Lack of human relevance for rat developmental toxicity of flumioxazin is revealed by comparative heme synthesis assay using embryonic erythroid cells derived from human and rat pluripotent stem cells.

Fetal rat anemia from flumioxazin, an N-phenylimide herbicide, is caused by suppression of heme synthesis resulting from inhibition of protoporphyrinogen oxidase (PPO). A series of studies to investigate the effects of flumioxazin have revealed that developmental toxicity is caused in rats but not in rabbits, and the adverse effects are not likely to occur in humans. In this study, as a final weight-of-evidence approach for assessing the human safety of flumioxazin, we compared the toxic potential of inhibition of heme synthesis leading to anemia between human and rat embryonic erythroid cells, which were degenerated as the target of flumioxazin in the rat developmental toxicity.

Flumioxazin, a PPO inhibitor: A weight-of-evidence consideration of its mode of action as a developmental toxicant in the rat and its relevance to humans.

Flumioxazin, is a herbicide that has inhibitory activity on protoporphyrinogen oxidase (PPO), a key enzyme in the biosynthetic pathway for heme. Flumioxazin induces anemia and developmental toxicity in rats, including ventricular septal defect and embryofetal death. Studies to elucidate the mode of action (MOA) of flumioxazin as a developmental toxicant and to evaluate its relevance to humans have been undertaken.

Different effects of an N-phenylimide herbicide on heme biosynthesis between human and rat erythroid cells.

Rat developmental toxicity including embryolethality and teratogenicity (mainly ventricular septal defects and wavy ribs) were produced by S-53482, an N-phenylimide herbicide that inhibits protoporphyrinogen oxidase (PPO) common to chlorophyll and heme biosynthesis. The sequence of key biological events in the mode of action has been elucidated as follows: inhibition of PPO interferes with normal heme synthesis, which causes loss of blood cells leading to fetal anemia, embryolethality and the development of malformations. In this study we investigated whether the rat is a relevant model for the assessment of the human hazard of the herbicide.

An Atypical Acidophil Cell Line Tumor Showing Focal Differentiation Toward Both Growth Hormone and Prolactin Cells.

We report a case of giant pituitary adenoma in a child. Computerized tomography (CT) scan revealed a suprasellar extension tumor mass with hydrocephalus. There was no clinical evidence of acromegaly, gigantism, and other hormonal symptoms.

Mixed growth hormone cell- prolactin cell pituitary adenoma with acromegaly: α-subunit most growth hormone cells.

A 51 -year-old woman with mixed growth hormone (GH) cell-prolactin (PRL) cell pituitary adenoma is presented. She had clinical signs due to hypersecretion of GH and PRL. Resected tissue was studied immunohistochemically and morphologically.

Silent mixed growth hormone cell-prolactin cell pituitary adenoma.

The case of a 51 -year-old man with recurrent nonfunctioning pituitary adenoma is presented. Despite clinically and endocrinologically normal pituitary function in regard to growth hormone and prolactin, many growth hormone- and prolactin-positive cells were immunohis-tochemically detected in adenoma tissue. Furthermore, a quite rare tumor of silent mixed growth hormone cell-prolactin cell pituitary adenoma was confirmed by the double-labeling immunoelectron-microscopical study.