Although the translation of these findings to human is limited by the small study size and species differences,
these results from animals chronically exposed to up to 150 times the clinical UPA exposure are considered significant and supportive to the chronic administration of UPA for more than 3 months in women of reproductive age. (C) 2013 Elsevier Inc. All rights reserved.”
“Glucose oxidase (beta-D-glucose:oxygen 1-oxidoreductase; EC 184.108.40.206.4) is used in the food and beverage industry as a preservative and stabilizer and is commonly derived from the fungus Aspergillus niger. Although the safety of glucose oxidase preparations from A. niger is well-established, LY3023414 the use of preparations derived from other fungal species is of interest; however,
an assessment of their safety is warranted. https://www.selleckchem.com/products/Gemcitabine-Hydrochloride(Gemzar).html Here, we report on the safety of a glucose oxidase preparation derived from the fungus Penicilliurn chrysogenum (designated as PGO) for commercial use in food processing, as well as an ingredient in food. In a repeated dose 90-day oral toxicity study conducted in rats, PGO was without compound-related adverse effects at doses of up to 15,600 U/kg body weight/day, equivalent to 193 mg total organic solids/kg body weight/day. In addition, PGO was non-genotoxic in a series of genotoxicity tests, including a bacterial reverse mutation test, an in vitro mammalian chromosomal aberration test, and a combined in vivo mammalian erythrocyte micronucleus test and comet assay. The results of these studies support the safe use of PGO in food for human consumption. (C) 2013 Elsevier Inc. All rights reserved.”
“Styrene (S) is lung tumorigenic in mice but not in rats. Methisazone S and its alkene-oxidized metabolite styrene oxide (SO) were not lung toxic in CYP2F2(-/-) [knockout] mice,
indicating S-induced mouse lung tumors are mediated through mouse-specific CYP2F2-generated ring-oxidized metabolite(s) in lung bronchioles. The human relevance of the CYP2F MOA was assessed by insertion of a human CYP2F1, 2A13, 2B6 transgene into CYP2F2(-/-) mice; CYP2F1 expression and activity were confirmed in the transgenic (TG) mice. No evidence of cytotoxicity or increased cell proliferation (BrdU labeling) was seen in TG mice treated with either S or SO (200 mg/kg/day ip for 5 days). In contrast to S and SO, 4HS (105 mg/kg/day ip for 5 days) increased BrdU labeling 5-10-fold in WT mice, <3-fold increase in KO mice and 2-4-fold in TG mice. The limited response of 4HS in KO and TG mice may result from intrinsic toxicity or from further metabolism; regardless of the MOA, these findings indicate that the CYP2F-mediated tumorigenic MOA in WT mice is not operative for S, SO, or for 4HS putatively derived from metabolism of S by CYP2F1 in humans, and thus S-induced mouse lung tumors are unlikely to be relevant to human risk. (C) 2013 Published by Elsevier Inc.