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1.
J Appl Toxicol ; 43(9): 1332-1346, 2023 09.
Article En | MEDLINE | ID: mdl-36946007

There is a growing global interest in using peptides in the health industry for pharmaceuticals, cosmetics, and natural food products. Peptides contain two or more linked amino acids, whereas more than 50 amino acids are classified as polypeptides. Although there is a growing level of interest in the use of peptides in the health and wellness industry, there is a lack of literature pertaining to a specific tripeptide derived from arginine, alanine, and lysine (RAK) that is of interest for human dietary use. Therefore, a 90-day repeated-dose toxicity study was performed in rats to evaluate the subchronic oral toxicity of RAK. Eighty Han:WIST rats were administered RAK by gavage at doses of 0, 250, 500, or 1000 mg/kg bw/day. There were no mortalities or other treatment related effects, and no target organs were identified. A no-observed-adverse-effect-level (NOAEL) of 1000 mg/kg bw/day, the highest dose tested, was determined. This study will contribute to the body of research in regard to the safety of the use of RAK.


Alanine , Lysine , Humans , Rats , Animals , Lysine/toxicity , Alanine/toxicity , Arginine/toxicity , No-Observed-Adverse-Effect Level , Administration, Oral , Toxicity Tests, Subchronic
2.
J Appl Toxicol ; 43(6): 887-912, 2023 06.
Article En | MEDLINE | ID: mdl-36598355

Microorganisms have the potential to produce nutrient-rich products that can be consumed as food or feed. The protein-rich powder derived from heat treatment of the whole-cell biomass of polyhydroxybutyrate-deficient Cupriavidus necator, a metabolically versatile organism that uses elements found in the air, is an example of such a product. To assess the safety of the protein powder for use as a nutritional ingredient in human food, in accordance with internationally accepted standards, its genotoxic potential and repeated-dose oral toxicity were investigated. A bacterial reverse mutation test, an in vitro mammalian chromosomal aberration test, and an in vivo mammalian micronucleus test were performed. No evidence of mutagenicity or genotoxicity was found. Additionally, a 90-day repeated-dose oral toxicity study in rats was completed, in which a total of 100 male and female Wistar rats were exposed by gavage to daily doses of 1000, 2000, or 3000 mg/kg bw/day of the test material. Following 90 days of continuous exposure, no mortality or treatment-related adverse effects were observed and no target organs were identified. Therefore, a no observed adverse effect level was determined at 3000 mg/kg bw/day, the highest dose tested.


Cupriavidus necator , Rats , Male , Humans , Female , Animals , Rats, Wistar , Powders/toxicity , No-Observed-Adverse-Effect Level , Mutagenicity Tests , Mammals
3.
Food Chem Toxicol ; 161: 112844, 2022 Mar.
Article En | MEDLINE | ID: mdl-35134458

Gold nanocrystals (AuNC) are gold nanoparticles (AuNP) relatively homogenous in size at 8-28 nm with clean surfaces and crystalline structures. There are concerns and a lack of consensus in the scientific literature and major regulatory bodies regarding not only the safety of nanoparticles when consumed by humans, but exactly how to determine their safety and whether evidence from a nanoparticle with one set of physiochemical properties extends to one with a different set. Additionally, there are few general long-term toxicity data on AuNP. To our knowledge, the potential toxicity of AuNC specifically, with the above characteristics, or otherwise, has not been investigated in preclinical studies; thus, we conducted a battery of genetic toxicity tests and an oral repeated-dose toxicity test to further explore their safety. AuNC were not mutagenic or clastogenic in bacterial reverse mutation and in vitro mammalian chromosomal aberration tests, respectively, and did not exhibit in vivo genotoxicity in a micronucleus test in mice. In a 60-day, repeated-dose oral toxicity study, rats were administered 0, 2.5, 5, or 10 mg/kg bw/day of AuNC by gavage. No toxicity was identified. Therefore, a no observed adverse effect level was determined as 10 mg/kg body weight/day.


Gold/chemistry , Gold/toxicity , Metal Nanoparticles/chemistry , Metal Nanoparticles/toxicity , Animals , Cell Line , Cricetinae , Female , Lung/cytology , Male , Mice , Micronucleus Tests , No-Observed-Adverse-Effect Level , Rats , Rats, Wistar
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