RESUMO
Fenitrothion (FNT), a commonly used organophosphate, can cause oxidative damage and apoptosis on various organs. However, the underlying mechanisms for FNT-induced cardiotoxicity did not formally report. Here, we have evaluated the possible ameliorative roles of resveratrol (RSV) against FNT-induced cardiac apoptosis in male rats through the sirtuin1 (SIRT1)/c-Jun N-terminal kinase (c-JNK)/p53 pathway concerning pro-oxidant and inflammatory cytokines. Forty-eight male rats were equally grouped into control, RSV (20 mg/kg), 5-FNT (5 mg/kg), 10-FNT (10 mg/kg), 20-FNT (20 mg/kg), 5-FNT-RSV, 10-FNT-RSV, and 20-FNT-RSV where all doses administrated by gavage for four weeks. The present findings demonstrated that RSV markedly diminished the level of hyperlipidemia and elevation in lactate dehydrogenase (LDH), total creatine kinase (CK-T), and troponin T (TnT) levels following FNT intoxication. Furthermore, RSV significantly reduced FNT-induced cardiac oxidative injury by reducing malondialdehyde (MDA) level and improving the levels of glutathione (GSH), glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT), and acetylcholinesterase (AchE). Also, the levels of interleukin-1ß (IL1ß,), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were significantly attenuated in the co-treated groups. Moreover, RSV alleviated the histopathological changes promoted by FNT and repaired the transcript levels of SIRT1, c-JNK, and caspase-9/3 along with p53 immunoreactivity. In silico study revealed that the free binding energies of RSV complexes with protein and DNA sequences of SIRT1 were lower than docked complexes of FNT. Therefore, RSV reserved myocardial injury-induced apoptosis following exposure to FNT by modulating the SIRT1/c-JNK/p53 pathway through cellular redox status and inflammatory response improvements.
Assuntos
Fenitrotion/toxicidade , Miócitos Cardíacos/metabolismo , Resveratrol/farmacologia , Acetilcolinesterase/metabolismo , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Cardiotoxicidade/tratamento farmacológico , Fenitrotion/efeitos adversos , Fenitrotion/farmacologia , Glutationa/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Masculino , Miócitos Cardíacos/efeitos dos fármacos , Oxirredução , Estresse Oxidativo , Ratos , Espécies Reativas de Oxigênio/metabolismo , Resveratrol/metabolismo , Transdução de Sinais , Sirtuína 1/metabolismo , Superóxido Dismutase/metabolismo , Proteína Supressora de Tumor p53/metabolismoRESUMO
Although a considerable number of studies about the effect of different insecticides on plant physiology and metabolism have been carried out, research work about the comparative action of structurally different classes of insecticide on physiological and biochemical properties of soybean seed germination and early growth has not been found. The objective of this study was to investigate the effect of different classes of insecticides on soybean seed germination and early plant growth. Soybean seeds of Bosuk cultivar were soaked for 24h in distilled water or recommended dose (2mLL(-1), 1mLL(-1), 0.5gL(-1), and 0.5gL(-1) water for insecticides Mepthion, Myungtaja, Actara, and Stonate, respectively) of pesticide solutions of four structurally different classes of insecticides - Mepthion (fenitrothion; organophosphate), Myungtaja (etofenprox; pyrethroid), Actara (thiamethoxam; neonicotinoid), and Stonate (lambda-cyhalothrin cum thiamethoxam; pyrethroid cum neonicotinoid) - which are used for controlling stink bugs in soybean crop. Insecticides containing thiamethoxam and lamda-cyhalothrin cum thiamethoxam showed positive effects on seedling biomass and content of polyphenol and flavonoid, however fenitrothion insecticide reduced the seed germination, seed and seedling vigor, and polyphenol and flavonoid contents in soybean. Results of this study reveal that different classes of insecticide have differential influence on physiologic and metabolic actions like germination, early growth, and antioxidant activities of soybean and this implies that yield and nutrient content also might be affected with the application of different types of insecticide.
