Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 89
Filtrar
Mais filtros










Intervalo de ano de publicação
1.
Environ Toxicol Pharmacol ; 35(2): 200-6, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23328119

RESUMO

This paper provides new information related to the mechanism of OPI (organophosphorus insecticides) teratogenesis. The COMFA (comparative molecular field analysis) and COMSIA (comparative molecular similarity indices analysis) suggest that the electrostatic and steric fields are the best predictors of OPI structural requirements to inhibit in ovo chicken embryo yolk sac membrane kynurenine formamidase, the proposed target for OPI teratogens. The dominant electrostatic interactions are localized at nitrogen-1, nitrogen-3, nitrogen of 2-amino substituent of the pyrimidinyl of pyrimidinyl phosphorothioates, and the oxygen of crotonamide carbonyl in crotonamide phosphates. Bulkiness of the substituents at carbon-2 and carbon-6 of the pyrimidinyls and/or N-substituents and carbon-3 substituents of crotonamides are the steric structural components that contribute to superiority of those OPI as in ovo inhibitors of kynurenine formamidase.


Assuntos
Arilformamidase/antagonistas & inibidores , Inseticidas/química , Inseticidas/toxicidade , Compostos Organofosforados/química , Compostos Organofosforados/toxicidade , Relação Quantitativa Estrutura-Atividade , Teratógenos/toxicidade , Saco Vitelino/enzimologia , Animais , Embrião de Galinha , Inibidores Enzimáticos/química , Inibidores Enzimáticos/toxicidade , Leptofós/química , Leptofós/toxicidade , Modelos Moleculares , Paration/química , Paration/toxicidade , Eletricidade Estática , Teratógenos/química , Saco Vitelino/efeitos dos fármacos
2.
Int J Mol Sci ; 11(8): 2856-63, 2010 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-21152278

RESUMO

We have evaluated in vitro the potency of 23 oximes to reactivate human erythrocyte acetylcholinesterase (AChE) and plasma butyrylcholinesterase (BChE) inhibited by racemic leptophos-oxon (O-[4-bromo-2,5-dichlorophenyl]-O-methyl phenyl-phosphonate), a toxic metabolite of the pesticide leptophos. Compounds were assayed in concentrations of 10 and 100 µM. In case of leptophos-oxon inhibited AChE, the best reactivation potency was achieved with methoxime, trimedoxime, obidoxime and oxime K027. The most potent reactivators of inhibited BChE were K033, obidoxime, K117, bis-3-PA, K075, K074 and K127. The reactivation efficacy of tested oximes was lower in case of leptophos-oxon inhibited BChE.


Assuntos
Acetilcolinesterase/química , Butirilcolinesterase/química , Leptofós/análogos & derivados , Oximas/química , Praguicidas/química , Eritrócitos/efeitos dos fármacos , Eritrócitos/enzimologia , Humanos , Leptofós/química , Leptofós/farmacologia , Praguicidas/farmacologia
3.
Ecotoxicol Environ Saf ; 55(2): 236-42, 2003 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12742374

RESUMO

Enantiomers of leptophos were separated by high-performance liquid chromatography with a Whelk-O1 column using 3% dichloromethane in n-hexane as mobile phase. Toxicity tests of leptophos enantiomers and racemate were performed with daphnia. Enzyme inhibition of leptohpos was carried out by using butyryl cholinesterase from horse serum and acetylcholinesterase from housefly heads. From the inhibition test of butyrylcholinesterase, the half-inhibitory concentrations, IC(50), of (+)-leptophos, (-)-leptophos, and (+/-)-leptophos were 0.241, 1.17, and 1.05 gmL(-1), respectively. No significant difference in IC(50) in (-)-leptophos and (+/-)- leptophos was found. However, the IC(50) of (+)-leptophos was significantly different from those of the others. In the inhibition test of acetylcholinesterase, the IC(50) values of (+)-leptophos, (-)-leptophos, and (+/-)-leptophos were 14.01, 24.32, and 13.22 gmL(-1), respectively. There was no significant difference in IC(50) in (+)-leptophos and (+/-)-leptophos, although the IC(50) of (-)-leptophos was significantly different from those of the others. From these results, leptophos-both enantiomers and racemate-seems to have higher neurotoxicity for mammals than for the target insects. In the toxicity test of daphnia, the half-lethal concentrations, LC(50), of (+)-leptophos, (-)-leptophos, and (+/-)-leptophos were 0.0387, 0.802, and 0.0409 gL(-1), respectively. There is no significant difference in LC(50) in (+)-leptophos and (+/-)-leptophos. The LC(50) of (-)-leptophos is significantly higher than those of the others. From these results, (-)-leptophos has lower toxicity to daphnia.


