Development, Qualification, Validation and Application of the Ames Test Using a VITROCELL VC10 Smoke Exposure System

Overview

Journal Toxicol Rep

Date 2018 Jun 2

PMID 29854624

Citations 7

Authors

Kathy Fowler

Wanda Fields

Victoria Hargreaves

Lesley Reeve

Betsy Bombick

Affiliations

Soon will be listed here.

Abstract

The Ames test has established use in the assessment of potential mutagenicity of tobacco products but has generally been performed using partitioned exposures (e.g. total particulate matter [TPM], gas vapor phase [GVP]) rather than whole smoke (WS). The VITROCELLVC10 smoke exposure system offers multiple platforms for air liquid interface (ALI), or air agar interface (AAI) in the case of the Ames test exposure to mimic -like conditions for assessing the toxicological impact of fresh WS in assays. The goals of this study were to 1) qualify the VITROCELLVC10 to demonstrate functionality of the system, 2) develop and validate the Ames test following WS exposure with the VITROCELLVC10 and 3) assess the ability of the Ames test to differentiate between a reference combustible product (3R4F Kentucky reference cigarette) and a primarily tobacco heating product (Eclipse). Based on critical function assessments, the VITROCELLVC10 was demonstrated to be fit for the purpose of consistent generation of WS. Assay validation was conducted for 5 bacterial strains (TA97, TA98, TA100, TA1535 and TA102) and reproducible exposure-related changes in revertants were observed for TA98 and TA100 in the presence of rat liver S-9 following exposure to 3R4F WS. In the comparative studies, exposure-related changes in mutagenicity following exposure of TA98 and TA100 in the presence of S9 to both 3R4F and Eclipse WS were observed, with the response for Eclipse being significantly less than that for 3R4F (p < 0.001) which is consistent with the fewer chemical constituents liberated by primarily-heating the product.

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