In Vitro Mouse Lymphoma Cell (L5178Y Tk+/− −3.7.2.C) Forward Mutation Assay

Schisler, Melissa R.; Moore, Martha M.; Gollapudi, B. Bhaskar

doi:10.1007/978-1-4939-9646-9_1

Cited by 4 publications

(1 citation statement)

References 23 publications

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“…Increases were observed both with and without S9, and there was no evidence for a preferential induction of small versus large colonies. Since MLA detects a wide range of genetic events (point mutations, deletions, chromosomal rearrangements, and mitotic recombination Schisler, et al, 2019 ), the genetic events responsible for the increased MF are unknown. However, given the absence of mutagenic activity in bacteria, it appears that 3‐CAA and/or its metabolites are unlikely to be DNA‐reactive.…”

Section: Disscussionmentioning

confidence: 99%

In vitro and in vivo assessments of the genotoxic potential of 3‐chloroallyl alcohol

Redmond¹,

Zhang

Cheng³

et al. 2022

Environ and Mol Mutagen

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3‐Chloroallyl alcohol (3‐CAA) can be found in the environment following the application of plant protection products. 3‐CAA is formed in groundwater following the injection of 1,3‐dichloropropene, a fumigant used to control nematodes. 3‐CAA is also formed, in leafy crops, as a glycoside conjugate following application of the herbicide, clethodim. Human exposure may occur from groundwater used as drinking water or through dietary consumption. To characterize 3‐CAA's potential to cause genotoxicity in mammals, in vitro and in vivo studies were conducted. 3‐CAA was negative in an Ames test and positive in a mouse lymphoma forward mutation assay. 3‐CAA was negative in an acute in vivo CD‐1 mouse bone marrow micronucleus assay when administered up to a dose level of 125 mg/kg/day for two consecutive days. In a combined gene mutation assay and erythrocyte micronucleus assay, using transgenic Big Blue® Fischer 344 rats, 3‐CAA was administered via drinking water at targeted dose levels of 0, 10, 30, and 100 mg/kg/day for 29 days. Peripheral blood samples, collected at the end of treatment, were analyzed for micronucleus induction in reticulocytes using flow cytometry. Liver and bone marrow samples, collected 2 days after the termination of the treatment, were analyzed for the induction of mutations at the cII locus. 3‐CAA did not induce an increase in mutant frequency or micronuclei under the experimental conditions. In conclusion, the mutagenic response observed in the in vitro mouse lymphoma assay is not confirmed in the whole animal. 3‐CAA is not considered to pose a mutagenic risk.

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Section: Disscussionmentioning

confidence: 99%

In vitro and in vivo assessments of the genotoxic potential of 3‐chloroallyl alcohol

Redmond¹,

Zhang

Cheng³

et al. 2022

Environ and Mol Mutagen

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Genetic Toxicology: Basics and Practical Insights into Its Appropriate Application

Pottenger¹,

Gollapudi²,

Moore³

2023

Patty's Toxicology

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Genetic toxicology data play an important role in a variety of regulatory applications. Thus, industrial hygienists and toxicologists need a basic understanding of the principles and testing approaches for the evaluation of genotoxicity. Genetox tests are used for hazard assessment, to support the classification of chemicals as carcinogens or mutagens, and to support the evaluation of modes of action for tumor induction. Genetic toxicology has primarily been used in the evaluation of potential carcinogens, and for predicting potential germ cell and heritable risk. More recent considerations include using genetic damage as a standalone adverse outcome. Many genetox tests are recommended for regulatory use, with OECD test guidelines that describe conduct and data interpretation. Since these recommendations have evolved over the years, data from older studies must be carefully evaluated before accepting study conclusions. In silico models now contribute by complementing the biological tests. This chapter includes our insights into strategies for selecting appropriate tests and generating optimal data sets to address specific questions and advice for conducting weight of the evidence evaluations on information from multiple endpoints and tests. Genetic toxicology data provide not only qualitative results, but with careful study design, can also provide information useful to address dose–response issues.

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Whole-genome high-fidelity sequencing: A novel approach to detecting and characterization of mutagenicity in vivo

Dobrovolsky,

Matsuda,

McKinzie

et al. 2023

Mutation Research/Genetic Toxicology and Environmental Mutagene

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In Vitro Mouse Lymphoma Cell (L5178Y Tk+/− −3.7.2.C) Forward Mutation Assay

Cited by 4 publications

References 23 publications

In vitro and in vivo assessments of the genotoxic potential of 3‐chloroallyl alcohol

In vitro and in vivo assessments of the genotoxic potential of 3‐chloroallyl alcohol

Genetic Toxicology: Basics and Practical Insights into Its Appropriate Application

Whole-genome high-fidelity sequencing: A novel approach to detecting and characterization of mutagenicity in vivo

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