Assuntos
Germinação/efeitos dos fármacos , Glycine max/efeitos dos fármacos , Inseticidas/farmacologia , Plântula/efeitos dos fármacos , Fenitrotion/farmacologia , Neonicotinoides , Nitrilas/farmacologia , Nitrocompostos/farmacologia , Oxazinas/farmacologia , Piretrinas/farmacologia , Plântula/crescimento & desenvolvimento , Glycine max/crescimento & desenvolvimento , Tiametoxam , Tiazóis/farmacologiaRESUMO
An experiment was conducted under laboratory conditions to investigate the effect of increasing concentrations of fenitrothion (2, 10 and 200 mg a.i./kg soil), diuron (1.5, 7.5 and 150 mg a.i./kg soil) and thiram (3.5, 17.5 and 350 mg a.i./kg soil) on soil respiration, bacterial counts and changes in culturable fraction of soil bacteria. To ascertain these changes, the community structure, bacterial biodiversity and process of colony formation, based on the r/K strategy concept, EP- and CD-indices and the FOR model, respectively, were determined. The results showed that the measured parameters were generally unaffected by the lowest dosages of pesticides, corresponding to the recommended field rates. The highest dosages of fenitrothion and thiram suppressed the peak SIR by 15-70% and 20-80%, respectively, while diuron increased respiration rate by 17-25% during the 28-day experiment. Also, the total numbers of bacteria increased in pesticide-treated soils. However, the reverse effect on day 1 and, in addition, in case of the highest dosages of insecticide on days 14 and 28, was observed. Analysis of the community structure revealed that in all soil treatments bacterial communities were generally dominated by K-strategists. Moreover, differences in the distribution of individual bacteria classes and the gradual domination of bacteria populations belonging to r-strategists during the experiment, as compared to control, was observed. However, on day 1, at the highest pesticide dosages, fast growing bacteria constituted only 1-10% of the total colonies number during 48 h of plate incubation, whereas in remaining samples they reached from 20 to 40% of total cfu. This effect, in case of fenitrothion, lasted till the end of the experiment. At the highest dosages of fenitrothion, diuron and at all dosages of thiram the decrease of biodiversity, as indicated by EP- and CD-indices on day 1, was found. At the next sampling time, no significant retarding or stimulating effect was detected. However, in case of CD values the higher differences were observed. The significant impact of pesticides on the physiological state of soil bacteria was not found. They were generally in dormant state (lambda < 0.5), but immediately after pesticides application, the additional reduction of frequency of bacterial cell proliferation (max. decrease of lambda value to 0.15 for thiram on day 14) and prolonged retardation time of colony appearance (max. increase of t(r) value to 1.39 for fenitrothion on day 1) on agar plates were found.
Assuntos
Bactérias/efeitos dos fármacos , Praguicidas/farmacologia , Microbiologia do Solo , Poluentes do Solo/farmacologia , Bactérias/classificação , Bactérias/crescimento & desenvolvimento , Técnicas Bacteriológicas , Biodiversidade , Biomassa , Contagem de Colônia Microbiana , Diurona/farmacologia , Fenitrotion/farmacologia , Tiram/farmacologiaRESUMO
The tumor-promoting activities of 5 commercial compounds used in termiticides were measured by a cell-transformation assay employing Bhas 42 cells. Their initiating activities were also measured by the microsuspension assay employing S. typhimurium TA98 and TA100 strains. The results of the transformation assay confirmed the tumor-promoting activities of fenitrothion, silafluofen and bifenthrin. Furthermore, the mutagenicity of S-421 and fenitrothion were also confirmed. Consideration of 2-stage carcinogenesis suggests that concurrent use of and long-term exposure to these compounds that have tumor-promoting and initiator activity, and compounds exhibiting either type of activity individually should be avoided as much as possible.
