ISSN:0098-4108    

DOI:10.1080/15287398109530105

出版商:Taylor & Francis Group    

年代:1981

数据来源: Taylor

摘要:

Plasma and brain levels of chlordecone in chlordecone‐induced motor impairment, lethal levels of chlordecone, and cumulative LD50 of chlordecone in the mouse are presented. In terms of biochemical events, the possible contributory role of neuro‐transmitters in chlordecone‐induced neurotoxicity is also discussed. On the basis of the data obtained so far, it is suggested that the dopaminergic pathway and its interaction with other neurotransmitter systems in the basal ganglia may be primarily involved in chlordecone‐induced neurotoxicity.

ISSN:0098-4108    

DOI:10.1080/15287398109530106

出版商:Taylor & Francis Group    

年代:1981

数据来源: Taylor

摘要:

The neurotoxic organochlorine insecticide chlordecone (Kepone) was examined in severalin vitroandin vivoneurochemical systems in an attempt to identify neuro‐chemical alterations that might be relevant to the central nervous system manifestations of chlordecone toxicity in humans.In vitro, chlordecone was a remarkably potent inhibitor of brain mitochondrial oxidative phosphorylation and associated Ca2+transport (Ki= 10−7M). At a high concentration of chlordecone (10−5M), destabilization of biological membranes was observed. Both of these effects appeared to contribute to inhibition of synaptosomal Ca2+uptake, which was accompanied by a pronounced, although paradoxical, stimulation of neurotransmitter release. Studies of the disposition of [14C]chlordecone revealed that the concentrations that elicited neurochemical changesin vitrowere comparable to the brain tissue chlordecone concentrations achieved with a 40 mg/kg tremorigenic dose in intact animals. However, no neurochemical correlates of chlordecone toxicity were observed in studies of dopamine and norepinephrine turnover in chlordecone‐intoxicated animals. These findings are discussed in relation to the development of neurochemical assays appropriate for investigating neurotoxic agents.

ISSN:0098-4108    

DOI:10.1080/15287398109530107

出版商:Taylor & Francis Group    

年代:1981

数据来源: Taylor

摘要:

Chlordecone (Kepone) is a close structural analog of mirex, but it differs considerably from mirex in toxic action. Chiordecone primarily produces neurotoxic symptoms such as tremors in humans and animals. As with other organochlorine pesticides, the mechanism of the toxic action of chiordecone is not completely understood. An attempt is made in this paper to review the effects of chiordecone on the membrane‐bound adenosinetriphosphatases (ATPases) and related phenomena. Chiordecone is shown to be a potent inhibitor of A TPases in different tissue preparations of several species. The order of sensitivity of the ATPases tested to chiordecone was: oligomycin‐sensitive (mitochondrial) Mg2+‐A TPase > Na+, K+‐ATPase > Ca2+‐ATPase > oligomycin‐insensitive Mg2+‐ATPase. Compared to other tissues tested, brain Na+K+‐ATPase and heart mitochondrial Mg2+‐A TPase were more sensitive to chiordecone. Oligomycin‐insensitive Mg2+‐A TPase was the least affected enzyme.

ISSN:0098-4108    

DOI:10.1080/15287398109530108

出版商:Taylor & Francis Group    

年代:1981

数据来源: Taylor

摘要:

