RESUMEN
Phenoxyacetate herbicides, such as 2,4-D and MCPA, having a high toxicity to non-target organisms are commonly used for controlling broadleaf weeds in agriculture. However, novel and environmentally friendly analogs are constantly sought after. For this purpose, various substituents at the phenyl group have been tested to find the optimal balance between the potent herbicidal activity and safety for non-target species. In this work, we investigated the influence of the oxygen by sulfur replacement in the phenoxy moiety of ammonium chlorophenoxyacetates on the toxicity towards aquatic organisms, such as bacteria (Vibrio fischeri), water flea (Daphnia magna) and freshwater fish (Pimephales promelas) by determining experimental (Microtox® test - V. fischeri) and predicted (ACD Lab Percepta software - D. magna, P. promelas) EC50/LC50 values. The achieved results showed that in contrary to the literature observations, where O-compounds were more toxic than their S-analogs (urea/thiourea), the O/S replacement in chlorophenoxyacetate significantly increased ecotoxicity of the S-analogs (up to 11 times). Moreover, one- and two-substituted phenoxyacetates in the form of ammonium salts were less toxic to V. fischeri than the commercially available phenoxy herbicides in the acid form. The logP/logD values were also calculated to understand hydro/lipophilic nature of the investigated compounds and differences in their toxicity.
Asunto(s)
Aliivibrio fischeri/efectos de los fármacos , Compuestos de Amonio/toxicidad , Cyprinidae , Daphnia/efectos de los fármacos , Herbicidas/toxicidad , Fenoxiacetatos/toxicidad , Contaminantes Químicos del Agua/toxicidad , Aliivibrio fischeri/metabolismo , Compuestos de Amonio/química , Animales , Herbicidas/química , Dosificación Letal Mediana , Luminiscencia , Oxígeno/química , Fenoxiacetatos/química , Azufre/química , Contaminantes Químicos del Agua/químicaRESUMEN
Systemic treatment of rats with peroxisome proliferator-activated receptor (PPAR) agonists (mainly of dual alpha/gamma activity) has indicated that they may invoke non-genotoxic carcinogenesis in the epithelial lining of the urinary tract (urothelium). Although there is evidence in the male rat to support an indirect effect via a crystaluria-induced urothelial damage response, there is other evidence to indicate a direct signalling effect on the urothelium and hence the full implication for using these drugs in man is unclear. Numerous reports have demonstrated that PPARs are expressed within the urothelium of different species, including man, and from an early developmental stage. We have developed methods to maintain normal human urothelial (NHU) cells in culture, where the cells retain PPAR expression and express a highly proliferative phenotype, mediated via autocrine stimulation of the epidermal growth factor (EGF) receptor. We have shown that specific activation of PPARgamma results in a programme of gene expression changes associated with late/terminal cytodifferentiation, including induction of cytokeratins CK13 and CK20, tight junction-associated claudin 3, and uroplakins UPK1a and UPK2, but this is dependent upon inhibition of the signalling cascade downstream of the EGF receptor. This indicates a subtle balance in the regulation of proliferation and differentiation in urothelium, with PPARgamma agonists promoting differentiation. Our data indicate that human urothelium is a target tissue for PPARgamma signalling, but it has yet to be determined whether dual agonists could have a modulatory effect on the proliferation/differentiation balance.