Assuntos
Transformação Celular Neoplásica/induzido quimicamente , Inseticidas/farmacocinética , Inseticidas/toxicidade , Biotransformação , Éteres/farmacocinética , Éteres/toxicidade , Fenitrotion/farmacologia , Fenitrotion/toxicidade , Testes de Mutagenicidade , Compostos de Organossilício/farmacocinética , Compostos de Organossilício/toxicidade , Permetrina/farmacocinética , Permetrina/toxicidade , Piretrinas/farmacocinética , Piretrinas/toxicidade , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/genéticaAssuntos
Cádmio/efeitos adversos , Cádmio/farmacologia , Drosophila melanogaster/fisiologia , Fenitrotion/efeitos adversos , Fenitrotion/farmacologia , Inseticidas/efeitos adversos , Inseticidas/farmacologia , Aranhas/fisiologia , Acetilcolinesterase/efeitos dos fármacos , Acetilcolinesterase/farmacologia , Animais , Biomarcadores/análise , Interações Medicamentosas , Exposição Ambiental , Cadeia AlimentarRESUMO
To date, within the field of endocrine disruption, much focus has been placed on chemicals that mimic oestrogens (so-called xenoestrogens), and the number of such chemicals apparently detected continues to grow steadily. Less effort has been expended on investigating chemicals that mimic, or antagonize, other hormones. Nevertheless, a number of chemicals have been reported to have a weak affinity for the androgen receptor, all of which have, to date, been found to have anti-androgenic activity in vivo. In this report, we present evidence that the insecticide fenitrothion can interact with the androgen, but not with the oestrogen, receptor. Using recombinant yeast expressing the human androgen receptor, we found that fenitrothion behaved as an androgen agonist in vitro when tested alone, and that it could antagonize the androgen DHT when both chemicals competed for the androgen receptor in vitro. In vivo studies using both intact and castrated male rats showed no conclusive androgenic or anti-androgenic responses. Changes in organ weights suggestive of anti-androgenic effects were mitigated against by the reduced body weights of fenitrothion-treated rats. The toxicity of the compound precluded the use of higher dose levels to substantiate any tentative findings. Interestingly, fenitrothion (and related insecticides) is structurally similar to flutamide, an anti-androgen used clinically that gives clearly positive responses in both intact and castrated rats.
Assuntos
Androgênios/farmacologia , Fenitrotion/farmacologia , Inseticidas/farmacologia , Receptores Androgênicos/efeitos dos fármacos , Receptores de Estrogênio/efeitos dos fármacos , Animais , Castração , Fenitrotion/toxicidade , Humanos , Inseticidas/toxicidade , Camundongos , Ratos , LevedurasRESUMO
Organophosphate insecticides represent one of the most widely used classes of pesticides with high potential for human exposure in both rural and residential environments. We investigated the interaction of the organophosphothioate pesticide fenitrothion (O,O-dimethyl O-(4-nitro-m-tolyl) phosphorothioate) with the human androgen receptor (AR). Fenitrothion blocked dihydrotestosterone-dependent AR activity in a concentration-dependent and competitive manner in HepG2 human hepatoma liver cells transiently transfected with human AR and an AR-dependent luciferase reporter gene. Schild regression analysis yielded an equilibrium dissociation constant value of 2.18 x 10(-8) M. To determine the antiandrogenic potential of fenitrothion in vivo, 7-week-old castrated Sprague-Dawley rats were dosed once a day for 7 days with testosterone propionate (50 microg/day, sc) plus gavage doses of either corn oil vehicle or fenitrothion (15 or 30 mg/kg/day). An additional group of rats was given testosterone propionate and flutamide (50 mg/kg/day). Motor activity and acetylcholinesterase activity in whole blood and brain were also assessed. Both fenitrothion and the reference antiandrogen flutamide caused significant decreases in the ventral prostate, seminal vesicle, and levator ani plus bulbocavernosus muscles tissue weights. In contrast, blood acetylcholinesterase activity, a standard biomarker of organophosphate poisoning, was only inhibited at the higher dose of fenitrothion (30 mg/kg). Our results demonstrate that fenitrothion is a competitive AR antagonist, comparable in potency to the pharmaceutical antiandrogen flutamide and more potent, based on in vitro assays, than the known environmental antiandrogens linuron and p,p'-, 2,2-bis(p-hydroxyphenyl)-1,1-dichloroethylene ( p,p'-DDE).