Assuntos
Daphnia/fisiologia , Inseticidas/química , Inseticidas/toxicidade , Leptofós/química , Leptofós/toxicidade , Acetilcolinesterase/metabolismo , Algoritmos , Animais , Butirilcolinesterase/metabolismo , Cromatografia Líquida de Alta Pressão , Inseticidas/isolamento & purificação , Leptofós/isolamento & purificação , Dose Letal Mediana , Estereoisomerismo
4.
Toxicol Lett ; 143(1): 65-71, 2003 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-12697382

RESUMO

To examine whether delayed neuropathy is prevented or alleviated when Ca is administered to experimental animals before or after organophosphorus compounds (OPs) dosing, we observed the effects of Calcicol administration as a calcium tonic on delayed neurotoxicity by OPs in hens. The hens (n=28) were randomly divided into seven groups (four in each group). One group received glycerol formal as vehicle group, two groups received 30 mg/kg leptophos or 40 mg/kg triortho-cresyl phosphate (TOCP) (L group and T group), two groups received 2.4 mg/kg Ca(2+) (0.3 ml/kg Calcicol) 24 h before leptophos or TOCP administration, and the last two groups received 2.4 mg/kg Ca after leptophos or TOCP administration, respectively. Although delayed polyneuropathy induced by OPs could not be prevented completely by Calcicol, the clinical signs of organophosphorus-induced delayed neuropathy (OPIDN) in hens that received Calcicol soon before or after OPs administration were less severe than those in hens that received only OPs and there were significant differences in OPIDN score between groups (P<0.05). This shows that polyneuropathy and the recovery function of nerves and muscles suffering from polyneuropathy can be alleviated, as long as calcium tonic is administered before the clinical signs develop. This study offers hope of recovery to humans who are exposed to these OPs because of work, attempted suicide, accidental ingestion or other accidents, etc. Meanwhile, our results indicate further that there is a relationship between a decrease in Ca(2+) concentration in tissues and induction of delayed neuropathy.


Assuntos
Gluconato de Cálcio/farmacologia , Cálcio/metabolismo , Galinhas/fisiologia , Síndromes Neurotóxicas/prevenção & controle , Compostos Organofosforados/antagonistas & inibidores , Compostos Organofosforados/toxicidade , Animais , Comportamento Animal/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Cálcio/sangue , Feminino , Marcha Atáxica/induzido quimicamente , Inseticidas/antagonistas & inibidores , Inseticidas/toxicidade , Leptofós/antagonistas & inibidores , Leptofós/toxicidade , Paralisia/induzido quimicamente , Tritolil Fosfatos/antagonistas & inibidores , Tritolil Fosfatos/toxicidade
5.
Toxicol In Vitro ; 17(1): 115-20, 2003 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-12537969

RESUMO

The neurodegenerative properties of the organophosphate ester leptophos (LEP) and the carbamate ester carbaryl (CB), both of which can cause neuropathic effects in animals, were investigated in differentiating mouse N2a neuroblastoma cells. At a sublethal concentration of 3 microM, both LEP and CB were able to inhibit the outgrowth of axon-like processes from N2a cells after only 4 h of exposure. Extracts of cells exposed to LEP showed decreased cross-reactivities with monoclonal antibodies that recognise the neurofilament heavy chain (NFH) and the growth-associated protein GAP-43. However, they exhibited increased cross-reactivity with a monoclonal antibody that recognises the heat shock protein HSP-70. In contrast, no changes were noted in the levels of antibody binding in blots of extracts of cells exposed to CB. It is concluded that, although both LEP and CB inhibit the formation of axons in vitro, the early biochemical changes underlying the neurodegenerative effects of the two compounds are different.