Effects of the insecticide chlordecone (Kepone) on female reproduction in birds and mammals were reviewed. In different avian species, chlordecone inhibited or reduced reproduction and decreased egg hatchability and survival of the newborn. In Japanese quail, chronic chlordecone ingestion decreased total egg production and clutch size and increased egg breakage. Eggs produced by treated quail were significantly weaker and thinner. Chlordecone also decreased follicular development, induced ovarian regression, and inhibited ovulation and egg laying. Histological studies showed that when chlordecone was fed to sexually immature quail, the oviducts exhibited accelerated growth, cytodifferentiation, cellular hypertrophy, secretory activity, and maturation. Ultrastructure of the oviduct surface showed increased growth of microvilli and profuse ciliation. Chlordecone also stimulated granular endoplasmic reticulum and Golgi development and induced full secretory activity in the cytoplasm of estrogen‐sensitive quail oviduct cells. In addition to mimicking estrogen in the quail oviduct, chlordecone produced abnormal apical protrusions of oviduct cells, disoriented and twisted cilia, disorganized Golgi apparatus, induced myelin figure formation, and swollen or abnormal mitochondria in oviduct cells that produce egg white protein and eggshell. Chlordecone also detrimentally effected mammalian reproduction. Mice ingesting chlordecone produced decreased litters, and the adult females exhibited constant estrus, decreased corpora lutea, and hormonal imbalance resulting in decreased luteinizing hormone levels. In pregnant mice and rats, chlordecone produced fetal toxicity, abnormalities, and malformations. In neonatal or weanling rats, chlordecone induced rapid uterine growth, precocious vaginal opening, decreased corpora lutea, and persistent vaginal estrus. In adult rats, chlordecone inhibited female reproduction, which was only partially restored after chlordecone ingestion ceased. In neonatal female mice, chlordecone induced development of the entire reproductive tract. Both oviduct and uterus showed accelerated growth, cellular hypertrophy, and hyperplasia, whereas vaginal epithelium became keratinized. Ultra‐structure of chlordecone‐treated neonatal mouse oviduct and uterus surfaces revealed increased cell size and cell surfaces, rapid growth of microvilli and cilia, and discharge of numerous secretory granules. However, numerous oviduct and uterine cells exhibited severe apical protrusions in the form of swelling, and in the oviduct cilia appeared disorganized and twisted. In immature avian and mammalian reproductive tracts, chlordecone appears to produce similar alterations and abnormalities. Such stimulatory changes are not surprising, since recent reports indicate that chlordecone estrogenicity is apparently due to its competition for and binding to estrogen receptors in mammalian uterus and avian oviduct cells.

ISSN:0098-4108    

DOI:10.1080/15287398109530109

出版商:Taylor & Francis Group    

年代:1981

数据来源: Taylor

摘要:

Chlordecone (Kepone) is a decachloroketone analog of the dodecachlorohydrocarbon mirex and is used as a stomach poison insecticide. Despite the structural similarity to mirex, chlordecone is unlike mirex in general and organ‐specific toxic properties. Chlordecone is primarily accumulated in the liver, where it causes a variety of morphological and biochemical alterations. Although less effective than mirex as a hepatotoxin, it causes liver enlargement, focal necrosis, mitochondrial changes, fatty infiltration of hepatocytes, and proliferation of endoplasmic reticulum. Chlordecone accumulation and morphological alterations in the liver were also observed in occupationally exposed human patients. Induction of hepatic microsomal mixed‐function oxidases (MFOs) and impaired production and utilization of hepatocellular energy are the principal biochemical aberrations produced by chlordecone. Chronic exposure causes carcinogenesis in mice and rats. Hyperplastic nodules, which progress to hepatocellular carcinomas, are the principal pathological lesions. Acute and chronic exposures to chlordecone result in hepatobiliary dysfunction manifested as impaired excretion of anionic compounds accompanied by choleresis. Exposure to chlordecone results in greatly potentiated haloalkane hepatotoxicity, representing a most potent toxic interaction at otherwise individually nontoxic levels. In view of the demonstrated carcinogenic effect of chlordecone, such interactions at very low levels assume extraordinary significance in terms of chronic toxicological and pathological manifestations induced by combinations of toxic chemicals.

ISSN:0098-4108    

DOI:10.1080/15287398109530110

出版商:Taylor & Francis Group    

年代:1981

数据来源: Taylor

摘要:

Due to lack of adequate industrial safety measures, workers in a small factory that manufactured the organochlorine pesticide chlordecone were exposed to large amounts of this toxic material for many months. High concentrations of chlordecone were present in samples of blood, liver, and fat from these workers. Toxic manifestations prominently involved the nervous system, liver and testes. Although a plasmaphoresis experiment indicated that chlordecone is rapidly transferred from tissues to blood, attempts to employ hemoperfusion as a means for removing chlordecone from the body were unsuccessful because chlordecone is avidly bound by plasma proteins and was not extracted by the hemoperfusion sorbents. An alternative approach to therapy was based on the observations that stool contains only a small fraction of the substantial amounts of chlordecone excreted in bile. Oral administration of cholestyramine, a nonabsorbable resin that binds chlordeconein vitro, increased fecal excretion of chlordecone and accelerated its disappearance from the body. This treatment was accompanied by amelioration of the clinical manifestations of toxicity, indicating that the subacute toxic effects of chlordecone are reversible. Studies of chlordecone excretion in one patient with a surgically created bile fistula disclosed the existence of a novel, nonbiliary mechanism for excretion of chlordecone in the stool. Further physiological studies are needed to explore the possible role of the gut in the excretion of many kinds of slowly eliminated lipophilic toxins.