Asunto(s)
Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Receptores Activados del Proliferador del Peroxisoma/agonistas , Urotelio/efectos de los fármacos , Muerte Celular/efectos de los fármacos , Células Cultivadas , Receptores ErbB/efectos de los fármacos , Receptores ErbB/metabolismo , Fenofibrato/toxicidad , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Hidrazinas , Receptores Activados del Proliferador del Peroxisoma/metabolismo , Fenoxiacetatos/toxicidad , Transducción de Señal/efectos de los fármacos , Tiazoles/toxicidad , Urotelio/metabolismo , Urotelio/patologíaRESUMEN
PURPOSE: To investigate if a platelet inhibitor (aurintricarboxylic acid [ATA]) and a heparin-mimicking antagonist (RG-13577) of basic fibroblast growth factor 2 (bFGF2) could be combined as a stable compound and attached to conventional bare metal stents to hinder thrombus formation and inflammatory reactions of stenting. METHODS: Fifteen domestic pigs were stented with RG-13577/ATA-coated (n=6), ATA-coated (n=12), and bare metal stents (n=12) in the left anterior descending (LAD) and left circumflex (LCX) coronary arteries. All surviving pigs were evaluated with contrast angiography and intravascular ultrasonography (IVUS) after 4 weeks. Histological analysis of the stented arteries was performed after hematoxylin-eosin staining. Tissue factor (TF) staining and scanning electron microscopy (SEM) were performed in animals with acute stent thrombosis. RESULTS: Five of the 6 animals receiving an RG-13577/ATA-coated stent experienced acute stent thrombosis, while no adverse events occurred in the animals of the other 2 groups. Follow-up angiography did not show significant in-stent stenosis in either bare or ATA-coated stents. However, histomorphometry revealed larger neointimal area (3.54+/-0.69 mm2 versus 1.82+/-0.27 mm2, p<0.05) and outward plaque area (1.56+/-0.34 mm2 versus 0.61+/-0.12 mm2, p<0.05) in ATA-coated stents. Three-dimensional IVUS analysis showed analogous results, with significantly larger neointimal volume and outward plaque volume in ATA-coated stents. There was a slight increase in TF staining around the stent struts, while SEM showed increased platelet adhesion and activity in RG-13577/ATA-coated stents versus the ATA-coated and bare metal stents. CONCLUSION: RG-13577/ATA-coated stents lead to acute stent thrombosis. The ATA coating alone did not lead to acute events, but resulted in higher neointimal hyperplasia and expansive remodeling. These results underline the importance of preclinical studies before using new coated stents in human arteries.
Asunto(s)
Ácido Aurintricarboxílico/farmacología , Ácido Aurintricarboxílico/toxicidad , Vasos Coronarios/efectos de los fármacos , Factor 2 de Crecimiento de Fibroblastos/antagonistas & inhibidores , Fenoxiacetatos/farmacología , Fenoxiacetatos/toxicidad , Inhibidores de Agregación Plaquetaria/farmacología , Inhibidores de Agregación Plaquetaria/toxicidad , Polímeros/farmacología , Polímeros/toxicidad , Stents , Trombosis/etiología , Animales , Ácido Aurintricarboxílico/administración & dosificación , Angiografía Coronaria , Reestenosis Coronaria/prevención & control , Vasos Coronarios/patología , Combinación de Medicamentos , Evaluación Preclínica de Medicamentos , Hiperplasia , Microscopía Electrónica de Rastreo , Fenoxiacetatos/administración & dosificación , Inhibidores de Agregación Plaquetaria/administración & dosificación , Polímeros/administración & dosificación , Stents/efectos adversos , Porcinos , Trombosis/diagnóstico por imagen , Trombosis/patología , Insuficiencia del Tratamiento , Túnica Íntima/efectos de los fármacos , Túnica Íntima/patologíaRESUMEN
The potential toxic and mutagenic action of 2,4-dichlorophenoxyacetic acid has been studied in different test systems, and the obtained results range from increased chromosomal damage to no effect at all. We reexamined the effect of this herbicide by simultaneous using three tests based on yeast, transformed hematopoietic, and mouse bone marrow cells. The results obtained demonstrated that 2,4-dichlorophenoxyacetic acid has cytotoxic and mutagenic effects. The positive response of yeast and transformed hematopoietic cells was verified in kinetics and dose-response experiments. The analysis of metaphase chromosomes indicated a statistically proved induction of breaks, deletions, and exchanges after the intraperitoneal administration of 2,4-dichlorophenoxyacetic acid in mice. The study of phenoxyacetic acid and its differently chlorinated derivatives showed that cytotoxicity and mutagenicity are induced by chlorine atoms at position 2 and/or 4 in the benzene ring. The mutagenic effect was abolished by introduction of a third chlorine atom at position 5. Thus 2,4,5-trichlorophenoxyacetic acid was found to have very weak, if any mutagenic effect; however, the herbicide preserved its toxic effect.