Assuntos
Axônios/efeitos dos fármacos , Carbaril/efeitos adversos , Inseticidas/efeitos adversos , Leptofós/efeitos adversos , Neuritos/efeitos dos fármacos , Animais , Anticorpos Monoclonais , Relação Dose-Resposta a Droga , Proteínas de Choque Térmico HSP70/análise , Camundongos , Sistema Nervoso/efeitos dos fármacos , Sistema Nervoso/patologia , Neuroblastoma/patologia , Células Tumorais Cultivadas
6.
Vet Hum Toxicol ; 41(5): 290-2, 1999 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10509429

RESUMO

The neurotoxic potential of trichlorfon, diazinon, phosmet, dichlorvos, phosphamidon and coumaphos was evaluated for their ability to inhibit brain neurotoxic esterase (NTE) activity in adult hens. Leptophos was used as a reference neurotoxic agent. All compounds were administered at high single oral doses and the NTE and acetylcholinesterase (AchE) activities were measured at 24 h and 6 w later. With the exception of leptophos, all compounds produced severe cholinergic signs associated with > 80% inhibition of brain AchE at 24 h. On the other hand, brain NTE activity was 86% inhibited by leptophos and to lesser extents by trichlorfon (76%), phosphamidon (74%), coumaphos (70%) and dichlorvos (70%). However, none of the latter compounds produced clinical delayed neurotoxicity as was observed with leptophos. It was concluded that trichlorfon, phosphamidon, coumaphos and dichlorvos are potentially neurotoxic because of their ability to inhibit brain NTE activity, but the extent of inhibition required for development of clinical delayed neurotoxicity (> 80%) is not likely to occur with any of these compounds due to their severe cholinergic activity.


Assuntos
Encéfalo/efeitos dos fármacos , Encéfalo/enzimologia , Esterases/metabolismo , Doenças do Sistema Nervoso/induzido quimicamente , Compostos Organofosforados/toxicidade , Animais , Galinhas , Cumafos/toxicidade , Diazinon/toxicidade , Diclorvós/toxicidade , Feminino , Leptofós/toxicidade , Fosmet/toxicidade , Fosfamidona/toxicidade , Triclorfon/toxicidade
7.
Tohoku J Exp Med ; 185(3): 161-71, 1998 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-9823777

RESUMO

Delayed neuropathy and inhibition of soluble neuropathy target esterase (NTE) and acetylcholinesterase (AChE) activities in different regions of brain and spinal cord of adult hens were studied after the intravenous administration of leptophos (30 mg/kg), tri-o-cresyl phosphate (TOCP 40 mg/kg) or dipterex (200 mg/kg). The level of NTE activity varied according to the regions of the central nervous system (CNS) of the control (normal) hen, being higher in the cerebrum (74.1 micromol of phenyl valerate hydrolyzed/10 minutes/mg protein) and in the cerebellum (68.7), and lower in the spinal cord (44.5 in cervical, 55.6 in thoracic and 50.0 in lumbar cord). Hens given leptophos and TOCP demonstrated delayed neuropathy with obvious inhibition of NTE, but the times of onset and the degrees of peak inhibition of NTE activity were different: 6-24 hours after dosing and 73-82% of normal activity for leptophos, and 24-48 hours and 45-80% for TOCP, respectively. Furthermore, the average inhibition of NTE during 6-48 hours after dosing, (called here 'period average inhibition') was also significantly different between the leptophos group (63-73%) and TOCP group (40-64%). Hens given dipterex did not demonstrate delayed neuropathy, and had the least peak inhibition and period average inhibition of NTE activity among the 3 groups. Ratios of NTE inhibition/AChE inhibition were higher in the leptophos group (0.91-1.24) and TOCP group (1.13-2.45) than in the dipterex group (0.25-0.79). These results indicate that the distribution of NTE in the soluble fraction of membrane proteins is different in different regions of the CNS, and that the degree of peak inhibition of NTE activity and the time of onset of peak inhibition induced by organophosphorus compounds (OPs) also differ for different OPs. Thus, practical and useful NTE measurements should identify the peak inhibition and period inhibition in several nervous tissue regions.