ISSN:0098-4108    

DOI:10.1080/15287398109530111

出版商:Taylor & Francis Group    

年代:1981

数据来源: Taylor

摘要:

Mercury distribution, food consumption, body weight, andin vivoprotein synthesis were compared as criteria for evaluating the efficacy of D‐penicillamine (DPA) in treating experimental methyl mercury (MM) intoxication. Female rats were orally administered MM hydroxide at 40 mg/kg and, after a 7‐ to 8‐d latency period, displayed characteristic neurological signs of MM intoxication. Within 24 h of MM exposure food consumption decreased 75%, causing a 12‐g drop in body weight, and synthesis of whole blood and kidney protein increased. Protein synthesis in lifer was increased 39% by MM after 3 d, and that in cerebellum was decreased 15% after 7 d. Treatment with DPA (1.2 g/kg·d sc on d 2, 3, and 4) prevented the appearance of neurological signs. DPA lowered the Hg content of all tissues; restored food consumption to control levels; increased the onset and amount of body weight gain; returned synthesis of blood, liver, and kidney proteins to control levels; and prevented the decrease in protein synthesis in cerebellum. By itself, DPA produced a transitory decrease in both food consumption and body weight, which could be prevented with vitamin B6. Vitamin B6antagonized DPA's reversal of MM's action on protein synthesis. Furthermore, DPA and/or vitamin B6had a variety of effects on protein synthesis in control rats. Thus it was not possible to use protein synthesis to predict the efficacy of the combination of DPA and vitamin B6as found for the parameters of food consumption, body weight, and Hg distribution. Since changes in body weight and food consumption were the earliest and most pronounced and consistent responses to MM and effective DPA treatment, they were considered the best criteria for evaluating treatment efficacy in experimental MM poisoning in rats.

ISSN:0098-4108    

DOI:10.1080/15287398109530112

出版商:Taylor & Francis Group    

年代:1981

数据来源: Taylor

摘要:

The influence of intrauterine position on fetal body weight was statistically evaluated for 199 Dutch belted rabbit litters from does receiving various treatments during teratological studies. The data consisted of the number, type (live, dead, resorted), and position of implantation sites in the left and right uterine horns. Body weights of live fetuses were also recorded. No statistically significant relation was found between the number of live, dead, or resorted fetuses and intrauterine position. An effect related to differences in position between the left and right uterine horns for the proportions of largest fetuses was statistically significant. This uterine horn effect was not seen for the proportions of smallest fetuses. Positional differences within the uterine horns were significant and indicated a decrease in the proportion of largest fetuses and an increase in the proportion of smallest fetuses with increasing position number (ovarian to cervical end). Mean fetal weights differed significantly between the two uterine horns and among positions. There was a monotonic decrease in fetal weight with increasing position number. There were no significant associations between uterine horn or position and mean weight for the largest fetuses, but statistical evidence of a position effect was seen for weights of the smallest fetuses.

ISSN:0098-4108    

DOI:10.1080/15287398109530113

出版商:Taylor & Francis Group    

年代:1981

数据来源: Taylor

摘要:

Two groups of Mongolian gerbils (Meriones unguiculatus) were continuously exposed to 150 ppm trichloroethylene (TCE) for 77 and 106 d, respectively. The behavior of the animals was tested in a symmetrical maze baited with sunflower seeds during a period of 23 d, beginning at the end of exposure. One additional group was exposed for 150 d and then allowed 40 d free from exposure before the start of the maze test Comparisons between the TCE‐ and air‐exposed animals showed differences in the number of correct choices and the number of seeds consumed in the maze, both after 71 and 106 d of exposure and at the end of the 40‐d rehabilitation period that followed the 150‐d exposure. The results were interpreted in terms of the “emotionality” of the animals.

ISSN:0098-4108    

DOI:10.1080/15287398109530114

出版商:Taylor & Francis Group    

年代:1981

数据来源: Taylor