Craniofacial ossification in rat fetuses following prenatal exposure to dimethoate and carbosulfan insecticides

Pesticides, including insecticides, occupy a unique position among many chemicals that man encounters daily for the purpose of pest control in all agricultural programs. In fact, most of such chemicals are not highly selective and constitute potential hazard to many non-target species including man and other animals. The present study aimed to study the teratogenic effects of both dimethoate and carbosulfan insecticides on the ossification of craniofacial bones in albino rat fetuses. In this study, fifty female albino rats were allocated to ten groups [5/each group]; control, low dose dimethoate 1/40 LD50 [8.25 mg/kg], medium dose dimethoate 1/20 LD5O [16.5 mg/kg], high dose dimethoate 1/10 LD50 [33 mg/kg], low dose carbosulfan 1/40 LD50 [5.2 mg/kg], medium dose carbosulfan 1/20 LD50 [10.45 mg/kg], high dose carbosulfan 1/40 LD50 [20.9 mg/kg], mixed low doses of dimethoate and carbosulfan, mixed medium doses of dimethoate and carbosulfan, and mixed high doses of dimethoate and carbosulfan. Animals of all groups were sacrificed in the morning of 20[th] day of gestation. Then all specimens were stained with alizarin red stain for evaluation of ossification of skeletal system. The results of the present study revealed that both dimethoate and carbosulfan insecticides, had a deleterious effect on the ossification of craniofacial bones and that the most affected bones were supraoccipital, presphenoid, and interparietal bones. These effects were marked in the high doses and mixed low dose groups. It is concluded that the deleterious effects were increased with the increasing dose of either dimethoate or carbosulfan insecticides and that the mixture of low doses had an effect near to that of medium and sometimes high doses

Dimethoate 40 percent organosphosphorous pesticide toxicity in Prochilodus lineatus (Prochilodontidae, Characiformes) eggs and larvae

Os testes de toxicidade com os primeiros estágios de vida de peixes são de elevada importância no que se refere ao comprometimento das fases de crescimento, reprodução e sobrevivência dos organismos em ambientes poluídos, constituindo uma ferramenta importante para um adequado monitoramento ambiental. Entretanto, um pequeno número de bioensaios desta natureza tem sido desenvolvido no Brasil. O curimbatá (Prochilodus linetaus) é um peixe da ordem Characidae de grande interesse comercial e muito abundante na América do Sul. A espécie foi utilizada para testar diferentes concentrações de dimetoato 40%, um pesticida organofosforado inibidor da enzima acetilcolinesterase (AChE) utilizado em grande escala no Brasil. A CL50 (48h) para ovos é superior a 16,0 µg.L-1; entretanto para larvas recém-eclodidas foi significativamente mais baixa (11,81 µg.L-1 , variando de 10.23 a 13,65) de acordo com o teste-t para amostras independentes (p = 0.03). A CL50 para larvas com 3 dias de vida foi de 10,44 µg.L-1 (8,03-13,57), apresentando-se similar ao resultado encontrado para larvas recém-eclodidas (p = 0.76). A mobilidade das larvas foi reduzida na presença deste pesticida.

Biochemical effects of some organophosphorus pesticides on the ovaries of albino rats.

An evaluation of the toxic effects of three organophosphates; monocrotophos, dimethoate and methyl parathion on female reproduction was made by biochemical estimations of cytoplasmic and membrance bound proteins, lipids, phospholipids and cholesterol in the rat ovaries after treatment with their low residual level doses (LD50 1/8-1/5) to three groups of six rats each for 90 days. All the three pesticides caused degenerative changes in the ovaries as evidenced by a significant decrease in the concentration of cytoplasmic as well as membrane bound proteins, total lipids, phospholipids and cholesterol. The observations are thus indicative of the reproductive toxicity caused by organophosphates at cellular and molecular level in the ovaries of rats.

Enzymatic changes induced by some organophosphorus pesticides in female rats.

An evaluation of toxic effects of three organophosphorus pesticides viz. monocrotophos, methyl parathion and dimethoate given orally daily for 90 days was done in terms of enzymatic changes in plasma and liver of female albino rats. A significant decrease was observed in the level of esterases in plasma with all the three pesticides. The activity of acid and alkaline phosphatases and aminotransferases increased significantly in plasma and significantly or marginally in liver with these pesticides. The results are thus indicative of the cellular toxicity of these organophosphates even after their subchronic administration in low doses for a long period.

Effect of Dimethoate (Rogor 30% EC) on the brain neurosecretory cells of third instar grubs of Oryctes rhinoceros L. (Coleoptera : Scarabaeidae).

The brain neurosecretory cells of III instar grubs of Oryctes rhinoceros were exposed to insecticide Dimethoate (Rogor 30% EC) in the laboratory condition. The sublethal doses (0.125, 0.25 and 0.5%) of Rogor at time intervals of 8, 16 and 24 h have produced marked changes in the structure and the secretory activities of medial and lateral neurosecretory cells. Rogor stimulates the synthetic activity of these cells at the initial stages of its action and results in the accumulation of neurosecretory materials (NSM) in the cytoplasm. The decreased neurosecretion at later stages of the action was due to its transportation through the axons before the death of treated grubs. Similarly, vacuolization, shrinking and degeneration of cells were also observed in treated grubs.

Development effect of technical dimethoate in rats: maternal and fetal toxicity evaluation.

