Novel N-phosphinoyl heterocycles were synthesized by the reaction of a heterocycle against a phosphorochloridate in the presence of the strong base (n-BuLi or NaH). Studies on the structure-activity relationships were carried out as to acaricidal, aphicidal and nematicidal activities, respectively. With respect to the heterocyclec portion, the acidity (pKa) of the parent heterocycles seems to control the pesticidal activities. It is also suggested that the unsymmetrical alkoxy(alkylthio)phosphinoyl structures with the proper length of alkyl groups are crucial to the high pesticidal activities. The effect of the chiral phosphorus atom was investigated as to 3-[ethoxy(sec-butylthio)phosphinoyl]-1, 3-thiazolidin-2-one. The levorotatory (-) isomer was shown to be more active against various pests.

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Groups of 80 male and 80 female F344 rats were given ziram at a constant dietary dose of 0, 20, 200 or 2000ppm (0, 0.70, 6.9 and 74mg/kg/day for males and 0, 0.83, 8.5 and 91mg/kg/day for females) for 104 weeks. Eight males and 8 females in each group were killed after Weeks 26, 52 and 78. In the dog study, 6 male and 6 female beagle dogs were allotted to each group which received the chemical in gelatin capsule at a dose level of 0, 0.2, 1.0 or 5.0mg/kg/day for 104 weeks. The rats in the 2000ppm group showed retarded growth together with decreased food intake. In the 200 and/or 2000ppm groups, males and/or females showed a variety of changes in clinical and pathological examinations as follows; slight anemia; increased levels of serum glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase, and decreased levels of total cholesterol and calcium; elevated weights of the thyroids, liver and spleen, and lowered weights of the kidney and calf muscle; increased incidences of hematopoiesis or extramedullary hematopoiesis in the bone marrow or spleen, hyperkeratosis in the forestomach, follicular hypertrophy of the thyroid, atrophy/degeneration of the sciatic nerve and calf muscle and retarded closure of epiphyseal plate of crus bone. Decreased occurrences were noted for the senile changes in the heart, liver and kidneys in both sexes, C-cell hyperplasia of the thyroid in males, and hyperplasia and adenoma/fibroma of the mammary gland in females. In addition, similar depression in incidence was observed in adenoma/adenocarcinoma of the pituitary in males of all treated groups. In the dog study, males and/or females in the 5.0mg/kg/day group showed persistent diarrhea and/or mucous stool as well as significant elevations of serum alkaline phosphatase, GOT and total cholesterol during the treatment while no treatment-related symptoms were observed in the groups of 1.0 and 0.2mg/kg/day. With these results, NOAEL was estimated as 20ppm for F344 rats (0.70mg/kg/day for males and 0.83mg/kg/day for females) and 1.0mg/kg/day for the beagle dogs of both sexes.

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In a study of sulfonylurea herbicides, we found that some thiophene sulfonylureas, substituted at the 3 position and possessing the sulfonylurea bridge at the 2 position of the thiophene ring, exhibit high herbicidal activities on paddy field application. Although most of them are phytotoxic to rice (Oryza sativa), introduction of a fluorine atom onto the substituent attached at the 3 position of the thiophene moiety improved the selectivity to rice. Namely, N-{(4, 6-dimethoxypyrimidin-2-yl)aminocarbonyl}-3-{(2, 2, 2-trifluoroethoxy)methyl}-2-thiophenesulfonamide and N-{(4, 6-dimethoxypyrimidin-2-yl)-aminocarbonyl}-3-{(2-fluoroethoxy)methyl}-2-thiophene sulfonamide were selected as good herbicides for paddy field application.

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[in Japanese]

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[in Japanese]

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[in Japanese]

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[in Japanese]

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[in Japanese]

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[in Japanese]

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Experimental approaches are described to find the primary mode of action of chloroacetamides using the microalga Scenedesmus as a model system. The data corroborate lipid metabolism as the target domain, particularly the processing of fatty acids. Incorporation of labeled oleic acid into a non-soluble cell-wall residue was found to be severely inhibited by chloro- and oxyacetamides with I₅₀ values down to 10^-8 molar. A quantitative rapid assay on acetamide activity based on this ¹⁴C-oleate incorporation was developed which correlated with phytotoxicity. Herbicidally active S-enantiomers exhibited activity in the new assay, not the R-forms.

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Cyproconazole technical was of low toxicity to rats, moderate toxicity to mice by oral administration. Its formulation was of low toxicity to rats and mice by oral administration. The technical and its formulation were of low acute dermal toxicity. The technical and its formulation were not skin irritant, although they were mildly irritating to eye. In a guinea pig skin sensitization study using the Maximization method no skin sensitization was induced by cyproconazole technical or its formulation.
In subacute toxicity studies in rats and dogs, clinical biochemistry parameters at middle or high dose levels were affected by treatment of cyproconazole technical. Decreased body weight gains and increased liver weights were found in rats and dogs receiving high dose levels of cyproconazole technical.
In a rat combined chronic toxicity/oncogenicity study, some parameters of haematology and clinical biochemistry mainly at high dose level were affected by treatment of cyproconazole technical. Decreased body weight gains and increased liver weights weree found at high dose level of cyproconazole technical. Histopathological examination revealed hepatocelluar fatty changes in male and hepatocellular hypertrophy in female at high dose. The incidence of neoplastic lesions was not affected by the treatment at the terminal or interim sacrifice.
In mice oncogenicity study, reduced body weight gains and increased liver weight were seen at upper-middle and high dose levels of cyproconazole technical. An incidence of hepatocytic neoplasia was increased in male at upper-middle or high and female at high dose level of cyproconazole technical. The mechanism leading to the observed tumours is tumour promotion as a result of hepatic enzyme induction, a non-genotoxic event.
In a dog chronic toxicity study, increased cytochrome P-450 activities were observed in both sexes at middle and high dose levels of cyproconazole technical. Reduced body weight gains in male and increased liver weight in both sexes were found at high dose level of cyproconazole technical. There were no treatment related findings in both sexes at low dose.
In a two-generation rat reproduction study, there were no treatment-related effects on the reproduction parameters. The only treatment-related finding was an increased hepatocellular fatty changes in F0 males at the high dose level of cyproconazole technical. In a rat teratology study, reduced body weight gains and increased postimplantation losses were observed at uppermiddle and high dose levels of cyproconazole technical. In a rabbit teratology study, reduced body weight gains and food consumption were observed at high dose level of cyproconazole technical. Postimplantation losses were increased at high dose level. There were no treatment-related external, skeletal or visceral abnormalities.
Cyproconazole technical did not induce mutations. in bacterial or mammalian system.
Cyproconazole is one of the important fungicides for field crops since its registration in 1995.

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