Asunto(s)
Mutágenos/toxicidad , Fenoxiacetatos/toxicidad , Ácido 2,4,5-Triclorofenoxiacético/toxicidad , Ácido 2,4-Diclorofenoxiacético/química , Ácido 2,4-Diclorofenoxiacético/toxicidad , Animales , Cloro/química , Cromosomas/efectos de los fármacos , Cromosomas/ultraestructura , Femenino , Células Madre Hematopoyéticas/efectos de los fármacos , Herbicidas/toxicidad , Masculino , Ratones , Ratones Endogámicos C57BL , Índice Mitótico , Mutágenos/química , Plaguicidas/química , Plaguicidas/toxicidad , Fenoxiacetatos/química , Saccharomyces cerevisiae/efectos de los fármacos , Saccharomyces cerevisiae/genética , Relación Estructura-ActividadRESUMEN
The mutagenic activity of the new antitumour agent 3 beta-hydroxy-13 alpha-amino-13,17-seco-5 alpha-androstan-17-oic-13,17-lactam- p-N,N-bis(2-chloroethyl)aminophenoxyacetate (NSC 294859) was studied in the Salmonella/microsome assay. It was found to induce base pair substitutions, causing dose-dependent increases in his+ revertants in strains TA100 and TA1535. The alkylating moiety, p-N,N-bis(2-chloroethyl)-aminophenoxyacetic acid, was shown to be less effective than the parent compound, while the modified steroid moiety, 3 beta-hydroxy-13 alpha-amino-13,17-seco-5 alpha-androstan-17-oic-13,17-lactam, showed no mutagenic effect in all strains used. The presence of metabolic activation enzymes in the test system induced a further increase in his+ revertants in strains TA100 and TA1535, in both the parent compound and the alkylating moiety of the parent compound, while it had no effect in the case of the steroidal lactam.
Asunto(s)
Antineoplásicos/toxicidad , Mutagénesis , Mutágenos/toxicidad , Compuestos de Mostaza Nitrogenada/toxicidad , Androstanos/toxicidad , Azaesteroides/toxicidad , Distribución de Chi-Cuadrado , Análisis Mutacional de ADN , ADN Bacteriano/genética , Mutación del Sistema de Lectura , Extractos Hepáticos , Microsomas Hepáticos/enzimología , Pruebas de Mutagenicidad , Compuestos de Mostaza Nitrogenada/química , Fenoxiacetatos/toxicidad , Mutación Puntual , Reproducibilidad de los Resultados , Salmonella typhimurium/efectos de los fármacos , Salmonella typhimurium/genéticaRESUMEN
The effects of ethyl 4-chloro-2-methylphenoxyacetate (MCPA) and other phenoxyacid compounds on hepatic xenobiotic metabolizing enzymes were studied in male rats. These compounds were administered orally 200 mg/kg/day to the rats for 2 weeks. Both MCPA and clofibrate increased the hepatic level of cytochrome P-450. In the MCPA-treated group, the activities of aniline hydroxylase and 7-ethoxycoumarin O-deethylase increased by 15% and 1.5-fold, respectively. The free acid form of MCPA increased these activities more potently than MCPA. Both MCPA and its free acid did not change the activity of aminopyrine N-demethylase. A marked increase in the activity of aniline hydroxylase was noted in the 2,4-dichlorophenoxyacetic acid-treated group, whereas the aminopyrine N-demethylase activity significantly decreased in the same group. Clofibrate also increased the activities of hepatic microsomal cytochrome P-450-mediated oxidation tested, but to a lesser extent when compared with the effects of MCPA. These results indicate that MCPA may have a potent effect on the hepatic metabolizing enzymes in rats, and also that the induction of xenobiotic metabolizing enzymes may change when the chemical moiety of phenoxyacid compounds is modified.