Assuntos
Hidrolases de Éster Carboxílico/antagonistas & inibidores , Doenças do Sistema Nervoso/induzido quimicamente , Compostos Organofosforados/farmacologia , Acetilcolinesterase/metabolismo , Animais , Galinhas , Feminino , Injeções Intravenosas , Leptofós/farmacologia , Doenças do Sistema Nervoso/enzimologia , Doenças do Sistema Nervoso/fisiopatologia , Valores de Referência , Solubilidade , Fatores de Tempo , Triclorfon/farmacologia , Tritolil Fosfatos/farmacologia
8.
J Toxicol Sci ; 22(2): 99-109, 1997 May.
Artigo em Inglês | MEDLINE | ID: mdl-9198007

RESUMO

To estimate the delayed neurotoxic effect of OPs on the next generation, we tried two examinations; one was on the distribution of leptophos in tissues and eggs of hens which are highly susceptible to the delayed neurotoxic effect of OPs but have no placenta, and the other was on the concentration of OPs in tissues of both pregnant and embryonic rats which are not susceptible to the delayed neurotoxic effect but have placenta, after leptophos was administered to the mother in both experiments. First, organophosphorus compound-induced delayed neurotoxicity (OPIDN) was checked in 4 hens and the concentration of leptophos was determined in the other 16 hens after 20 adult laying hens were given 30 mg/kg leptophos (iv), a neurotoxic organophosphate. Three out of 4 hens treated with leptophos showed OPIDN. The concentration of leptophos decreased sharply in the blood, liver, brain and spinal cord from 24 to 48 hr after leptophos administration, but clearance of leptophos was relatively slow in the ovary. Leptophos in laid egg yolk was detected every day for 10 days, and the highest concentration of leptophos in egg yolk was observed on the 6th day after administration to hens. Secondly, in order to investigate the transfer of leptophos to the embryo through the placenta, we divided the thirty-two pregnant rats into 2 groups. The first group received 10 mg/kg leptophos intraperitoneally on the 17th day of pregnancy and the second received 20 mg/kg leptophos on the same day. The time-course of leptophos concentration in the tissues of pregnant and embryonic rats was checked, and the correlation between findings in the pregnant rats and the embryos was determined. The time-course of leptophos concentration in the blood, liver, brain and placenta of the rats was similar to that in hens. Leptophos concentration in the liver and brain of the embryos was equal to approximately 60% of leptophos concentration in each tissue of the pregnant rats, and the concentration of leptophos in the liver and brain of embryonic rats correlated with that in the blood and placenta of pregnant rats (p < 0.01). In both groups treated with 10 and 20 mg/kg leptophos, the concentrations of leptophos in the liver and brain of embryos were lower than that of pregnant rats in the early period after dosing, but the concentrations in embryos were inversely higher than those in pregnant rats in the latter period (48 hr). Compared with the biological half-lives of leptophos in the liver and brain of pregnant rats, these parameters in embryonic rats were 1.58 and 1.87 times, respectively. These results indicate that some of the fat-soluble organophosphorus compounds readily pass through the blood-placenta barrier into the embryos and accumulate there. Therefore, the neurobehavioral development of F1 rats exposed to some organophosphorus compounds through the placenta of pregnant rats should be further examined.


Assuntos
Inseticidas/farmacocinética , Leptofós/farmacocinética , Neurotoxinas/farmacocinética , Efeitos Tardios da Exposição Pré-Natal , Animais , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/embriologia , Encéfalo/metabolismo , Embrião de Galinha/efeitos dos fármacos , Embrião de Galinha/metabolismo , Cromatografia Gasosa , Relação Dose-Resposta a Droga , Gema de Ovo/química , Gema de Ovo/efeitos dos fármacos , Feminino , Meia-Vida , Injeções Intraperitoneais , Inseticidas/administração & dosagem , Inseticidas/toxicidade , Leptofós/administração & dosagem , Leptofós/toxicidade , Fígado/efeitos dos fármacos , Fígado/embriologia , Fígado/metabolismo , Masculino , Neurotoxinas/administração & dosagem , Neurotoxinas/toxicidade , Ovário/efeitos dos fármacos , Ovário/embriologia , Ovário/metabolismo , Placenta/metabolismo , Gravidez , Ratos , Ratos Wistar , Medula Espinal/efeitos dos fármacos , Medula Espinal/embriologia , Medula Espinal/metabolismo , Distribuição Tecidual
9.
J Toxicol Sci ; 20(5): 609-17, 1995 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-8720167

