The food contaminant acetamide is not an in vivo clastogen, aneugen, or mutagen in rodent hematopoietic tissue
| Autor: | Manish Patel, Rajendra Nagane, Farzaneh Teymouri, Rance Nault, B. Bhaskar Gollapudi, Martha M. Moore, Tushar Khanvilkar, E. Ramesh, Bryan Bals, Nadeem Khan, Venkataraman Bringi, Avani M. Roy |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Male
Erythrocytes Food Contamination 010501 environmental sciences Pharmacology Gene mutation Toxicology medicine.disease_cause 030226 pharmacology & pharmacy 01 natural sciences Article 03 medical and health sciences chemistry.chemical_compound Clastogen Mice 0302 clinical medicine In vivo Mutagenicity Acetamides medicine Animals In vivo micronucleus test Rats Wistar Carcinogen 0105 earth and related environmental sciences Micronucleus Tests Toxicity Tests Subchronic Membrane Proteins General Medicine In vivoPig-A gene mutation assay chemistry Micronucleus test Mutation Female Aneugen Genotoxicity Acetamide |
| Zdroj: | Regulatory Toxicology and Pharmacology |
| ISSN: | 1096-0295 |
| Popis: | Acetamide (CAS 60-35-5) is classified by IARC as a Group 2B, possible human carcinogen, based on the induction of hepatocellular carcinomas in rats following chronic exposure to high doses. Recently, acetamide was found to be present in a variety of human foods, warranting further investigation. The regulatory body JECFA has previously noted conflicting reports on acetamide's ability to induce micronuclei (MN) in mice in vivo. To better understand the potential in vivo genotoxicity of acetamide, we performed acute MN studies in rats and mice, and a subchronic study in rats, the target species for liver cancer. In the acute exposure, animals were gavaged with water vehicle control, 250, 1000, or 2000 mg/kg acetamide, or the positive control (1 mg/kg mitomycin C). In the subchronic assay, bone marrow of rats gavaged at 1000 mg/kg/day (limit dose) for 28 days was evaluated. Both acute and subchronic exposures showed no change in the ratio of polychromatic to total erythrocytes (P/E) at any dose, nor was there any increase in the incidence of micronucleated polychromatic erythrocytes (MN-PCE). Potential mutagenicity of acetamide was evaluated in male rats gavaged with vehicle control or 1500 mg/kg/day acetamide using the in vivoPig-a gene mutation assay. There was no increase in mutant red blood cells or reticulocytes in acetamide-treated animals. In both acute and sub-chronic studies, elevated blood plasma acetamide in treated animals provided evidence of systemic exposure. We conclude based on this study that acetamide is not clastogenic, aneugenic, or mutagenic in vivo in rodent hematopoietic tissue warranting a formal regulatory re-evaluation. Highlights • In vivo micronucleus tests with acetamide in mice and rats. • Acetamide blood plasma levels demonstrated evidence of exposure. • Acetamide does not induce micronuclei in rats and mice. • Acetamide does not increase mutations in the rat Pig-a gene mutation assay. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect