There is evidence of major species-dependent differences in the extent of de-epoxidation of nivalenol in non-ruminants, which may occur in the lower parts of the gastrointestinal tract in some species. The de-epoxy metabolite has been detected in feces of rats, pigs and laying hens, but not in mice or broiler chickens and, based on in vitro studies, it is unlikely to be formed in humans.
来源:Hazardous Substances Data Bank (HSDB)
代谢
反刍动物中，与其他三线菌素一样，雪腐镰刀菌烯醇在吸收前可能在瘤胃中发生广泛的去环氧化反应。
In ruminants, it is likely that, as for other trichothecenes, extensive de-epoxidation of nivalenol may occur in the rumen prior to absorption.
来源:Hazardous Substances Data Bank (HSDB)
代谢
Nivalenol is metabolized to de-epoxy nivalenol.
尼瓦连醇被代谢为脱环氧尼瓦连醇。
The cytotoxicity of the de-epoxy metabolites of trichothecenes nivalenol (NIV) and deoxynivalenol (DON) was determined and compared with the cytotoxicity of the respective toxin with an intact epoxy group and their acetylated derivatives. The cytotoxic effects was determined by using the 5-bromo-2'-deoxyuridine (BrdU) incorporation assay assessing DNA-synthesis. The toxicity of NIV and DON expressed as the concentration inhibiting 50% of the DNA synthesis (IC(50)), was occurring at similar micromolar concentrations (1.19+/-0.06 and 1.50+/-0.34 uM). The toxicity of fusarenon X (4-acetyl NIV) in the assay was similar to the toxicity of NIV, and the toxicity of 15-AcDON was equal to the toxicity of DON. 3-AcDON was less toxic than DON and 15-AcDON. The IC(50) value for de-epoxy DON was 54 times higher in the assay than the IC(50) for DON, while the IC(50) of de-epoxy NIV was 55 times higher than the IC(50) for NIV. The results verify previous findings that the de-epoxidation is a detoxification reaction.
Evaluation: There is inadequate evidence in humans for the carcinogenicity of toxins derived from Fusarium graminearum. No data were available on the carcinogenicity to humans of toxins derived from F. crookwellense and F. culmorum. ... There is inadequate evidence in experimental animals for the carcinogenicity of nivalenol. ... Overall evaluation: Toxins derived from Fusarium graminearum, F. culmorum and F. crookwellense are not classifiable as to their carcinogenicity to humans (Group 3).
来源:Hazardous Substances Data Bank (HSDB)
毒理性
副作用
Dermatotoxin - 皮肤烧伤。
Dermatotoxin - Skin burns.
来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases
A feeding trial was conducted in order to determine the effects of a Fusarium poae extract on the health and performances of broiler chickens and the possible protective effect of a natural zeolite. The F. poae extract contained nivalenol, T-2 toxin and diacetoxyscirpenol and demonstrated high toxicity when administered i.p. to rats. One-day-old broiler chickens were fed ad libitum over a period of 28 days with the following diets: group I - control; group II - 0.5% zeolite; group III -F. poae extract; group IV-0.5% zeolite andF. poae extract. Broilers were sacrificed at 28 days for the measurement of relative organs weights, leukocyte counts and serum biochemical values. No mortality was recorded over the experiment. Body weight gains, feed intake, feed utilization and water consumption were depressed by the F. poae extract (p<0.05). A decrease of these parameters was also observed in group IV which received the diet with zeolite and the F. poae extract. No significant differences were seen in group II when compared to control. In groups III and IV the relative weights of liver, kidney, heart and gizzard were significantly increased (p<0.05), while in group II only the relative liver weight was increased. F. poae extract, administered singly or in combination with zeolite, significantly decreased leukocytes count, serum total protein and serum albumin. Zeolite and F. poae extract, singly or combined, increased serum creatinine and uric acid concentrations (p<0.05). These findings indicate that sublethal doses of F. poae extract can affect adversely the performances and the health in broiler chickens. By adding zeolite these impairments could not be diminished and for some parameters the zeolite additive increased the adverse effects of the F. poae extract.
Deoxynivalenol (DON) and nivalenol (NIV) are toxic Fusarium secondary trichothecene metabolites that often co-occur regularly in cereal grains. These compounds were compared for their toxicity towards C57BL/6 mice on several parameters including alteration in plasma biochemistry, immune system reactivity and hepatic drug metabolism capacity. Mice received individual or combined oral doses of each toxin: 0.071 or 0.355 mg/kg of body weight, administrated three days a week for 4 weeks. Food consumption was altered by the single administration of 0.355 mg/kg of NIV, although no noticeable change of body and organ weights or liver protein contents was detected. NIV administration did cause also significant changes in total CO2 and uric acid concentrations in plasma. Individual toxin exposures led to increases in plasma IgA without no detectable change in the ex vivo production of cytokine by splenocytes. The liver ethoxyresorufin O-deealkylase, pentoxyresorufin O-depenthylase and glutathione S-transferase activities were increased in concert with cytochrome P4501a and P4502b subfamily expression. Administration of combinations of DON and NIV resulted in responses similar to that observed using individual doses of each toxin. However, depending on the ratio of toxin doses and biochemical parameters, some responses could be also additive (plasma IgA and hepatic DCNB conjugation) or synergistic (plasma uric acid).