Assuntos
Antagonistas de Receptores de Andrógenos , Fenitrotion/farmacologia , Inseticidas/farmacologia , Acetilcolinesterase/sangue , Animais , Peso Corporal/efeitos dos fármacos , Carcinoma Hepatocelular/metabolismo , Inibidores da Colinesterase/farmacologia , Relação Dose-Resposta a Droga , Flutamida/farmacologia , Genitália Masculina/efeitos dos fármacos , Genitália Masculina/patologia , Humanos , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/patologia , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Transfecção , Células Tumorais CultivadasRESUMO
The effects of the organophosphorous insecticide fenitrothion (phosphorothioic acid, O,O-dimethyl O-(3-methyl-4-nitrophenyl) ester; FS) on the physical state of pure dipalmitoyl (DPPC) and 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) membranes were investigated. FS lowers the phase transition temperature of DPPC. It has no large effects on the DPPC gel phase, but it increases the order of the liquid-crystalline state of DPPC and POPC. FS also decreases 1,6-diphenyl-1,3,5-hexatriene (DPH) lifetime (tau) in the DPPC and POPC liquid-crystalline states. Since a direct quenching of DPH emission by FS was ruled out, tau shortening is assigned to an increased water penetration in the bilayer. The effect of FS is different from most perturbing agents for which an increased order is accompanied by a higher tau. Furthermore, quenching of DPH by KI was increased by FS in POPC liposomes indicating an increased accessibility of the quencher to the hydrophobic core where DPH distributes. The effect of FS on dipole relaxation at the hydrophilic-hydrophobic interface of POPC bilayers was studied with 2-dimethylamino-6-lauroylnaphthalene (Laurdan). FS produces a decrease in Laurdan tau and a narrowing of its emission band. FS significantly increases the generalized polarization values at both emission band ends. These results indicate that FS may allow the coexistence of microdomains that have different physical properties.
Assuntos
Fenitrotion/farmacologia , Inseticidas/farmacologia , Bicamadas Lipídicas/química , 1,2-Dipalmitoilfosfatidilcolina/química , Anisotropia , Cristalização , Géis , Fosfatidilcolinas/química , Espectrometria de FluorescênciaAssuntos
Inibidores da Colinesterase/farmacologia , Monitoramento Ambiental/métodos , Esterases/análise , Inseticidas/farmacologia , Moluscos/efeitos dos fármacos , Poluentes Químicos da Água/farmacologia , Animais , Argentina , Esterases/antagonistas & inibidores , Fenitrotion/farmacologia , Moluscos/enzimologia , Paraoxon/farmacologia , Paration/farmacologiaRESUMO
Responses of three chemical senses, olfaction, taste, and pit organ sense, to three pesticides were studied electrophysiologically in carp, Cyprinus carpio. Only olfaction was responsive to the three pesticides at behavioral avoidance levels, which were determined in a previous study. The olfactory thresholds for benthiocarb, isoprothiolane, and fenitrothion were 1.7 x 10(-1) micrograms/l (4 log units lower concentration than 48-h LC50), 6.7 x 10(-3) micrograms/l (6 log units lower than 48-h LC50), and 4.9 x 10(2) micrograms/l (1 log unit lower than 48-h LC50), respectively. There were two distinctive features in the olfactory response to pesticides. One is that these pesticides barely indicated the concentration dependency that is usually recognized in the olfactory response to a typical stimulant such as L-alanine or NaCl. Another is that these pesticides indicated a power spectrum with an overall increase in frequency ranges of less than 10.0 Hz, unlike L-alanine or NaCl, which show a marked peak ranging from 8.0 to 12.0 Hz. These findings suggest that there is a specific mechanism in the chemoreception for these pesticides.
Assuntos
Carpas/fisiologia , Células Quimiorreceptoras/fisiologia , Praguicidas/farmacologia , Órgãos dos Sentidos/fisiologia , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Células Quimiorreceptoras/efeitos dos fármacos , Eletroencefalografia/efeitos dos fármacos , Eletrofisiologia , Nervo Facial/efeitos dos fármacos , Nervo Facial/fisiologia , Feminino , Fenitrotion/farmacologia , Fungicidas Industriais/farmacologia , Herbicidas/farmacologia , Inseticidas/farmacologia , Masculino , Órgãos dos Sentidos/efeitos dos fármacos , Olfato/fisiologia , Paladar/fisiologia , Tiocarbamatos/farmacologia , Tiofenos/farmacologia , Nervo Trigêmeo/efeitos dos fármacos , Nervo Trigêmeo/fisiologiaRESUMO
The genotoxic effects of 4 organophosphorous pesticides, i.e. ekatin, fenitrothion, methylparathion and phorate, were examined employing the micronucleus test in bone marrow cells of the rat. Methylparathion and phorate were found to be mutagenic, while ekatin was weakly mutagenic. The frequency of micronuclei induction by fenitrothion did not differ significantly from that noticed in negative control.