Asunto(s)
Ácido 2-Metil-4-clorofenoxiacético/toxicidad , Hígado/efectos de los fármacos , Xenobióticos/metabolismo , Animales , Clofibrato/toxicidad , Metabolismo de los Lípidos , Hígado/metabolismo , Masculino , Estructura Molecular , Fenoxiacetatos/química , Fenoxiacetatos/toxicidad , Proteínas/metabolismo , Ratas , Ratas EndogámicasRESUMEN
Chick embryos were treated on day 0 of incubation with two phenoxy herbicides, 2-methyl-4-chlorophenoxyacetic acid (MCPA) (0.4, 2 mg/egg) and 2,4-dichlorophenoxyacetic acid (2, 4-D) (1, 2, 4 mg/egg). Both herbicides seemed to exert toxic effects mainly on the liver of 19-day-old embryos. Specific histological analysis indicated biliary stasis. Ethoxycoumarin O-deethylase was depressed by MCPA but raised by 2, 4-D. Other hepatic monooxygenase activities were unaffected by the herbicides and no significant changes were found in cytochromes. The higher dose of MCPA increased NADPH-cytochrome P450 reductase. 2,4-D treatment increased by activity of glutathione-S-transferases in the hepatic post-microsomal fraction while MCPA increased them at the lower dose and significantly reduced them at the higher. The phenoxyacetic herbicides appear thus to have some effects on hepatic drug metabolizing enzymes of the chick embryo which cannot be easily interpreted. Biliary retention, produced in particular by MCPA, could be partly responsible for these effects.
Asunto(s)
Herbicidas/toxicidad , Hígado/enzimología , Oxigenasas de Función Mixta/metabolismo , Fenoxiacetatos/toxicidad , Ácido 2,4-Diclorofenoxiacético/toxicidad , Ácido 2-Metil-4-clorofenoxiacético/toxicidad , Animales , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Embrión de Pollo , Hígado/efectos de los fármacos , Hígado/patología , Tamaño de los Órganos/efectos de los fármacosRESUMEN
In a case-control study including 237 cases with soft tissue sarcoma and 237 controls, previous jobs and exposures to different agents, including pesticides, were assessed. Exposure to phenoxyacetic acids or chlorophenols gave a statistically significant increased rate ratio (RR) of 1.80 [95% confidence interval (CI) = 1.02-3.18] for soft tissue sarcoma. Exposure to phenoxyacetic acids of all types gave a nonsignificantly increased RR of 1.34 (95% CI = 0.70-2.56). During the 1950s, exposure to 2,4,5-trichlorophenoxyacetic acid gave a threefold significantly increased risk. High-grade exposure to chlorophenols, which are also contaminated by dioxins, gave an RR of 5.25 (95% CI = 1.69-16.34). The increased risk was thus attributed to dioxin-contaminated phenoxyacetic acids or chlorophenols that gave an RR of 2.43 (95% CI = 1.30-4.54).