Deoxynivalenol (DON) is the most prevalent trichothecene mycotoxin in crops in Europe and North America. DON is often present with other type B trichothecenes such as 3-acetyldeoxynivalenol (3-ADON), 15-acetyldeoxynivalenol (15-ADON), nivalenol (NIV) and fusarenon-X (FX). Although the cytotoxicity of individual mycotoxins has been widely studied, data on the toxicity of mycotoxin mixtures are limited. The aim of this study was to assess interactions caused by co-exposure to Type B trichothecenes on intestinal epithelial cells. Proliferating Caco-2 cells were exposed to increasing doses of Type B trichothecenes, alone or in binary or ternary mixtures. The MTT test and neutral red uptake, respectively linked to mitochondrial and lysosomal functions, were used to measure intestinal epithelial cytotoxicity. The five tested mycotoxins had a dose-dependent effect on proliferating enterocytes and could be classified in increasing order of toxicity: 3-ADON<15-ADON =~ DON<NIV << FX. Binary or ternary mixtures also showed a dose-dependent effect. At low concentrations (cytotoxic effect between 10 and 30-40%), mycotoxin combinations were synergistic; however DON-NIV-FX mixture showed antagonism. At higher concentrations (cytotoxic effect around 50%), the combinations had an additive or nearly additive effect. These results indicate that the simultaneous presence of low doses of mycotoxins in food commodities and diet may be more toxic than predicted from the mycotoxins alone. Considering the frequent co-occurrence of trichothecenes in the diet and the concentrations of toxins to which consumers are exposed, this synergy should be taken into account.
After long term oral administration of nivalenol to male rats, the dose was recovered as fecal nivalenol (7%), fecal de-epoxy nivalenol (80%), urinary nivalenol (1%) and urinary de-epoxy nivalenol (1%).
In order to investigate the comparative fates of nivalenol (NIV) and 4-acetyl derivative of NIV (fusarenon-X, FX) in mice, (3)H-FX or (3)H-NIV was given p.o. to mice. Radioactivity was excreted mainly via the urine in mice given (3)H-FX, but mainly via the feces in mice given (3)H-NIV. The plasma radioactivity reached a peak at 30 or 60 min after the administration of (3)H-FX or (3)H-NIV, respectively. The plasma peak level was 5 times higher, and the area under curve (AUC) was 10 times higher, in (3)H-FX-administered than (3)H-NIV-administered mice. These findings clearly demonstrate that FX is absorbed from the gastrointestinal tract more rapidly and efficiently than NIV. The HPLC profile of radioactivity of acetonitrile extracts of urine and feces indicated that FX is rapidly metabolized to NIV after being absorbed from the gastrointestinal tract. In vitro incubation of tissue homogenates with (3)H-FX demonstrated that the liver and kidney are the organs responsible for the FX-to-NIV conversion. Thus this study demonstrated that the higher oral toxicity of FX than NIV that has been observed in mice and rats is due to the efficient absorption of FX than NIV from the gastrointestinal tract, followed by its rapid conversion to NIV by the liver and kidney.
HERBICIDAL AND FUNGICIDAL 5-OXY-SUBSTITUTED 3-PHENYLISOXAZOLINE-5-CARBOXAMIDES AND 5-OXY-SUBSTITUTED 3-PHENYLISOXAZOLINE-5-THIOAMIDES
申请人：BAYER CROPSCIENCE AG
公开号：US20150245616A1
公开（公告）日：2015-09-03
Herbicidally and fungicidally active 5-oxy-substituted 3-phenylisoxazoline-5-carboxamides and 5-oxy-substituted 3-phenylisoxazoline-5-thioamides of the formula (I) are described.
In this formula (I), X, X
2
to X
6
, R
1
to R
4
are radicals such as hydrogen, halogen and organic radicals such as substituted alkyl. A is a bond or a divalent unit. Y is a chalcogen.
The present invention relates to processes for preparing certain 2-pyridones and 2-pyridinols, to novel compounds of these two types and to their use as biologically active compounds, in particular for controlling harmful microorganisms in crop protection, in the medicinal field and in the protection of materials.
[EN] AZABICYCLIC(THIO)AMIDES AS FUNGICIDAL COMPOUNDS<br/>[FR] (THIO)AMIDES AZABICYCLIQUES EN TANT QUE COMPOSÉS FONGICIDES
申请人：BAYER AG
公开号：WO2021233861A1
公开（公告）日：2021-11-25
The present invention relates to azabicyclic (thio)amide compounds and the uses thereof for controlling phytopathogenic microorganisms such as phytopathogenic fungi. It also relates to processes and intermediates for preparing these compounds
[EN] TRISUBSTITUTEDSILYLMETHYLPHENOXYQUINOLINES AND ANALOGUES<br/>[FR] SILYLMÉTHYLPHÉNOXYQUINOLÉINES TRISUBSTITUÉS ET ANALOGUES
申请人：BAYER AG
公开号：WO2018202712A1
公开（公告）日：2018-11-08
The present disclosure relates to fungicidal active compounds, more specifically to trisubstitutedsilylmethylphenoxyquinolines and analogues thereof, processes and, intermediates for their 5 preparation and use thereof as fungicidal active compound, particularly in the form of fungicide compositions. The present disclosure also relates to methods for the control of phytopathogenic fungi of plants using these compounds or compositions comprising thereof.
HERBICIDALLY AND FUNGICIDALLY ACTIVE 3-PHENYLISOXAZOLINE-5-CARBOXAMIDES AND 3-PHENYLISOXAZOLINE-5-THIOAMIDES
申请人：Willms Lothar
公开号：US20140100108A1
公开（公告）日：2014-04-10
3-Phenylisoxazoline-5-carboxamides and 3-phenylisoxazoline-5-thioamides of the formula (I) and their use as herbicides and fungicides are described.
In this formula (I), X, X
2
to X
6
, R
1
to R
4
are radicals such as hydrogen, halogen and organic radicals such as substituted alkyl. A is a bond or a divalent unit. Y is a chalcogen.