Assuntos
Medula Óssea/efeitos dos fármacos , Núcleo Celular/efeitos dos fármacos , Inseticidas/farmacologia , Organotiofosfatos , Fuso Acromático/efeitos dos fármacos , Animais , Núcleo Celular/ultraestrutura , Fenitrotion/farmacologia , Masculino , Metil Paration/farmacologia , Metilnitronitrosoguanidina/farmacologia , Testes de Mutagenicidade , Forato/farmacologia , Ratos , Ratos EndogâmicosRESUMO
The effect of subtoxic concentrations (SC) of carbofuran 3% granules (G), a carbamate (5 ppm) and fenitrothion 50% emulsifiable concentrate (EC), an organophosphate (1.5 ppm) on protein-bound iodine (PBI) levels in the blood plasma of Channa punctatus were studied. Exposure to fenitrothion caused more decline in PBI levels than did carbofuran exposure.
Assuntos
Proteínas Sanguíneas/metabolismo , Carbofurano/farmacologia , Fenitrotion/farmacologia , Inseticidas/farmacologia , Iodo/sangue , Animais , Peixes/sangue , Adeno-Hipófise/metabolismo , Glândula Tireoide/efeitos dos fármacos , Hormônios Tireóideos/metabolismo , Fatores de TempoRESUMO
Sumithion is the most active cholinesterase inhibitor. The cholinesterase inhibiting action of the organophosphates (OPs) is better compensated by vitamin E in normal animals, but by vitamin A in vitamin A-deficient animals. The lipid peroxidation (LP) is enhanced by the antioxidant vitamins in the liver of normal rats; although they decrease it in the liver of vitamin A-deficient animals, in no case do they prevent the LP-enhancing effect of the OPs examined. The OPs examined inhibit protein synthesis in the liver of vitamin A-deficient animals.
Assuntos
Fenitrotion/farmacologia , Fígado/efeitos dos fármacos , Triclorfon/farmacologia , Animais , Catalase/metabolismo , Colinesterases/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Feminino , Peróxidos Lipídicos/metabolismo , Fígado/enzimologia , Fígado/metabolismo , Oxirredução , Ratos , Ratos Endogâmicos , Superóxido Dismutase/metabolismo , Vitamina E/farmacologiaAssuntos
Acetaminofen/antagonistas & inibidores , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Fenitrotion/farmacologia , Animais , Doença Hepática Induzida por Substâncias e Drogas/enzimologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Glutationa/metabolismo , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos , Oxigenases de Função Mista/metabolismoRESUMO
The neurosecretory material is found depleted in the medial neurosecretory cells in adult cockroaches poisoned with insecticide. It is, however, scanty in the neurosecretory pathway but abundant in the corpora cardiaca of these insects. The administration of toxicated haemolymph in the normal cockroach results in scanty material in medial neurosecretory cells, but the accumulation of the neurosecretory material in corpora cardiaca. The toxicated tissue extracts have also caused depletion of neurosecretory material from the medial neurosecretory cells as well as from the axonal tract and its accumulation in the corpora cardiaca. Thus effect is comparatively more pronounced by the extract from the Malpighian tubules and nerve cord than than of brain extract. Thus the effect produced by insecticide on the stimulation--secretion coupling mechanism of neurosecretion is comparable to the produced by the toxicated haemolymph and tissue extract. The possibility of involvement of the adrenergic system in regulating the action of neuroactive material on neurosecretory cells is suggested in the insects.