Asunto(s)
Dioxinas/toxicidad , Sarcoma/inducido químicamente , Adulto , Anciano , Estudios de Casos y Controles , Clorofenoles/toxicidad , Relación Dosis-Respuesta a Droga , Humanos , Masculino , Persona de Mediana Edad , Fenoxiacetatos/toxicidad , Factores de Riesgo , Encuestas y Cuestionarios , SueciaRESUMEN
The induction of hepatic peroxisome proliferation and drug metabolizing enzymes and of sister chromatid exchange (SCE) in lymphocytes was studied in male Han/Wistar rats after exposing them for 2 weeks to a commercial chlorophenolate formulation (Ky-5) (100 mg/kg/day), to 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD; 0.05-5 micrograms/kg/wk) and to the pure phenoxyacetic acids, 2,4-dichlorophenoxyacetic acid (2,4-D; 100 mg/kg/day) and 2-chloro-4-methylphenoxyacetic acid (MCPA; 100 mg/kg/day). The chlorophenolate formulation and pure 2,4-D and MCPA caused significant increases in the number of peroxisomes in liver cells, although the average size of peroxisomes was not affected, whereas the effect of even the highest dose of 2,3,7,8-TCDD remained small. This finding indicates that dioxin impurities do not account for the peroxisome proliferation induced by chlorophenolate. The relative weight of the liver increased significantly in rats treated with the chlorophenolate formulation and with 2,3,7,8-TCDD (5.0 and 0.5 micrograms/kg). The pattern of induction of xenobiotic metabolizing enzymes showed some differences between chlorophenolate treatment and 2,3,7,8-TCDD treatment. Furthermore, the effects of pure phenoxyacetic acids were different from that seen with chlorophenolate and 2,3,7,8-TCDD. The highest dose of 2,3,7,8-TCDD increased the frequency of SCE in circulating lymphocytes slightly, but significantly.
Asunto(s)
Dioxinas/toxicidad , Glicolatos/toxicidad , Insecticidas/toxicidad , Hígado/efectos de los fármacos , Microcuerpos/efectos de los fármacos , Fenoxiacetatos/toxicidad , Dibenzodioxinas Policloradas/toxicidad , Intercambio de Cromátides Hermanas/efectos de los fármacos , Xenobióticos/metabolismo , Animales , Peso Corporal/efectos de los fármacos , Glutatión/metabolismo , Hígado/patología , Hígado/ultraestructura , Masculino , Tamaño de los Órganos/efectos de los fármacos , Ratas , Ratas EndogámicasRESUMEN
A population-based case-control study was conducted in western Washington State to evaluate the relationship between occupational exposure of men aged 20-79 to phenoxyacetic acid herbicides and chlorinated phenols and the risks of developing soft tissue sarcoma (STS) and non-Hodgkin's lymphoma (NHL). Occupational histories and other data were obtained by personal interviews for 128 STS cases and 576 NHL cases, diagnosed between 1981 and 1984, and for 694 randomly selected controls without cancer. Among the study subjects with any past occupational exposure to phenoxyherbicides, the estimated relative risk and 95% confidence interval of developing STS was 0.80 (0.5-1.2), and of developing NHL, 1.07 (0.8-1.4). Risk estimates of developing STS and NHL associated with past chlorophenol exposure were 0.99 (0.7-1.5) and 0.99 (0.8-1.2), respectively. No increasing risk of either cancer was associated with overall duration or intensity of chemical exposure or with exposure to any specific phenoxyherbicide per se. However, estimated risks of NHL were elevated among men who had been farmers, 1.33 (1.03-1.7), forestry herbicide applicators, 4.80 (1.2-19.4), and for those potentially exposed to phenoxyherbicides in any occupation for 15 years or more during the period prior to 15 years before cancer diagnosis, 1.71 (1.04-2.8). Increased risks of NHL were also observed among those with occupational exposure to organochlorine insecticides, such as DDT [1.82 (1.04-3.2)] and organic solvents [1.35 (1.06-1.7)], and to other chemicals typically encountered in the agricultural, forestry, or wood products industries. These results demonstrate small but significantly increased risks of developing NHL in association with some occupational activities where phenoxyherbicides have been used in combination with other types of chemicals, particularly for prolonged periods. They do not demonstrate a positive association between increased cancer risks and exposure to any specific phenoxyherbicide product alone. Moreover, these findings provide no evidence of increased risks of developing NHL associated with chlorinated phenol exposure or of developing STS associated with exposure to either class of chemical.
