1. Academic Validation
  2. The food contaminant acetamide is not an in vivo clastogen, aneugen, or mutagen in rodent hematopoietic tissue

The food contaminant acetamide is not an in vivo clastogen, aneugen, or mutagen in rodent hematopoietic tissue

  • Regul Toxicol Pharmacol. 2019 Nov;108:104451. doi: 10.1016/j.yrtph.2019.104451.
Martha M Moore 1 Bhaskar Gollapudi 2 Rajendra Nagane 3 Nadeem Khan 4 Manish Patel 5 Tushar Khanvilkar 6 Avani M Roy 7 E Ramesh 8 Bryan Bals 9 Farzaneh Teymouri 10 Rance Nault 11 Venkataraman Bringi 12
Affiliations

Affiliations

  • 1 Ramboll, 23 Alban Lane, Little Rock, AR, 72223, USA. Electronic address: [email protected].
  • 2 Exponent, 1800 Diagonal Rd Suite 500, Alexandria, VA, 22314, USA. Electronic address: [email protected].
  • 3 Jai Research Foundation India, NH-8 Near Daman Ganga Bridge Valvada, Vapi, Gujarat, 396 105, India. Electronic address: [email protected].
  • 4 Jai Research Foundation India, NH-8 Near Daman Ganga Bridge Valvada, Vapi, Gujarat, 396 105, India. Electronic address: [email protected].
  • 5 Jai Research Foundation India, NH-8 Near Daman Ganga Bridge Valvada, Vapi, Gujarat, 396 105, India. Electronic address: [email protected].
  • 6 Jai Research Foundation India, NH-8 Near Daman Ganga Bridge Valvada, Vapi, Gujarat, 396 105, India. Electronic address: [email protected].
  • 7 Jai Research Foundation India, NH-8 Near Daman Ganga Bridge Valvada, Vapi, Gujarat, 396 105, India.
  • 8 Eurofins Advinus Limited, Peenya II Phase, Bangalore, 560 058, India. Electronic address: [email protected].
  • 9 MBI International, 3815 Technology Blvd, Lansing, MI, 48910, USA. Electronic address: [email protected].
  • 10 MBI International, 3815 Technology Blvd, Lansing, MI, 48910, USA. Electronic address: [email protected].
  • 11 Department of Biochemistry and Molecular Biology, Institute for Integrative Toxicology, Michigan State University, 1129 Farm Lane Rm 248, East Lansing, MI, 48824, USA. Electronic address: [email protected].
  • 12 Department of Chemical Engineering and Materials Science, Michigan State University, 428 S Shaw Lane Rm 2100, East Lansing, MI, 48824, USA. Electronic address: [email protected].
Abstract

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.

Keywords

Genotoxicity; In vivo micronucleus test; In vivoPig-A gene mutation assay; Mutagenicity.

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