PMID- 31507242 OWN - NLM STAT- MEDLINE DCOM- 20200522 LR - 20200522 IS - 1528-7394 (Print) IS - 0098-4108 (Linking) VI - 82 IP - 15 DP - 2019 TI - Assessment of skin sensitizing potential of metals with beta-galactosidase-expressing E. coli culture system. PG - 879-889 LID - 10.1080/15287394.2019.1664958 [doi] AB - It has been a challenge to develop in vitro alternative test methods for accurate prediction of metallic products which may exert skin sensitization, as several test methods adopted by OECD were relatively ineffective in assessing the capacity for metallic compounds to exert sensitizing reactions, compared with organic test substances. Based upon these findings, a system that incorporates beta-galactosidase producing E. coli cultures was tested for its predictive capacity to well-known metallic sensitizers. In this system, E. coli cells were incubated with metal salts at various concentrations and beta-galactosidase suppression by each test metal was determined. Fourteen local lymph node assay (LLNA) categorized metal salts were examined. Although color interference from metal salts was minimal, a fluorometric detection system was also employed using 4-methylumbelliferyl galactopyranoside as a substrate for beta-galactosidase to avoid the color interference, concomitantly with the original UV-spectrometric method. Data demonstrated that two detection methods were comparable and complementary. In addition, most of the metallic sensitizers were correctly identified at 0.6 and 0.8 mM concentrations. Despite the lower specificity obtained in the current study and small number of substances tested, the developed method appears to be a relatively simple and effective in vitro method for detecting metallic sensitizers. When 61 chemicals tested in the beta-galactosidase producing E. coli cultures including the present study were collectively analyzed, the prediction capacity was as high as other OECD-adopted tests: 95.6% of sensitivity, 66.7% of specificity, and 88.5% of accuracy. It is important to emphasize that animals or mammalian cell cultures were not required in the current method, which are in accordance with the EU guidelines on restricted or banned animal testing. FAU - Nepal, Mahesh Raj AU - Nepal MR AD - College of Pharmacy, Yeungnam University , Gyeongsan , South Korea. FAU - Kim, Geon Ho AU - Kim GH AD - College of Pharmacy, Yeungnam University , Gyeongsan , South Korea. FAU - Cha, Dong Ho AU - Cha DH AD - College of Pharmacy, Yeungnam University , Gyeongsan , South Korea. FAU - Jeong, Tae Cheon AU - Jeong TC AD - College of Pharmacy, Yeungnam University , Gyeongsan , South Korea. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190911 PL - England TA - J Toxicol Environ Health A JT - Journal of toxicology and environmental health. Part A JID - 100960995 RN - 0 (Metals) RN - 367-93-1 (Isopropyl Thiogalactoside) RN - EC 3.2.1.23 (beta-Galactosidase) SB - IM MH - Animal Testing Alternatives/methods MH - *Dermatitis, Allergic Contact MH - Escherichia coli/enzymology/*genetics MH - Fluorometry MH - Gene Expression Regulation, Enzymologic/*drug effects MH - Isopropyl Thiogalactoside MH - Metals/*toxicity MH - Sensitivity and Specificity MH - Skin/drug effects MH - beta-Galactosidase/*antagonists & inhibitors/genetics/*metabolism OTO - NOTNLM OT - alternative test OT - metals OT - skin sensitization OT - beta-galactosidase EDAT- 2019/09/12 06:00 MHDA- 2020/05/23 06:00 CRDT- 2019/09/12 06:00 PHST- 2019/09/12 06:00 [pubmed] PHST- 2020/05/23 06:00 [medline] PHST- 2019/09/12 06:00 [entrez] AID - 10.1080/15287394.2019.1664958 [doi] PST - ppublish SO - J Toxicol Environ Health A. 2019;82(15):879-889. doi: 10.1080/15287394.2019.1664958. Epub 2019 Sep 11.