethroids will not occur except as a reversible transient effect on the skin. This minor warning response is due to the primary action of pyrethroids on sodium channels, a reversible interaction.

ISSN:1040-8444    

DOI:10.3109/10408449009089874

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

AbstractNeuroexcitatory symptoms of acute poisoning of vertebrates by pyrethroids are related to the ability of these insecticides to modify electrical activity in various parts of the nervous system.Repetitive nerve activity, particularly in the sensory nervous system, membrane depolarization, and enhanced neurotransmitter release, eventually followed by block of excitation, result from a prolongation of the sodium current during membrane excitation. This effect is caused by a stereoselective and structure-related interaction with voltage-dependent sodium channels, the primary target site of the pyrethroids.Near-lethal doses of pyrethroids cause sparse axonal damage that is reversed in surviving animals. After prolonged exposure to lower doses of pyrethroids axonal damage is not observed.Occupational exposure to pyrethroids frequently leads to paresthesia and respiratory irritation, which are probably due to repetitive firing of sensory nerve endings. Massive exposure may lead to severe human poisoning symptoms, which are generally treated well by symptomatic and supportive measures.VI. SummaryAlthough pyrethroid insecticides have been introduced on a large scale fairly recently, extensive data have been published on their mode of action, and valuable information is available on potential side effects in man.The basic mechanism of action of the pyrethroids on the vertebrate nervous system has been investigated in detail. All available evidence clearly indicates that the primary neurotoxic target site of this chemically diverse class of insecticides is confined to the voltage-dependent sodium channels in excitable membranes. The stereoselective interaction of pyrethroids with a fraction of the sodium channels results in a prolongation of the inward sodium current during excitation, as pyrethroid-modified sodium channels stay open much longer than normal. The prolonged sodium current induced by the pyrethroids results in pronounced repetitive activity, notably in sense organs, but—depending on pyrethroid structure—also in sensory nerve fibers, motor nerve terminals, and skeletal muscle fibers. Besides repetitive firing, membrane depolarization resulting in enhanced neurotransmitter release and eventually block of excitation may also occur.Studies on sense organs in the vertebrate skin have shown that the cyano pyrethroids evoke more intense repetitive activity than the noncyano pyrethroids. This is accounted for by large, quantitative differences in the prolongation of the sodium current by cyano and noncyano pyrethroids. For a range of pyrethroids the symptoms observed in experimental animal poisoning correlate well with the extent to which the sodium current is prolonged.Postsynaptic neurotransmitter responses are unaffected by concentrations of pyrethroids that cause marked sodium channel modification. At high concentrations insecticidal as well as noninsecticidal pyrethroid isomers cause a nonspecific suppressive effect on the postsynaptic neurotransmitter response.Cardiovascular effects of pyrethroids can be attributed to modification of presynaptic as well as postsynaptic sodium channels.Paresthesia and other peripheral sensory phenomena, e.g., respiratory irritation, are repeatedly experienced in man after occupational exposure to cyano pyrethroids in particular. These symptoms, which are most likely caused by repetitive firing of sensory nerve endings, should be considered a warning of overexposure, indicating that adequate preventive measures should be taken. The quality as well as the intensity of the peripheral sensory phenomena depends not only on pyrethroid structure, but also varies with the formulation and with environmental factors.The question whether repeated occurrence of peripheral repetitive firing may eventually lead to injury of sensory nerve endings or central sensory adaptation remains unanswered. The guinea pig flank provides an adequate model to quantify the cutaneous sensations of pyrethroids. This model may be particularly useful to compare the degree of skin sensory irritation caused by different formulations of pyrethroids and could also be of value to investigate possible chronic effects.Lethal and near-lethal doses of pyrethroids cause sparse axonal damage in a fraction of the exposed animals, which is reversed after cessation of exposure. Threshold concentrations from acute and chronic studies are available. After prolonged chronic exposure to lower doses of pyrethroids axonal damage has not been observed. It has been suggested that the histopathological changes are unrelated to the basic neuroexcitatory action of pyrethroids. The hen sciatic nerve is not suitable for studying pyrethroid-induced nerve damage, as—in contrast to organophosphates—birds are highly insensitive to pyrethroids.The limited information available on neurobehavioral effects of pyrethroids is difficult to evaluate, as the significance of such data for toxicological risk assessment is still under debate.Established anticonvulsants are only moderately effective in the treatment of acute pyrethroid poisoning in animals and man. The results of animal experiments indicate that mephenesin and related compounds, combined with atropine to suppress cholinergic side effects, are the more promising antidotes presently known.Although severe acute human poisoning with pyrethroids in the Western Hemisphere seems very unlikely, recent experience in the People's Republic of China shows that these insecticides should certainly not be considered harmless. However, with adequate therapeutic treatment, the prognosis of acute pyrethroid poisoning is generally good.

ISSN:1040-8444    

DOI:10.3109/10408449009089875

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

AbstractThe critical events that lead to the transition from reversible to irreversible injury remain unclear. Studies are reviewed that have suggested that a rise in cytosolic free Ca2+initiates plasma membrane bleb formation and a sequence of events that leads ultimately to cell death. In recent studies, we have measured changes in cytosolic free Ca2+, mitochondrial membrane potential, cytosolic pH, and cell surface blebbing in relation to the onset of irreversible injury and cell death following anoxic and toxic injury to single hepatocytes utilizing multiparameter digitized video microscopy (MDVM). MDVM is an emerging new technology that permits single living cells to be labeled with multiple probes whose fluorescence is responsive to specific cellular parameters of interest. Fluorescence images specific for each probe are collected over time, and then digitized and stored. Image analysis and processing then permits quantitation of the spatial distribution of the various parameters within the single living cells. Our results indicate the following: (1) formation of plasma membrane blebs accompanies all types of injury in hepatocytes; (2) cell death is a rapid event, initiated by rupture of a plasma membrane bleb, and is coincident with the onset of irreversible injury; (3) an increase of cytosolic free Ca2+is not the stimulus for bleb formation or the final common pathway leading to cell death; (4) a decrease of mitochondrial membrane potential precedes loss of cell viability; (5) cytosolic pH falls by more than 1 pH unit during chemical hypoxia. This acidosis protects against the onset of cell death.

ISSN:1040-8444    

DOI:10.3109/10408449009089876

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

AbstractFluorine-containing monomers form the basis for production of a large number of commercially important polymers. Most of the polymerization occurs as gas-phase reactions, hence the hazards associated with the monomers arises primarily from inhalation. The chemicals covered in this review include bromotrifluoroethylene (BTFE), chlorotrifluoroethylene (CTFE), hexafluoroacetone (HFA), hexafluoroisobutylene (HFIB), hexafluoropropylene (HFP), perfluorobutylene (PFBE), tetrafluoroethylene (TFE), trichloropropene (TFP), vinyl fluoride (VF), and vinylidene fluoride (VF2). The amount of toxicologic information available on the compounds is relatively small and for certain of these the information consists is short-term or acute, hence the current need to make predictions of biologic activity based on analogy or chemical reactivity is great. In animal models and in man, these monomers may be absorbed into the body at varying rates and the metabolism ranges from extensive to little in a species, dose, and chemical specific fashion. The major toxicologic target of these materials is the kidney, and the degree of involvement depends greatly on the excretion patterns and metabolic profiles of the monomers. However, other target sites exist, such as the reproductive system for HFA, making the use of structure-activity relationships difficult.

ISSN:1040-8444    

DOI:10.3109/10408449009089877

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor