Difference in developmental toxicity among structurally similar N-phenylimide herbicides in rats and rabbits.

  title={Difference in developmental toxicity among structurally similar N-phenylimide herbicides in rats and rabbits.},
  author={Satoshi Kawamura and Terushige Kato and Noboru Kannan and Alan G. Fantel},
  journal={Birth defects research. Part B, Developmental and reproductive toxicology},
  volume={98 6},
BACKGROUND S-53482 is an N-phenylimide herbicide and shows a remarkable species difference in developmental toxicity between rats and rabbits. The herbicide produced embryolethality, teratogenicity (mainly ventricular septal defects and wavy ribs), and growth retardation in rats, but not in rabbits. Our objective in this study was to investigate differences in developmental toxicity among N-phenylimide compounds structurally similar to S-53482 to better characterize the developmental effects of… Expand
Dermal developmental toxicity of N-phenylimide herbicides in rats.
Dermal exposure of rats to S-53482 and S-23121 produced patterns of developmental toxicity similar to those resulting from oral exposure as well as teratogenic when administered dermally to pregnant rats as were the compounds administered orally. Expand
Mechanism of Developmental Effects in Rats Caused by an N-Phenylimide Herbicide: Transient Fetal Anemia and Sequelae during Mid-to-Late Gestation.
Developmental toxicity results from PPO inhibition in primitive erythroblasts, causing transient fetal anemia followed by death, and inhibition of PPO in rats, rabbits, and humans by the herbicides in vitro is proposed. Expand
Different Effects of an N-Phenylimide Herbicide on Heme Biosynthesis between Human and Rat Erythroid Cells.
It is suggested that the rat would be an inappropriate model for assessing the developmental toxicity of S-53482 in humans as rats are specifically sensitive to PPO inhibition by the herbicide. Expand
Close link between protoporphyrin IX accumulation and developmental toxicity induced by N-phenylimide herbicides in rats.
The peak period of PPIX accumulation corresponded to that of developmental effects, suggesting a close link between PPO inhibition and developmental abnormality. Expand
Molecular dynamics mechanism to generate species differences in inhibition of protoporphyrinogen oxidase by flumioxazin
Abstract Flumioxazin is an N-phenylimide herbicide and shows a remarkable species difference in developmental toxicity between rats and rabbits. The species difference is corresponded well to theExpand
Immunophenotyping of Rabbit Testicular Germ and Sertoli Cells Across Maturational Stages
  • B. Banco, G. Grilli, +4 authors V. Grieco
  • Biology, Medicine
  • The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society
  • 2016
During testicular maturation, both Sertoli cells (SCs) and germ cells (GCs) switch from an immature to a mature immunophenotype. The reexpression of markers of immaturity in adults has been reportedExpand
Features of oxa-bridge cleavage in hexahydro-3a,6-epoxyisoindol-1(4H)-ones: A concise method to access acetylisoindolones possessing anti-viral activity
Abstract Unusual stereo- and regioselective methods for epoxy-bridge cleavage in perhydro-3a,6-epoxyisoindolones, under the action of the BF3·Et2O/Ac2O system, were discovered. The reaction pathwayExpand


Species Difference in Developmental Toxicity of an N‐Phenylimide Herbicide between Rats and Rabbits and Sensitive Period of the Toxicity to Rat Embryos
It is likely that there is a common mechanism for the three types of developmental toxicity and that S‐53482 does not produce VSD by its direct damage to embryonic heart tissue. Expand
Species difference in protoporphyrin IX accumulation produced by an N-phenylimide herbicide in embryos between rats and rabbits.
The species difference in PPIX accumulation corresponded very well to that of the developmental toxicity exhibited by S-53482, an N-phenylimide photobleaching herbicide between rats and rabbits. Expand
Histological changes in rat embryonic blood cells as a possible mechanism for ventricular septal defects produced by an N-phenylimide herbicide.
The herbicide may induce VSD due to hematological dysfunction caused by the inhibition of heme biosynthesis rather than by direct injurious effects on the heart. Expand
Structure-activity relationships in the developmental toxicity of substituted phenols: in vivo effects.
The properties of these phenolic congeners that promote maternal toxicity are different from those that contribute to developmental toxicity, and it is likely that the mechanisms of toxicity behind these effects are also different. Expand
Teratogenic effects mediated by inhibition of histone deacetylases: evidence from quantitative structure activity relationships of 20 valproic acid derivatives.
It is demonstrated that only VPA derivatives with a teratogenic potential in mice are able to induce a hyperacetylation in core histone H4 in teratocarcinoma F9 cells, and a quantitative correlation between the IC50(HDAC) and the ter atogenic potential of Vpa derivatives, which clearly points toward HDACs as the formerly describedTeratogenic receptors of VPA-induced neural tube defects (NTDs). Expand
Metabolism of N-[4-chloro-2-fluoro-5-[(1-methyl-2-propynyl)oxy]phenyl]-3,4,5,6- tetrahydrophthalimide (S-23121) in the rat. II. Absorption, disposition, excretion and biotransformation.
The radiocarbon was almost completely eliminated from the rat within 7 days after administration for both dose groups and sulphonic acid conjugates were not detected in urine, blood, kidney or liver. Expand
Metabolism of Pentyl 2-Chloro-4-fluoro-5-(3,4,5,6-tetrahydrophthal- imido)phenoxyacetate (Flumiclorac Pentyl, S-23031) in Rats. 2. Absorption, Distribution, Biotransformation, and Excretion
Male and female Sprague-Dawley rats, 7 weeks old, were given a single oral dose of [phenyl- 14 C]-S-23031 [pentyl 2-chloro-4-fluoro-5-(3,4,5,6-tetrahydrophthalimido)phenoxyacetate] orExpand
Pyrazole phenyl ether herbicides inhibit protoporphyrinogen oxidase
Abstract Two isomeric pairs of pyrazole phenyl ether herbicides [AH 2.429, 4-chloro-1-methyl-5-(4-nitrophenoxy)-3-(trifluoromethyl)-1 H -pyrazole; AH 2.430,Expand
Metabolism of 7-fluoro-6-(3,4,5,6-tetrahydrophthalimido)-4- (2-propynyl)-2H-1,4-benzoxazin-3(4H)-one (S-53482) in rat. 1. Identification of a sulfonic acid type conjugate.
The metabolic pathways of S-53482 in rats are proposed on the basis of the metabolites identified in this study and these pathways were proposed using NMR and MS techniques. Expand
Metabolism of 7-fluoro-6-(3,4,5,6-tetrahydrophthalimido)-4- (2-propynyl)-2H-1,4-benzoxazin-3(4H)-one (S-53482, flumioxazin) in the rat: II. Identification of reduced metabolites.
Five urinary and four fecal metabolites were identified using chromatographic techniques and spectroanalyses (NMR and MS) and three of five identified metabolites were unique forms, reduced at the 1,2-double bond of the 3,4,5, 6-tetrahydrophthalimide moiety. Expand