RESUMO

Delayed neurotoxicity induced by leptophos, an organophosphorus insecticide, was intensified in hens when phenylmethylsulfonyl fluoride (PMSF) at dose of 30, 60, and 120 mg/kg body weight was administered at different time intervals (24 hr, 3 days, and 5 days) for each dose of PMSF after the hens were exposed to 30 mg/kg (i.v.) of leptophos. The scores for organophosphorus-induced delayed neuropathy (OPIDN) in all groups treated with 120 mg/kg PMSF were significantly higher than those in the group treated with leptophos only (P<0.05 or P<0.01) and the initial signs of OPIDN appeared 2 or 3 days earlier in the former groups than in the latter group. Further, the greater the PMSF post-treatment dose, the more severe were the signs of OPIDN. These findings indicate that post-treatment with PMSF promotes leptophos-induced OPIDN and reduces the period to OPIDN onset. We also examined the effects of various time intervals between PMSF administration and exposure to leptophos on the development of OPIDN. The OPIDN scores in the two groups of hen treated with PMSF on days 3 and 5 after leptophos exposure were high, especially the score of the 5 days treated group became significantly higher on the 18th and 19th day after leptophos administration than even that of the 24 hr treated group with PMSF (P<0.05). These findings suggest that variations in both the dose of PMSF and the time intervals of PMSF post-treatment may affect the delayed neurotoxicity induced by leptophos. Moreover, these results also indicate that PMSF should not be used for either the treatment or the prevention of OPIDN.


Assuntos
Inseticidas/toxicidade , Leptofós/toxicidade , Sistema Nervoso/efeitos dos fármacos , Fluoreto de Fenilmetilsulfonil/farmacologia , Animais , Peso Corporal/efeitos dos fármacos , Galinhas , Feminino , Fatores de Tempo
10.
J Environ Sci Health B ; 28(3): 275-90, 1993 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-7685784

RESUMO

Changes in acetylcholinesterase (AChE) levels in the brain and various segments of the spinal cord of birds fed subchronic repeated oral doses of 0-(4-bromo-2,5 dichlorophenyl) 0-methyl phenylphosphonothioate, (leptophos, 15 mg/kg/day) is reported. The effect of leptophos on the histological structure of the spinal cord has also been described. Three birds each of four groups tested were sacrificed 7, 14, 21 and 35 days after treatment. AChE levels in the cervical, thoracic and lumbar cord were depressed from 29%-33% after 7 days to 34%-56% after 14 days of leptophos administration. This was followed by a gradual recovery at 21 days post treatment with a further decrease (23%-48%) at 35 days post treatment. Similar decreases in brain AChE levels were also observed. Spinal cord lesions in the cervical and thoracic segments were restricted to the anterior and lateral columns, while lumbar cord lesions were restricted to the anterior column. It is concluded that routine histopathology correlated with AChE levels in the cervical, thoracic and lumbar sections of the spinal cord may be useful in monitoring the onset of clinical neuropathy in laboratory animals fed prolonged subacute doses of neurotoxicants.


Assuntos
Inibidores da Colinesterase/toxicidade , Doenças Desmielinizantes/induzido quimicamente , Leptofós/toxicidade , Degeneração Neural , Medula Espinal/efeitos dos fármacos , Animais , Encéfalo/enzimologia , Galinhas , Inibidores da Colinesterase/administração & dosagem , Feminino , Leptofós/administração & dosagem , Medula Espinal/enzimologia , Medula Espinal/patologia
11.
Neurotoxicol Teratol ; 13(1): 91-7, 1991.
Artigo em Inglês | MEDLINE | ID: mdl-1710763

RESUMO

The relationship among inhibition of acetylcholinesterase (AChE), inhibition of neuropathy target enzyme (NTE), and developmental toxicity of the organophosphorus ester desbromoleptophos (DBL) was evaluated in chicks exposed on day 3 or day 15 of incubation or 10 days posthatching. DBL induced prolonged inhibition of AChE and NTE when administered either early or late in incubation, structural malformations if administered before organogenesis, posthatching paresis if administered after organogenesis, and delayed deficits of gait if administered after hatching. The posthatching paresis and abnormal gait are not determined solely by either AChE inhibition of NTE inhibition, since they occur in the absence of the latter and are not invariably seen in the presence of the former (Toxicology 49: 253-261; 1988).