Asunto(s)
Clorofenoles/toxicidad , Glicolatos/toxicidad , Herbicidas/toxicidad , Linfoma no Hodgkin/inducido químicamente , Enfermedades Profesionales/inducido químicamente , Fenoxiacetatos/toxicidad , Sarcoma/inducido químicamente , Neoplasias de los Tejidos Blandos/inducido químicamente , Adulto , Anciano , Humanos , Persona de Mediana Edad , Dibenzodioxinas Policloradas/toxicidad , Riesgo , Factores de Tiempo , WashingtónRESUMEN
Uricosuric diuretics have been developed to counteract renal urate retention accompanying diuretic-induced extracellular volume contraction. Their intrinsic uricosuric activity would prevent diuretic-induced hyperuricemia. Ticrynafen, a prototype uricosuric diuretic, has largely fallen into disuse because of hepatic toxicity. However, one lesson learned during the short period that ticrynafen was available in the US is that the administration of a potent uricosuric agent to a patient previously trated with diuretics can precipitate acute renal failure, possibly as a consequence of uric acid nephropathy. Another novel uricosuric diuretic, indacrinone, is composed of two enantiomorphic isomers exhibiting predominantly either a uricosuric or a natriuretic action. Manipulation of the isomer ratio currently is being attempted with a view toward obtaining a combination that produces little change in the serum urate during chronic diuretic therapy. Uricosuric diuretics have the therapeutic potential to treat hypertension and edematous states without increasing the serum urate. Although current information suggests that chronic asymptomatic hyperuricemia poses very little health hazard, future data could indicate that it may be desirable to maintain the serum urate near the normal range
Asunto(s)
Humanos , Ácido Úrico/efectos adversos , Uricosúricos/uso terapéutico , Diuréticos/uso terapéutico , Ácido Acético/metabolismo , Ácido Acético/farmacocinética , Ácido Acético/uso terapéutico , Ácido Acético/toxicidad , Uricosúricos/efectos adversos , Uricosúricos/farmacocinética , Diuréticos/efectos adversos , Fenoxiacetatos/metabolismo , Fenoxiacetatos/farmacocinética , Fenoxiacetatos/uso terapéutico , Fenoxiacetatos/toxicidad , Ticrinafeno/metabolismo , Ticrinafeno/farmacocinética , Ticrinafeno/uso terapéutico , Ticrinafeno/toxicidadRESUMEN
Peroxisomal beta-oxidation of fatty acids and the activities of glutathione-metabolizing enzymes in rat liver were measured after administration of 2,4-dichlorophenoxyacetic acid (2,4-D), 4-chloro-2-methylphenoxyacetic acid (MCPA), clofibrate [ethyl], 2-(p-chlorophenoxy)-2-methylpropionate], glyphosate (N-phosphonomethyl glycine, a herbicide not structurally related to phenoxy acids) or saline for 14 days. beta-Oxidation increased by 6-fold in the group given clofibrate, 3-fold in the 2,4-D-treated group, and 2-fold in the MCPA-treated group over the level in the controls (saline-treated). Glyphosate did not increase beta-oxidation. No significant change in reduced glutathione content from that in controls was found in any of the treated groups. Glutathione reductase activity increased by about 40% after administration of either 2,4-D or MCPA, and glutathione peroxidase activity increased by 30% in animals given MCPA. A slight decrease in glutathione S-transferase activity was found in the group treated with clofibrate. The marked increases in peroxisomal beta-oxidation of fatty acids were accompanied by only minor changes in the activities of enzymes involved in glutathione-dependent inactivation of organic hydroperoxides and other oxygen-centred reactive agents.