Assuntos
Baratas/fisiologia , Neurossecreção , Sistemas Neurossecretores/fisiologia , Animais , Fenitrotion/farmacologia , Hemolinfa/fisiologia , Sistemas Neurossecretores/citologia , Sistemas Neurossecretores/efeitos dos fármacos , Paralisia/fisiopatologiaRESUMO
The authors irradiated albino rats with I microc/gr strontium89 with previously modelled liver injury by FOS (Agria 1050). A temporary inhibition of the methodical activity was established as well as aberrant mitoses and strongly manifested polyploidity of the hepatic cells. Those phenomena faded quickly (within 8 days), with the exception of polyploidity, which as a sign of physiological regeneration the authors admit to be adaptive reaction directed to the restoration of the functional level of the liver on account of the hepatocytes preserved. Prior to the onset of tissue regeneration, the cellular one should be terminated, due to which, the mytotic activity was highly inhibited on the 3rd day of the irradiation, the DNA-synthesis cycle being lengthened and mainly on account of tgi, i.e. during the reparative biosynthesis the cell is incapable/of developing in the mitotic phase. After the presynthetic period is over the hepatocytes rapidly overcome the inhibition, tgi is considerably shortened and from presynthesis they almost immediately enter the period of mitosis. That requires an additional protein synthesis, manifested by the changes in serum protein. S and G1 proved to be most sensitive to DNA-synthesis blocking. The presynthetic period is essentially lengthened due to lesions of the cellular structures, synthesizing substances, necessary for entering S - i.e. the hepatocytes pass T, equal to the inhibition between G1 and S, its duration being proportional to the degree of the lesion of the organ.
Assuntos
Relógios Biológicos/efeitos dos fármacos , DNA/biossíntese , Fenitrotion/farmacologia , Inseticidas/farmacologia , Fígado/efeitos dos fármacos , Estrôncio/farmacologia , Animais , Relógios Biológicos/efeitos da radiação , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/efeitos da radiação , DNA/efeitos da radiação , Fígado/metabolismo , Fígado/efeitos da radiação , Ratos , Radioisótopos de Estrôncio , Fatores de TempoRESUMO
In experiments on male Wistar rats the action of organophosphorus pesticides (chlorophos and methylnitrophos) and cineb, belonging to compounds of the carbamine series, on the LDH and H-6-PDH of the testes tissues and their isoenzymatic spectra, was studied. The results of investigations demonstrated substantial changes in the activity of the LDH and H-6-PDH isoenzymes occurring with a long-term priming for 9 months of chlorophos in a dose of 1 mg/kg of the mass. On the other hand, with introduction of methylnitrophos (in a dose of 0.5 mg/kg mass) and cineb (in a dose of 2.5 mg/kg) no statistically significant changes in the activity of the LDH and H-6-PDH were in evidence. Introduction in the same doses of chlorophos, methylnitrophos and cineb for 3 months did not have any essential influence on the activity of the LDH and H-6-PDH isoenzyme fractions, nor on their isoenzymatic profile by comparison with controls.
Assuntos
Glucosefosfato Desidrogenase/metabolismo , Isoenzimas/metabolismo , L-Lactato Desidrogenase/metabolismo , Praguicidas/farmacologia , Testículo/enzimologia , Animais , Fenitrotion/farmacologia , Masculino , Ratos , Triclorfon/farmacologia , Zineb/farmacologiaAssuntos
Microssomos Hepáticos/efeitos dos fármacos , Praguicidas/farmacologia , Testosterona/metabolismo , Animais , Sistema Enzimático do Citocromo P-450/análise , Compostos de Etilmercúrio/farmacologia , Fenitrotion/farmacologia , Hexaclorocicloexano/farmacologia , Masculino , Microssomos Hepáticos/metabolismo , Paration/farmacologia , CoelhosRESUMO
The mutagenic activity of fenitrothion was studied in rats given 0,10,40 or 80 ppm of fenitrothion in the diet. The study combined the dominant lethal test with cytogenetic analysis of chromosomal aberrations. Dominant lethal mutations were investigated: 1. by their so-called tentative determination in single mating in P-to F3 generation males and females following 200 days exposure; 2. by assessing the effect of the agent at individual stages of spermatogenesis, with F2 and F4 generation males having been exposed for 100 days and mated to unexposed females for 10 weeks. Chromosome aberrations were analyzed in the bone marrow of F2 generation males following 200-days exposure and F3 generation (males) following 500-day exposure to a dose of 80 ppm. Negative results were obtained in all experiments in relation both to dose and generation. Hence fenitrothion is not considered to be a substance with a mutagenic activity. The metodical advantages of the proposed combination of reproduction and mutagenic-activity studies of an agent for toxicological evaluation are discussed.