Use of the bacterial reverse mutation assay to predict carcinogenicity of N-nitrosamines
Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved..
Under ICH M7, impurities are assessed using the bacterial reverse mutation assay (i.e., Ames test) when predicted positive using in silico methodologies followed by expert review. N-Nitrosamines (NAs) have been of recent concern as impurities in pharmaceuticals, mainly because of their potential to be highly potent mutagenic carcinogens in rodent bioassays. The purpose of this analysis was to determine the sensitivity of the Ames assay to predict the carcinogenic outcome with curated proprietary Vitic (n = 131) and Leadscope (n = 70) databases. NAs were selected if they had corresponding rodent carcinogenicity assays. Overall, the sensitivity/specificity of the Ames assay was 93-97% and 55-86%, respectively. The sensitivity of the Ames assay was not significantly impacted by plate incorporation (84-89%) versus preincubation (82-89%). Sensitivity was not significantly different between use of rat and hamster liver induced S9 (80-93% versus 77-96%). The sensitivity of the Ames is high when using DMSO as a solvent (87-88%). Based on the analysis of these databases, the Ames assay conducted under OECD 471 guidelines is highly sensitive for detecting the carcinogenic hazards of NAs.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2022 |
|---|---|
| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:135 |
|---|---|
| Enthalten in: |
Regulatory toxicology and pharmacology : RTP - 135(2022) vom: 15. Nov., Seite 105247 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Trejo-Martin, Alejandra [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Ames |
|---|
| Anmerkungen: |
Date Completed 18.10.2022 Date Revised 18.10.2022 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.yrtph.2022.105247 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM345172175 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM345172175 | ||
| 003 | DE-627 | ||
| 005 | 20231226024448.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.yrtph.2022.105247 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1150.xml |
| 035 | |a (DE-627)NLM345172175 | ||
| 035 | |a (NLM)35998738 | ||
| 035 | |a (PII)S0273-2300(22)00134-9 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Trejo-Martin, Alejandra |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Use of the bacterial reverse mutation assay to predict carcinogenicity of N-nitrosamines |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 18.10.2022 | ||
| 500 | |a Date Revised 18.10.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a Under ICH M7, impurities are assessed using the bacterial reverse mutation assay (i.e., Ames test) when predicted positive using in silico methodologies followed by expert review. N-Nitrosamines (NAs) have been of recent concern as impurities in pharmaceuticals, mainly because of their potential to be highly potent mutagenic carcinogens in rodent bioassays. The purpose of this analysis was to determine the sensitivity of the Ames assay to predict the carcinogenic outcome with curated proprietary Vitic (n = 131) and Leadscope (n = 70) databases. NAs were selected if they had corresponding rodent carcinogenicity assays. Overall, the sensitivity/specificity of the Ames assay was 93-97% and 55-86%, respectively. The sensitivity of the Ames assay was not significantly impacted by plate incorporation (84-89%) versus preincubation (82-89%). Sensitivity was not significantly different between use of rat and hamster liver induced S9 (80-93% versus 77-96%). The sensitivity of the Ames is high when using DMSO as a solvent (87-88%). Based on the analysis of these databases, the Ames assay conducted under OECD 471 guidelines is highly sensitive for detecting the carcinogenic hazards of NAs | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Ames | |
| 650 | 4 | |a Carcinogenicity | |
| 650 | 4 | |a Impurities | |
| 650 | 4 | |a Nitrosamines | |
| 650 | 4 | |a OECD 471 | |
| 650 | 4 | |a Pharmaceuticals | |
| 650 | 4 | |a Sensitivity | |
| 650 | 7 | |a Carcinogens |2 NLM | |
| 650 | 7 | |a Nitrosamines |2 NLM | |
| 650 | 7 | |a Pharmaceutical Preparations |2 NLM | |
| 650 | 7 | |a Solvents |2 NLM | |
| 650 | 7 | |a Dimethyl Sulfoxide |2 NLM | |
| 650 | 7 | |a YOW8V9698H |2 NLM | |
| 700 | 1 | |a Bercu, Joel P |e verfasserin |4 aut | |
| 700 | 1 | |a Thresher, Andrew |e verfasserin |4 aut | |
| 700 | 1 | |a Tennant, Rachael E |e verfasserin |4 aut | |
| 700 | 1 | |a Thomas, Robert F |e verfasserin |4 aut | |
| 700 | 1 | |a Cross, Kevin |e verfasserin |4 aut | |
| 700 | 1 | |a Czich, Andreas |e verfasserin |4 aut | |
| 700 | 1 | |a Waese, Kerstin |e verfasserin |4 aut | |
| 700 | 1 | |a Nicolette, John J |e verfasserin |4 aut | |
| 700 | 1 | |a Murray, Joel |e verfasserin |4 aut | |
| 700 | 1 | |a Sonders, Paul |e verfasserin |4 aut | |
| 700 | 1 | |a Kondratiuk, Alison |e verfasserin |4 aut | |
| 700 | 1 | |a Cheung, Jennifer R |e verfasserin |4 aut | |
| 700 | 1 | |a Thomas, Dean |e verfasserin |4 aut | |
| 700 | 1 | |a Lynch, Anthony |e verfasserin |4 aut | |
| 700 | 1 | |a Harvey, James |e verfasserin |4 aut | |
| 700 | 1 | |a Glowienke, Susanne |e verfasserin |4 aut | |
| 700 | 1 | |a Custer, Laura |e verfasserin |4 aut | |
| 700 | 1 | |a Escobar, Patricia A |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Regulatory toxicology and pharmacology : RTP |d 1983 |g 135(2022) vom: 15. Nov., Seite 105247 |w (DE-627)NLM012598453 |x 1096-0295 |7 nnns |
| 773 | 1 | 8 | |g volume:135 |g year:2022 |g day:15 |g month:11 |g pages:105247 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.yrtph.2022.105247 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 135 |j 2022 |b 15 |c 11 |h 105247 | ||