Asunto(s)
Ácidos Grasos/metabolismo , Glutatión/metabolismo , Glicolatos/toxicidad , Hígado/ultraestructura , Microcuerpos/metabolismo , Fenoxiacetatos/toxicidad , Ácido 2,4-Diclorofenoxiacético/toxicidad , Ácido 2-Metil-4-clorofenoxiacético/toxicidad , Animales , Clofibrato/toxicidad , Glutatión Peroxidasa/metabolismo , Glutatión Reductasa/metabolismo , Glutatión Transferasa/metabolismo , Glicina/análogos & derivados , Glicina/toxicidad , Herbicidas/toxicidad , Masculino , Microcuerpos/efectos de los fármacos , Oxidación-Reducción , Ratas , Ratas Endogámicas , GlifosatoAsunto(s)
Glicolatos/metabolismo , Fenoxiacetatos/metabolismo , Propionatos/metabolismo , Ácido 2,4,5-Triclorofenoxiacético/metabolismo , Ácido 2,4,5-Triclorofenoxiacético/toxicidad , Ácido 2,4-Diclorofenoxiacético/metabolismo , Ácido 2,4-Diclorofenoxiacético/toxicidad , Ácido 2-Metil-4-clorofenoxiacético/análogos & derivados , Ácido 2-Metil-4-clorofenoxiacético/metabolismo , Ácido 2-Metil-4-clorofenoxiacético/toxicidad , Absorción , Animales , Fenómenos Químicos , Química , Masculino , Fenoxiacetatos/toxicidad , Propionatos/toxicidad , Ratas , Relación Estructura-Actividad , Factores de TiempoRESUMEN
The herbicide 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) and two structurally related compounds, phenoxyacetic acid and 2,4,5-trichlorophenol, were suspended in a 1:1 solution of honey:water and administered by gavage to pregnant mice on one of gestation days 8-15 (copulation plug day = day 1) or on three consecutive days (7-9, 10-12, or 13-15). Doses were 800-900 mg/kg for single and 250-300 mg/kg/day for multiple treatments. With the exception of 2,4,5-trichlorophenol treatment on day 14, only 2,4,5-T treatment significantly increased prenatal mortality, and only 2,4,5-T was associated with decreased fetal weight when comparisons were made with the solvent controls. Although low incidences were seen in all treatment groups, only 2,4,5-T significantly increased cleft palate or other gross malformations. Significant skeletal, visceral or histopathological defects were not observed. These results indicate that both the carboxyl group and chlorination of the aromatic ring are essential for an unambiguous teratogenic response.
Asunto(s)
Ácido 2,4,5-Triclorofenoxiacético/toxicidad , Clorofenoles/toxicidad , Feto/efectos de los fármacos , Glicolatos/toxicidad , Fenoxiacetatos/toxicidad , Anomalías Inducidas por Medicamentos , Animales , Peso Corporal/efectos de los fármacos , Fisura del Paladar/inducido químicamente , Femenino , Muerte Fetal/inducido químicamente , Edad Gestacional , Herbicidas/toxicidad , Ratones , EmbarazoAsunto(s)
Hidrocarburos Clorados/toxicidad , Animales , Carcinógenos , Sistema Nervioso Central/efectos de los fármacos , Clorobencenos/toxicidad , Clorofenoles/toxicidad , DDT/toxicidad , Hexaclorociclohexano/toxicidad , Humanos , Inmunidad/efectos de los fármacos , Insecticidas/toxicidad , Riñón/efectos de los fármacos , Hígado/efectos de los fármacos , Mutágenos , Fenoxiacetatos/toxicidad , Bifenilos Policlorados/toxicidad , Dibenzodioxinas Policloradas/toxicidad , Reproducción/efectos de los fármacos , Especificidad de la EspecieRESUMEN
Animal experiments ascertained that the repellent N,N-diethylamide of phenoxyacetic acid (P-203) increases the frequency of chromosomal aberration in the bone marrow cells of mice following its intraperitoneal introduction and also in the cells of a regenerating liver of rats after its repeated skin application. Dimethylphthalate displayed a mutagenic action only with respect to the rats' hepatocytes when applied repeatedly to the skin.