Technical dimethoate was administered orally to pregnant rats through day 6-20 of gestation at doses 3.75, 7.5, 15 and 30 mg/kg/day. Dose of 30 mg/kg/day produced high mortality rate in dams and was not considered for developmental toxicity evaluation. Dimethoate produced enzymatic changes in liver of dams associated with mild pathomorphological changes in liver and brain. Significant fetotoxic effects were not observed at the tested dose levels as evidenced by total number of implantations, percentage resorption, and live fetuses except reduction in fetal weight. Reduced acetylcholinesterase activity in fetal brain and placenta at higher dose levels indicated possible transmigration of dimethoate from dams to fetuses. The absence of anomalies in fetal gross, visceral morphology and skeleton suggests technical dimethoate as non teratogenic in rat at tested dose levels.

Changes in serum lipid profile and esterases of rats after sublethal daily doses of dimethoate

Male Wistar rats were injected by dimethoate [10 mg/0.5 ml] daily for 8 successive days. Controls received the same amount of saline. A group of 5 rats were anesthetized at 0, 2, 4, 6 and 8 days of injection. Blood was withdrawn from heart. Serum lipid components and 4 species of serum esterases were assayed for each group. A general decrease in the activities of serum esterases was observed. - A marked decrease also was observed in lipids profile during the 8 days course of experiment

Simposio. Avances recientes con ifosfamida/mesna en el tratamiento de tumores sólidos malignos: estudio fase II con ifosfamida, mesna y carboplatino en el tratamiento del cáncer cervicouterino etapa IIB / Symposium. Recent Advances with ifosfamide/Mesna in the treatment of malignant solid tumors: Phase II study in carcinoma of the uterine cervix clinical stage IIB with ifosfamide, mesna and carboplatin

Los casos de carcinoma cervicouterino se diagnostican en la mayoría de las pacientes en etapas localmente avanzadas. Esto evita el abordaje quirúrgico. La quimioterapia combinada neoadyuvante ha demostrado reducción tumoral en más de la mitad de los casos tratados. En el Instituto Nacional de Cancerología, elaboramos un estudio fase II con objeto de determinar la eficacia y la toxicidad de la combinación de ifosfamida+mesna+carboplatino. También se evaluó la posibilidad de intervenir quirúrgicamente a las enfermas con carcinoma cervicouterino etapa IIB. Se incluyeron 20 pacientes sin tratamiento previo y con edad promedio de 42 años. Todas recibieron tres ciclos de quimioterapia cada cuatro semanas con carboplatino 300 mg/m² el día 1+ifosfamida 3g/m²/día por dos días en infusión contínua de 24 horas; mesna 600mg por vía intravenosa (bolo) directo antes de ifosfamida; 3,000 mg en la solución de la ifosfamida en infusión de 24 horas por dos días. Al término de ésta se administró 1,500 mg de mesna en 1,00 ml de solución glucosada en infusión de 12 horas. Se obtuvieron cuatro respuestas completas y nueve parciales; tres pacientes cursaron con enfermedad estable y cuatro progresaron. En dos enfermas sometidas a cirugía, los especímenes mostraron: carcinoma in situ residual en una mujer y en la otra no hubo actividad tumoral. De 18 pacientes que recibieron radioterapia posterior a la quimioterapia, 13 tuvieron respuesta completa, una mostró respuesta parcial y cuatro progresaron. La toxicidad para 54 ciclos de quimioterapia fue predominantemente medular; neutropenia grado 1-2 (6 por ciento), grado 3-4 (62 por ciento); plaquetopenia grado 0 (90 por ciento), grado 1-2 (44 por ciento) y grado 3 (4 por ciento). No se observó ningún proceso séptico asociado a la neutropenia. Se presentó emesis grado 2-3 en el 42 por ciento y alopecia grado 3 en el 75 por ciento. El seguimiento promedio para todas la pacientes fue de 12 meses. El intervalo libre de progresión en 14 casos con respuesta completa (13 con quimioterapia+radioterapia y uno con quimioterapia+cirugía) fue de 14.3 meses promedio (extremos 6-19 meses). Los resultados obtenidos con esta combinación confirman un alto índice de respuestas objetivas (65 por ciento) y completas (20 por ciento) con toxicidad moderada. La quimioterapia neoadyuvante puede reducir suficientemente el volumen tumoral; esto permite la cirugía en pacientes tradicionalmente consideradas con enfermedad irresecable

Toxicity of dimethoate on urinary hydroxyproline in rats.

The effect of the administration of three different concentrations (2.25, 1.13 and 0.56 mg/100 g body weight) of dimethoate on the urinary excretion of total, non dialysable and free hydroxyproline were studied in female albino rats. Compared to controls, the urine contents were significantly lower in higher concentration (2.25 mg/100 g body weight) of dimethoate treated rats. The results clearly indicate that the urine contents were not much affected in lower concentration (0.56 mg/100 g body weight) of dimethoate treated rats compared to the other concentrations (1.13 and 0.56 mg/100 g body weight) of dimethoate treated rats.

Effect of dimethoate and fenvalerate on conditioned avoidance and passive avoidance responses.

Dimethoate at 24.75 and 49.5 mg/kg (i.e., 1/10 and 1/5th LD50 respectively) impaired the learning process and retrieval of memory in rats while it did not affect permanent memory. Fenvalerate / 10.12 and 20 mg/kg (i.e., 1/20 and 1/10th LD50 respectively) had no effect on learning process, retrieval of memory and permanent memory traces.

Mutagenicity of systemic organophosphate pesticides metasystox and rogor.

Mutagenicity of metasystox and rogor could not be detected on the basis of tests employing Ames Salmonella/microsome assay even in the presence of wheat seedling or rat liver microsomal activation systems.