Pre-validation of an alternative test method for prediction of developmental neurotoxicity

被引：1

作者：

Jeong, SunHwa ^{[1
]}

Park, Seon-Mi ^{[1
]}

Jo, Na Rea ^{[2
]}

Kwon, Jin-Sook ^{[1
]}

Lee, Jimin ^{[1
]}

Kim, KangMin ^{[1
]}

Go, Seon Myeong ^{[1
]}

Cai, Lian ^{[3
]}

Ahn, Dohee ^{[4
]}

Lee, Sung Duck ^{[2
]}

Hyun, Sang-Hwan ^{[3
]}

Choi, Kyung-Chul ^{[4
]}

Jeung, Eui-Bae ^{[1
,5
,6
]}

机构：

[1] Chungbuk Natl Univ, Coll Vet Med, Lab Vet Biochem & Mol Biol LVBMB, Cheongju 28644, Chungbuk, South Korea

[2] Chungbuk Natl Univ, Coll Nat Sci, Dept Informat & Stat DIS, Cheongju 28644, Chungbuk, South Korea

[3] Chungbuk Natl Univ, Coll Nat Sci, Lab Vet Embryol & Biotechnol LVEB, Cheongju 28644, Chungbuk, South Korea

[4] Chungbuk Natl Univ, Coll Vet Med, Lab Biochem & Immunol LBI, Cheongju 28644, Chungbuk, South Korea

[5] Chungbuk Natl Univ, Vet Med Ctr, Lab Vet Biochem & Mol Biol, Cheongju 28644, Chungbuk, South Korea

[6] Chungbuk Natl Univ, Coll Vet Med, Cheongju 28644, Chungbuk, South Korea

来源：

FOOD AND CHEMICAL TOXICOLOGY | 2022年 / 164卷

关键词：

Validation; Developmental neurotoxicity; 46C; Embryonic stem cell; NEURAL PROGENITOR CELLS; NICOTINE; NEUROSPHERES; CHEMICALS; EXPOSURE;

D O I：

10.1016/j.fct.2022.113070

中图分类号：

TS2 [食品工业];

学科分类号：

0832 ;

摘要：

Exposure to neurodevelopmental toxicants can cause permanent brain injury. Hance, determining the neurotoxicity of unknown substances is essential for the safety of substance. As an alternative method to animal studies, developmental neurotoxicity test (DNT) and the first discriminant function (DF) were established in previous study. This study aimed to increase the predictability of the DNT method and perform a mobility test. Two endpoints of 29 newly investigated substances were used to establish a second-generation DF (2nd GDF). As two endpoints, the half-inhibitory concentration of the cell viability (IC50) was determined using a cell counting kit-8 assay. The half-inhibitory concentration of differentiation (ID50) was determined by measuring the green fluorescent protein (GFP) intensity in 46C cells. The substances were treated dose-dependently to measure IC50 and ID50. The 2nd GDF classified 29 chemicals accurately as toxic and non-toxic. Four participants of three independent laboratories were enrolled to test the mobility. The results of the test set were highly accurate in reproducibility (100% of accuracy, sensitivity, and specificity) and mobility (accuracy 93.33%, sensitivity 90.91%, and specificity 100%). In conclusion, the protocol is transferable, reproducible, and accurate. Therefore, this could be a standardizing method for determining a neurotoxicant as an alternative for animal experiments.

引用

页数：9

共 24 条

[1] Reference Compounds for Alternative Test Methods to Indicate Developmental Neurotoxicity (DNT) Potential of Chemicals: Example Lists and Criteria for their Selection and Use [J].