Assuntos
Leptofós/análogos & derivados , Sistema Nervoso/efeitos dos fármacos , Anormalidades Induzidas por Medicamentos , Animais , Hidrolases de Éster Carboxílico/antagonistas & inibidores , Embrião de Galinha , Galinhas , Inibidores da Colinesterase , Marcha/efeitos dos fármacos , Leptofós/toxicidade , Paresia/induzido quimicamente
12.
Nihon Eiseigaku Zasshi ; 43(6): 1159-68, 1989 Feb.
Artigo em Japonês | MEDLINE | ID: mdl-2473232

RESUMO

In an attempt to carry out a pharmacokinetic study of the organophosphorous insecticide leptophos, which is known to produce delayed neurotoxicity (DNT), a practical method for the analysis of leptophos in tissue samples has been developed by utilizing high-performance liquid chromatography. Using this method, the pharmacokinetics of intravenously administered leptophos in hens were investigated. The following results were obtained: 1. The proposed method was suitable for the analysis of leptophos in biological tissues. The detection limit was 0.5 ng and the recovery rate was over 90%. 2. The disappearance rate of leptophos in hens after administration was 70% at 6 hours and 93% at 96 hours. The half-lives calculated bi-exponentially were 1.37 hours for the early phase and 45.53 hours for the late phase. Since the leptophos detected in excreta was only 0.1% of the administered dose, its disappearance from the hen's body was due to its metabolization in the hen's tissue. 3. The half-lives of leptophos in blood calculated bi-exponentially were 0.50 and 7.57 hours. 4. The decline patterns of leptophos in tissue were considerably different from each other. While leptophos concentrations in adipose tissue and sciatic nerves decreased mono-exponentially, leptophos in other tissues (liver, kidney, heart muscle, leg muscle, brain and spinal cord) decreased bi-exponentially. The distribution of leptophos from blood to tissue seemed to be very rapid; however, redistribution from tissue to blood was extremely limited. 5. The long half-life of leptophos in sciatic nerves was especially noteworthy considering the manifestation of DNT. 6. The short half-life of leptophos in liver indicated the predominant role of liver in leptophos metabolism. 7. The results of this study do not coincide with the hypothesis that the metabolism of leptophos in species susceptible to DNT such as hens is slower than in non-susceptible species such as rats and mice. That is, in spite of the fact that this study was carried out under experimental conditions in which nerve damage would normally be manifested, leptophos was metabolized rapidly.


Assuntos
Inseticidas/farmacocinética , Leptofós/farmacocinética , Animais , Galinhas , Cromatografia Líquida de Alta Pressão , Feminino , Meia-Vida , Distribuição Tecidual
13.
J Toxicol Sci ; 14(1): 11-21, 1989 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-2472490

RESUMO

The repeated intravenous injections (RIVInj) of 5 mg/kg/day leptophos [O-(4-bromo-2, 5-dichlorophenyl) O-methyl phenylphosphonothioate] for 3 consecutive days caused delayed ataxia in 4 out of 9 hens (44.4%). And one out of 9 hens (11.1%) given RIVInj of 3 mg/kg leptophos for 5 days was affected with ataxia. Twenty hens, however, which received a single intravenous injection (SIVInj) of 15 mg/kg leptophos did not exhibit any delayed neuropathic signs at all. Thus, delayed neurotoxicity was increased by the subdividing RIVInj of the critical dose which was shown in the SIVInj of leptophos. The leptophos concentration in plasma and liver decreased very rapidly after finish of either SIVInj or RIVInj. Although no significant differences were observed in the biological half life of leptophos in plasma by different dosages, the mean level of leptophos decreased significantly with frequency of injections. On the contrary, the evident accumulation of leptophos was observed in only sciatic nerve with RIVInj. Leg muscle maintained relatively high level of leptophos after the last injection. These results suggest that leptophos seems to transfer from blood to affinitive tissues such as sciatic nerve or leg muscles and to accumulate there easily in initial stage after repeated iv injections, and that this causes the enhancement of neuropathy with repeated administrations of divided critical dose of leptophos in both iv and oral administration.


