干旱区生态环境知识资源中心(Arid): Integrated in silico and in vitro genotoxicity assessment of thirteen datapoor substances

Arid

DOI	10.1016/j.yrtph.2019.104427
	Integrated in silico and in vitro genotoxicity assessment of thirteen datapoor substances
	Tran, Yen K.; Buick, Julie K.; Keir, Jennifer L. A.; Williams, Andrew; Swartz, Carol D.; Recio, Leslie; White, Paul A.; Lambert, Iain B.; Yauk, Carole L.
通讯作者	Yauk, CL (corresponding author), Environm Hlth Ctr, 50 Columbine Driveway,PL 0803A, Ottawa, ON K1A 0K9, Canada.
来源期刊	REGULATORY TOXICOLOGY AND PHARMACOLOGY
ISSN	0273-2300
EISSN	1096-0295
出版年	2019
卷号	107
英文摘要	The Canadian Domestic Substances List (DSL) contains chemicals that have not been tested for genotoxicity as their use pre-dates regulatory requirements. In the present study, (quantitative) structure-activity relationships ((Q)SAR) model predictions and in vitro tests were conducted for genotoxicity assessment of 13 data-poor chemicals from the DSL (i.e. CAS numbers 19286-75-0, 13676-91-0, 2478-20-8, 6408-20-8, 74499-36-8, 26694-69-9, 29036-02-0, 120-24-1, 84696-48-9, 4051-63-2, 5718-26-3, 632-51-9, and 600-14-6). First, chemicals were screened by (Q)SAR models in Leadscope (R) and OASIS TIMES; two chemicals were excluded from (Q)SAR as they are complex mixtures. Six were flagged by (Q)SAR as potentially mutagenic and were subsequently confirmed as mutagens using the Ames assay. Of nine chemicals with clastogenic (Q)SAR flags, eight induced micronuclei in TK6 cells. Benchmark dose analysis was used to evaluate the potency of the chemicals. Four chemicals were bacterial mutagens with similar potencies. Three chemicals were more potent in micronuclei induction than the prototype alkylating agent methyl methanesulfonate and three were equipotent to the mutagenic carcinogen benzo[a]pyrene in the presence of rat liver S9. Overall, 11 of the 13 DSL chemicals demonstrated at least one type of genotoxicity in vitro. This study demonstrates the application of genotoxic potency analysis for prioritizing further investigations.
英文关键词	Genetic toxicology QSAR Ames assay Micronucleus assay Benchmark dose Anthraquinones
类型	Article
语种	英语
收录类别	SCI-E
WOS记录号	WOS:000513225500032
WOS关键词	INCORPORATING MOLECULAR FLEXIBILITY ; HUMAN TK6 CELLS ; METABOLIC-ACTIVATION ; GENETIC TOXICOLOGY ; STRUCTURAL REQUIREMENTS ; NONGENOTOXIC CHEMICALS ; MICRONUCLEUS ASSAY ; FLOW-CYTOMETRY ; PREDICTION ; BIOMARKER
WOS类目	Medicine, Legal ; Pharmacology & Pharmacy ; Toxicology
WOS研究方向	Legal Medicine ; Pharmacology & Pharmacy ; Toxicology
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/369805
作者单位	[Tran, Yen K.; Buick, Julie K.; Keir, Jennifer L. A.; Williams, Andrew; White, Paul A.; Yauk, Carole L.] Hlth Canada, Environm Hlth Sci & Res Bur, Ottawa, ON K1A 0K9, Canada; [Tran, Yen K.; Lambert, Iain B.; Yauk, Carole L.] Carleton Univ, Dept Biol, Ottawa, ON K1S 5B6, Canada; [Keir, Jennifer L. A.; White, Paul A.] Univ Ottawa, Dept Biol, Ottawa, ON K1N 6N5, Canada; [Swartz, Carol D.; Recio, Leslie] Integrated Lab Syst Inc, Durham, NC 27709 USA
推荐引用方式 GB/T 7714	Tran, Yen K.,Buick, Julie K.,Keir, Jennifer L. A.,et al. Integrated in silico and in vitro genotoxicity assessment of thirteen datapoor substances[J],2019,107.
APA	Tran, Yen K..,Buick, Julie K..,Keir, Jennifer L. A..,Williams, Andrew.,Swartz, Carol D..,...&Yauk, Carole L..(2019).Integrated in silico and in vitro genotoxicity assessment of thirteen datapoor substances.REGULATORY TOXICOLOGY AND PHARMACOLOGY,107.
MLA	Tran, Yen K.,et al."Integrated in silico and in vitro genotoxicity assessment of thirteen datapoor substances".REGULATORY TOXICOLOGY AND PHARMACOLOGY 107(2019).