Assuntos
Ataxia/induzido quimicamente , Inseticidas/toxicidade , Leptofós/toxicidade , Animais , Galinhas , Feminino , Meia-Vida , Injeções Intravenosas/métodos , Perna (Membro) , Leptofós/administração & dosagem , Leptofós/farmacocinética , Músculos/metabolismo , Nervo Isquiático/metabolismo , Fatores de Tempo , Distribuição Tecidual , Redução de Peso/efeitos dos fármacos
14.
J Biochem Toxicol ; 4(3): 201-3, 1989.
Artigo em Inglês | MEDLINE | ID: mdl-2481746

RESUMO

The oxidative desulfuration of the three phosphorothionate insecticides--chlorpyrifos, chlorpyrifos-methyl, and leptophos--was studied in rat brain and liver. Hepatic microsomes demonstrated activities of 4-28 nmol/g/min, with male activity 2- to 4-fold higher than female activity. Very low desulfuration activity of all three compounds was observed in both microsomal and crude mitochondrial fractions from brain (3-27 pmol/g/min). There were no sex differences in the brain. Although the liver displayed 140- to 2100-fold greater activity than brain on a wet-weight basis, the brain desulfuration activities of these three compounds as well as those of some previously reported phosphorothionates generally correlate well with the toxicity and may be important in determining the overall acute toxicity levels of phosphorothionate insecticides.


Assuntos
Encéfalo/metabolismo , Clorpirifos/análogos & derivados , Clorpirifos/metabolismo , Inseticidas/metabolismo , Leptofós/metabolismo , Fígado/metabolismo , Animais , Feminino , Técnicas In Vitro , Masculino , Microssomos/metabolismo , Microssomos Hepáticos/metabolismo , Mitocôndrias/metabolismo , Oxirredução , Ratos , Ratos Endogâmicos
15.
Mem. Inst. Oswaldo Cruz ; 84(supl.4): 267-273, 1989. ilus
Artigo em Português | LILACS | ID: lil-623878

RESUMO

The author redescribes the males of Fidena (Leptofidena) morio (Wulp, 1881) based on details of external morphology and of the dissected genitalia hitherto not studied.


Assuntos
Dípteros , Dípteros/fisiologia , Genitália Masculina/anatomia & histologia , Leptofós
16.
Toxicology ; 49(2-3): 253-61, 1988 May.
Artigo em Inglês | MEDLINE | ID: mdl-2453943

RESUMO

Previous studies have demonstrated that gait is affected in chicks exposed to organophosphorus esters (OPs) that induce delayed neurotoxicity (OPIDN) in adult hens. To investigate the developmental relationship between such functional deficits and OPIDN, chicks were exposed to 3 OPs with different OPIDN potential. Desbromoleptophos (DBL) induces OPIDN in adult hens; fenthion (FEN) has uncertain OPIDN potential; fenitrothion (FTR) does not induce OPIDN. Chicks were treated by injection into the egg on day 15 of incubation, after the presumed period of OP-induced structural teratogenesis. AChE and neurotoxic esterase (NTE) were assayed during incubation and in parallel with post-hatching evaluations of gait. DBL, 125 mg/kg in ovo, caused paralysis in 70% of chicks after hatching. The gait of surviving chicks was affected for at least 6 weeks and marked by toes curling under. NTE was inhibited until 10 days post-hatching and AChE until hatching. FEN did not inhibit NTE significantly, but AChE was significantly inhibited until hatching. Chicks exposed as embryos to FEN were hyperactive and aggressive. Gait was still affected 6 weeks after treatment with 3 mg/kg FEN. FTR at 125 mg/kg inhibited AChE until day 10 post-hatching, but neither inhibited NTE nor affected gait. The growth of OP-exposed chicks was not significantly decreased, so the decreased length and increased width of the stride could not be ascribed to stunted growth. We conclude that OPs cause irreversible effects on gait that are not related to their defined neurotoxic effects, since altered gait (1) occurs below the age of sensitivity to OPIDN, (2) is seen in the absence of NTE inhibition and (3) does not invariably accompany AChE inhibition.


Assuntos
Hidrolases de Éster Carboxílico/antagonistas & inibidores , Inibidores da Colinesterase/toxicidade , Fenitrotion/toxicidade , Fention/toxicidade , Marcha/efeitos dos fármacos , Inseticidas/toxicidade , Leptofós/toxicidade , Animais , Embrião de Galinha , Galinhas , Leptofós/análogos & derivados
17.
J Toxicol Environ Health ; 23(2): 217-28, 1988.
Artigo em Inglês | MEDLINE | ID: mdl-2449534

RESUMO

The effects of multiple doses of desbromoleptophos, fenitrothion, and pure fenthion on brain acetylcholinesterase (AChE), brain neurotoxic esterase (NTE), and walking were investigated in immature chicks, below the age of sensitivity to organophosphorus ester-induced delayed neurotoxicity (OPIDN). Ten milligrams per kilogram per day of delayed neurotoxicant desbromoleptophos (DBL), 15 mg/kg.d of the non-neurotoxicant fenitrothion (FTR), and 3 mg/kg.d of the suspected neurotoxicant fenthion (FEN) were given orally for 7 d to 3-d-old chicks. Behavioral testing was performed for treated and control chicks on various days after treatment. Brain NTE and AChE assays were carried out for treated and control chicks on each day of behavioral testing. DBL altered gait and inhibited both NTE and AChE; FEN altered gait and inhibited AChE but not NTE; and FTR did not affect gait, while inhibiting AChE but not NTE. NTE and AChE inhibition were 70% and 55%, respectively, 24 h after the last treatment, for the chicks treated with DBL. NTE returned to normal levels by around d 25 and AChE by 20 d after the last treatment. FTR caused more than 50% AChE inhibition but no NTE inhibition, 24 h after last treatment. NTE inhibition for the FEN-treated chicks never exceeded 11% during the whole period of the experiment, whereas 54% inhibition of AChE was seen 1 d after last treatment. DBL and FEN significantly altered the gait of treated chicks, but the non-OPIDN-inducing FTR did not. This study confirms that alterations in the gait of young chicks are not direct consequences of either NTE or AChE inhibition, and that fenthion-induced functional deficits can be distinguished from classical OPIDN.


Assuntos
Fenitrotion/toxicidade , Fention/toxicidade , Inseticidas/toxicidade , Leptofós/toxicidade , Animais , Peso Corporal/efeitos dos fármacos , Hidrolases de Éster Carboxílico/antagonistas & inibidores , Galinhas , Inibidores da Colinesterase/toxicidade , Feminino , Marcha/efeitos dos fármacos , Leptofós/análogos & derivados , Fatores de Tempo
18.
Neurotoxicology ; 9(2): 249-71, 1988.
Artigo em Inglês | MEDLINE | ID: mdl-2462700

RESUMO

The acute biocidal effects of organophosphorus pesticides are a central feature of modern agricultural chemistry, and also define the concerns of regulatory toxicology. Less well known, but more complex and idiosyncratic, is the potential for some agents to produce a delayed and progressive polyneuropathy--Organophosphorus Induced Delayed Neurotox-icity (OPIDN). On three occasions during the past ten years, the National Institute for Occupational Safety and Health (NIOSH) had been asked to evaluate human delayed neurotoxicity from three commercially available pesticides. These were leptophos, fenthion, and isofenphos. In each case, human disease was either observed or suggested by specialized toxicity testing. The reasons that federally recommended screening measures failed to identify a potential for human neurotoxicity were not accidental, but stem from a systematic approach that focuses on a traditional definition of acute lethal toxicity. The oral single dose study on one species appears to be insufficient for recognizing the delayed neurotoxic hazard of many representatives of this chemical class. The recent addition of a recommended biochemical assay--neurotoxic esterase (NTE)--to federal guidelines potentially improves sensitivity, but it is purely adjunctive and does not amend underlying ambiguities in selecting the dose and route of administration. It is also quite probable that human neurotoxicity may be a potential hazard from exposure to more than the handful of organophosphorus pesticides that have been described in the literature.


Assuntos
Doenças do Sistema Nervoso/induzido quimicamente , Compostos Organotiofosforados/toxicidade , Fention/toxicidade , Humanos , Leptofós/toxicidade
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...